Alzheimer's Disease
Conditions
Keywords
Early Alzheimer's Disease (AD), Mild Cognitive Impairment (MCI), Mild Alzheimer's Disease (AD), Tau, Early dementia, Tauopathies, AD, Neurodegenerative diseases, Memory loss, Nervous system diseases
Brief summary
This study seeks to evaluate the efficacy and safety of ABBV-8E12 in participants with early Alzheimer's disease (AD).
Interventions
DRUGABBV-8E12
ABBV-8E12 solution for IV infusion
DRUGplacebo for ABBV-8E12
placebo solution for intravenous (IV) infusion
Sponsors
AbbVie
Study design
Allocation
RANDOMIZED
Intervention model
PARALLEL
Primary purpose
TREATMENT
Masking
QUADRUPLE (Subject, Caregiver, Investigator, Outcomes Assessor)
Eligibility
Sex/Gender
ALL
Age
55 Years to 85 Years
Healthy volunteers
No
Inclusion criteria
* Subject who meets the National Institute on Aging and the Alzheimer's Association (NIA-AA) clinical criteria for mild cognitive impairment or probable AD, and have: * Clinical Dementia Rating (CDR)-Global Score of 0.5 * Mini-Mental State Examination (MMSE) score of 22 to 30, inclusive * Repeatable Battery for the Assessment of Neuropsychological Status-Delayed Memory Index (RBANS - DMI) score of 85 or lower * Subject has a positive amyloid positron emission tomography (PET) scan. * Subject has a Modified Hachinski Ischemic Scale (MHIS) score of ≤ 4. * The subject has an identified, reliable, study partner (e.g., family member). * If using medications to treat symptoms related to AD, doses must be stable for at least 12 weeks prior to randomization.
Exclusion criteria
* Subject has any contraindications or inability to tolerate brain magnetic resonance imaging (MRI), PET scans or lumbar puncture. * Subject has evidence of any other clinically significant neurological disorder other than early AD. * In the opinion of the investigator, the subject has any clinically significant or uncontrolled medical or psychiatric illness, or has had an infection requiring medical intervention in the past 30 days. * Subject has had a myocardial infarction, unstable angina, stroke, transient ischemic attack or required intervention for any of these conditions within 6 months of Screening.
Design outcomes
Primary
| Measure | Time frame | Description |
|---|---|---|
| Change From Baseline Over Time in CDR-SB Score | Baseline, Week 24, Week 48, Week 72, Week 96 | The CDR-SB is a numeric scale used to quantify the severity of symptoms of dementia. A qualified health professional assesses a participant's cognitive and functional performance in 6 areas: memory, orientation, judgment and problem solving, community affairs, home and hobbies, and personal care. The CDR scale gives a score from 0 to 3 for each of the 6 areas, with a lower value being desirable. The sum of these 6 areas, the CDR-SB score, can range from 0 to 18, with a lower value being desirable. |
| Number of Participants With Treatment Emergent Adverse Events (TEAEs) | From first dose of study drug up to last dose of study drug plus 20 weeks (up to Week 112) | A TEAE was defined as an adverse event (AE) that began on or after the first study drug dose date and no more than 20 weeks after the last dose of study drug. An adverse event (AE) was defined as any untoward medical occurrence which does not necessarily have a causal relationship with this treatment. Serious AEs (SAEs) were defined as an event that results in death, is life-threatening, results in hospitalization or prolongs hospitalization, is a congenital abnormality, results in persistent or significant disability/incapacity, or is an important medical event. Events were rated in severity as mild, moderate, or severe, and were categorized as having a reasonable possibility or no reasonable possibility of relationship to study drug. |
Secondary
| Measure | Time frame | Description |
|---|---|---|
| Serum Concentration at the End of a Dose Interval (Ctrough) for ABBV-8E12 Over the Dosing Interval After the First and Fourth Doses | Day 1 (Dose 1): Pre-infusion, post-infusion (within 15 minutes), 1 and 2 hours post-infusion; Days 5 and 15. Day 85 (Dose 4): Pre-infusion (0 hour), post-infusion (within 15 minutes) and 1 and 2 hours post-infusion; Days 89 and 99. | — |
| Half-Life (T1/2) for ABBV-8E12 Over the Dosing Interval After the First and Fourth Doses | Day 1 (Dose 1): Pre-infusion, post-infusion (within 15 minutes), 1 and 2 hours post-infusion; Days 5 and 15. Day 85 (Dose 4): Pre-infusion (0 hour), post-infusion (within 15 minutes) and 1 and 2 hours post-infusion; Days 89 and 99. | Harmonic mean is presented in the data table. |
| Area Under the Concentration-Time Curve From Dosing (Time 0) to Day 28 (AUC0-28) for ABBV-8E12 Over the Dosing Interval After the First and Fourth Doses | Day 1 (Dose 1): pre-infusion, up to Day 29 (trough level before Dose 2). Day 85 (Dose 4): pre-infusion, up to Day 113 (trough level before Dose 5). See Outcome Measure description above for complete time point details. | * The AUC0-28 for Dose 1 included the following timepoints: pre-infusion, post-infusion (within 15 min), 1 and 2 hours post-infusion, Day 5, Day 15 and Day 29 (trough level before Dose 2). * The AUC0-28 for Dose 4 included the following timepoints: Day 85 pre-infusion, post-infusion (within 15 min), 1 and 2 hours post-infusion, Day 89, Day 99 and Day 113 (trough level before Dose 5). |
| Cmax/Dose for ABBV-8E12 Over the Dosing Interval After the First and Fourth Doses | Day 1 (Dose 1): Pre-infusion, post-infusion (within 15 minutes), 1 and 2 hours post-infusion; Days 5 and 15. Day 85 (Dose 4): Pre-infusion (0 hour), post-infusion (within 15 minutes) and 1 and 2 hours post-infusion; Days 89 and 99. | — |
| AUC0-28/Dose for ABBV-8E12 Over the Dosing Interval After the First and Fourth Doses | Day 1 (Dose 1): pre-infusion, up to Day 29 (trough level before Dose 2). Day 85 (Dose 4): pre-infusion, up to Day 113 (trough level before Dose 5). See Outcome Measure description above for complete time point details. | * The AUC0-28/dose for Dose 1 included the following timepoints: pre-infusion, post-infusion (within 15 min), 1 and 2 hours post-infusion, Day 5, Day 15 and Day 29 (trough level before Dose 2). * The AUC0-28/dose for Dose 4 included the following timepoints: Day 85 pre-infusion, post-infusion (within 15 min), 1 and 2 hours post-infusion, Day 89, Day 99 and Day 113 (trough level before Dose 5). |
| Change From Baseline Over Time in Alzheimer's Disease Assessment Scale (14-Item) Cognition Portion (ADAS-Cog-14) Total Score | Baseline, Week 24, Week 48, Week 72, Week 96 | The ADAS-Cog was designed to assess the cognitive impairments most common in AD. The ADAS-Cog-14 includes the original 11 items from the ADAS-Cog-11 \[1. Spoken language ability, 2. Comprehension of spoken language, 3. Recall of test instructions, 4. Word-findings difficulty in spontaneous speech, 5. Following commands, 6. Naming objects and fingers, 7. Constructional praxis, 8. Ideational praxis, 9. Orientation, 10. Word-recall task, 11. Word-recognition task\] and includes 3 additional tasks \[12. Number cancellation task, 13. Delayed word recall task, 14. Executive functioning\], for increased sensitivity in mild cognitive impairment (MCI) patients. The Total Score of the ADAS-Cog-14 ranges from 0 to 90, with a higher score representing greater impairment. |
| Change From Baseline Over Time in ADAS-Cog-14 Comprehension of Spoken Language Score | Baseline, Week 24, Week 48, Week 72, Week 96 | The ADAS-Cog was designed to assess the cognitive impairments most common in AD. The ADAS-Cog-14 includes the original 11 items from the ADAS-Cog-11 \[1. Spoken language ability, 2. Comprehension of spoken language, 3. Recall of test instructions, 4. Word-findings difficulty in spontaneous speech, 5. Following commands, 6. Naming objects and fingers, 7. Constructional praxis, 8. Ideational praxis, 9. Orientation, 10. Word-recall task, 11. Word-recognition task\] and includes 3 additional tasks \[12. Number cancellation task, 13. Delayed word recall task, 14. Executive functioning\], for increased sensitivity in MCI patients. The Comprehension of Spoken Language score of the ADAS-Cog-14 ranges from 0 to 5, with a higher score representing greater impairment. |
| Change From Baseline Over Time in ADAS-Cog-14 Constructional Praxis Score | Baseline, Week 24, Week 48, Week 72, Week 96 | The ADAS-Cog was designed to assess the cognitive impairments most common in AD. The ADAS-Cog-14 includes the original 11 items from the ADAS-Cog-11 \[1. Spoken language ability, 2. Comprehension of spoken language, 3. Recall of test instructions, 4. Word-findings difficulty in spontaneous speech, 5. Following commands, 6. Naming objects and fingers, 7. Constructional praxis, 8. Ideational praxis, 9. Orientation, 10. Word-recall task, 11. Word-recognition task\] and includes 3 additional tasks \[12. Number cancellation task, 13. Delayed word recall task, 14. Executive functioning\], for increased sensitivity in MCI patients. The Constructional Praxis Score of the ADAS-Cog-14 ranges from 0 to 5, with a higher score representing greater impairment. |
| Change From Baseline Over Time in ADAS-Cog-14 Commands Score | Baseline, Week 24, Week 48, Week 72, Week 96 | The ADAS-Cog was designed to assess the cognitive impairments most common in AD. The ADAS-Cog-14 includes the original 11 items from the ADAS-Cog-11 \[1. Spoken language ability, 2. Comprehension of spoken language, 3. Recall of test instructions, 4. Word-findings difficulty in spontaneous speech, 5. Following commands, 6. Naming objects and fingers, 7. Constructional praxis, 8. Ideational praxis, 9. Orientation, 10. Word-recall task, 11. Word-recognition task\] and includes 3 additional tasks \[12. Number cancellation task, 13. Delayed word recall task, 14. Executive functioning\], for increased sensitivity in MCI patients. The Commands Score of the ADAS-Cog-14 ranges from 0 to 5, with a higher score representing greater impairment. |
| Change From Baseline Over Time in ADAS-Cog-14 Delayed Word Recall Score | Baseline, Week 24, Week 48, Week 72, Week 96 | The ADAS-Cog was designed to assess the cognitive impairments most common in AD. The ADAS-Cog-14 includes the original 11 items from the ADAS-Cog-11 \[1. Spoken language ability, 2. Comprehension of spoken language, 3. Recall of test instructions, 4. Word-findings difficulty in spontaneous speech, 5. Following commands, 6. Naming objects and fingers, 7. Constructional praxis, 8. Ideational praxis, 9. Orientation, 10. Word-recall task, 11. Word-recognition task\] and includes 3 additional tasks \[12. Number cancellation task, 13. Delayed word recall task, 14. Executive functioning\], for increased sensitivity in MCI patients. The Delayed Word Recall Score of the ADAS-Cog-14 ranges from 0 to 10, with a higher score representing greater impairment. |
| Change From Baseline Over Time in ADAS-Cog-14 Ideational Praxis Score | Baseline, Week 24, Week 48, Week 72, Week 96 | The ADAS-Cog was designed to assess the cognitive impairments most common in AD. The ADAS-Cog-14 includes the original 11 items from the ADAS-Cog-11 \[1. Spoken language ability, 2. Comprehension of spoken language, 3. Recall of test instructions, 4. Word-findings difficulty in spontaneous speech, 5. Following commands, 6. Naming objects and fingers, 7. Constructional praxis, 8. Ideational praxis, 9. Orientation, 10. Word-recall task, 11. Word-recognition task\] and includes 3 additional tasks \[12. Number cancellation task, 13. Delayed word recall task, 14. Executive functioning\], for increased sensitivity in MCI patients. The Ideational Praxis Score of the ADAS-Cog-14 ranges from 0 to 5, with a higher score representing greater impairment. |
| Change From Baseline Over Time in ADAS-Cog-14 Maze Task Score | Baseline, Week 24, Week 48, Week 72, Week 96 | The ADAS-Cog was designed to assess the cognitive impairments most common in AD. The ADAS-Cog-14 includes the original 11 items from the ADAS-Cog-11 \[1. Spoken language ability, 2. Comprehension of spoken language, 3. Recall of test instructions, 4. Word-findings difficulty in spontaneous speech, 5. Following commands, 6. Naming objects and fingers, 7. Constructional praxis, 8. Ideational praxis, 9. Orientation, 10. Word-recall task, 11. Word-recognition task\] and includes 3 additional tasks \[12. Number cancellation task, 13. Delayed word recall task, 14. Executive functioning\], for increased sensitivity in MCI patients. The Maze Task Score of the ADAS-Cog-14 ranges from 0 to 5, with a higher score representing greater impairment. |
| Change From Baseline Over Time in ADAS-Cog-14 Number Cancellation Score | Baseline, Week 24, Week 48, Week 72, Week 96 | The ADAS-Cog was designed to assess the cognitive impairments most common in AD. The ADAS-Cog-14 includes the original 11 items from the ADAS-Cog-11 \[1. Spoken language ability, 2. Comprehension of spoken language, 3. Recall of test instructions, 4. Word-findings difficulty in spontaneous speech, 5. Following commands, 6. Naming objects and fingers, 7. Constructional praxis, 8. Ideational praxis, 9. Orientation, 10. Word-recall task, 11. Word-recognition task\] and includes 3 additional tasks \[12. Number cancellation task, 13. Delayed word recall task, 14. Executive functioning\], for increased sensitivity in MCI patients. The Number Cancellation Score of the ADAS-Cog-14 ranges from 0 to 5, with a higher score representing greater impairment. |
| Change From Baseline Over Time in ADAS-Cog-14 Naming Score | Baseline, Week 24, Week 48, Week 72, Week 96 | The ADAS-Cog was designed to assess the cognitive impairments most common in AD. The ADAS-Cog-14 includes the original 11 items from the ADAS-Cog-11 \[1. Spoken language ability, 2. Comprehension of spoken language, 3. Recall of test instructions, 4. Word-findings difficulty in spontaneous speech, 5. Following commands, 6. Naming objects and fingers, 7. Constructional praxis, 8. Ideational praxis, 9. Orientation, 10. Word-recall task, 11. Word-recognition task\] and includes 3 additional tasks \[12. Number cancellation task, 13. Delayed word recall task, 14. Executive functioning\], for increased sensitivity in MCI patients. The Naming Score of the ADAS-Cog-14 ranges from 0 to 5 with a higher score representing greater impairment. |
| Change From Baseline Over Time in ADAS-Cog-14 Orientation Score | Baseline, Week 24, Week 48, Week 72, Week 96 | The ADAS-Cog was designed to assess the cognitive impairments most common in AD. The ADAS-Cog-14 includes the original 11 items from the ADAS-Cog-11 \[1. Spoken language ability, 2. Comprehension of spoken language, 3. Recall of test instructions, 4. Word-findings difficulty in spontaneous speech, 5. Following commands, 6. Naming objects and fingers, 7. Constructional praxis, 8. Ideational praxis, 9. Orientation, 10. Word-recall task, 11. Word-recognition task\] and includes 3 additional tasks \[12. Number cancellation task, 13. Delayed word recall task, 14. Executive functioning\], for increased sensitivity in MCI patients. The Orientation Score of the ADAS-Cog-14 ranges from 0 to 8, with a higher score representing greater impairment. |
| Change From Baseline Over Time in ADAS-Cog-14 Word Recall - Number of Words Not Recalled Score | Baseline, Week 24, Week 48, Week 72, Week 96 | The ADAS-Cog was designed to assess the cognitive impairments most common in AD. The ADAS-Cog-14 includes the original 11 items from the ADAS-Cog-11 \[1. Spoken language ability, 2. Comprehension of spoken language, 3. Recall of test instructions, 4. Word-findings difficulty in spontaneous speech, 5. Following commands, 6. Naming objects and fingers, 7. Constructional praxis, 8. Ideational praxis, 9. Orientation, 10. Word-recall task, 11. Word-recognition task\] and includes 3 additional tasks \[12. Number cancellation task, 13. Delayed word recall task, 14. Executive functioning\], for increased sensitivity in MCI patients. The Word Recall - Number of Words Not Recalled Score of the ADAS-Cog-14 ranges from 0 to 10, with a higher score representing greater impairment. |
| Change From Baseline Over Time in ADAS-Cog-14 Remember Word Recognition Instructions Score | Baseline, Week 24, Week 48, Week 72, Week 96 | The ADAS-Cog was designed to assess the cognitive impairments most common in AD. The ADAS-Cog-14 includes the original 11 items from the ADAS-Cog-11 \[1. Spoken language ability, 2. Comprehension of spoken language, 3. Recall of test instructions, 4. Word-findings difficulty in spontaneous speech, 5. Following commands, 6. Naming objects and fingers, 7. Constructional praxis, 8. Ideational praxis, 9. Orientation, 10. Word-recall task, 11. Word-recognition task\] and includes 3 additional tasks \[12. Number cancellation task, 13. Delayed word recall task, 14. Executive functioning\], for increased sensitivity in MCI patients. The Remember Word Recognition Instructions Score of the ADAS-Cog-14 ranges from 0 to 5, with a higher score representing greater impairment. |
| Change From Baseline Over Time in ADAS-Cog-14 Spoken Language Ability Score | Baseline, Week 24, Week 48, Week 72, Week 96 | The ADAS-Cog was designed to assess the cognitive impairments most common in AD. The ADAS-Cog-14 includes the original 11 items from the ADAS-Cog-11 \[1. Spoken language ability, 2. Comprehension of spoken language, 3. Recall of test instructions, 4. Word-findings difficulty in spontaneous speech, 5. Following commands, 6. Naming objects and fingers, 7. Constructional praxis, 8. Ideational praxis, 9. Orientation, 10. Word-recall task, 11. Word-recognition task\] and includes 3 additional tasks \[12. Number cancellation task, 13. Delayed word recall task, 14. Executive functioning\], for increased sensitivity in MCI patients. The Spoken Language Ability Score of the ADAS-Cog-14 ranges from 0 to 5, with a higher score representing greater impairment. |
| Change From Baseline Over Time in ADAS-Cog-14 Word Find Difficulty Spontaneous Speech Score | Baseline, Week 24, Week 48, Week 72, Week 96 | The ADAS-Cog was designed to assess the cognitive impairments most common in AD. The ADAS-Cog-14 includes the original 11 items from the ADAS-Cog-11 \[1. Spoken language ability, 2. Comprehension of spoken language, 3. Recall of test instructions, 4. Word-findings difficulty in spontaneous speech, 5. Following commands, 6. Naming objects and fingers, 7. Constructional praxis, 8. Ideational praxis, 9. Orientation, 10. Word-recall task, 11. Word-recognition task\] and includes 3 additional tasks \[12. Number cancellation task, 13. Delayed word recall task, 14. Executive functioning\], for increased sensitivity in MCI patients. The Word Find Difficulty Spontaneous Speech Score of the ADAS-Cog-14 ranges from 0 to 5, with a higher score representing greater impairment. |
| Change From Baseline Over Time in ADAS-Cog-14 Word Recognition Score | Baseline, Week 24, Week 48, Week 72, Week 96 | The ADAS-Cog was designed to assess the cognitive impairments most common in AD. The ADAS-Cog-14 includes the original 11 items from the ADAS-Cog-11 \[1. Spoken language ability, 2. Comprehension of spoken language, 3. Recall of test instructions, 4. Word-findings difficulty in spontaneous speech, 5. Following commands, 6. Naming objects and fingers, 7. Constructional praxis, 8. Ideational praxis, 9. Orientation, 10. Word-recall task, 11. Word-recognition task\] and includes 3 additional tasks \[12. Number cancellation task, 13. Delayed word recall task, 14. Executive functioning\], for increased sensitivity in MCI patients. The Word Recognition Score of the ADAS-Cog-14 ranges from 0 to 12, with a higher score representing greater impairment. |
| Change From Baseline Over Time in Functional Activities Questionnaire (FAQ) Score | Baseline, Week 24, Week 48, Week 72, Week 96 | The FAQ measures level of assistance (functional disability) needed for carrying out instrumental activities in daily living (iADLs). The FAQ score ranges from 0 - 30 and consists of 10 items (each scored from 0 - 3), which measure a specific iADL in the past 4-weeks: \[1) writing checks, paying bills, keeping financial records; 2) assembling tax or business records; 3) shopping alone; 4) playing a game of skill; 5) making coffee or tea; 6) preparing a balanced meal; 7) keeping track of current events; 8) attending to and understanding a television program, book, or magazine; 9) remembering appointments, family occasions, medications; and 10) traveling out of the neighborhood\]. Performance in each category is rated from 0 - 3 as follows: 0 - normal; 1 - has difficulty, but does by self; 2 - requires assistance; or 3 - dependent. The FAQ was administered by a trained interviewer. Higher scores indicate a greater requirement of assistance. |
| Change From Baseline Over Time in Alzheimer's Disease Cooperative Study Clinical Global Impression of Change for Mild Cognitive Impairment (ADCS-CGIC-MCI) General Condition Score | Baseline, Week 48, Week 96 | The instrument assesses the physician's global impression of change in 4 major cognitive domains. The instrument covers 4 major domains: 1. General condition , 2. Cognition, 3. Behavior, and 4. Social and daily functioning. Scoring is based on a 7-point Likert Scale: 1, marked improvement; 2, moderate improvement; 3, minimal improvement; 4, no change; 5, minimal worsening; 6, moderate worsening; 7, marked worsening. Higher score indicates greater worsening. |
| Change From Baseline Over Time in ADCS-CGIC-MCI Cognition Score | Baseline, Week 48, Week 96 | The instrument assesses the physician's global impression of change in 4 major cognitive domains. The instrument covers 4 major domains: 1. General condition , 2. Cognition, 3. Behavior, and 4. Social and daily functioning. Scoring is based on a 7-point Likert Scale: 1, marked improvement; 2, moderate improvement; 3, minimal improvement; 4, no change; 5, minimal worsening; 6, moderate worsening; 7, marked worsening. Higher score indicates greater worsening. |
| Change From Baseline Over Time in ADCS-CGIC-MCI Behavior Score | Baseline, Week 48, Week 96 | The instrument assesses the physician's global impression of change in 4 major cognitive domains. The instrument covers 4 major domains: 1. General condition , 2. Cognition, 3. Behavior, and 4. Social and daily functioning. Scoring is based on a 7-point Likert Scale: 1, marked improvement; 2, moderate improvement; 3, minimal improvement; 4, no change; 5, minimal worsening; 6, moderate worsening; 7, marked worsening. Higher score indicates greater worsening. |
| Change From Baseline Over Time in ADCS-CGIC-MCI Functional Abilities Score | Baseline, Week 48, Week 96 | The instrument assesses the physician's global impression of change in 4 major cognitive domains. The instrument covers 4 major domains: 1. General condition , 2. Cognition, 3. Behavior, and 4. Social and daily functioning (functional abilities). Scoring is based on a 7-point Likert Scale: 1, marked improvement; 2, moderate improvement; 3, minimal improvement; 4, no change; 5, minimal worsening; 6, moderate worsening; 7, marked worsening. Higher score indicates greater worsening. |
| Change From Baseline Over Time in University of California's Performance Based Skills Assessment, Brief Version (UPSA-Brief) - Total Score | Baseline, Week 48, Week 96 | The UPSA-Brief is a performance-based instrument which uses a series of tasks and roleplay scenarios to evaluate a person's functional capacity in two areas of basic living skills (i.e., financial skills and communication skills). Scores range from 0 to 100; a higher score of the UPSA-Brief is desirable. |
| Change From Baseline Over Time in 24-Item Alzheimer's Disease Cooperative Study/Activities of Daily Living Scale Adapted for Patients With Mild Cognitive Impairment (ADCS-MCI-ADL-24) Total Score | Baseline, Week 48, Week 96 | The ADCS-MCI-ADL-24 is a 24-item, study partner-based assessment of activities of daily living designed specifically for AD patients and is completed by a trained rater. The scale assesses functional activities such as cooking, household chores, shopping, keeping appointments, social interactions and hobbies. Items are assessed according to whether they were performed in the past 4 weeks and, if so, some items are further assessed as to whether they were performed independently, with supervision, or with physical help. Scores on the ADCS-ADL-MCI range from 0 to 69, where higher score indicates greater capability to carry out activities of daily living. |
| Change From Baseline Over Time in Repeatable Battery for Assessment of Neuropsychological Status (RBANS) - Total Scale Score | Baseline, Week 24, Week 48, Week 72, Week 96 | The RBANS is a 25-minute, standardized neurocognitive battery with North American population-based normative data. The RBANS measures five neurocognitive domains, with age-based scaling. Twelve subtests measure cognitive decline or improvement across the following domains: 1. Immediate Memory - List Learning and Story Memory, 2. Visuospatial/Constructional - Figure Copy and Line Orientation, 3. Language - Picture naming and Semantic Fluency, 4. Attention - Digit Span and Coding, and 5. Delayed Memory - List Recall, List Recognition, Story Memory, and Figure Recall. Total score can range from 40 to 160 with a higher score representing a better outcome. |
| Change From Baseline Over Time in RBANS - Coding Total Score | Baseline, Week 24, Week 48, Week 72, Week 96 | The RBANS is a 25-minute, standardized neurocognitive battery with North American population-based normative data. The RBANS measures five neurocognitive domains, with age-based scaling. Twelve subtests measure cognitive decline or improvement across the following domains: 1. Immediate Memory - List Learning and Story Memory, 2. Visuospatial/Constructional - Figure Copy and Line Orientation, 3. Language - Picture naming and Semantic Fluency, 4. Attention - Digit Span and Coding, and 5. Delayed Memory - List Recall, List Recognition, Story Memory, and Figure Recall. The Coding Total Score of the RBANS ranges from 0 to 89, with a higher score representing a better outcome. |
| Change From Baseline Over Time in RBANS - Digit Span Total Score | Baseline, Week 24, Week 48, Week 72, Week 96 | The RBANS is a 25-minute, standardized neurocognitive battery with North American population-based normative data. The RBANS measures five neurocognitive domains, with age-based scaling. Twelve subtests measure cognitive decline or improvement across the following domains: 1. Immediate Memory - List Learning and Story Memory, 2. Visuospatial/Constructional - Figure Copy and Line Orientation, 3. Language - Picture naming and Semantic Fluency, 4. Attention - Digit Span and Coding, and 5. Delayed Memory - List Recall, List Recognition, Story Memory, and Figure Recall. The Digit Span Total Score of the RBANS ranges from 0 to 8, with a higher score representing a better outcome. |
| Change From Baseline Over Time in RBANS - Figure Copy Total Score | Baseline, Week 24, Week 48, Week 72, Week 96 | The RBANS is a 25-minute, standardized neurocognitive battery with North American population-based normative data. The RBANS measures five neurocognitive domains, with age-based scaling. Twelve subtests measure cognitive decline or improvement across the following domains: 1. Immediate Memory - List Learning and Story Memory, 2. Visuospatial/Constructional - Figure Copy and Line Orientation, 3. Language - Picture naming and Semantic Fluency, 4. Attention - Digit Span and Coding, and 5. Delayed Memory - List Recall, List Recognition, Story Memory, and Figure Recall. The Figure Copy Total Score of the RBANS ranges from 0 to 20, with a higher score representing a better outcome. |
| Change From Baseline Over Time in RBANS - Figure Recall Total Score | Baseline, Week 24, Week 48, Week 72, Week 96 | The RBANS is a 25-minute, standardized neurocognitive battery with North American population-based normative data. The RBANS measures five neurocognitive domains, with age-based scaling. Twelve subtests measure cognitive decline or improvement across the following domains: 1. Immediate Memory - List Learning and Story Memory, 2. Visuospatial/Constructional - Figure Copy and Line Orientation, 3. Language - Picture naming and Semantic Fluency, 4. Attention - Digit Span and Coding, and 5. Delayed Memory - List Recall, List Recognition, Story Memory, and Figure Recall. The Figure Recall Total Score of the RBANS ranges from 0 to 18, with a higher score representing a better outcome. |
| Change From Baseline Over Time in RBANS - List Recognition Total Score | Baseline, Week 24, Week 48, Week 72, Week 96 | The RBANS is a 25-minute, standardized neurocognitive battery with North American population-based normative data. The RBANS measures five neurocognitive domains, with age-based scaling. Twelve subtests measure cognitive decline or improvement across the following domains: 1. Immediate Memory - List Learning and Story Memory, 2. Visuospatial/Constructional - Figure Copy and Line Orientation, 3. Language - Picture naming and Semantic Fluency, 4. Attention - Digit Span and Coding, and 5. Delayed Memory - List Recall, List Recognition, Story Memory, and Figure Recall. The List Recognition Total Score of the RBANS ranges from 0 to 20, with a higher score representing a better outcome. |
| Change From Baseline Over Time in RBANS - List Learning Total Score | Baseline, Week 24, Week 48, Week 72, Week 96 | The RBANS is a 25-minute, standardized neurocognitive battery with North American population-based normative data. The RBANS measures five neurocognitive domains, with age-based scaling. Twelve subtests measure cognitive decline or improvement across the following domains: 1. Immediate Memory - List Learning and Story Memory, 2. Visuospatial/Constructional - Figure Copy and Line Orientation, 3. Language - Picture naming and Semantic Fluency, 4. Attention - Digit Span and Coding, and 5. Delayed Memory - List Recall, List Recognition, Story Memory, and Figure Recall. The List Learning Total Score of the RBANS ranges from 0 to 40, with a higher score representing a better outcome. |
| Change From Baseline Over Time in RBANS - Line Orientation Total Score | Baseline, Week 24, Week 48, Week 72, Week 96 | The RBANS is a 25-minute, standardized neurocognitive battery with North American population-based normative data. The RBANS measures five neurocognitive domains, with age-based scaling. Twelve subtests measure cognitive decline or improvement across the following domains: 1. Immediate Memory - List Learning and Story Memory, 2. Visuospatial/Constructional - Figure Copy and Line Orientation, 3. Language - Picture naming and Semantic Fluency, 4. Attention - Digit Span and Coding, and 5. Delayed Memory - List Recall, List Recognition, Story Memory, and Figure Recall. The Line Orientation Total Score of the RBANS ranges from 0 to 20, with a higher score representing a better outcome. |
| Change From Baseline Over Time in RBANS - List Recall Total Score | Baseline, Week 24, Week 48, Week 72, Week 96 | The RBANS is a 25-minute, standardized neurocognitive battery with North American population-based normative data. The RBANS measures five neurocognitive domains, with age-based scaling. Twelve subtests measure cognitive decline or improvement across the following domains: 1. Immediate Memory - List Learning and Story Memory, 2. Visuospatial/Constructional - Figure Copy and Line Orientation, 3. Language - Picture naming and Semantic Fluency, 4. Attention - Digit Span and Coding, and 5. Delayed Memory - List Recall, List Recognition, Story Memory, and Figure Recall. The List Recall Total Score of the RBANS ranges from 0 to 10, with a higher score representing a better outcome. |
| Change From Baseline Over Time in RBANS - Picture Naming Total Score | Baseline, Week 24, Week 48, Week 72, Week 96 | The RBANS is a 25-minute, standardized neurocognitive battery with North American population-based normative data. The RBANS measures five neurocognitive domains, with age-based scaling. Twelve subtests measure cognitive decline or improvement across the following domains: 1. Immediate Memory - List Learning and Story Memory, 2. Visuospatial/Constructional - Figure Copy and Line Orientation, 3. Language - Picture naming and Semantic Fluency, 4. Attention - Digit Span and Coding, and 5. Delayed Memory - List Recall, List Recognition, Story Memory, and Figure Recall. The Picture Naming Total Score of the RBANS ranges from 0 to 10, with a higher score representing a better outcome. |
| Change From Baseline Over Time in RBANS - Semantic Fluency Total Score | Baseline, Week 24, Week 48, Week 72, Week 96 | The RBANS is a 25-minute, standardized neurocognitive battery with North American population-based normative data. The RBANS measures five neurocognitive domains, with age-based scaling. Twelve subtests measure cognitive decline or improvement across the following domains: 1. Immediate Memory - List Learning and Story Memory, 2. Visuospatial/Constructional - Figure Copy and Line Orientation, 3. Language - Picture naming and Semantic Fluency, 4. Attention - Digit Span and Coding, and 5. Delayed Memory - List Recall, List Recognition, Story Memory, and Figure Recall. The Semantic Fluency Total Score of the RBANS ranges from 0 to 40, with a higher score representing a better outcome. |
| Change From Baseline Over Time in RBANS - Story Memory Total Score | Baseline, Week 24, Week 48, Week 72, Week 96 | The RBANS is a 25-minute, standardized neurocognitive battery with North American population-based normative data. The RBANS measures five neurocognitive domains, with age-based scaling. Twelve subtests measure cognitive decline or improvement across the following domains: 1. Immediate Memory - List Learning and Story Memory, 2. Visuospatial/Constructional - Figure Copy and Line Orientation, 3. Language - Picture naming and Semantic Fluency, 4. Attention - Digit Span and Coding, and 5. Delayed Memory - List Recall, List Recognition, Story Memory, and Figure Recall. The Story Memory Total Score of the RBANS ranges from 0 to 24, with a higher score representing a better outcome. |
| Maximum Observed Serum Concentration (Cmax) for ABBV-8E12 Over the Dosing Interval After the First and Fourth Doses | Day 1 (Dose 1): Pre-infusion, post-infusion (within 15 minutes), 1 and 2 hours post-infusion; Days 5 and 15. Day 85 (Dose 4): Pre-infusion (0 hour), post-infusion (within 15 minutes) and 1 and 2 hours post-infusion; Days 89 and 99. | — |
| Change From Baseline Over Time in Mini-Mental State Examination (MMSE) Total Score | Baseline, Week 24, Week 48, Week 72, Week 96 | The MMSE is a brief, 30-point questionnaire, administered by a trained rater, which provides a quantitative measure of cognitive status in adults and is widely used to screen for cognitive impairment and to estimate the severity of cognitive impairment at a given point in time in AD participants. The MMSE ranges from 0 to 30, with lower scores indicating greater impairment. |
| Change From Baseline Over Time in Neuropsychiatry Inventory (NPI) Total Score | Baseline, Week 24, Week 48, Week 72, Week 96 | The NPI is used to assess changes in the participant's behavior that occurred in a defined period of time (4 weeks). The NPI assesses 12 behavioral domains on the dimensions of frequency and severity. Frequency is rated on a scale where 0 = absent, 1 = occasionally, 2 = often, 3 = frequently, 4 = very frequently. Severity is rated on a scale where 0 = absent, 1 = mild, 2 = moderate, 3 = severe. For each of the domains, 3 scores are obtained: frequency, severity, and total (product of frequency and severity; ranges from 0 to 12, with a lower score desirable). A total NPI score can be calculated by summing the domain total scores. Total Score ranges from 0 to 144 with a lower score desirable. |
| Change From Baseline Over Time in Alzheimer's Disease Composite Score (ADCOMS) Score | Baseline, Week 24, Week 48, Week 72, Week 96 | ADCOMS score is a composite score which is a weighted linear combination of the selected individual scale items from ADAS-Cog-14 (see description in Outcome Measure 10) , MMSE (see description in Outcome Measure 45), and CDR-SB (see description in Outcome Measure 1) scales. The ADCOMS score ranges from 0 to 1.97, with a lower score desirable. |
| Change From Baseline Over Time in RBANS - Story Recall Total Score | Baseline, Week 24, Week 48, Week 72, Week 96 | The RBANS is a 25-minute, standardized neurocognitive battery with North American population-based normative data. The RBANS measures five neurocognitive domains, with age-based scaling. Twelve subtests measure cognitive decline or improvement across the following domains: 1. Immediate Memory - List Learning and Story Memory, 2. Visuospatial/Constructional - Figure Copy and Line Orientation, 3. Language - Picture naming and Semantic Fluency, 4. Attention - Digit Span and Coding, and 5. Delayed Memory - List Recall, List Recognition, Story Memory, and Figure Recall. The Story Recall Total Score of the RBANS ranges from 0 to 12, with a higher score representing a better outcome. |
| Time to Cmax (Tmax) for ABBV-8E12 Over the Dosing Interval After the First and Fourth Doses | Day 1 (Dose 1): Pre-infusion, post-infusion (within 15 minutes), 1 and 2 hours post-infusion; Days 5 and 15. Day 85 (Dose 4): Pre-infusion (0 hour), post-infusion (within 15 minutes) and 1 and 2 hours post-infusion; Days 89 and 99. | — |
Countries
Australia, Belgium, Canada, Denmark, Finland, Italy, Netherlands, New Zealand, Spain, Sweden, United States
Participant flow
Participants by arm
| Arm | Count |
|---|---|
| Placebo Placebo for ABBV-8E12 every 4 weeks for 96 weeks | 116 |
| ABBV-8E12 300 mg ABBV-8E12 300 mg every 4 weeks for 96 weeks | 108 |
| ABBV-8E12 1000 mg ABBV-8E12 1000 mg every 4 weeks for 96 weeks | 116 |
| ABBV-8E12 2000 mg ABBV-8E12 2000 mg every 4 weeks for 96 weeks | 113 |
| Total | 453 |
Withdrawals & dropouts
| Period | Reason | FG000 | FG001 | FG002 | FG003 |
|---|---|---|---|---|---|
| Overall Study | Adverse Event | 3 | 6 | 5 | 4 |
| Overall Study | COVID-19 Logistical Restrictions | 1 | 2 | 0 | 0 |
| Overall Study | Lost to Follow-up | 0 | 1 | 0 | 0 |
| Overall Study | Other, Not Specified | 4 | 2 | 0 | 3 |
| Overall Study | Withdrawal by Subject | 9 | 4 | 6 | 11 |
Baseline characteristics
| Characteristic | Total | Placebo | ABBV-8E12 300 mg | ABBV-8E12 1000 mg | ABBV-8E12 2000 mg |
|---|---|---|---|---|---|
| Age, Customized < 65 years | 85 Participants | 15 Participants | 24 Participants | 17 Participants | 29 Participants |
| Age, Customized >= 65 years | 368 Participants | 101 Participants | 84 Participants | 99 Participants | 84 Participants |
| Clinical Dementia Rating Scale - Sum of Boxes (CDR-SB) Score | 3.0 score on a scale STANDARD_DEVIATION 1.18 | 3.0 score on a scale STANDARD_DEVIATION 1.22 | 3.0 score on a scale STANDARD_DEVIATION 1.12 | 3.1 score on a scale STANDARD_DEVIATION 1.24 | 2.9 score on a scale STANDARD_DEVIATION 1.14 |
| Race/Ethnicity, Customized Hispanic or Latino | 17 Participants | 4 Participants | 6 Participants | 4 Participants | 3 Participants |
| Race/Ethnicity, Customized None | 436 Participants | 112 Participants | 102 Participants | 112 Participants | 110 Participants |
| Race (NIH/OMB) American Indian or Alaska Native | 0 Participants | 0 Participants | 0 Participants | 0 Participants | 0 Participants |
| Race (NIH/OMB) Asian | 5 Participants | 2 Participants | 3 Participants | 0 Participants | 0 Participants |
| Race (NIH/OMB) Black or African American | 7 Participants | 2 Participants | 3 Participants | 1 Participants | 1 Participants |
| Race (NIH/OMB) More than one race | 3 Participants | 1 Participants | 0 Participants | 1 Participants | 1 Participants |
| Race (NIH/OMB) Native Hawaiian or Other Pacific Islander | 1 Participants | 0 Participants | 0 Participants | 1 Participants | 0 Participants |
| Race (NIH/OMB) Unknown or Not Reported | 0 Participants | 0 Participants | 0 Participants | 0 Participants | 0 Participants |
| Race (NIH/OMB) White | 437 Participants | 111 Participants | 102 Participants | 113 Participants | 111 Participants |
| Sex: Female, Male Female | 234 Participants | 70 Participants | 45 Participants | 60 Participants | 59 Participants |
| Sex: Female, Male Male | 219 Participants | 46 Participants | 63 Participants | 56 Participants | 54 Participants |
Adverse events
| Event type | EG000 affected / at risk | EG001 affected / at risk | EG002 affected / at risk | EG003 affected / at risk |
|---|---|---|---|---|
| deaths Total, all-cause mortality | 1 / 116 | 2 / 108 | 2 / 116 | 1 / 113 |
| other Total, other adverse events | 83 / 116 | 68 / 108 | 86 / 116 | 91 / 113 |
| serious Total, serious adverse events | 26 / 116 | 19 / 108 | 22 / 116 | 17 / 113 |
Outcome results
Primary
Change From Baseline Over Time in CDR-SB Score
The CDR-SB is a numeric scale used to quantify the severity of symptoms of dementia. A qualified health professional assesses a participant's cognitive and functional performance in 6 areas: memory, orientation, judgment and problem solving, community affairs, home and hobbies, and personal care. The CDR scale gives a score from 0 to 3 for each of the 6 areas, with a lower value being desirable. The sum of these 6 areas, the CDR-SB score, can range from 0 to 18, with a lower value being desirable.
Time frame: Baseline, Week 24, Week 48, Week 72, Week 96
Population: Intent-to-Treat Data Set: all randomized participants who received at least 1 dose of study drug. Participants with an assessment at given time point.
| Arm | Measure | Group | Value (LEAST_SQUARES_MEAN) | Dispersion |
|---|---|---|---|---|
| Placebo | Change From Baseline Over Time in CDR-SB Score | Change to Week 24 | 0.60 score on a scale | Standard Error 0.125 |
| Placebo | Change From Baseline Over Time in CDR-SB Score | Change to Week 48 | 1.06 score on a scale | Standard Error 0.155 |
| Placebo | Change From Baseline Over Time in CDR-SB Score | Change to Week 72 | 1.90 score on a scale | Standard Error 0.213 |
| Placebo | Change From Baseline Over Time in CDR-SB Score | Change to Week 96 | 2.54 score on a scale | Standard Error 0.271 |
| ABBV-8E12 300 mg | Change From Baseline Over Time in CDR-SB Score | Change to Week 48 | 1.15 score on a scale | Standard Error 0.161 |
| ABBV-8E12 300 mg | Change From Baseline Over Time in CDR-SB Score | Change to Week 72 | 1.88 score on a scale | Standard Error 0.22 |
| ABBV-8E12 300 mg | Change From Baseline Over Time in CDR-SB Score | Change to Week 96 | 2.47 score on a scale | Standard Error 0.277 |
| ABBV-8E12 300 mg | Change From Baseline Over Time in CDR-SB Score | Change to Week 24 | 0.66 score on a scale | Standard Error 0.129 |
| ABBV-8E12 1000 mg | Change From Baseline Over Time in CDR-SB Score | Change to Week 72 | 1.85 score on a scale | Standard Error 0.212 |
| ABBV-8E12 1000 mg | Change From Baseline Over Time in CDR-SB Score | Change to Week 48 | 1.05 score on a scale | Standard Error 0.154 |
| ABBV-8E12 1000 mg | Change From Baseline Over Time in CDR-SB Score | Change to Week 96 | 2.48 score on a scale | Standard Error 0.267 |
| ABBV-8E12 1000 mg | Change From Baseline Over Time in CDR-SB Score | Change to Week 24 | 0.44 score on a scale | Standard Error 0.125 |
| ABBV-8E12 2000 mg | Change From Baseline Over Time in CDR-SB Score | Change to Week 96 | 2.70 score on a scale | Standard Error 0.279 |
| ABBV-8E12 2000 mg | Change From Baseline Over Time in CDR-SB Score | Change to Week 48 | 0.99 score on a scale | Standard Error 0.161 |
| ABBV-8E12 2000 mg | Change From Baseline Over Time in CDR-SB Score | Change to Week 24 | 0.63 score on a scale | Standard Error 0.13 |
| ABBV-8E12 2000 mg | Change From Baseline Over Time in CDR-SB Score | Change to Week 72 | 1.81 score on a scale | Standard Error 0.219 |
Comparison: Week 24p-value: 0.7495% CI: [-0.291, 0.409]repeated measures model
Comparison: Week 24
Comparison: Week 24p-value: 0.36795% CI: [-0.504, 0.187]repeated measures model
Comparison: Week 24
Comparison: Week 24p-value: 0.84395% CI: [-0.318, 0.389]repeated measures model
Comparison: Week 24
Comparison: Week 48p-value: 0.70395% CI: [-0.351, 0.52]repeated measures model
Comparison: Week 48
Comparison: Week 48p-value: 0.94795% CI: [-0.442, 0.413]repeated measures model
Comparison: Week 48
Comparison: Week 48p-value: 0.73295% CI: [-0.514, 0.361]repeated measures model
Comparison: Week 48
Comparison: Week 72p-value: 0.93995% CI: [-0.623, 0.576]repeated measures model
Comparison: Week 72
Comparison: Week 72p-value: 0.87295% CI: [-0.637, 0.54]repeated measures model
Comparison: Week 72
Comparison: Week 72p-value: 0.77395% CI: [-0.688, 0.512]repeated measures model
Comparison: Week 72
Comparison: Week 96p-value: 0.84895% CI: [-0.834, 0.686]repeated measures model
Comparison: Week 96
Comparison: Week 96p-value: 0.86995% CI: [-0.81, 0.684]repeated measures model
Comparison: Week 96
Comparison: Week 96p-value: 0.67995% CI: [-0.603, 0.925]repeated measures model
Comparison: Week 96
Primary
Number of Participants With Treatment Emergent Adverse Events (TEAEs)
A TEAE was defined as an adverse event (AE) that began on or after the first study drug dose date and no more than 20 weeks after the last dose of study drug. An adverse event (AE) was defined as any untoward medical occurrence which does not necessarily have a causal relationship with this treatment. Serious AEs (SAEs) were defined as an event that results in death, is life-threatening, results in hospitalization or prolongs hospitalization, is a congenital abnormality, results in persistent or significant disability/incapacity, or is an important medical event. Events were rated in severity as mild, moderate, or severe, and were categorized as having a reasonable possibility or no reasonable possibility of relationship to study drug.
Time frame: From first dose of study drug up to last dose of study drug plus 20 weeks (up to Week 112)
Population: Safety Dataset: participants who received at least 1 dose of study drug.
| Arm | Measure | Group | Value (NUMBER) |
|---|---|---|---|
| Placebo | Number of Participants With Treatment Emergent Adverse Events (TEAEs) | Any TEAE | 108 participants |
| Placebo | Number of Participants With Treatment Emergent Adverse Events (TEAEs) | Fatal TEAE | 1 participants |
| Placebo | Number of Participants With Treatment Emergent Adverse Events (TEAEs) | TEAE Leading to Discontinuation of Study Drug | 4 participants |
| Placebo | Number of Participants With Treatment Emergent Adverse Events (TEAEs) | Severe TEAE | 12 participants |
| Placebo | Number of Participants With Treatment Emergent Adverse Events (TEAEs) | All Deaths | 1 participants |
| Placebo | Number of Participants With Treatment Emergent Adverse Events (TEAEs) | TEAE With a Reasonable Possibility to Study Drug | 28 participants |
| Placebo | Number of Participants With Treatment Emergent Adverse Events (TEAEs) | SAE | 26 participants |
| ABBV-8E12 300 mg | Number of Participants With Treatment Emergent Adverse Events (TEAEs) | Fatal TEAE | 2 participants |
| ABBV-8E12 300 mg | Number of Participants With Treatment Emergent Adverse Events (TEAEs) | SAE | 19 participants |
| ABBV-8E12 300 mg | Number of Participants With Treatment Emergent Adverse Events (TEAEs) | TEAE With a Reasonable Possibility to Study Drug | 32 participants |
| ABBV-8E12 300 mg | Number of Participants With Treatment Emergent Adverse Events (TEAEs) | TEAE Leading to Discontinuation of Study Drug | 6 participants |
| ABBV-8E12 300 mg | Number of Participants With Treatment Emergent Adverse Events (TEAEs) | All Deaths | 2 participants |
| ABBV-8E12 300 mg | Number of Participants With Treatment Emergent Adverse Events (TEAEs) | Severe TEAE | 13 participants |
| ABBV-8E12 300 mg | Number of Participants With Treatment Emergent Adverse Events (TEAEs) | Any TEAE | 94 participants |
| ABBV-8E12 1000 mg | Number of Participants With Treatment Emergent Adverse Events (TEAEs) | SAE | 22 participants |
| ABBV-8E12 1000 mg | Number of Participants With Treatment Emergent Adverse Events (TEAEs) | Any TEAE | 108 participants |
| ABBV-8E12 1000 mg | Number of Participants With Treatment Emergent Adverse Events (TEAEs) | Severe TEAE | 14 participants |
| ABBV-8E12 1000 mg | Number of Participants With Treatment Emergent Adverse Events (TEAEs) | TEAE With a Reasonable Possibility to Study Drug | 31 participants |
| ABBV-8E12 1000 mg | Number of Participants With Treatment Emergent Adverse Events (TEAEs) | TEAE Leading to Discontinuation of Study Drug | 6 participants |
| ABBV-8E12 1000 mg | Number of Participants With Treatment Emergent Adverse Events (TEAEs) | Fatal TEAE | 2 participants |
| ABBV-8E12 1000 mg | Number of Participants With Treatment Emergent Adverse Events (TEAEs) | All Deaths | 2 participants |
| ABBV-8E12 2000 mg | Number of Participants With Treatment Emergent Adverse Events (TEAEs) | TEAE With a Reasonable Possibility to Study Drug | 33 participants |
| ABBV-8E12 2000 mg | Number of Participants With Treatment Emergent Adverse Events (TEAEs) | All Deaths | 1 participants |
| ABBV-8E12 2000 mg | Number of Participants With Treatment Emergent Adverse Events (TEAEs) | Fatal TEAE | 1 participants |
| ABBV-8E12 2000 mg | Number of Participants With Treatment Emergent Adverse Events (TEAEs) | Severe TEAE | 11 participants |
| ABBV-8E12 2000 mg | Number of Participants With Treatment Emergent Adverse Events (TEAEs) | Any TEAE | 104 participants |
| ABBV-8E12 2000 mg | Number of Participants With Treatment Emergent Adverse Events (TEAEs) | TEAE Leading to Discontinuation of Study Drug | 4 participants |
| ABBV-8E12 2000 mg | Number of Participants With Treatment Emergent Adverse Events (TEAEs) | SAE | 17 participants |
Secondary
Area Under the Concentration-Time Curve From Dosing (Time 0) to Day 28 (AUC0-28) for ABBV-8E12 Over the Dosing Interval After the First and Fourth Doses
* The AUC0-28 for Dose 1 included the following timepoints: pre-infusion, post-infusion (within 15 min), 1 and 2 hours post-infusion, Day 5, Day 15 and Day 29 (trough level before Dose 2). * The AUC0-28 for Dose 4 included the following timepoints: Day 85 pre-infusion, post-infusion (within 15 min), 1 and 2 hours post-infusion, Day 89, Day 99 and Day 113 (trough level before Dose 5).
Time frame: Day 1 (Dose 1): pre-infusion, up to Day 29 (trough level before Dose 2). Day 85 (Dose 4): pre-infusion, up to Day 113 (trough level before Dose 5). See Outcome Measure description above for complete time point details.
Population: Intensive Pharmacokinetic Cohort: Among the first 48 participants enrolled in the study, those who received ABBV-8E12 and had an evaluable PK assessment at given time point.
| Arm | Measure | Group | Value (GEOMETRIC_MEAN) | Dispersion |
|---|---|---|---|---|
| Placebo | Area Under the Concentration-Time Curve From Dosing (Time 0) to Day 28 (AUC0-28) for ABBV-8E12 Over the Dosing Interval After the First and Fourth Doses | First Dosing Interval | 2520 µg.day/mL | Geometric Coefficient of Variation 28 |
| Placebo | Area Under the Concentration-Time Curve From Dosing (Time 0) to Day 28 (AUC0-28) for ABBV-8E12 Over the Dosing Interval After the First and Fourth Doses | Fourth Dosing Interval | 4230 µg.day/mL | Geometric Coefficient of Variation 33 |
| ABBV-8E12 300 mg | Area Under the Concentration-Time Curve From Dosing (Time 0) to Day 28 (AUC0-28) for ABBV-8E12 Over the Dosing Interval After the First and Fourth Doses | First Dosing Interval | 6090 µg.day/mL | Geometric Coefficient of Variation 37 |
| ABBV-8E12 300 mg | Area Under the Concentration-Time Curve From Dosing (Time 0) to Day 28 (AUC0-28) for ABBV-8E12 Over the Dosing Interval After the First and Fourth Doses | Fourth Dosing Interval | 13100 µg.day/mL | Geometric Coefficient of Variation 36 |
| ABBV-8E12 1000 mg | Area Under the Concentration-Time Curve From Dosing (Time 0) to Day 28 (AUC0-28) for ABBV-8E12 Over the Dosing Interval After the First and Fourth Doses | Fourth Dosing Interval | 30200 µg.day/mL | Geometric Coefficient of Variation 36 |
| ABBV-8E12 1000 mg | Area Under the Concentration-Time Curve From Dosing (Time 0) to Day 28 (AUC0-28) for ABBV-8E12 Over the Dosing Interval After the First and Fourth Doses | First Dosing Interval | 14800 µg.day/mL | Geometric Coefficient of Variation 25 |
Secondary
AUC0-28/Dose for ABBV-8E12 Over the Dosing Interval After the First and Fourth Doses
* The AUC0-28/dose for Dose 1 included the following timepoints: pre-infusion, post-infusion (within 15 min), 1 and 2 hours post-infusion, Day 5, Day 15 and Day 29 (trough level before Dose 2). * The AUC0-28/dose for Dose 4 included the following timepoints: Day 85 pre-infusion, post-infusion (within 15 min), 1 and 2 hours post-infusion, Day 89, Day 99 and Day 113 (trough level before Dose 5).
Time frame: Day 1 (Dose 1): pre-infusion, up to Day 29 (trough level before Dose 2). Day 85 (Dose 4): pre-infusion, up to Day 113 (trough level before Dose 5). See Outcome Measure description above for complete time point details.
Population: Intensive Pharmacokinetic Cohort: Among the first 48 participants enrolled in the study, those who received ABBV-8E12 and had an evaluable PK assessment at given time point.
| Arm | Measure | Group | Value (GEOMETRIC_MEAN) | Dispersion |
|---|---|---|---|---|
| Placebo | AUC0-28/Dose for ABBV-8E12 Over the Dosing Interval After the First and Fourth Doses | First Dosing Interval | 8.40 µg.day/mL/mg | Geometric Coefficient of Variation 28 |
| Placebo | AUC0-28/Dose for ABBV-8E12 Over the Dosing Interval After the First and Fourth Doses | Fourth Dosing Interval | 14.1 µg.day/mL/mg | Geometric Coefficient of Variation 33 |
| ABBV-8E12 300 mg | AUC0-28/Dose for ABBV-8E12 Over the Dosing Interval After the First and Fourth Doses | First Dosing Interval | 6.09 µg.day/mL/mg | Geometric Coefficient of Variation 37 |
| ABBV-8E12 300 mg | AUC0-28/Dose for ABBV-8E12 Over the Dosing Interval After the First and Fourth Doses | Fourth Dosing Interval | 13.1 µg.day/mL/mg | Geometric Coefficient of Variation 36 |
| ABBV-8E12 1000 mg | AUC0-28/Dose for ABBV-8E12 Over the Dosing Interval After the First and Fourth Doses | First Dosing Interval | 7.41 µg.day/mL/mg | Geometric Coefficient of Variation 25 |
| ABBV-8E12 1000 mg | AUC0-28/Dose for ABBV-8E12 Over the Dosing Interval After the First and Fourth Doses | Fourth Dosing Interval | 15.1 µg.day/mL/mg | Geometric Coefficient of Variation 36 |
Secondary
Change From Baseline Over Time in 24-Item Alzheimer's Disease Cooperative Study/Activities of Daily Living Scale Adapted for Patients With Mild Cognitive Impairment (ADCS-MCI-ADL-24) Total Score
The ADCS-MCI-ADL-24 is a 24-item, study partner-based assessment of activities of daily living designed specifically for AD patients and is completed by a trained rater. The scale assesses functional activities such as cooking, household chores, shopping, keeping appointments, social interactions and hobbies. Items are assessed according to whether they were performed in the past 4 weeks and, if so, some items are further assessed as to whether they were performed independently, with supervision, or with physical help. Scores on the ADCS-ADL-MCI range from 0 to 69, where higher score indicates greater capability to carry out activities of daily living.
Time frame: Baseline, Week 48, Week 96
Population: Intent-to-Treat Data Set: all randomized participants who received at least 1 dose of study drug. Participants with an assessment at baseline and given time point.
| Arm | Measure | Group | Value (LEAST_SQUARES_MEAN) | Dispersion |
|---|---|---|---|---|
| Placebo | Change From Baseline Over Time in 24-Item Alzheimer's Disease Cooperative Study/Activities of Daily Living Scale Adapted for Patients With Mild Cognitive Impairment (ADCS-MCI-ADL-24) Total Score | Change to Week 48 | -3.72 score on a scale | Standard Error 0.723 |
| Placebo | Change From Baseline Over Time in 24-Item Alzheimer's Disease Cooperative Study/Activities of Daily Living Scale Adapted for Patients With Mild Cognitive Impairment (ADCS-MCI-ADL-24) Total Score | Change to Week 96 | -9.21 score on a scale | Standard Error 1.134 |
| ABBV-8E12 300 mg | Change From Baseline Over Time in 24-Item Alzheimer's Disease Cooperative Study/Activities of Daily Living Scale Adapted for Patients With Mild Cognitive Impairment (ADCS-MCI-ADL-24) Total Score | Change to Week 96 | -10.25 score on a scale | Standard Error 1.135 |
| ABBV-8E12 300 mg | Change From Baseline Over Time in 24-Item Alzheimer's Disease Cooperative Study/Activities of Daily Living Scale Adapted for Patients With Mild Cognitive Impairment (ADCS-MCI-ADL-24) Total Score | Change to Week 48 | -4.51 score on a scale | Standard Error 0.738 |
| ABBV-8E12 1000 mg | Change From Baseline Over Time in 24-Item Alzheimer's Disease Cooperative Study/Activities of Daily Living Scale Adapted for Patients With Mild Cognitive Impairment (ADCS-MCI-ADL-24) Total Score | Change to Week 48 | -2.91 score on a scale | Standard Error 0.712 |
| ABBV-8E12 1000 mg | Change From Baseline Over Time in 24-Item Alzheimer's Disease Cooperative Study/Activities of Daily Living Scale Adapted for Patients With Mild Cognitive Impairment (ADCS-MCI-ADL-24) Total Score | Change to Week 96 | -9.16 score on a scale | Standard Error 1.112 |
| ABBV-8E12 2000 mg | Change From Baseline Over Time in 24-Item Alzheimer's Disease Cooperative Study/Activities of Daily Living Scale Adapted for Patients With Mild Cognitive Impairment (ADCS-MCI-ADL-24) Total Score | Change to Week 48 | -3.65 score on a scale | Standard Error 0.74 |
| ABBV-8E12 2000 mg | Change From Baseline Over Time in 24-Item Alzheimer's Disease Cooperative Study/Activities of Daily Living Scale Adapted for Patients With Mild Cognitive Impairment (ADCS-MCI-ADL-24) Total Score | Change to Week 96 | -10.60 score on a scale | Standard Error 1.163 |
Comparison: Week 48p-value: 0.43895% CI: [-2.798, 1.214]repeated measures model
Comparison: Week 48
Comparison: Week 48p-value: 0.41995% CI: [-1.164, 2.788]repeated measures model
Comparison: Week 48
Comparison: Week 48p-value: 0.94895% CI: [-1.959, 2.092]repeated measures model
Comparison: Week 48
Comparison: Week 96p-value: 0.51695% CI: [-4.18, 2.101]repeated measures model
Comparison: Week 96
Comparison: Week 96p-value: 0.97195% CI: [-3.055, 3.168]repeated measures model
Comparison: Week 96
Comparison: Week 96p-value: 0.39295% CI: [-4.577, 1.8]repeated measures model
Comparison: Week 96
Secondary
Change From Baseline Over Time in ADAS-Cog-14 Commands Score
The ADAS-Cog was designed to assess the cognitive impairments most common in AD. The ADAS-Cog-14 includes the original 11 items from the ADAS-Cog-11 \[1. Spoken language ability, 2. Comprehension of spoken language, 3. Recall of test instructions, 4. Word-findings difficulty in spontaneous speech, 5. Following commands, 6. Naming objects and fingers, 7. Constructional praxis, 8. Ideational praxis, 9. Orientation, 10. Word-recall task, 11. Word-recognition task\] and includes 3 additional tasks \[12. Number cancellation task, 13. Delayed word recall task, 14. Executive functioning\], for increased sensitivity in MCI patients. The Commands Score of the ADAS-Cog-14 ranges from 0 to 5, with a higher score representing greater impairment.
Time frame: Baseline, Week 24, Week 48, Week 72, Week 96
Population: Intent-to-Treat Data Set: all randomized participants who received at least 1 dose of study drug. Participants with an assessment at given time point.
| Arm | Measure | Group | Value (LEAST_SQUARES_MEAN) | Dispersion |
|---|---|---|---|---|
| Placebo | Change From Baseline Over Time in ADAS-Cog-14 Commands Score | Change at Week 24 | 0.09 score on a scale | Standard Error 0.066 |
| Placebo | Change From Baseline Over Time in ADAS-Cog-14 Commands Score | Change at Week 48 | 0.17 score on a scale | Standard Error 0.072 |
| Placebo | Change From Baseline Over Time in ADAS-Cog-14 Commands Score | Change at Week 72 | 0.09 score on a scale | Standard Error 0.078 |
| Placebo | Change From Baseline Over Time in ADAS-Cog-14 Commands Score | Change at Week 96 | 0.30 score on a scale | Standard Error 0.102 |
| ABBV-8E12 300 mg | Change From Baseline Over Time in ADAS-Cog-14 Commands Score | Change at Week 48 | 0.12 score on a scale | Standard Error 0.076 |
| ABBV-8E12 300 mg | Change From Baseline Over Time in ADAS-Cog-14 Commands Score | Change at Week 72 | 0.11 score on a scale | Standard Error 0.081 |
| ABBV-8E12 300 mg | Change From Baseline Over Time in ADAS-Cog-14 Commands Score | Change at Week 96 | 0.36 score on a scale | Standard Error 0.103 |
| ABBV-8E12 300 mg | Change From Baseline Over Time in ADAS-Cog-14 Commands Score | Change at Week 24 | 0.10 score on a scale | Standard Error 0.067 |
| ABBV-8E12 1000 mg | Change From Baseline Over Time in ADAS-Cog-14 Commands Score | Change at Week 72 | 0.36 score on a scale | Standard Error 0.079 |
| ABBV-8E12 1000 mg | Change From Baseline Over Time in ADAS-Cog-14 Commands Score | Change at Week 48 | 0.09 score on a scale | Standard Error 0.071 |
| ABBV-8E12 1000 mg | Change From Baseline Over Time in ADAS-Cog-14 Commands Score | Change at Week 96 | 0.40 score on a scale | Standard Error 0.1 |
| ABBV-8E12 1000 mg | Change From Baseline Over Time in ADAS-Cog-14 Commands Score | Change at Week 24 | 0.09 score on a scale | Standard Error 0.065 |
| ABBV-8E12 2000 mg | Change From Baseline Over Time in ADAS-Cog-14 Commands Score | Change at Week 96 | 0.40 score on a scale | Standard Error 0.106 |
| ABBV-8E12 2000 mg | Change From Baseline Over Time in ADAS-Cog-14 Commands Score | Change at Week 48 | 0.22 score on a scale | Standard Error 0.075 |
| ABBV-8E12 2000 mg | Change From Baseline Over Time in ADAS-Cog-14 Commands Score | Change at Week 24 | 0.09 score on a scale | Standard Error 0.068 |
| ABBV-8E12 2000 mg | Change From Baseline Over Time in ADAS-Cog-14 Commands Score | Change at Week 72 | 0.21 score on a scale | Standard Error 0.08 |
Comparison: Week 24p-value: 0.94595% CI: [-0.177, 0.19]repeated measures model
Comparison: Week 24
Comparison: Week 24p-value: 0.97495% CI: [-0.184, 0.178]repeated measures model
Comparison: Week 24
p-value: 0.96395% CI: [-0.19, 0.181]repeated measures model
Comparison: Week 24
Comparison: Week 48p-value: 0.62595% CI: [-0.255, 0.154]repeated measures model
Comparison: Week 48
Comparison: Week 48p-value: 0.46895% CI: [-0.272, 0.125]repeated measures model
Comparison: Week 48
Comparison: Week 48p-value: 0.63695% CI: [-0.155, 0.254]repeated measures model
Comparison: Week 48
Comparison: Week 72p-value: 0.88795% CI: [-0.204, 0.236]repeated measures model
Comparison: Week 72
Comparison: Week 72p-value: 0.01695% CI: [0.051, 0.486]repeated measures model
Comparison: Week 72
Comparison: Week 72p-value: 0.27295% CI: [-0.097, 0.342]repeated measures model
Comparison: Week 72
Comparison: Week 96p-value: 0.67195% CI: [-0.223, 0.347]repeated measures model
Comparison: Week 96
Comparison: Week 96p-value: 0.49395% CI: [-0.183, 0.378]repeated measures model
Comparison: Week 96
Comparison: Week 96p-value: 0.50195% CI: [-0.19, 0.387]repeated measures model
Comparison: Week 96
Secondary
Change From Baseline Over Time in ADAS-Cog-14 Comprehension of Spoken Language Score
The ADAS-Cog was designed to assess the cognitive impairments most common in AD. The ADAS-Cog-14 includes the original 11 items from the ADAS-Cog-11 \[1. Spoken language ability, 2. Comprehension of spoken language, 3. Recall of test instructions, 4. Word-findings difficulty in spontaneous speech, 5. Following commands, 6. Naming objects and fingers, 7. Constructional praxis, 8. Ideational praxis, 9. Orientation, 10. Word-recall task, 11. Word-recognition task\] and includes 3 additional tasks \[12. Number cancellation task, 13. Delayed word recall task, 14. Executive functioning\], for increased sensitivity in MCI patients. The Comprehension of Spoken Language score of the ADAS-Cog-14 ranges from 0 to 5, with a higher score representing greater impairment.
Time frame: Baseline, Week 24, Week 48, Week 72, Week 96
Population: Intent-to-Treat Data Set: all randomized participants who received at least 1 dose of study drug. Participants with an assessment at given time point.
| Arm | Measure | Group | Value (LEAST_SQUARES_MEAN) | Dispersion |
|---|---|---|---|---|
| Placebo | Change From Baseline Over Time in ADAS-Cog-14 Comprehension of Spoken Language Score | Change at Week 24 | 0.01 score on a scale | Standard Error 0.038 |
| Placebo | Change From Baseline Over Time in ADAS-Cog-14 Comprehension of Spoken Language Score | Change at Week 48 | 0.03 score on a scale | Standard Error 0.044 |
| Placebo | Change From Baseline Over Time in ADAS-Cog-14 Comprehension of Spoken Language Score | Change at Week 72 | 0.17 score on a scale | Standard Error 0.064 |
| Placebo | Change From Baseline Over Time in ADAS-Cog-14 Comprehension of Spoken Language Score | Change at Week 96 | 0.30 score on a scale | Standard Error 0.083 |
| ABBV-8E12 300 mg | Change From Baseline Over Time in ADAS-Cog-14 Comprehension of Spoken Language Score | Change at Week 48 | 0.09 score on a scale | Standard Error 0.046 |
| ABBV-8E12 300 mg | Change From Baseline Over Time in ADAS-Cog-14 Comprehension of Spoken Language Score | Change at Week 72 | 0.11 score on a scale | Standard Error 0.066 |
| ABBV-8E12 300 mg | Change From Baseline Over Time in ADAS-Cog-14 Comprehension of Spoken Language Score | Change at Week 96 | 0.26 score on a scale | Standard Error 0.083 |
| ABBV-8E12 300 mg | Change From Baseline Over Time in ADAS-Cog-14 Comprehension of Spoken Language Score | Change at Week 24 | 0.03 score on a scale | Standard Error 0.038 |
| ABBV-8E12 1000 mg | Change From Baseline Over Time in ADAS-Cog-14 Comprehension of Spoken Language Score | Change at Week 72 | 0.14 score on a scale | Standard Error 0.064 |
| ABBV-8E12 1000 mg | Change From Baseline Over Time in ADAS-Cog-14 Comprehension of Spoken Language Score | Change at Week 48 | 0.07 score on a scale | Standard Error 0.044 |
| ABBV-8E12 1000 mg | Change From Baseline Over Time in ADAS-Cog-14 Comprehension of Spoken Language Score | Change at Week 96 | 0.19 score on a scale | Standard Error 0.08 |
| ABBV-8E12 1000 mg | Change From Baseline Over Time in ADAS-Cog-14 Comprehension of Spoken Language Score | Change at Week 24 | 0.04 score on a scale | Standard Error 0.037 |
| ABBV-8E12 2000 mg | Change From Baseline Over Time in ADAS-Cog-14 Comprehension of Spoken Language Score | Change at Week 96 | 0.29 score on a scale | Standard Error 0.085 |
| ABBV-8E12 2000 mg | Change From Baseline Over Time in ADAS-Cog-14 Comprehension of Spoken Language Score | Change at Week 48 | 0.12 score on a scale | Standard Error 0.046 |
| ABBV-8E12 2000 mg | Change From Baseline Over Time in ADAS-Cog-14 Comprehension of Spoken Language Score | Change at Week 24 | 0.08 score on a scale | Standard Error 0.039 |
| ABBV-8E12 2000 mg | Change From Baseline Over Time in ADAS-Cog-14 Comprehension of Spoken Language Score | Change at Week 72 | 0.31 score on a scale | Standard Error 0.066 |
Comparison: Week 24p-value: 0.6995% CI: [-0.083, 0.126]repeated measures model
Comparison: Week 24
Comparison: Week 24p-value: 0.59595% CI: [-0.075, 0.131]repeated measures model
Comparison: Week 24
Comparison: Week 24p-value: 0.20195% CI: [0.037, 0.175]repeated measures model
Comparison: Week 24
Comparison: Week 48p-value: 0.36195% CI: [-0.067, 0.184]repeated measures model
Comparison: Week 48
Comparison: Week 48p-value: 0.52295% CI: [-0.082, 0.162]repeated measures model
Comparison: Week 48
Comparison: Week 48p-value: 0.14795% CI: [-0.033, 0.219]repeated measures model
Comparison: Week 48
Comparison: Week 72p-value: 0.49295% CI: [-0.243, 0.117]repeated measures model
Comparison: Week 72
Comparison: Week 72p-value: 0.69195% CI: [-0.213, 0.141]repeated measures model
Comparison: Week 72
Comparison: Week 72p-value: 0.13595% CI: [-0.043, 0.317]repeated measures model
Comparison: Week 72
Comparison: Week 96p-value: 0.71395% CI: [-0.273, 0.187]repeated measures model
Comparison: Week 96
Comparison: Week 96p-value: 0.31895% CI: [-0.341, 0.111]repeated measures model
Comparison: Week 96
Comparison: Week 96p-value: 0.92795% CI: [-0.244, 0.222]repeated measures model
Comparison: Week 96
Secondary
Change From Baseline Over Time in ADAS-Cog-14 Constructional Praxis Score
The ADAS-Cog was designed to assess the cognitive impairments most common in AD. The ADAS-Cog-14 includes the original 11 items from the ADAS-Cog-11 \[1. Spoken language ability, 2. Comprehension of spoken language, 3. Recall of test instructions, 4. Word-findings difficulty in spontaneous speech, 5. Following commands, 6. Naming objects and fingers, 7. Constructional praxis, 8. Ideational praxis, 9. Orientation, 10. Word-recall task, 11. Word-recognition task\] and includes 3 additional tasks \[12. Number cancellation task, 13. Delayed word recall task, 14. Executive functioning\], for increased sensitivity in MCI patients. The Constructional Praxis Score of the ADAS-Cog-14 ranges from 0 to 5, with a higher score representing greater impairment.
Time frame: Baseline, Week 24, Week 48, Week 72, Week 96
Population: Intent-to-Treat Data Set: all randomized participants who received at least 1 dose of study drug. Participants with an assessment at given time point.
| Arm | Measure | Group | Value (LEAST_SQUARES_MEAN) | Dispersion |
|---|---|---|---|---|
| Placebo | Change From Baseline Over Time in ADAS-Cog-14 Constructional Praxis Score | Change at Week 72 | 0.25 score on a scale | Standard Error 0.069 |
| Placebo | Change From Baseline Over Time in ADAS-Cog-14 Constructional Praxis Score | Change at Week 96 | 0.41 score on a scale | Standard Error 0.089 |
| Placebo | Change From Baseline Over Time in ADAS-Cog-14 Constructional Praxis Score | Change at Week 24 | 0.11 score on a scale | Standard Error 0.057 |
| Placebo | Change From Baseline Over Time in ADAS-Cog-14 Constructional Praxis Score | Change at Week 48 | 0.07 score on a scale | Standard Error 0.073 |
| ABBV-8E12 300 mg | Change From Baseline Over Time in ADAS-Cog-14 Constructional Praxis Score | Change at Week 48 | 0.23 score on a scale | Standard Error 0.077 |
| ABBV-8E12 300 mg | Change From Baseline Over Time in ADAS-Cog-14 Constructional Praxis Score | Change at Week 24 | 0.05 score on a scale | Standard Error 0.058 |
| ABBV-8E12 300 mg | Change From Baseline Over Time in ADAS-Cog-14 Constructional Praxis Score | Change at Week 96 | 0.25 score on a scale | Standard Error 0.089 |
| ABBV-8E12 300 mg | Change From Baseline Over Time in ADAS-Cog-14 Constructional Praxis Score | Change at Week 72 | 0.22 score on a scale | Standard Error 0.072 |
| ABBV-8E12 1000 mg | Change From Baseline Over Time in ADAS-Cog-14 Constructional Praxis Score | Change at Week 24 | -0.02 score on a scale | Standard Error 0.056 |
| ABBV-8E12 1000 mg | Change From Baseline Over Time in ADAS-Cog-14 Constructional Praxis Score | Change at Week 48 | 0.17 score on a scale | Standard Error 0.072 |
| ABBV-8E12 1000 mg | Change From Baseline Over Time in ADAS-Cog-14 Constructional Praxis Score | Change at Week 96 | 0.026 score on a scale | Standard Error 0.086 |
| ABBV-8E12 1000 mg | Change From Baseline Over Time in ADAS-Cog-14 Constructional Praxis Score | Change at Week 72 | 0.16 score on a scale | Standard Error 0.07 |
| ABBV-8E12 2000 mg | Change From Baseline Over Time in ADAS-Cog-14 Constructional Praxis Score | Change at Week 96 | 0.33 score on a scale | Standard Error 0.092 |
| ABBV-8E12 2000 mg | Change From Baseline Over Time in ADAS-Cog-14 Constructional Praxis Score | Change at Week 72 | 0.16 score on a scale | Standard Error 0.071 |
| ABBV-8E12 2000 mg | Change From Baseline Over Time in ADAS-Cog-14 Constructional Praxis Score | Change at Week 48 | 0.20 score on a scale | Standard Error 0.077 |
| ABBV-8E12 2000 mg | Change From Baseline Over Time in ADAS-Cog-14 Constructional Praxis Score | Change at Week 24 | 0.09 score on a scale | Standard Error 0.059 |
Comparison: Week 24p-value: 0.45695% CI: [-0.219, 0.098]repeated measures model
Comparison: Week 24
Comparison: Week 24p-value: 0.09395% CI: [-0.29, 0.023]repeated measures model
Comparison: Week 24
Comparison: Week 24p-value: 0.7595% CI: [-0.187, 0.135]repeated measures model
Comparison: Week 24
Comparison: Week 48p-value: 0.13495% CI: [-0.049, 0.366]repeated measures model
Comparison: Week 48
Comparison: Week 48p-value: 0.31695% CI: [-0.099, 0.305]repeated measures model
Comparison: Week 48
Comparison: Week 48p-value: 0.21895% CI: [-0.078, 0.339]repeated measures model
Comparison: Week 48
Comparison: Week 72p-value: 0.79995% CI: [-0.219, 0.169]repeated measures model
Comparison: Week 72
Comparison: Week 72p-value: 0.40695% CI: [-0.273, 0.111]repeated measures model
Comparison: Week 72
Comparison: Week 72p-value: 0.36395% CI: [-0.285, 0.105]repeated measures model
Comparison: Week 72
Comparison: Week 96p-value: 0.2295% CI: [-0.4, 0.093]repeated measures model
Comparison: Week 96
Comparison: Week 96p-value: 0.24595% CI: [-0.386, 0.099]repeated measures model
Comparison: Week 96
Comparison: Week 96p-value: 0.56995% CI: [-0.323, 0.178]repeated measures model
Comparison: Week 96
Secondary
Change From Baseline Over Time in ADAS-Cog-14 Delayed Word Recall Score
The ADAS-Cog was designed to assess the cognitive impairments most common in AD. The ADAS-Cog-14 includes the original 11 items from the ADAS-Cog-11 \[1. Spoken language ability, 2. Comprehension of spoken language, 3. Recall of test instructions, 4. Word-findings difficulty in spontaneous speech, 5. Following commands, 6. Naming objects and fingers, 7. Constructional praxis, 8. Ideational praxis, 9. Orientation, 10. Word-recall task, 11. Word-recognition task\] and includes 3 additional tasks \[12. Number cancellation task, 13. Delayed word recall task, 14. Executive functioning\], for increased sensitivity in MCI patients. The Delayed Word Recall Score of the ADAS-Cog-14 ranges from 0 to 10, with a higher score representing greater impairment.
Time frame: Baseline, Week 24, Week 48, Week 72, Week 96
Population: Intent-to-Treat Data Set: all randomized participants who received at least 1 dose of study drug. Participants with an assessment at baseline and given time point.
| Arm | Measure | Group | Value (LEAST_SQUARES_MEAN) | Dispersion |
|---|---|---|---|---|
| Placebo | Change From Baseline Over Time in ADAS-Cog-14 Delayed Word Recall Score | Change at Week 24 | 0.11 score on a scale | Standard Error 0.133 |
| Placebo | Change From Baseline Over Time in ADAS-Cog-14 Delayed Word Recall Score | Change at Week 48 | 0.41 score on a scale | Standard Error 0.133 |
| Placebo | Change From Baseline Over Time in ADAS-Cog-14 Delayed Word Recall Score | Change at Week 72 | 0.39 score on a scale | Standard Error 0.132 |
| Placebo | Change From Baseline Over Time in ADAS-Cog-14 Delayed Word Recall Score | Change at Week 96 | 0.86 score on a scale | Standard Error 0.135 |
| ABBV-8E12 300 mg | Change From Baseline Over Time in ADAS-Cog-14 Delayed Word Recall Score | Change at Week 48 | 0.30 score on a scale | Standard Error 0.138 |
| ABBV-8E12 300 mg | Change From Baseline Over Time in ADAS-Cog-14 Delayed Word Recall Score | Change at Week 72 | 0.61 score on a scale | Standard Error 0.136 |
| ABBV-8E12 300 mg | Change From Baseline Over Time in ADAS-Cog-14 Delayed Word Recall Score | Change at Week 96 | 0.80 score on a scale | Standard Error 0.135 |
| ABBV-8E12 300 mg | Change From Baseline Over Time in ADAS-Cog-14 Delayed Word Recall Score | Change at Week 24 | 0.17 score on a scale | Standard Error 0.135 |
| ABBV-8E12 1000 mg | Change From Baseline Over Time in ADAS-Cog-14 Delayed Word Recall Score | Change at Week 72 | 0.52 score on a scale | Standard Error 0.133 |
| ABBV-8E12 1000 mg | Change From Baseline Over Time in ADAS-Cog-14 Delayed Word Recall Score | Change at Week 48 | 0.32 score on a scale | Standard Error 0.131 |
| ABBV-8E12 1000 mg | Change From Baseline Over Time in ADAS-Cog-14 Delayed Word Recall Score | Change at Week 96 | 0.60 score on a scale | Standard Error 0.131 |
| ABBV-8E12 1000 mg | Change From Baseline Over Time in ADAS-Cog-14 Delayed Word Recall Score | Change at Week 24 | -0.04 score on a scale | Standard Error 0.131 |
| ABBV-8E12 2000 mg | Change From Baseline Over Time in ADAS-Cog-14 Delayed Word Recall Score | Change at Week 96 | 0.66 score on a scale | Standard Error 0.138 |
| ABBV-8E12 2000 mg | Change From Baseline Over Time in ADAS-Cog-14 Delayed Word Recall Score | Change at Week 48 | 0.27 score on a scale | Standard Error 0.138 |
| ABBV-8E12 2000 mg | Change From Baseline Over Time in ADAS-Cog-14 Delayed Word Recall Score | Change at Week 24 | -0.09 score on a scale | Standard Error 0.137 |
| ABBV-8E12 2000 mg | Change From Baseline Over Time in ADAS-Cog-14 Delayed Word Recall Score | Change at Week 72 | 0.67 score on a scale | Standard Error 0.135 |
Comparison: Week 24p-value: 0.74295% CI: [-0.307, 0.431]repeated measures model
Comparison: Week 24
Comparison: Week 24p-value: 0.43195% CI: [-0.511, 0.218]repeated measures model
Comparison: Week 24
Comparison: Week 24p-value: 0.2995% CI: [-0.574, 0.172]repeated measures model
Comparison: Week 24
Comparison: Week 48p-value: 0.54195% CI: [-0.492, 0.258]repeated measures model
Comparison: Week 48
Comparison: Week 48p-value: 0.61795% CI: [-0.459, 0.272]repeated measures model
Comparison: Week 48
Comparison: Week 48p-value: 0.45795% CI: [-0.517, 0.233]repeated measures model
Comparison: Week 48
Comparison: Week 72p-value: 0.24595% CI: [-0.151, 0.59]repeated measures model
Comparison: Week 72
Comparison: Week 72p-value: 0.49195% CI: [-0.238, 0.496]repeated measures model
Comparison: Week 72
Comparison: Week 72p-value: 0.13295% CI: [-0.085, 0.652]repeated measures model
Comparison: Week 72
Comparison: Week 96p-value: 0.75195% CI: [-0.434, 0.313]repeated measures model
Comparison: Week 96
Comparison: Week 96p-value: 0.15795% CI: [-0.635, 0.103]repeated measures model
Comparison: Week 96
Comparison: Week 96p-value: 0.28395% CI: [-0.585, 0.172]repeated measures model
Comparison: Week 24
Secondary
Change From Baseline Over Time in ADAS-Cog-14 Ideational Praxis Score
The ADAS-Cog was designed to assess the cognitive impairments most common in AD. The ADAS-Cog-14 includes the original 11 items from the ADAS-Cog-11 \[1. Spoken language ability, 2. Comprehension of spoken language, 3. Recall of test instructions, 4. Word-findings difficulty in spontaneous speech, 5. Following commands, 6. Naming objects and fingers, 7. Constructional praxis, 8. Ideational praxis, 9. Orientation, 10. Word-recall task, 11. Word-recognition task\] and includes 3 additional tasks \[12. Number cancellation task, 13. Delayed word recall task, 14. Executive functioning\], for increased sensitivity in MCI patients. The Ideational Praxis Score of the ADAS-Cog-14 ranges from 0 to 5, with a higher score representing greater impairment.
Time frame: Baseline, Week 24, Week 48, Week 72, Week 96
Population: Intent-to-Treat Data Set: all randomized participants who received at least 1 dose of study drug. Participants with an assessment at given time point.
| Arm | Measure | Group | Value (LEAST_SQUARES_MEAN) | Dispersion |
|---|---|---|---|---|
| Placebo | Change From Baseline Over Time in ADAS-Cog-14 Ideational Praxis Score | Change at Week 24 | 0.05 score on a scale | Standard Error 0.057 |
| Placebo | Change From Baseline Over Time in ADAS-Cog-14 Ideational Praxis Score | Change at Week 48 | 0.21 score on a scale | Standard Error 0.075 |
| Placebo | Change From Baseline Over Time in ADAS-Cog-14 Ideational Praxis Score | Change at Week 72 | 0.18 score on a scale | Standard Error 0.083 |
| Placebo | Change From Baseline Over Time in ADAS-Cog-14 Ideational Praxis Score | Change at Week 96 | 0.35 score on a scale | Standard Error 0.111 |
| ABBV-8E12 300 mg | Change From Baseline Over Time in ADAS-Cog-14 Ideational Praxis Score | Change at Week 48 | 0.12 score on a scale | Standard Error 0.078 |
| ABBV-8E12 300 mg | Change From Baseline Over Time in ADAS-Cog-14 Ideational Praxis Score | Change at Week 72 | 0.25 score on a scale | Standard Error 0.086 |
| ABBV-8E12 300 mg | Change From Baseline Over Time in ADAS-Cog-14 Ideational Praxis Score | Change at Week 96 | 0.26 score on a scale | Standard Error 0.112 |
| ABBV-8E12 300 mg | Change From Baseline Over Time in ADAS-Cog-14 Ideational Praxis Score | Change at Week 24 | 0.13 score on a scale | Standard Error 0.058 |
| ABBV-8E12 1000 mg | Change From Baseline Over Time in ADAS-Cog-14 Ideational Praxis Score | Change at Week 72 | 0.21 score on a scale | Standard Error 0.083 |
| ABBV-8E12 1000 mg | Change From Baseline Over Time in ADAS-Cog-14 Ideational Praxis Score | Change at Week 48 | 0.09 score on a scale | Standard Error 0.073 |
| ABBV-8E12 1000 mg | Change From Baseline Over Time in ADAS-Cog-14 Ideational Praxis Score | Change at Week 96 | 0.41 score on a scale | Standard Error 0.108 |
| ABBV-8E12 1000 mg | Change From Baseline Over Time in ADAS-Cog-14 Ideational Praxis Score | Change at Week 24 | 0.02 score on a scale | Standard Error 0.056 |
| ABBV-8E12 2000 mg | Change From Baseline Over Time in ADAS-Cog-14 Ideational Praxis Score | Change at Week 96 | 0.42 score on a scale | Standard Error 0.114 |
| ABBV-8E12 2000 mg | Change From Baseline Over Time in ADAS-Cog-14 Ideational Praxis Score | Change at Week 48 | 0.16 score on a scale | Standard Error 0.078 |
| ABBV-8E12 2000 mg | Change From Baseline Over Time in ADAS-Cog-14 Ideational Praxis Score | Change at Week 24 | 0.18 score on a scale | Standard Error 0.059 |
| ABBV-8E12 2000 mg | Change From Baseline Over Time in ADAS-Cog-14 Ideational Praxis Score | Change at Week 72 | 0.35 score on a scale | Standard Error 0.085 |
Comparison: Week 24p-value: 0.36395% CI: [-0.085, 0.231]repeated measures model
Comparison: Week 24
Comparison: Week 24p-value: 0.68895% CI: [-0.188, 0.124]repeated measures model
Comparison: Week 24
Comparison: Week 24p-value: 0.13795% CI: [-0.039, 0.281]repeated measures model
Comparison: Week 24
Comparison: Week 48p-value: 0.40895% CI: [-0.3, 0.122]repeated measures model
Comparison: Week 48
Comparison: Week 48p-value: 0.24995% CI: [-0.325, 0.085]repeated measures model
Comparison: Week 48
Comparison: Week 48p-value: 0.61695% CI: [-0.265, 0.157]repeated measures model
Comparison: Week 48
Comparison: Week 72p-value: 0.55595% CI: [-0.163, 0.304]repeated measures model
Comparison: Week 72
Comparison: Week 72p-value: 0.81595% CI: [-0.203, 0.258]repeated measures model
Comparison: Week 72
Comparison: Week 72p-value: 0.13895% CI: [-0.057, 0.409]repeated measures model
Comparison: Week 72
Comparison: Week 96p-value: 0.57395% CI: [-0.397, 0.22]repeated measures model
Comparison: Week 96
Comparison: Week 96p-value: 0.68995% CI: [-0.241, 0.365]repeated measures model
Comparison: Week 96
Comparison: Week 96p-value: 0.66295% CI: [-0.243, 0.382]repeated measures model
Comparison: Week 96
Secondary
Change From Baseline Over Time in ADAS-Cog-14 Maze Task Score
The ADAS-Cog was designed to assess the cognitive impairments most common in AD. The ADAS-Cog-14 includes the original 11 items from the ADAS-Cog-11 \[1. Spoken language ability, 2. Comprehension of spoken language, 3. Recall of test instructions, 4. Word-findings difficulty in spontaneous speech, 5. Following commands, 6. Naming objects and fingers, 7. Constructional praxis, 8. Ideational praxis, 9. Orientation, 10. Word-recall task, 11. Word-recognition task\] and includes 3 additional tasks \[12. Number cancellation task, 13. Delayed word recall task, 14. Executive functioning\], for increased sensitivity in MCI patients. The Maze Task Score of the ADAS-Cog-14 ranges from 0 to 5, with a higher score representing greater impairment.
Time frame: Baseline, Week 24, Week 48, Week 72, Week 96
Population: Intent-to-Treat Data Set: all randomized participants who received at least 1 dose of study drug. Participants with an assessment at baseline and given time point.
| Arm | Measure | Group | Value (LEAST_SQUARES_MEAN) | Dispersion |
|---|---|---|---|---|
| Placebo | Change From Baseline Over Time in ADAS-Cog-14 Maze Task Score | Change at Week 24 | 0.15 score on a scale | Standard Error 0.13 |
| Placebo | Change From Baseline Over Time in ADAS-Cog-14 Maze Task Score | Change at Week 48 | 0.37 score on a scale | Standard Error 0.147 |
| Placebo | Change From Baseline Over Time in ADAS-Cog-14 Maze Task Score | Change at Week 72 | 0.32 score on a scale | Standard Error 0.16 |
| Placebo | Change From Baseline Over Time in ADAS-Cog-14 Maze Task Score | Change at Week 96 | 0.52 score on a scale | Standard Error 0.184 |
| ABBV-8E12 300 mg | Change From Baseline Over Time in ADAS-Cog-14 Maze Task Score | Change at Week 48 | 0.07 score on a scale | Standard Error 0.154 |
| ABBV-8E12 300 mg | Change From Baseline Over Time in ADAS-Cog-14 Maze Task Score | Change at Week 72 | 0.14 score on a scale | Standard Error 0.166 |
| ABBV-8E12 300 mg | Change From Baseline Over Time in ADAS-Cog-14 Maze Task Score | Change at Week 96 | 0.29 score on a scale | Standard Error 0.181 |
| ABBV-8E12 300 mg | Change From Baseline Over Time in ADAS-Cog-14 Maze Task Score | Change at Week 24 | -0.04 score on a scale | Standard Error 0.132 |
| ABBV-8E12 1000 mg | Change From Baseline Over Time in ADAS-Cog-14 Maze Task Score | Change at Week 72 | 0.04 score on a scale | Standard Error 0.162 |
| ABBV-8E12 1000 mg | Change From Baseline Over Time in ADAS-Cog-14 Maze Task Score | Change at Week 48 | 0.21 score on a scale | Standard Error 0.145 |
| ABBV-8E12 1000 mg | Change From Baseline Over Time in ADAS-Cog-14 Maze Task Score | Change at Week 96 | 0.60 score on a scale | Standard Error 0.179 |
| ABBV-8E12 1000 mg | Change From Baseline Over Time in ADAS-Cog-14 Maze Task Score | Change at Week 24 | -0.20 score on a scale | Standard Error 0.129 |
| ABBV-8E12 2000 mg | Change From Baseline Over Time in ADAS-Cog-14 Maze Task Score | Change at Week 96 | 0.52 score on a scale | Standard Error 0.19 |
| ABBV-8E12 2000 mg | Change From Baseline Over Time in ADAS-Cog-14 Maze Task Score | Change at Week 48 | 0.28 score on a scale | Standard Error 0.155 |
| ABBV-8E12 2000 mg | Change From Baseline Over Time in ADAS-Cog-14 Maze Task Score | Change at Week 24 | 0.17 score on a scale | Standard Error 0.134 |
| ABBV-8E12 2000 mg | Change From Baseline Over Time in ADAS-Cog-14 Maze Task Score | Change at Week 72 | 0.40 score on a scale | Standard Error 0.167 |
Comparison: Week 24p-value: 0.29195% CI: [-0.555, 0.167]repeated measures model
Comparison: Week 24
Comparison: Week 24p-value: 0.05195% CI: [-0.713, 0.001]repeated measures model
Comparison: Week 24
Comparison: Week 24p-value: 0.92195% CI: [-0.346, 0.383]repeated measures model
Comparison: Week 24
Comparison: Week 48p-value: 0.16395% CI: [-0.711, 0.12]repeated measures model
Comparison: Week 48
Comparison: Week 48p-value: 0.42495% CI: [-0.567, 0.239]repeated measures model
Comparison: Week 48
Comparison: Week 48p-value: 0.66495% CI: [-0.51, 0.326]repeated measures model
Comparison: Week 48
Comparison: Week 72p-value: 0.41795% CI: [-0.638, 0.265]repeated measures model
Comparison: Week 72
Comparison: Week 72p-value: 0.21795% CI: [-0.727, 0.166]repeated measures model
Comparison: Week 72
Comparison: Week 72p-value: 0.75395% CI: [-0.381, 0.526]repeated measures model
Comparison: Week 72
Comparison: Week 96p-value: 0.36295% CI: [-0.74, 0.27]repeated measures model
Comparison: Week 96
Comparison: Week 96p-value: 0.7895% CI: [-0.432, 0.575]repeated measures model
Comparison: Week 96
Comparison: Week 96p-value: 0.97495% CI: [-0.526, 0.509]repeated measures model
Comparison: Week 96
Secondary
Change From Baseline Over Time in ADAS-Cog-14 Naming Score
The ADAS-Cog was designed to assess the cognitive impairments most common in AD. The ADAS-Cog-14 includes the original 11 items from the ADAS-Cog-11 \[1. Spoken language ability, 2. Comprehension of spoken language, 3. Recall of test instructions, 4. Word-findings difficulty in spontaneous speech, 5. Following commands, 6. Naming objects and fingers, 7. Constructional praxis, 8. Ideational praxis, 9. Orientation, 10. Word-recall task, 11. Word-recognition task\] and includes 3 additional tasks \[12. Number cancellation task, 13. Delayed word recall task, 14. Executive functioning\], for increased sensitivity in MCI patients. The Naming Score of the ADAS-Cog-14 ranges from 0 to 5 with a higher score representing greater impairment.
Time frame: Baseline, Week 24, Week 48, Week 72, Week 96
Population: Intent-to-Treat Data Set: all randomized participants who received at least 1 dose of study drug. Participants with an assessment at baseline and given time point.
| Arm | Measure | Group | Value (LEAST_SQUARES_MEAN) | Dispersion |
|---|---|---|---|---|
| Placebo | Change From Baseline Over Time in ADAS-Cog-14 Naming Score | Change at Week 24 | 0.02 score on a scale | Standard Error 0.048 |
| Placebo | Change From Baseline Over Time in ADAS-Cog-14 Naming Score | Change at Week 48 | 0.11 score on a scale | Standard Error 0.049 |
| Placebo | Change From Baseline Over Time in ADAS-Cog-14 Naming Score | Change at Week 72 | 0.21 score on a scale | Standard Error 0.063 |
| Placebo | Change From Baseline Over Time in ADAS-Cog-14 Naming Score | Change at Week 96 | 0.34 score on a scale | Standard Error 0.085 |
| ABBV-8E12 300 mg | Change From Baseline Over Time in ADAS-Cog-14 Naming Score | Change at Week 48 | 0.09 score on a scale | Standard Error 0.051 |
| ABBV-8E12 300 mg | Change From Baseline Over Time in ADAS-Cog-14 Naming Score | Change at Week 72 | 0.14 score on a scale | Standard Error 0.065 |
| ABBV-8E12 300 mg | Change From Baseline Over Time in ADAS-Cog-14 Naming Score | Change at Week 96 | 0.34 score on a scale | Standard Error 0.086 |
| ABBV-8E12 300 mg | Change From Baseline Over Time in ADAS-Cog-14 Naming Score | Change at Week 24 | 0.08 score on a scale | Standard Error 0.049 |
| ABBV-8E12 1000 mg | Change From Baseline Over Time in ADAS-Cog-14 Naming Score | Change at Week 72 | 0.08 score on a scale | Standard Error 0.063 |
| ABBV-8E12 1000 mg | Change From Baseline Over Time in ADAS-Cog-14 Naming Score | Change at Week 48 | 0.08 score on a scale | Standard Error 0.048 |
| ABBV-8E12 1000 mg | Change From Baseline Over Time in ADAS-Cog-14 Naming Score | Change at Week 96 | 0.28 score on a scale | Standard Error 0.082 |
| ABBV-8E12 1000 mg | Change From Baseline Over Time in ADAS-Cog-14 Naming Score | Change at Week 24 | -0.03 score on a scale | Standard Error 0.047 |
| ABBV-8E12 2000 mg | Change From Baseline Over Time in ADAS-Cog-14 Naming Score | Change at Week 96 | 0.20 score on a scale | Standard Error 0.087 |
| ABBV-8E12 2000 mg | Change From Baseline Over Time in ADAS-Cog-14 Naming Score | Change at Week 48 | 0.03 score on a scale | Standard Error 0.05 |
| ABBV-8E12 2000 mg | Change From Baseline Over Time in ADAS-Cog-14 Naming Score | Change at Week 24 | 0.05 score on a scale | Standard Error 0.05 |
| ABBV-8E12 2000 mg | Change From Baseline Over Time in ADAS-Cog-14 Naming Score | Change at Week 72 | 0.07 score on a scale | Standard Error 0.064 |
Comparison: Week 24p-value: 0.32595% CI: [-0.067, 0.202]repeated measures model
Comparison: Week 24
Comparison: Week 24p-value: 0.5195% CI: [-0.177, 0.088]repeated measures model
Comparison: Week 24
Comparison: Week 24p-value: 0.60195% CI: [-0.1, 0.172]repeated measures model
Comparison: Week 24
Comparison: Week 48p-value: 0.78395% CI: [-0.157, 0.119]repeated measures model
Comparison: Week 48
Comparison: Week 48p-value: 0.64695% CI: [-0.165, 0.103]repeated measures model
Comparison: Week 48
Comparison: Week 48p-value: 0.20995% CI: [-0.226, 0.05]repeated measures model
Comparison: Week 48
Comparison: Week 72p-value: 0.45495% CI: [-0.246, 0.11]repeated measures model
Comparison: Week 72
Comparison: Week 72p-value: 0.14195% CI: [-0.306, 0.043]repeated measures model
Comparison: Week 72
Comparison: Week 72p-value: 0.10795% CI: [-0.323, 0.031]repeated measures model
Comparison: Week 72
Comparison: Week 96p-value: 0.96195% CI: [-0.243, 0.232]repeated measures model
Comparison: Week 96
Comparison: Week 96p-value: 0.61895% CI: [-0.29, 0.173]repeated measures model
Comparison: Week 96
Comparison: Week 96p-value: 0.22795% CI: [-0.385, 0.092]repeated measures model
Comparison: Week 96
Secondary
Change From Baseline Over Time in ADAS-Cog-14 Number Cancellation Score
The ADAS-Cog was designed to assess the cognitive impairments most common in AD. The ADAS-Cog-14 includes the original 11 items from the ADAS-Cog-11 \[1. Spoken language ability, 2. Comprehension of spoken language, 3. Recall of test instructions, 4. Word-findings difficulty in spontaneous speech, 5. Following commands, 6. Naming objects and fingers, 7. Constructional praxis, 8. Ideational praxis, 9. Orientation, 10. Word-recall task, 11. Word-recognition task\] and includes 3 additional tasks \[12. Number cancellation task, 13. Delayed word recall task, 14. Executive functioning\], for increased sensitivity in MCI patients. The Number Cancellation Score of the ADAS-Cog-14 ranges from 0 to 5, with a higher score representing greater impairment.
Time frame: Baseline, Week 24, Week 48, Week 72, Week 96
Population: Intent-to-Treat Data Set: all randomized participants who received at least 1 dose of study drug. Participants with an assessment at baseline and given time point.
| Arm | Measure | Group | Value (LEAST_SQUARES_MEAN) | Dispersion |
|---|---|---|---|---|
| Placebo | Change From Baseline Over Time in ADAS-Cog-14 Number Cancellation Score | Change at Week 24 | 0.33 score on a scale | Standard Error 0.099 |
| Placebo | Change From Baseline Over Time in ADAS-Cog-14 Number Cancellation Score | Change at Week 48 | 0.43 score on a scale | Standard Error 0.114 |
| Placebo | Change From Baseline Over Time in ADAS-Cog-14 Number Cancellation Score | Change at Week 72 | 0.75 score on a scale | Standard Error 0.115 |
| Placebo | Change From Baseline Over Time in ADAS-Cog-14 Number Cancellation Score | Change at Week 96 | 0.87 score on a scale | Standard Error 0.138 |
| ABBV-8E12 300 mg | Change From Baseline Over Time in ADAS-Cog-14 Number Cancellation Score | Change at Week 48 | 0.42 score on a scale | Standard Error 0.118 |
| ABBV-8E12 300 mg | Change From Baseline Over Time in ADAS-Cog-14 Number Cancellation Score | Change at Week 72 | 0.68 score on a scale | Standard Error 0.117 |
| ABBV-8E12 300 mg | Change From Baseline Over Time in ADAS-Cog-14 Number Cancellation Score | Change at Week 96 | 0.84 score on a scale | Standard Error 0.137 |
| ABBV-8E12 300 mg | Change From Baseline Over Time in ADAS-Cog-14 Number Cancellation Score | Change at Week 24 | 0.33 score on a scale | Standard Error 0.1 |
| ABBV-8E12 1000 mg | Change From Baseline Over Time in ADAS-Cog-14 Number Cancellation Score | Change at Week 72 | 0.44 score on a scale | Standard Error 0.115 |
| ABBV-8E12 1000 mg | Change From Baseline Over Time in ADAS-Cog-14 Number Cancellation Score | Change at Week 48 | 0.42 score on a scale | Standard Error 0.112 |
| ABBV-8E12 1000 mg | Change From Baseline Over Time in ADAS-Cog-14 Number Cancellation Score | Change at Week 96 | 0.74 score on a scale | Standard Error 0.133 |
| ABBV-8E12 1000 mg | Change From Baseline Over Time in ADAS-Cog-14 Number Cancellation Score | Change at Week 24 | 0.35 score on a scale | Standard Error 0.097 |
| ABBV-8E12 2000 mg | Change From Baseline Over Time in ADAS-Cog-14 Number Cancellation Score | Change at Week 96 | 0.77 score on a scale | Standard Error 0.143 |
| ABBV-8E12 2000 mg | Change From Baseline Over Time in ADAS-Cog-14 Number Cancellation Score | Change at Week 48 | 0.22 score on a scale | Standard Error 0.118 |
| ABBV-8E12 2000 mg | Change From Baseline Over Time in ADAS-Cog-14 Number Cancellation Score | Change at Week 24 | 0.32 score on a scale | Standard Error 0.102 |
| ABBV-8E12 2000 mg | Change From Baseline Over Time in ADAS-Cog-14 Number Cancellation Score | Change at Week 72 | 0.68 score on a scale | Standard Error 0.118 |
Comparison: Week 24p-value: 0.97695% CI: [-0.269, 0.278]repeated measures model
Comparison: Week 24
Comparison: Week 24p-value: 0.8595% CI: [-0.244, 0.296]repeated measures model
Comparison: Week 24
Comparison: Week 24p-value: 0.98195% CI: [-0.281, 0.275]repeated measures model
Comparison: Week 24
Comparison: Week 48p-value: 0.98995% CI: [-0.323, 0.318]repeated measures model
Comparison: Week 48
Comparison: Week 48p-value: 0.9795% CI: [-0.319, 0.307]repeated measures model
Comparison: Week 48
Comparison: Week 48p-value: 0.21595% CI: [-0.526, 0.119]repeated measures model
Comparison: Week 48
Comparison: Week 72p-value: 0.66595% CI: [-0.392, 0.25]repeated measures model
Comparison: Week 72
Comparison: Week 72p-value: 0.05995% CI: [-0.625, 0.012]repeated measures model
Comparison: Week 72
Comparison: Week 72p-value: 0.66395% CI: [-0.394, 0.251]repeated measures model
Comparison: Week 72
Comparison: Week 96p-value: 0.86695% CI: [-0.413, 0.348]repeated measures model
Comparison: Week 96
Comparison: Week 96p-value: 0.47195% CI: [-0.514, 0.238]repeated measures model
Comparison: Week 96
Comparison: Week 96p-value: 0.60495% CI: [-0.493, 0.287]repeated measures model
Comparison: Week 96
Secondary
Change From Baseline Over Time in ADAS-Cog-14 Orientation Score
The ADAS-Cog was designed to assess the cognitive impairments most common in AD. The ADAS-Cog-14 includes the original 11 items from the ADAS-Cog-11 \[1. Spoken language ability, 2. Comprehension of spoken language, 3. Recall of test instructions, 4. Word-findings difficulty in spontaneous speech, 5. Following commands, 6. Naming objects and fingers, 7. Constructional praxis, 8. Ideational praxis, 9. Orientation, 10. Word-recall task, 11. Word-recognition task\] and includes 3 additional tasks \[12. Number cancellation task, 13. Delayed word recall task, 14. Executive functioning\], for increased sensitivity in MCI patients. The Orientation Score of the ADAS-Cog-14 ranges from 0 to 8, with a higher score representing greater impairment.
Time frame: Baseline, Week 24, Week 48, Week 72, Week 96
Population: Intent-to-Treat Data Set: all randomized participants who received at least 1 dose of study drug. Participants with an assessment at given time point.
| Arm | Measure | Group | Value (LEAST_SQUARES_MEAN) | Dispersion |
|---|---|---|---|---|
| Placebo | Change From Baseline Over Time in ADAS-Cog-14 Orientation Score | Change at Week 24 | 0.08 score on a scale | Standard Error 0.127 |
| Placebo | Change From Baseline Over Time in ADAS-Cog-14 Orientation Score | Change at Week 48 | 0.63 score on a scale | Standard Error 0.147 |
| Placebo | Change From Baseline Over Time in ADAS-Cog-14 Orientation Score | Change at Week 72 | 1.01 score on a scale | Standard Error 0.166 |
| Placebo | Change From Baseline Over Time in ADAS-Cog-14 Orientation Score | Change at Week 96 | 1.26 score on a scale | Standard Error 0.196 |
| ABBV-8E12 300 mg | Change From Baseline Over Time in ADAS-Cog-14 Orientation Score | Change at Week 48 | 0.77 score on a scale | Standard Error 0.154 |
| ABBV-8E12 300 mg | Change From Baseline Over Time in ADAS-Cog-14 Orientation Score | Change at Week 72 | 0.84 score on a scale | Standard Error 0.172 |
| ABBV-8E12 300 mg | Change From Baseline Over Time in ADAS-Cog-14 Orientation Score | Change at Week 96 | 1.46 score on a scale | Standard Error 0.197 |
| ABBV-8E12 300 mg | Change From Baseline Over Time in ADAS-Cog-14 Orientation Score | Change at Week 24 | 0.42 score on a scale | Standard Error 0.13 |
| ABBV-8E12 1000 mg | Change From Baseline Over Time in ADAS-Cog-14 Orientation Score | Change at Week 72 | 1.02 score on a scale | Standard Error 0.167 |
| ABBV-8E12 1000 mg | Change From Baseline Over Time in ADAS-Cog-14 Orientation Score | Change at Week 48 | 0.45 score on a scale | Standard Error 0.145 |
| ABBV-8E12 1000 mg | Change From Baseline Over Time in ADAS-Cog-14 Orientation Score | Change at Week 96 | 1.28 score on a scale | Standard Error 0.191 |
| ABBV-8E12 1000 mg | Change From Baseline Over Time in ADAS-Cog-14 Orientation Score | Change at Week 24 | 0.08 score on a scale | Standard Error 0.125 |
| ABBV-8E12 2000 mg | Change From Baseline Over Time in ADAS-Cog-14 Orientation Score | Change at Week 96 | 2.00 score on a scale | Standard Error 0.202 |
| ABBV-8E12 2000 mg | Change From Baseline Over Time in ADAS-Cog-14 Orientation Score | Change at Week 48 | 0.61 score on a scale | Standard Error 0.153 |
| ABBV-8E12 2000 mg | Change From Baseline Over Time in ADAS-Cog-14 Orientation Score | Change at Week 24 | 0.49 score on a scale | Standard Error 0.132 |
| ABBV-8E12 2000 mg | Change From Baseline Over Time in ADAS-Cog-14 Orientation Score | Change at Week 72 | 1.05 score on a scale | Standard Error 0.171 |
Comparison: Week 24p-value: 0.05695% CI: [-0.009, 0.697]repeated measures model
Comparison: Week 24
Comparison: Week 24p-value: 0.99795% CI: [-0.348, 0.349]repeated measures model
Comparison: Week 24
Comparison: Week 24p-value: 0.02395% CI: [0.056, 0.772]repeated measures model
Comparison: Week 24
Comparison: Week 48p-value: 0.50295% CI: [-0.274, 0.558]repeated measures model
Comparison: Week 48
Comparison: Week 48p-value: 0.37995% CI: [-0.587, 0.224]repeated measures model
Comparison: Week 48
Comparison: Week 48p-value: 0.91695% CI: [-0.439, 0.394]repeated measures model
Comparison: Week 48
Comparison: Week 72p-value: 0.48795% CI: [-0.633, 0.302]repeated measures model
Comparison: Week 72
Comparison: Week 72p-value: 0.96395% CI: [-0.451, 0.473]repeated measures model
Comparison: Week 72
Comparison: Week 72p-value: 0.85695% CI: [-0.424, 0.51]repeated measures model
Comparison: Week 72
Comparison: Week 96p-value: 0.46395% CI: [-0.341, 0.748]repeated measures model
Comparison: Week 96
Comparison: Week 96p-value: 0.94395% CI: [-0.518, 0.557]repeated measures model
Comparison: Week 96
Comparison: Week 96p-value: 0.00995% CI: [0.191, 1.295]repeated measures model
Comparison: Week 96
Secondary
Change From Baseline Over Time in ADAS-Cog-14 Remember Word Recognition Instructions Score
The ADAS-Cog was designed to assess the cognitive impairments most common in AD. The ADAS-Cog-14 includes the original 11 items from the ADAS-Cog-11 \[1. Spoken language ability, 2. Comprehension of spoken language, 3. Recall of test instructions, 4. Word-findings difficulty in spontaneous speech, 5. Following commands, 6. Naming objects and fingers, 7. Constructional praxis, 8. Ideational praxis, 9. Orientation, 10. Word-recall task, 11. Word-recognition task\] and includes 3 additional tasks \[12. Number cancellation task, 13. Delayed word recall task, 14. Executive functioning\], for increased sensitivity in MCI patients. The Remember Word Recognition Instructions Score of the ADAS-Cog-14 ranges from 0 to 5, with a higher score representing greater impairment.
Time frame: Baseline, Week 24, Week 48, Week 72, Week 96
Population: Intent-to-Treat Data Set: all randomized participants who received at least 1 dose of study drug. Participants with an assessment at given time point.
| Arm | Measure | Group | Value (LEAST_SQUARES_MEAN) | Dispersion |
|---|---|---|---|---|
| Placebo | Change From Baseline Over Time in ADAS-Cog-14 Remember Word Recognition Instructions Score | Change at Week 24 | 0.03 score on a scale | Standard Error 0.05 |
| Placebo | Change From Baseline Over Time in ADAS-Cog-14 Remember Word Recognition Instructions Score | Change at Week 48 | 0.27 score on a scale | Standard Error 0.071 |
| Placebo | Change From Baseline Over Time in ADAS-Cog-14 Remember Word Recognition Instructions Score | Change at Week 72 | 0.24 score on a scale | Standard Error 0.091 |
| Placebo | Change From Baseline Over Time in ADAS-Cog-14 Remember Word Recognition Instructions Score | Change at Week 96 | 0.40 score on a scale | Standard Error 0.112 |
| ABBV-8E12 300 mg | Change From Baseline Over Time in ADAS-Cog-14 Remember Word Recognition Instructions Score | Change at Week 48 | 0.10 score on a scale | Standard Error 0.074 |
| ABBV-8E12 300 mg | Change From Baseline Over Time in ADAS-Cog-14 Remember Word Recognition Instructions Score | Change at Week 72 | 0.19 score on a scale | Standard Error 0.094 |
| ABBV-8E12 300 mg | Change From Baseline Over Time in ADAS-Cog-14 Remember Word Recognition Instructions Score | Change at Week 96 | 0.45 score on a scale | Standard Error 0.113 |
| ABBV-8E12 300 mg | Change From Baseline Over Time in ADAS-Cog-14 Remember Word Recognition Instructions Score | Change at Week 24 | 0.03 score on a scale | Standard Error 0.051 |
| ABBV-8E12 1000 mg | Change From Baseline Over Time in ADAS-Cog-14 Remember Word Recognition Instructions Score | Change at Week 72 | 0.29 score on a scale | Standard Error 0.091 |
| ABBV-8E12 1000 mg | Change From Baseline Over Time in ADAS-Cog-14 Remember Word Recognition Instructions Score | Change at Week 48 | 0.19 score on a scale | Standard Error 0.07 |
| ABBV-8E12 1000 mg | Change From Baseline Over Time in ADAS-Cog-14 Remember Word Recognition Instructions Score | Change at Week 96 | 0.27 score on a scale | Standard Error 0.111 |
| ABBV-8E12 1000 mg | Change From Baseline Over Time in ADAS-Cog-14 Remember Word Recognition Instructions Score | Change at Week 24 | 0.15 score on a scale | Standard Error 0.049 |
| ABBV-8E12 2000 mg | Change From Baseline Over Time in ADAS-Cog-14 Remember Word Recognition Instructions Score | Change at Week 96 | 0.46 score on a scale | Standard Error 0.117 |
| ABBV-8E12 2000 mg | Change From Baseline Over Time in ADAS-Cog-14 Remember Word Recognition Instructions Score | Change at Week 48 | 0.06 score on a scale | Standard Error 0.074 |
| ABBV-8E12 2000 mg | Change From Baseline Over Time in ADAS-Cog-14 Remember Word Recognition Instructions Score | Change at Week 24 | -0.02 score on a scale | Standard Error 0.052 |
| ABBV-8E12 2000 mg | Change From Baseline Over Time in ADAS-Cog-14 Remember Word Recognition Instructions Score | Change at Week 72 | 0.26 score on a scale | Standard Error 0.093 |
Comparison: Week 24p-value: 0.97595% CI: [-0.138, 0.142]repeated measures model
Comparison: Week 24
Comparison: Week 24p-value: 0.07895% CI: [-0.014, 0.261]repeated measures model
Comparison: Week 24
Comparison: Week 24p-value: 0.51495% CI: [-0.188, 0.094]repeated measures model
Comparison: Week 24
Comparison: Week 48p-value: 0.10795% CI: [-0.367, 0.036]repeated measures model
Comparison: Week 48
Comparison: Week 48p-value: 0.42595% CI: [-0.275, 0.116]repeated measures model
Comparison: Week 48
Comparison: Week 48p-value: 0.03995% CI: [-0.413, -0.011]repeated measures model
Comparison: Week 48
Comparison: Week 72p-value: 0.72995% CI: [-0.302, 0.212]repeated measures model
Comparison: Week 72
Comparison: Week 72p-value: 0.67195% CI: [-0.198, 0.307]repeated measures model
Comparison: Week 72
Comparison: Week 72p-value: 0.87695% CI: [-0.235, 0.276]repeated measures model
Comparison: Week 72
Comparison: Week 96p-value: 0.76395% CI: [-0.266, 0.362]repeated measures model
Comparison: Week 96
Comparison: Week 96p-value: 0.42995% CI: [-0.434, 0.185]repeated measures model
Comparison: Week 96
Comparison: Week 96p-value: 0.70195% CI: [-0.256, 0.381]repeated measures model
Comparison: Week 96
Secondary
Change From Baseline Over Time in ADAS-Cog-14 Spoken Language Ability Score
The ADAS-Cog was designed to assess the cognitive impairments most common in AD. The ADAS-Cog-14 includes the original 11 items from the ADAS-Cog-11 \[1. Spoken language ability, 2. Comprehension of spoken language, 3. Recall of test instructions, 4. Word-findings difficulty in spontaneous speech, 5. Following commands, 6. Naming objects and fingers, 7. Constructional praxis, 8. Ideational praxis, 9. Orientation, 10. Word-recall task, 11. Word-recognition task\] and includes 3 additional tasks \[12. Number cancellation task, 13. Delayed word recall task, 14. Executive functioning\], for increased sensitivity in MCI patients. The Spoken Language Ability Score of the ADAS-Cog-14 ranges from 0 to 5, with a higher score representing greater impairment.
Time frame: Baseline, Week 24, Week 48, Week 72, Week 96
Population: Intent-to-Treat Data Set: all randomized participants who received at least 1 dose of study drug. Participants with an assessment at given time point.
| Arm | Measure | Group | Value (LEAST_SQUARES_MEAN) | Dispersion |
|---|---|---|---|---|
| Placebo | Change From Baseline Over Time in ADAS-Cog-14 Spoken Language Ability Score | Change at Week 24 | 0.07 score on a scale | Standard Error 0.045 |
| Placebo | Change From Baseline Over Time in ADAS-Cog-14 Spoken Language Ability Score | Change at Week 48 | 0.14 score on a scale | Standard Error 0.051 |
| Placebo | Change From Baseline Over Time in ADAS-Cog-14 Spoken Language Ability Score | Change at Week 72 | 0.23 score on a scale | Standard Error 0.066 |
| Placebo | Change From Baseline Over Time in ADAS-Cog-14 Spoken Language Ability Score | Change at Week 96 | 0.29 score on a scale | Standard Error 0.089 |
| ABBV-8E12 300 mg | Change From Baseline Over Time in ADAS-Cog-14 Spoken Language Ability Score | Change at Week 48 | 0.04 score on a scale | Standard Error 0.054 |
| ABBV-8E12 300 mg | Change From Baseline Over Time in ADAS-Cog-14 Spoken Language Ability Score | Change at Week 72 | 0.11 score on a scale | Standard Error 0.069 |
| ABBV-8E12 300 mg | Change From Baseline Over Time in ADAS-Cog-14 Spoken Language Ability Score | Change at Week 96 | 0.23 score on a scale | Standard Error 0.09 |
| ABBV-8E12 300 mg | Change From Baseline Over Time in ADAS-Cog-14 Spoken Language Ability Score | Change at Week 24 | 0.08 score on a scale | Standard Error 0.046 |
| ABBV-8E12 1000 mg | Change From Baseline Over Time in ADAS-Cog-14 Spoken Language Ability Score | Change at Week 72 | 0.19 score on a scale | Standard Error 0.066 |
| ABBV-8E12 1000 mg | Change From Baseline Over Time in ADAS-Cog-14 Spoken Language Ability Score | Change at Week 48 | 0.03 score on a scale | Standard Error 0.051 |
| ABBV-8E12 1000 mg | Change From Baseline Over Time in ADAS-Cog-14 Spoken Language Ability Score | Change at Week 96 | 0.25 score on a scale | Standard Error 0.087 |
| ABBV-8E12 1000 mg | Change From Baseline Over Time in ADAS-Cog-14 Spoken Language Ability Score | Change at Week 24 | 0.06 score on a scale | Standard Error 0.045 |
| ABBV-8E12 2000 mg | Change From Baseline Over Time in ADAS-Cog-14 Spoken Language Ability Score | Change at Week 96 | 0.43 score on a scale | Standard Error 0.092 |
| ABBV-8E12 2000 mg | Change From Baseline Over Time in ADAS-Cog-14 Spoken Language Ability Score | Change at Week 48 | 0.11 score on a scale | Standard Error 0.053 |
| ABBV-8E12 2000 mg | Change From Baseline Over Time in ADAS-Cog-14 Spoken Language Ability Score | Change at Week 24 | 0.11 score on a scale | Standard Error 0.047 |
| ABBV-8E12 2000 mg | Change From Baseline Over Time in ADAS-Cog-14 Spoken Language Ability Score | Change at Week 72 | 0.24 score on a scale | Standard Error 0.068 |
Comparison: Week 24p-value: 0.86795% CI: [-0.115, 0.137]repeated measures model
Comparison: Week 24
Comparison: Week 24p-value: 0.89895% CI: [-0.132, 0.116]repeated measures model
Comparison: Week 24
Comparison: Week 24p-value: 0.53795% CI: [-0.088, 0.168]repeated measures model
Comparison: Week 24
Comparison: Week 48p-value: 0.17695% CI: [-0.245, 0.045]repeated measures model
Comparison: Week 48
Comparison: Week 48p-value: 0.12595% CI: [-0.251, 0.031]repeated measures model
Comparison: Week 48
Comparison: week 48p-value: 0.67695% CI: [-0.176, 0.114]repeated measures model
Comparison: Week 48
Comparison: Week 72p-value: 0.22695% CI: [-0.301, 0.071]repeated measures model
Comparison: Week 72
Comparison: Week 72p-value: 0.68395% CI: [-0.222, 0.145]repeated measures model
Comparison: Week 72
Comparison: Week 72p-value: 0.84895% CI: [-0.168, 0.204]repeated measures model
Comparison: Week 72
Comparison: Week 96p-value: 0.65695% CI: [-0.305, 0.192]repeated measures model
Comparison: Week 96
Comparison: Week 96p-value: 0.77795% CI: [-0.279, 0.209]repeated measures model
Comparison: Week 96
Comparison: Week 96p-value: 0.25695% CI: [-0.106, 0.397]repeated measures model
Comparison: Week 96
Secondary
Change From Baseline Over Time in ADAS-Cog-14 Word Find Difficulty Spontaneous Speech Score
The ADAS-Cog was designed to assess the cognitive impairments most common in AD. The ADAS-Cog-14 includes the original 11 items from the ADAS-Cog-11 \[1. Spoken language ability, 2. Comprehension of spoken language, 3. Recall of test instructions, 4. Word-findings difficulty in spontaneous speech, 5. Following commands, 6. Naming objects and fingers, 7. Constructional praxis, 8. Ideational praxis, 9. Orientation, 10. Word-recall task, 11. Word-recognition task\] and includes 3 additional tasks \[12. Number cancellation task, 13. Delayed word recall task, 14. Executive functioning\], for increased sensitivity in MCI patients. The Word Find Difficulty Spontaneous Speech Score of the ADAS-Cog-14 ranges from 0 to 5, with a higher score representing greater impairment.
Time frame: Baseline, Week 24, Week 48, Week 72, Week 96
Population: Intent-to-Treat Data Set: all randomized participants who received at least 1 dose of study drug. Participants with an assessment at given time point.
| Arm | Measure | Group | Value (LEAST_SQUARES_MEAN) | Dispersion |
|---|---|---|---|---|
| Placebo | Change From Baseline Over Time in ADAS-Cog-14 Word Find Difficulty Spontaneous Speech Score | Change at Week 24 | 0.21 score on a scale | Standard Error 0.071 |
| Placebo | Change From Baseline Over Time in ADAS-Cog-14 Word Find Difficulty Spontaneous Speech Score | Change at Week 48 | 0.25 score on a scale | Standard Error 0.077 |
| Placebo | Change From Baseline Over Time in ADAS-Cog-14 Word Find Difficulty Spontaneous Speech Score | Change at Week 72 | 0.47 score on a scale | Standard Error 0.093 |
| Placebo | Change From Baseline Over Time in ADAS-Cog-14 Word Find Difficulty Spontaneous Speech Score | Change at Week 96 | 0.58 score on a scale | Standard Error 0.117 |
| ABBV-8E12 300 mg | Change From Baseline Over Time in ADAS-Cog-14 Word Find Difficulty Spontaneous Speech Score | Change at Week 48 | 0.19 score on a scale | Standard Error 0.081 |
| ABBV-8E12 300 mg | Change From Baseline Over Time in ADAS-Cog-14 Word Find Difficulty Spontaneous Speech Score | Change at Week 72 | 0.28 score on a scale | Standard Error 0.096 |
| ABBV-8E12 300 mg | Change From Baseline Over Time in ADAS-Cog-14 Word Find Difficulty Spontaneous Speech Score | Change at Week 96 | 0.35 score on a scale | Standard Error 0.119 |
| ABBV-8E12 300 mg | Change From Baseline Over Time in ADAS-Cog-14 Word Find Difficulty Spontaneous Speech Score | Change at Week 24 | 0.14 score on a scale | Standard Error 0.073 |
| ABBV-8E12 1000 mg | Change From Baseline Over Time in ADAS-Cog-14 Word Find Difficulty Spontaneous Speech Score | Change at Week 72 | 0.44 score on a scale | Standard Error 0.094 |
| ABBV-8E12 1000 mg | Change From Baseline Over Time in ADAS-Cog-14 Word Find Difficulty Spontaneous Speech Score | Change at Week 48 | 0.21 score on a scale | Standard Error 0.077 |
| ABBV-8E12 1000 mg | Change From Baseline Over Time in ADAS-Cog-14 Word Find Difficulty Spontaneous Speech Score | Change at Week 96 | 0.47 score on a scale | Standard Error 0.114 |
| ABBV-8E12 1000 mg | Change From Baseline Over Time in ADAS-Cog-14 Word Find Difficulty Spontaneous Speech Score | Change at Week 24 | 0.11 score on a scale | Standard Error 0.07 |
| ABBV-8E12 2000 mg | Change From Baseline Over Time in ADAS-Cog-14 Word Find Difficulty Spontaneous Speech Score | Change at Week 96 | 0.60 score on a scale | Standard Error 0.121 |
| ABBV-8E12 2000 mg | Change From Baseline Over Time in ADAS-Cog-14 Word Find Difficulty Spontaneous Speech Score | Change at Week 48 | 0.31 score on a scale | Standard Error 0.081 |
| ABBV-8E12 2000 mg | Change From Baseline Over Time in ADAS-Cog-14 Word Find Difficulty Spontaneous Speech Score | Change at Week 24 | 0.23 score on a scale | Standard Error 0.074 |
| ABBV-8E12 2000 mg | Change From Baseline Over Time in ADAS-Cog-14 Word Find Difficulty Spontaneous Speech Score | Change at Week 72 | 0.42 score on a scale | Standard Error 0.096 |
Comparison: Week 24p-value: 0.47995% CI: [-0.269, 0.126]repeated measures model
Comparison: Week 24
Comparison: Week 24p-value: 0.29595% CI: [-0.299, 0.091]repeated measures model
Comparison: Week 24
Comparison: Week 24p-value: 0.88495% CI: [-0.186, 0.215]repeated measures model
Comparison: Week 24
Comparison: Week 48p-value: 0.56995% CI: [-0.281, 0.155]repeated measures model
Comparison: Week 48
Comparison: Week 48p-value: 0.70295% CI: [-0.254, 0.171]repeated measures model
Comparison: Week 48
Comparison: Week 48p-value: 0.56695% CI: [-0.155, 0.283]repeated measures model
Comparison: Week 48
Comparison: Week 72p-value: 0.14195% CI: [-0.458, 0.065]repeated measures model
Comparison: Week 72
Comparison: Week 72p-value: 0.83495% CI: [-0.285, 0.23]repeated measures model
Comparison: Week 72
Comparison: Week 72p-value: 0.72495% CI: [-0.309, 0.215]repeated measures model
Comparison: Week 72
Comparison: Week 96p-value: 0.16395% CI: [-0.559, 0.095]repeated measures model
Comparison: Week 96
Comparison: Week 96p-value: 0.49795% CI: [-0.432, 0.21]repeated measures model
Comparison: Week 96
Comparison: Week 96p-value: 0.91995% CI: [-0.314, 0.349]repeated measures model
Comparison: Week 96
Secondary
Change From Baseline Over Time in ADAS-Cog-14 Word Recall - Number of Words Not Recalled Score
The ADAS-Cog was designed to assess the cognitive impairments most common in AD. The ADAS-Cog-14 includes the original 11 items from the ADAS-Cog-11 \[1. Spoken language ability, 2. Comprehension of spoken language, 3. Recall of test instructions, 4. Word-findings difficulty in spontaneous speech, 5. Following commands, 6. Naming objects and fingers, 7. Constructional praxis, 8. Ideational praxis, 9. Orientation, 10. Word-recall task, 11. Word-recognition task\] and includes 3 additional tasks \[12. Number cancellation task, 13. Delayed word recall task, 14. Executive functioning\], for increased sensitivity in MCI patients. The Word Recall - Number of Words Not Recalled Score of the ADAS-Cog-14 ranges from 0 to 10, with a higher score representing greater impairment.
Time frame: Baseline, Week 24, Week 48, Week 72, Week 96
Population: Intent-to-Treat Data Set: all randomized participants who received at least 1 dose of study drug. Participants with an assessment at given time point.
| Arm | Measure | Group | Value (LEAST_SQUARES_MEAN) | Dispersion |
|---|---|---|---|---|
| Placebo | Change From Baseline Over Time in ADAS-Cog-14 Word Recall - Number of Words Not Recalled Score | Change at Week 24 | 0.16 score on a scale | Standard Error 0.098 |
| Placebo | Change From Baseline Over Time in ADAS-Cog-14 Word Recall - Number of Words Not Recalled Score | Change at Week 48 | 0.39 score on a scale | Standard Error 0.101 |
| Placebo | Change From Baseline Over Time in ADAS-Cog-14 Word Recall - Number of Words Not Recalled Score | Change at Week 72 | 0.58 score on a scale | Standard Error 0.113 |
| Placebo | Change From Baseline Over Time in ADAS-Cog-14 Word Recall - Number of Words Not Recalled Score | Change at Week 96 | 1.04 score on a scale | Standard Error 0.131 |
| ABBV-8E12 300 mg | Change From Baseline Over Time in ADAS-Cog-14 Word Recall - Number of Words Not Recalled Score | Change at Week 48 | 0.32 score on a scale | Standard Error 0.105 |
| ABBV-8E12 300 mg | Change From Baseline Over Time in ADAS-Cog-14 Word Recall - Number of Words Not Recalled Score | Change at Week 72 | 0.64 score on a scale | Standard Error 0.117 |
| ABBV-8E12 300 mg | Change From Baseline Over Time in ADAS-Cog-14 Word Recall - Number of Words Not Recalled Score | Change at Week 96 | 0.97 score on a scale | Standard Error 0.132 |
| ABBV-8E12 300 mg | Change From Baseline Over Time in ADAS-Cog-14 Word Recall - Number of Words Not Recalled Score | Change at Week 24 | 0.03 score on a scale | Standard Error 0.1 |
| ABBV-8E12 1000 mg | Change From Baseline Over Time in ADAS-Cog-14 Word Recall - Number of Words Not Recalled Score | Change at Week 72 | 0.60 score on a scale | Standard Error 0.114 |
| ABBV-8E12 1000 mg | Change From Baseline Over Time in ADAS-Cog-14 Word Recall - Number of Words Not Recalled Score | Change at Week 48 | 0.41 score on a scale | Standard Error 0.1 |
| ABBV-8E12 1000 mg | Change From Baseline Over Time in ADAS-Cog-14 Word Recall - Number of Words Not Recalled Score | Change at Week 96 | 0.89 score on a scale | Standard Error 0.127 |
| ABBV-8E12 1000 mg | Change From Baseline Over Time in ADAS-Cog-14 Word Recall - Number of Words Not Recalled Score | Change at Week 24 | 0.16 score on a scale | Standard Error 0.097 |
| ABBV-8E12 2000 mg | Change From Baseline Over Time in ADAS-Cog-14 Word Recall - Number of Words Not Recalled Score | Change at Week 96 | 0.91 score on a scale | Standard Error 0.135 |
| ABBV-8E12 2000 mg | Change From Baseline Over Time in ADAS-Cog-14 Word Recall - Number of Words Not Recalled Score | Change at Week 48 | 0.38 score on a scale | Standard Error 0.105 |
| ABBV-8E12 2000 mg | Change From Baseline Over Time in ADAS-Cog-14 Word Recall - Number of Words Not Recalled Score | Change at Week 24 | 0.11 score on a scale | Standard Error 0.101 |
| ABBV-8E12 2000 mg | Change From Baseline Over Time in ADAS-Cog-14 Word Recall - Number of Words Not Recalled Score | Change at Week 72 | 0.70 score on a scale | Standard Error 0.116 |
Comparison: Week 24p-value: 0.32595% CI: [-0.408, 0.136]repeated measures model
Comparison: Week 24
Comparison: Week 24p-value: 0.96695% CI: [-0.274, 0.263]repeated measures model
Comparison: Week 24
Comparison: Week 24p-value: 0.69595% CI: [-0.33, 0.22]repeated measures model
Comparison: Week 24
Comparison: Week 48p-value: 0.66295% CI: [-0.348, 0.221]repeated measures model
Comparison: Week 48
Comparison: Week 48p-value: 0.84995% CI: [-0.25, 0.304]repeated measures model
Comparison: Week 48
Comparison: Week 48p-value: 0.99595% CI: [-0.286, 0.284]repeated measures model
Comparison: Week 48
Comparison: Week 72p-value: 0.70795% CI: [-0.256, 0.378]repeated measures model
Comparison: Week 72
Comparison: Week 72p-value: 0.90195% CI: [-0.294, 0.333]repeated measures model
Comparison: Week 72
Comparison: Week 72p-value: 0.45195% CI: [-0.195, 0.439]repeated measures model
Comparison: Week 72
Comparison: Week 96p-value: 0.72295% CI: [-0.429, 0.298]repeated measures model
Comparison: Week 96
Comparison: Week 96p-value: 0.4295% CI: [-0.503, 0.21]repeated measures model
Comparison: Week 96
Comparison: Week 96p-value: 0.49895% CI: [-0.495, 0.241]repeated measures model
Comparison: Week 96
Secondary
Change From Baseline Over Time in ADAS-Cog-14 Word Recognition Score
The ADAS-Cog was designed to assess the cognitive impairments most common in AD. The ADAS-Cog-14 includes the original 11 items from the ADAS-Cog-11 \[1. Spoken language ability, 2. Comprehension of spoken language, 3. Recall of test instructions, 4. Word-findings difficulty in spontaneous speech, 5. Following commands, 6. Naming objects and fingers, 7. Constructional praxis, 8. Ideational praxis, 9. Orientation, 10. Word-recall task, 11. Word-recognition task\] and includes 3 additional tasks \[12. Number cancellation task, 13. Delayed word recall task, 14. Executive functioning\], for increased sensitivity in MCI patients. The Word Recognition Score of the ADAS-Cog-14 ranges from 0 to 12, with a higher score representing greater impairment.
Time frame: Baseline, Week 24, Week 48, Week 72, Week 96
Population: Intent-to-Treat Data Set: all randomized participants who received at least 1 dose of study drug. Participants with an assessment at given time point.
| Arm | Measure | Group | Value (LEAST_SQUARES_MEAN) | Dispersion |
|---|---|---|---|---|
| Placebo | Change From Baseline Over Time in ADAS-Cog-14 Word Recognition Score | Change at Week 24 | 0.53 score on a scale | Standard Error 0.248 |
| Placebo | Change From Baseline Over Time in ADAS-Cog-14 Word Recognition Score | Change at Week 48 | 1.35 score on a scale | Standard Error 0.257 |
| Placebo | Change From Baseline Over Time in ADAS-Cog-14 Word Recognition Score | Change at Week 72 | 0.65 score on a scale | Standard Error 0.245 |
| Placebo | Change From Baseline Over Time in ADAS-Cog-14 Word Recognition Score | Change at Week 96 | 1.98 score on a scale | Standard Error 0.287 |
| ABBV-8E12 300 mg | Change From Baseline Over Time in ADAS-Cog-14 Word Recognition Score | Change at Week 48 | 0.92 score on a scale | Standard Error 0.27 |
| ABBV-8E12 300 mg | Change From Baseline Over Time in ADAS-Cog-14 Word Recognition Score | Change at Week 72 | 1.05 score on a scale | Standard Error 0.255 |
| ABBV-8E12 300 mg | Change From Baseline Over Time in ADAS-Cog-14 Word Recognition Score | Change at Week 96 | 1.97 score on a scale | Standard Error 0.287 |
| ABBV-8E12 300 mg | Change From Baseline Over Time in ADAS-Cog-14 Word Recognition Score | Change at Week 24 | 0.25 score on a scale | Standard Error 0.253 |
| ABBV-8E12 1000 mg | Change From Baseline Over Time in ADAS-Cog-14 Word Recognition Score | Change at Week 72 | 0.78 score on a scale | Standard Error 0.249 |
| ABBV-8E12 1000 mg | Change From Baseline Over Time in ADAS-Cog-14 Word Recognition Score | Change at Week 48 | 0.73 score on a scale | Standard Error 0.254 |
| ABBV-8E12 1000 mg | Change From Baseline Over Time in ADAS-Cog-14 Word Recognition Score | Change at Week 96 | 1.53 score on a scale | Standard Error 0.283 |
| ABBV-8E12 1000 mg | Change From Baseline Over Time in ADAS-Cog-14 Word Recognition Score | Change at Week 24 | -0.20 score on a scale | Standard Error 0.245 |
| ABBV-8E12 2000 mg | Change From Baseline Over Time in ADAS-Cog-14 Word Recognition Score | Change at Week 96 | 2.09 score on a scale | Standard Error 0.301 |
| ABBV-8E12 2000 mg | Change From Baseline Over Time in ADAS-Cog-14 Word Recognition Score | Change at Week 48 | 0.80 score on a scale | Standard Error 0.268 |
| ABBV-8E12 2000 mg | Change From Baseline Over Time in ADAS-Cog-14 Word Recognition Score | Change at Week 24 | -0.02 score on a scale | Standard Error 0.257 |
| ABBV-8E12 2000 mg | Change From Baseline Over Time in ADAS-Cog-14 Word Recognition Score | Change at Week 72 | 0.88 score on a scale | Standard Error 0.252 |
Comparison: Week 24p-value: 0.42395% CI: [-0.974, 0.409]repeated measures model
Comparison: Week 24
Comparison: Week 24p-value: 0.03695% CI: [-1.408, -0.047]repeated measures model
Comparison: Week 24
Comparison: Week 24p-value: 0.12195% CI: [-1.25, 0.147]repeated measures model
Comparison: Week 24
Comparison: Week 48p-value: 0.24495% CI: [-1.163, 0.296]repeated measures model
Comparison: Week 48
Comparison: Week 48p-value: 0.08595% CI: [-1.33, 0.086]repeated measures model
Comparison: Week 48
Comparison: Week 48p-value: 0.13795% CI: [-1.28, 0.177]repeated measures model
Comparison: Week 48
Comparison: Week 72p-value: 0.25895% CI: [-0.294, 1.091]repeated measures model
Comparison: Week 72
Comparison: Week 72p-value: 0.71195% CI: [-0.555, 0.814]repeated measures model
Comparison: Week 72
Comparison: Week 72p-value: 0.50395% CI: [-0.454, 0.924]repeated measures model
Comparison: Week 72
Comparison: Week 96p-value: 0.97895% CI: [-0.806, 0.784]repeated measures model
Comparison: Week 96
Comparison: Week 96p-value: 0.26595% CI: [-1.239, 0.342]repeated measures model
Comparison: Week 96
Comparison: Week 96p-value: 0.78995% CI: [-0.704, 0.925]repeated measures model
Comparison: Effect size at a specific visit is calculated as LS mean difference (placebo - 8E12) divided by pooled standard deviation of change scores for a ABBV-8E12 dose and placebo at that visit.
Secondary
Change From Baseline Over Time in ADCS-CGIC-MCI Behavior Score
The instrument assesses the physician's global impression of change in 4 major cognitive domains. The instrument covers 4 major domains: 1. General condition , 2. Cognition, 3. Behavior, and 4. Social and daily functioning. Scoring is based on a 7-point Likert Scale: 1, marked improvement; 2, moderate improvement; 3, minimal improvement; 4, no change; 5, minimal worsening; 6, moderate worsening; 7, marked worsening. Higher score indicates greater worsening.
Time frame: Baseline, Week 48, Week 96
Population: Intent-to-Treat Data Set: all randomized participants who received at least 1 dose of study drug. Participants with an assessment at given time point.
| Arm | Measure | Group | Value (LEAST_SQUARES_MEAN) | Dispersion |
|---|---|---|---|---|
| Placebo | Change From Baseline Over Time in ADCS-CGIC-MCI Behavior Score | Change at Week 48 | 4.30 score on a scale | Standard Error 0.061 |
| Placebo | Change From Baseline Over Time in ADCS-CGIC-MCI Behavior Score | Change at Week 96 | 4.61 score on a scale | Standard Error 0.079 |
| ABBV-8E12 300 mg | Change From Baseline Over Time in ADCS-CGIC-MCI Behavior Score | Change at Week 96 | 4.49 score on a scale | Standard Error 0.078 |
| ABBV-8E12 300 mg | Change From Baseline Over Time in ADCS-CGIC-MCI Behavior Score | Change at Week 48 | 4.31 score on a scale | Standard Error 0.062 |
| ABBV-8E12 1000 mg | Change From Baseline Over Time in ADCS-CGIC-MCI Behavior Score | Change at Week 48 | 4.28 score on a scale | Standard Error 0.059 |
| ABBV-8E12 1000 mg | Change From Baseline Over Time in ADCS-CGIC-MCI Behavior Score | Change at Week 96 | 4.57 score on a scale | Standard Error 0.076 |
| ABBV-8E12 2000 mg | Change From Baseline Over Time in ADCS-CGIC-MCI Behavior Score | Change at Week 48 | 4.33 score on a scale | Standard Error 0.062 |
| ABBV-8E12 2000 mg | Change From Baseline Over Time in ADCS-CGIC-MCI Behavior Score | Change at Week 96 | 4.55 score on a scale | Standard Error 0.08 |
Comparison: Week 48p-value: 0.90395% CI: [-0.159, 0.18]repeated measures model
Comparison: Week 48
Comparison: Week 48p-value: 0.81195% CI: [-0.185, 0.145]repeated measures model
Comparison: Week 48
Comparison: Week 48p-value: 0.77595% CI: [-0.145, 0.194]repeated measures model
Comparison: Week 48
Comparison: Week 96p-value: 0.27395% CI: [-0.337, 0.096]repeated measures model
Comparison: Week 96
Comparison: Week 96p-value: 0.7495% CI: [-0.248, 0.176]repeated measures model
Comparison: Week 96
Comparison: Week 96p-value: 0.56795% CI: [-0.282, 0.155]repeated measures model
Comparison: Week 96
Secondary
Change From Baseline Over Time in ADCS-CGIC-MCI Cognition Score
The instrument assesses the physician's global impression of change in 4 major cognitive domains. The instrument covers 4 major domains: 1. General condition , 2. Cognition, 3. Behavior, and 4. Social and daily functioning. Scoring is based on a 7-point Likert Scale: 1, marked improvement; 2, moderate improvement; 3, minimal improvement; 4, no change; 5, minimal worsening; 6, moderate worsening; 7, marked worsening. Higher score indicates greater worsening.
Time frame: Baseline, Week 48, Week 96
Population: Intent-to-Treat Data Set: all randomized participants who received at least 1 dose of study drug. Participants with an assessment at given time point.
| Arm | Measure | Group | Value (LEAST_SQUARES_MEAN) | Dispersion |
|---|---|---|---|---|
| Placebo | Change From Baseline Over Time in ADCS-CGIC-MCI Cognition Score | Change at Week 48 | 4.85 score on a scale | Standard Error 0.08 |
| Placebo | Change From Baseline Over Time in ADCS-CGIC-MCI Cognition Score | Change at Week 96 | 5.30 score on a scale | Standard Error 0.092 |
| ABBV-8E12 300 mg | Change From Baseline Over Time in ADCS-CGIC-MCI Cognition Score | Change at Week 96 | 5.29 score on a scale | Standard Error 0.092 |
| ABBV-8E12 300 mg | Change From Baseline Over Time in ADCS-CGIC-MCI Cognition Score | Change at Week 48 | 4.81 score on a scale | Standard Error 0.081 |
| ABBV-8E12 1000 mg | Change From Baseline Over Time in ADCS-CGIC-MCI Cognition Score | Change at Week 48 | 4.83 score on a scale | Standard Error 0.077 |
| ABBV-8E12 1000 mg | Change From Baseline Over Time in ADCS-CGIC-MCI Cognition Score | Change at Week 96 | 5.22 score on a scale | Standard Error 0.088 |
| ABBV-8E12 2000 mg | Change From Baseline Over Time in ADCS-CGIC-MCI Cognition Score | Change at Week 48 | 4.92 score on a scale | Standard Error 0.081 |
| ABBV-8E12 2000 mg | Change From Baseline Over Time in ADCS-CGIC-MCI Cognition Score | Change at Week 96 | 5.34 score on a scale | Standard Error 0.093 |
Comparison: Week 48p-value: 0.72295% CI: [-0.26, 0.18]repeated measures model
Comparison: Week 48
Comparison: Week 48p-value: 0.87895% CI: [-0.232, 0.198]repeated measures model
Comparison: Week 48
Comparison: Week 48p-value: 0.53595% CI: [-0.151, 0.29]repeated measures model
Comparison: Week 48
Comparison: Week 96p-value: 0.91695% CI: [-0.266, 0.239]repeated measures model
Comparison: Week 96
Comparison: Week 96p-value: 0.51195% CI: [-0.33, 0.165]repeated measures model
Comparison: Week 96
Comparison: Week 96p-value: 0.77195% CI: [-0.217, 0.292]repeated measures model
Comparison: Week 96
Secondary
Change From Baseline Over Time in ADCS-CGIC-MCI Functional Abilities Score
The instrument assesses the physician's global impression of change in 4 major cognitive domains. The instrument covers 4 major domains: 1. General condition , 2. Cognition, 3. Behavior, and 4. Social and daily functioning (functional abilities). Scoring is based on a 7-point Likert Scale: 1, marked improvement; 2, moderate improvement; 3, minimal improvement; 4, no change; 5, minimal worsening; 6, moderate worsening; 7, marked worsening. Higher score indicates greater worsening.
Time frame: Baseline, Week 48, Week 96
Population: Intent-to-Treat Data Set: all randomized participants who received at least 1 dose of study drug. Participants with an assessment at given time point.
| Arm | Measure | Group | Value (LEAST_SQUARES_MEAN) | Dispersion |
|---|---|---|---|---|
| Placebo | Change From Baseline Over Time in ADCS-CGIC-MCI Functional Abilities Score | Change at Week 48 | 4.59 score on a scale | Standard Error 0.071 |
| Placebo | Change From Baseline Over Time in ADCS-CGIC-MCI Functional Abilities Score | Change at Week 96 | 4.97 score on a scale | Standard Error 0.088 |
| ABBV-8E12 300 mg | Change From Baseline Over Time in ADCS-CGIC-MCI Functional Abilities Score | Change at Week 96 | 4.95 score on a scale | Standard Error 0.088 |
| ABBV-8E12 300 mg | Change From Baseline Over Time in ADCS-CGIC-MCI Functional Abilities Score | Change at Week 48 | 4.58 score on a scale | Standard Error 0.072 |
| ABBV-8E12 1000 mg | Change From Baseline Over Time in ADCS-CGIC-MCI Functional Abilities Score | Change at Week 48 | 4.46 score on a scale | Standard Error 0.068 |
| ABBV-8E12 1000 mg | Change From Baseline Over Time in ADCS-CGIC-MCI Functional Abilities Score | Change at Week 96 | 4.98 score on a scale | Standard Error 0.085 |
| ABBV-8E12 2000 mg | Change From Baseline Over Time in ADCS-CGIC-MCI Functional Abilities Score | Change at Week 48 | 4.59 score on a scale | Standard Error 0.072 |
| ABBV-8E12 2000 mg | Change From Baseline Over Time in ADCS-CGIC-MCI Functional Abilities Score | Change at Week 96 | 5.03 score on a scale | Standard Error 0.09 |
Comparison: Week 48p-value: 0.93195% CI: [-0.204, 0.187]repeated measures model
Comparison: Week 48
Comparison: Week 48p-value: 0.18795% CI: [-0.32, 0.063]repeated measures model
Comparison: Week 48
Comparison: Week 48p-value: 0.96195% CI: [-0.191, 0.201]repeated measures model
Comparison: Week 96
Comparison: Week 96p-value: 0.89495% CI: [-0.26, 0.227]repeated measures model
Comparison: Week 96
Comparison: Week 96p-value: 0.91795% CI: [-0.226, 0.251]repeated measures model
Comparison: Week 96
Comparison: Week 96p-value: 0.63995% CI: [-0.186, 0.303]repeated measures model
Comparison: Week 96
Secondary
Change From Baseline Over Time in Alzheimer's Disease Assessment Scale (14-Item) Cognition Portion (ADAS-Cog-14) Total Score
The ADAS-Cog was designed to assess the cognitive impairments most common in AD. The ADAS-Cog-14 includes the original 11 items from the ADAS-Cog-11 \[1. Spoken language ability, 2. Comprehension of spoken language, 3. Recall of test instructions, 4. Word-findings difficulty in spontaneous speech, 5. Following commands, 6. Naming objects and fingers, 7. Constructional praxis, 8. Ideational praxis, 9. Orientation, 10. Word-recall task, 11. Word-recognition task\] and includes 3 additional tasks \[12. Number cancellation task, 13. Delayed word recall task, 14. Executive functioning\], for increased sensitivity in mild cognitive impairment (MCI) patients. The Total Score of the ADAS-Cog-14 ranges from 0 to 90, with a higher score representing greater impairment.
Time frame: Baseline, Week 24, Week 48, Week 72, Week 96
Population: Intent-to-Treat Data Set: all randomized participants who received at least 1 dose of study drug. Participants with an assessment at given time point.
| Arm | Measure | Group | Value (LEAST_SQUARES_MEAN) | Dispersion |
|---|---|---|---|---|
| Placebo | Change From Baseline Over Time in Alzheimer's Disease Assessment Scale (14-Item) Cognition Portion (ADAS-Cog-14) Total Score | Change at Week 24 | 1.82 score on a scale | Standard Error 0.492 |
| Placebo | Change From Baseline Over Time in Alzheimer's Disease Assessment Scale (14-Item) Cognition Portion (ADAS-Cog-14) Total Score | Change at Week 48 | 4.50 score on a scale | Standard Error 0.621 |
| Placebo | Change From Baseline Over Time in Alzheimer's Disease Assessment Scale (14-Item) Cognition Portion (ADAS-Cog-14) Total Score | Change at Week 72 | 5.26 score on a scale | Standard Error 0.718 |
| Placebo | Change From Baseline Over Time in Alzheimer's Disease Assessment Scale (14-Item) Cognition Portion (ADAS-Cog-14) Total Score | Change at Week 96 | 8.43 score on a scale | Standard Error 0.898 |
| ABBV-8E12 300 mg | Change From Baseline Over Time in Alzheimer's Disease Assessment Scale (14-Item) Cognition Portion (ADAS-Cog-14) Total Score | Change at Week 48 | 3.51 score on a scale | Standard Error 0.642 |
| ABBV-8E12 300 mg | Change From Baseline Over Time in Alzheimer's Disease Assessment Scale (14-Item) Cognition Portion (ADAS-Cog-14) Total Score | Change at Week 72 | 4.78 score on a scale | Standard Error 0.73 |
| ABBV-8E12 300 mg | Change From Baseline Over Time in Alzheimer's Disease Assessment Scale (14-Item) Cognition Portion (ADAS-Cog-14) Total Score | Change at Week 96 | 7.99 score on a scale | Standard Error 0.891 |
| ABBV-8E12 300 mg | Change From Baseline Over Time in Alzheimer's Disease Assessment Scale (14-Item) Cognition Portion (ADAS-Cog-14) Total Score | Change at Week 24 | 1.42 score on a scale | Standard Error 0.498 |
| ABBV-8E12 1000 mg | Change From Baseline Over Time in Alzheimer's Disease Assessment Scale (14-Item) Cognition Portion (ADAS-Cog-14) Total Score | Change at Week 72 | 5.00 score on a scale | Standard Error 0.706 |
| ABBV-8E12 1000 mg | Change From Baseline Over Time in Alzheimer's Disease Assessment Scale (14-Item) Cognition Portion (ADAS-Cog-14) Total Score | Change at Week 48 | 3.42 score on a scale | Standard Error 0.605 |
| ABBV-8E12 1000 mg | Change From Baseline Over Time in Alzheimer's Disease Assessment Scale (14-Item) Cognition Portion (ADAS-Cog-14) Total Score | Change at Week 96 | 7.84 score on a scale | Standard Error 0.872 |
| ABBV-8E12 1000 mg | Change From Baseline Over Time in Alzheimer's Disease Assessment Scale (14-Item) Cognition Portion (ADAS-Cog-14) Total Score | Change at Week 24 | 0.56 score on a scale | Standard Error 0.48 |
| ABBV-8E12 2000 mg | Change From Baseline Over Time in Alzheimer's Disease Assessment Scale (14-Item) Cognition Portion (ADAS-Cog-14) Total Score | Change at Week 96 | 9.46 score on a scale | Standard Error 0.935 |
| ABBV-8E12 2000 mg | Change From Baseline Over Time in Alzheimer's Disease Assessment Scale (14-Item) Cognition Portion (ADAS-Cog-14) Total Score | Change at Week 48 | 4.03 score on a scale | Standard Error 0.647 |
| ABBV-8E12 2000 mg | Change From Baseline Over Time in Alzheimer's Disease Assessment Scale (14-Item) Cognition Portion (ADAS-Cog-14) Total Score | Change at Week 24 | 1.86 score on a scale | Standard Error 0.503 |
| ABBV-8E12 2000 mg | Change From Baseline Over Time in Alzheimer's Disease Assessment Scale (14-Item) Cognition Portion (ADAS-Cog-14) Total Score | Change at Week 72 | 6.37 score on a scale | Standard Error 0.738 |
Comparison: Week 24p-value: 0.56295% CI: [-1.764, 0.96]repeated measures model
Comparison: Week 24
Comparison: Week 24p-value: 0.06695% CI: [-2.602, 0.081]repeated measures model
Comparison: Week 24
Comparison: Week 24p-value: 0.96295% CI: [-1.343, 1.41]repeated measures model
Comparison: Week 24
Comparison: Week 48p-value: 0.26595% CI: [-2.734, 0.755]repeated measures model
Comparison: Week 48
Comparison: Week 48p-value: 0.21295% CI: [-2.775, 0.618]repeated measures model
Comparison: Week 48
Comparison: Week 48p-value: 0.60295% CI: [-2.223, 1.29]repeated measures model
Comparison: Week 48
Comparison: Week 72p-value: 0.63595% CI: [-2.489, 1.519]repeated measures model
Comparison: Week 72
Comparison: Week 72p-value: 0.79595% CI: [-2.233, 1.712]repeated measures model
Comparison: Week 72
Comparison: Week 72p-value: 0.28195% CI: [-0.91, 3.128]repeated measures model
Comparison: Week 72
Comparison: Week 96p-value: 0.72995% CI: [-2.918, 2.043]repeated measures model
Comparison: Week 96
Comparison: Week 96p-value: 0.63695% CI: [-3.047, 1.863]repeated measures model
Comparison: Week 96
Comparison: Week 96p-value: 0.42795% CI: [-1.515, 3.575]repeated measures model
Comparison: Week 96
Secondary
Change From Baseline Over Time in Alzheimer's Disease Composite Score (ADCOMS) Score
ADCOMS score is a composite score which is a weighted linear combination of the selected individual scale items from ADAS-Cog-14 (see description in Outcome Measure 10) , MMSE (see description in Outcome Measure 45), and CDR-SB (see description in Outcome Measure 1) scales. The ADCOMS score ranges from 0 to 1.97, with a lower score desirable.
Time frame: Baseline, Week 24, Week 48, Week 72, Week 96
Population: Intent-to-Treat Data Set: all randomized participants who received at least 1 dose of study drug. Participants with an assessment at given time point.
| Arm | Measure | Group | Value (LEAST_SQUARES_MEAN) | Dispersion |
|---|---|---|---|---|
| Placebo | Change From Baseline Over Time in Alzheimer's Disease Composite Score (ADCOMS) Score | Change at Week 24 | 0.05 score on a scale | Standard Error 0.013 |
| Placebo | Change From Baseline Over Time in Alzheimer's Disease Composite Score (ADCOMS) Score | Change at Week 48 | 0.13 score on a scale | Standard Error 0.018 |
| Placebo | Change From Baseline Over Time in Alzheimer's Disease Composite Score (ADCOMS) Score | Change at Week 72 | 0.22 score on a scale | Standard Error 0.023 |
| Placebo | Change From Baseline Over Time in Alzheimer's Disease Composite Score (ADCOMS) Score | Change at Week 96 | 0.29 score on a scale | Standard Error 0.029 |
| ABBV-8E12 300 mg | Change From Baseline Over Time in Alzheimer's Disease Composite Score (ADCOMS) Score | Change at Week 48 | 0.15 score on a scale | Standard Error 0.018 |
| ABBV-8E12 300 mg | Change From Baseline Over Time in Alzheimer's Disease Composite Score (ADCOMS) Score | Change at Week 96 | 0.29 score on a scale | Standard Error 0.03 |
| ABBV-8E12 300 mg | Change From Baseline Over Time in Alzheimer's Disease Composite Score (ADCOMS) Score | Change at Week 24 | 0.08 score on a scale | Standard Error 0.013 |
| ABBV-8E12 300 mg | Change From Baseline Over Time in Alzheimer's Disease Composite Score (ADCOMS) Score | Change at Week 72 | 0.22 score on a scale | Standard Error 0.024 |
| ABBV-8E12 1000 mg | Change From Baseline Over Time in Alzheimer's Disease Composite Score (ADCOMS) Score | Change at Week 24 | 0.05 score on a scale | Standard Error 0.013 |
| ABBV-8E12 1000 mg | Change From Baseline Over Time in Alzheimer's Disease Composite Score (ADCOMS) Score | Change at Week 96 | 0.28 score on a scale | Standard Error 0.029 |
| ABBV-8E12 1000 mg | Change From Baseline Over Time in Alzheimer's Disease Composite Score (ADCOMS) Score | Change at Week 72 | 0.22 score on a scale | Standard Error 0.023 |
| ABBV-8E12 1000 mg | Change From Baseline Over Time in Alzheimer's Disease Composite Score (ADCOMS) Score | Change at Week 48 | 0.13 score on a scale | Standard Error 0.017 |
| ABBV-8E12 2000 mg | Change From Baseline Over Time in Alzheimer's Disease Composite Score (ADCOMS) Score | Change at Week 96 | 0.35 score on a scale | Standard Error 0.031 |
| ABBV-8E12 2000 mg | Change From Baseline Over Time in Alzheimer's Disease Composite Score (ADCOMS) Score | Change at Week 24 | 0.08 score on a scale | Standard Error 0.014 |
| ABBV-8E12 2000 mg | Change From Baseline Over Time in Alzheimer's Disease Composite Score (ADCOMS) Score | Change at Week 48 | 0.13 score on a scale | Standard Error 0.018 |
| ABBV-8E12 2000 mg | Change From Baseline Over Time in Alzheimer's Disease Composite Score (ADCOMS) Score | Change at Week 72 | 0.22 score on a scale | Standard Error 0.024 |
Comparison: Week 24p-value: 0.14795% CI: [-0.01, 0.064]repeated measures model
Comparison: Week 24
Comparison: Week 24p-value: 0.79595% CI: [-0.041, 0.031]repeated measures model
Comparison: Week 24
Comparison: Week 24p-value: 0.09595% CI: [-0.006, 0.069]repeated measures model
Comparison: Week 24
Comparison: Week 48p-value: 0.3995% CI: [-0.028, 0.072]repeated measures model
Comparison: Week 48
Comparison: Week 48p-value: 0.89895% CI: [-0.052, 0.045]repeated measures model
Comparison: Week 48
Comparison: Week 48p-value: 0.895% CI: [-0.044, 0.057]repeated measures model
Comparison: Week 48
Comparison: Week 72p-value: 0.97795% CI: [-0.066, 0.064]repeated measures model
Comparison: Week 72
Comparison: Week 72p-value: 0.9995% CI: [-0.063, 0.064]repeated measures model
Comparison: Week 72
Comparison: Week 72p-value: 0.94495% CI: [-0.063, 0.067]repeated measures model
Comparison: Week 72
Comparison: Week 96p-value: 0.94295% CI: [-0.079, 0.085]repeated measures model
Comparison: Week 96
Comparison: Week 96p-value: 0.87695% CI: [-0.087, 0.074]repeated measures model
Comparison: Week 96
Comparison: Week 96p-value: 0.16395% CI: [-0.024, 0.143]repeated measures model
Comparison: Week 96
Secondary
Change From Baseline Over Time in Alzheimer's Disease Cooperative Study Clinical Global Impression of Change for Mild Cognitive Impairment (ADCS-CGIC-MCI) General Condition Score
The instrument assesses the physician's global impression of change in 4 major cognitive domains. The instrument covers 4 major domains: 1. General condition , 2. Cognition, 3. Behavior, and 4. Social and daily functioning. Scoring is based on a 7-point Likert Scale: 1, marked improvement; 2, moderate improvement; 3, minimal improvement; 4, no change; 5, minimal worsening; 6, moderate worsening; 7, marked worsening. Higher score indicates greater worsening.
Time frame: Baseline, Week 48, Week 96
Population: Intent-to-Treat Data Set: all randomized participants who received at least 1 dose of study drug. Participants with an assessment at given time point.
| Arm | Measure | Group | Value (LEAST_SQUARES_MEAN) | Dispersion |
|---|---|---|---|---|
| Placebo | Change From Baseline Over Time in Alzheimer's Disease Cooperative Study Clinical Global Impression of Change for Mild Cognitive Impairment (ADCS-CGIC-MCI) General Condition Score | Change at Week 48 | 4.91 score on a scale | Standard Error 0.078 |
| Placebo | Change From Baseline Over Time in Alzheimer's Disease Cooperative Study Clinical Global Impression of Change for Mild Cognitive Impairment (ADCS-CGIC-MCI) General Condition Score | Change at Week 96 | 5.29 score on a scale | Standard Error 0.087 |
| ABBV-8E12 300 mg | Change From Baseline Over Time in Alzheimer's Disease Cooperative Study Clinical Global Impression of Change for Mild Cognitive Impairment (ADCS-CGIC-MCI) General Condition Score | Change at Week 96 | 5.28 score on a scale | Standard Error 0.087 |
| ABBV-8E12 300 mg | Change From Baseline Over Time in Alzheimer's Disease Cooperative Study Clinical Global Impression of Change for Mild Cognitive Impairment (ADCS-CGIC-MCI) General Condition Score | Change at Week 48 | 4.86 score on a scale | Standard Error 0.08 |
| ABBV-8E12 1000 mg | Change From Baseline Over Time in Alzheimer's Disease Cooperative Study Clinical Global Impression of Change for Mild Cognitive Impairment (ADCS-CGIC-MCI) General Condition Score | Change at Week 48 | 4.80 score on a scale | Standard Error 0.076 |
| ABBV-8E12 1000 mg | Change From Baseline Over Time in Alzheimer's Disease Cooperative Study Clinical Global Impression of Change for Mild Cognitive Impairment (ADCS-CGIC-MCI) General Condition Score | Change at Week 96 | 5.22 score on a scale | Standard Error 0.083 |
| ABBV-8E12 2000 mg | Change From Baseline Over Time in Alzheimer's Disease Cooperative Study Clinical Global Impression of Change for Mild Cognitive Impairment (ADCS-CGIC-MCI) General Condition Score | Change at Week 48 | 4.87 score on a scale | Standard Error 0.079 |
| ABBV-8E12 2000 mg | Change From Baseline Over Time in Alzheimer's Disease Cooperative Study Clinical Global Impression of Change for Mild Cognitive Impairment (ADCS-CGIC-MCI) General Condition Score | Change at Week 96 | 5.34 score on a scale | Standard Error 0.088 |
Comparison: Week 48p-value: 0.65195% CI: [-0.266, 0.166]repeated measures model
Comparison: Week 48
Comparison: Week 48p-value: 0.3295% CI: [-0.318, 0.104]repeated measures model
Comparison: Week 48
Comparison: Week 48p-value: 0.75795% CI: [-0.25, 0.182]repeated measures model
Comparison: Week 48
Comparison: Week 96p-value: 0.98495% CI: [-0.241, 0.236]repeated measures model
Comparison: Week 96
Comparison: Week 96p-value: 0.59595% CI: [-0.296, 0.17]repeated measures model
Comparison: Week 96
Comparison: Week 96p-value: 0.6795% CI: [-0.187, 0.291]repeated measures model
Comparison: Week 96
Secondary
Change From Baseline Over Time in Functional Activities Questionnaire (FAQ) Score
The FAQ measures level of assistance (functional disability) needed for carrying out instrumental activities in daily living (iADLs). The FAQ score ranges from 0 - 30 and consists of 10 items (each scored from 0 - 3), which measure a specific iADL in the past 4-weeks: \[1) writing checks, paying bills, keeping financial records; 2) assembling tax or business records; 3) shopping alone; 4) playing a game of skill; 5) making coffee or tea; 6) preparing a balanced meal; 7) keeping track of current events; 8) attending to and understanding a television program, book, or magazine; 9) remembering appointments, family occasions, medications; and 10) traveling out of the neighborhood\]. Performance in each category is rated from 0 - 3 as follows: 0 - normal; 1 - has difficulty, but does by self; 2 - requires assistance; or 3 - dependent. The FAQ was administered by a trained interviewer. Higher scores indicate a greater requirement of assistance.
Time frame: Baseline, Week 24, Week 48, Week 72, Week 96
Population: Intent-to-Treat Data Set: all randomized participants who received at least 1 dose of study drug. Participants with an assessment at given time point.
| Arm | Measure | Group | Value (LEAST_SQUARES_MEAN) | Dispersion |
|---|---|---|---|---|
| Placebo | Change From Baseline Over Time in Functional Activities Questionnaire (FAQ) Score | Change at Week 24 | 1.63 score on a scale | Standard Error 0.422 |
| Placebo | Change From Baseline Over Time in Functional Activities Questionnaire (FAQ) Score | Change at Week 48 | 3.37 score on a scale | Standard Error 0.48 |
| Placebo | Change From Baseline Over Time in Functional Activities Questionnaire (FAQ) Score | Change at Week 72 | 5.62 score on a scale | Standard Error 0.571 |
| Placebo | Change From Baseline Over Time in Functional Activities Questionnaire (FAQ) Score | Change at Week 96 | 6.14 score on a scale | Standard Error 0.65 |
| ABBV-8E12 300 mg | Change From Baseline Over Time in Functional Activities Questionnaire (FAQ) Score | Change at Week 48 | 3.53 score on a scale | Standard Error 0.498 |
| ABBV-8E12 300 mg | Change From Baseline Over Time in Functional Activities Questionnaire (FAQ) Score | Change at Week 72 | 5.09 score on a scale | Standard Error 0.588 |
| ABBV-8E12 300 mg | Change From Baseline Over Time in Functional Activities Questionnaire (FAQ) Score | Change at Week 96 | 7.11 score on a scale | Standard Error 0.663 |
| ABBV-8E12 300 mg | Change From Baseline Over Time in Functional Activities Questionnaire (FAQ) Score | Change at Week 24 | 1.84 score on a scale | Standard Error 0.435 |
| ABBV-8E12 1000 mg | Change From Baseline Over Time in Functional Activities Questionnaire (FAQ) Score | Change at Week 72 | 4.57 score on a scale | Standard Error 0.568 |
| ABBV-8E12 1000 mg | Change From Baseline Over Time in Functional Activities Questionnaire (FAQ) Score | Change at Week 48 | 2.83 score on a scale | Standard Error 0.477 |
| ABBV-8E12 1000 mg | Change From Baseline Over Time in Functional Activities Questionnaire (FAQ) Score | Change at Week 96 | 5.80 score on a scale | Standard Error 0.638 |
| ABBV-8E12 1000 mg | Change From Baseline Over Time in Functional Activities Questionnaire (FAQ) Score | Change at Week 24 | 1.19 score on a scale | Standard Error 0.423 |
| ABBV-8E12 2000 mg | Change From Baseline Over Time in Functional Activities Questionnaire (FAQ) Score | Change at Week 96 | 7.94 score on a scale | Standard Error 0.667 |
| ABBV-8E12 2000 mg | Change From Baseline Over Time in Functional Activities Questionnaire (FAQ) Score | Change at Week 48 | 3.58 score on a scale | Standard Error 0.496 |
| ABBV-8E12 2000 mg | Change From Baseline Over Time in Functional Activities Questionnaire (FAQ) Score | Change at Week 24 | 2.06 score on a scale | Standard Error 0.439 |
| ABBV-8E12 2000 mg | Change From Baseline Over Time in Functional Activities Questionnaire (FAQ) Score | Change at Week 72 | 6.31 score on a scale | Standard Error 0.586 |
Comparison: Week 48p-value: 0.81395% CI: [-1.187, 1.512]repeated measures model
Comparison: Week 24p-value: 0.7295% CI: [-0.965, 1.395]repeated measures model
Comparison: Week 24
Comparison: Week 24p-value: 0.45595% CI: [-1.607, 0.722]repeated measures model
Comparison: Week 24
Comparison: Week 24p-value: 0.47395% CI: [-0.755, 1.625]repeated measures model
Comparison: Week 24
Comparison: Week 48
Comparison: Week 48p-value: 0.42195% CI: [-1.863, 0.78]repeated measures model
Comparison: Week 48
Comparison: Week 48p-value: 0.75895% CI: [-1.139, 1.564]repeated measures model
Comparison: Week 48
Comparison: Week 72p-value: 0.51195% CI: [-2.14, 1.066]repeated measures model
Comparison: Week 72
Comparison: Week 72p-value: 0.19295% CI: [-2.623, 0.527]repeated measures model
Comparison: Week 72
Comparison: Week 72p-value: 0.39895% CI: [-0.914, 2.294]repeated measures model
Comparison: Week 72
Comparison: Week 96p-value: 0.29695% CI: [-0.851, 2.784]repeated measures model
Comparison: Week 96
Comparison: Week 96p-value: 0.70695% CI: [-2.126, 1.442]repeated measures model
Comparison: Week 96
Comparison: Week 96p-value: 0.05595% CI: [-0.036, 3.617]repeated measures model
Comparison: Week 96
Secondary
Change From Baseline Over Time in Mini-Mental State Examination (MMSE) Total Score
The MMSE is a brief, 30-point questionnaire, administered by a trained rater, which provides a quantitative measure of cognitive status in adults and is widely used to screen for cognitive impairment and to estimate the severity of cognitive impairment at a given point in time in AD participants. The MMSE ranges from 0 to 30, with lower scores indicating greater impairment.
Time frame: Baseline, Week 24, Week 48, Week 72, Week 96
Population: Intent-to-Treat Data Set: all randomized participants who received at least 1 dose of study drug. Participants with an assessment at baseline and given time point.
| Arm | Measure | Group | Value (LEAST_SQUARES_MEAN) | Dispersion |
|---|---|---|---|---|
| Placebo | Change From Baseline Over Time in Mini-Mental State Examination (MMSE) Total Score | Change at Week 96 | -3.95 score on a scale | Standard Error 0.478 |
| Placebo | Change From Baseline Over Time in Mini-Mental State Examination (MMSE) Total Score | Change at Week 72 | -2.83 score on a scale | Standard Error 0.376 |
| Placebo | Change From Baseline Over Time in Mini-Mental State Examination (MMSE) Total Score | Change at Week 24 | -0.60 score on a scale | Standard Error 0.255 |
| Placebo | Change From Baseline Over Time in Mini-Mental State Examination (MMSE) Total Score | Change at Week 48 | -1.78 score on a scale | Standard Error 0.294 |
| ABBV-8E12 300 mg | Change From Baseline Over Time in Mini-Mental State Examination (MMSE) Total Score | Change at Week 48 | -1.81 score on a scale | Standard Error 0.305 |
| ABBV-8E12 300 mg | Change From Baseline Over Time in Mini-Mental State Examination (MMSE) Total Score | Change at Week 24 | -0.83 score on a scale | Standard Error 0.26 |
| ABBV-8E12 300 mg | Change From Baseline Over Time in Mini-Mental State Examination (MMSE) Total Score | Change at Week 72 | -2.92 score on a scale | Standard Error 0.388 |
| ABBV-8E12 300 mg | Change From Baseline Over Time in Mini-Mental State Examination (MMSE) Total Score | Change at Week 96 | -4.06 score on a scale | Standard Error 0.488 |
| ABBV-8E12 1000 mg | Change From Baseline Over Time in Mini-Mental State Examination (MMSE) Total Score | Change at Week 72 | -2.43 score on a scale | Standard Error 0.375 |
| ABBV-8E12 1000 mg | Change From Baseline Over Time in Mini-Mental State Examination (MMSE) Total Score | Change at Week 96 | -3.70 score on a scale | Standard Error 0.469 |
| ABBV-8E12 1000 mg | Change From Baseline Over Time in Mini-Mental State Examination (MMSE) Total Score | Change at Week 48 | -1.60 score on a scale | Standard Error 0.29 |
| ABBV-8E12 1000 mg | Change From Baseline Over Time in Mini-Mental State Examination (MMSE) Total Score | Change at Week 24 | -0.48 score on a scale | Standard Error 0.252 |
| ABBV-8E12 2000 mg | Change From Baseline Over Time in Mini-Mental State Examination (MMSE) Total Score | Change at Week 96 | -4.71 score on a scale | Standard Error 0.494 |
| ABBV-8E12 2000 mg | Change From Baseline Over Time in Mini-Mental State Examination (MMSE) Total Score | Change at Week 24 | -1.56 score on a scale | Standard Error 0.263 |
| ABBV-8E12 2000 mg | Change From Baseline Over Time in Mini-Mental State Examination (MMSE) Total Score | Change at Week 48 | -2.17 score on a scale | Standard Error 0.305 |
| ABBV-8E12 2000 mg | Change From Baseline Over Time in Mini-Mental State Examination (MMSE) Total Score | Change at Week 72 | -3.34 score on a scale | Standard Error 0.386 |
Comparison: Week 24p-value: 0.53495% CI: [-0.935, 0.485]repeated measures model
Comparison: Week 24
Comparison: Week 24p-value: 0.73595% CI: [-0.58, 0.821]repeated measures model
Comparison: Week 24
Comparison: Week 24p-value: 0.00995% CI: [-1.673, -0.24]repeated measures model
Comparison: Week 24
Comparison: Week 48p-value: 0.95495% CI: [-0.854, 0.806]repeated measures model
Comparison: Week 48
Comparison: Week 48p-value: 0.64995% CI: [-0.622, 0.997]repeated measures model
Comparison: Week 48
Comparison: Week 48p-value: 0.35895% CI: [-1.22, 0.443]repeated measures model
Comparison: Week 48
Comparison: Week 72p-value: 0.85995% CI: [-1.155, 0.963]repeated measures model
Comparison: Week 72
Comparison: Week 72p-value: 0.45595% CI: [-0.644, 1.437]repeated measures model
Comparison: Week 72
Comparison: Week 72p-value: 0.33595% CI: [-1.578, 0.539]repeated measures model
Comparison: Week 72
Comparison: Week 96p-value: 0.87595% CI: [-1.447, 1.233]repeated measures model
Comparison: Week 96
Comparison: Week 96p-value: 0.71295% CI: [-1.068, 1.561]repeated measures model
Comparison: Week 96
Comparison: Week 96p-value: 0.26995% CI: [-2.112, 0.59]repeated measures model
Comparison: Week 96
Secondary
Change From Baseline Over Time in Neuropsychiatry Inventory (NPI) Total Score
The NPI is used to assess changes in the participant's behavior that occurred in a defined period of time (4 weeks). The NPI assesses 12 behavioral domains on the dimensions of frequency and severity. Frequency is rated on a scale where 0 = absent, 1 = occasionally, 2 = often, 3 = frequently, 4 = very frequently. Severity is rated on a scale where 0 = absent, 1 = mild, 2 = moderate, 3 = severe. For each of the domains, 3 scores are obtained: frequency, severity, and total (product of frequency and severity; ranges from 0 to 12, with a lower score desirable). A total NPI score can be calculated by summing the domain total scores. Total Score ranges from 0 to 144 with a lower score desirable.
Time frame: Baseline, Week 24, Week 48, Week 72, Week 96
Population: Intent-to-Treat Data Set: all randomized participants who received at least 1 dose of study drug. Participants with an assessment at given time point.
| Arm | Measure | Group | Value (LEAST_SQUARES_MEAN) | Dispersion |
|---|---|---|---|---|
| Placebo | Change From Baseline Over Time in Neuropsychiatry Inventory (NPI) Total Score | Change at Week 24 | 0.93 score on a scale | Standard Error 0.551 |
| Placebo | Change From Baseline Over Time in Neuropsychiatry Inventory (NPI) Total Score | Change at Week 36 | -0.03 score on a scale | Standard Error 0.487 |
| Placebo | Change From Baseline Over Time in Neuropsychiatry Inventory (NPI) Total Score | Change at Week 72 | 1.34 score on a scale | Standard Error 0.742 |
| Placebo | Change From Baseline Over Time in Neuropsychiatry Inventory (NPI) Total Score | Change at Week 96 | 2.38 score on a scale | Standard Error 0.784 |
| ABBV-8E12 300 mg | Change From Baseline Over Time in Neuropsychiatry Inventory (NPI) Total Score | Change at Week 36 | 0.84 score on a scale | Standard Error 0.505 |
| ABBV-8E12 300 mg | Change From Baseline Over Time in Neuropsychiatry Inventory (NPI) Total Score | Change at Week 72 | 1.52 score on a scale | Standard Error 0.767 |
| ABBV-8E12 300 mg | Change From Baseline Over Time in Neuropsychiatry Inventory (NPI) Total Score | Change at Week 96 | 2.03 score on a scale | Standard Error 0.794 |
| ABBV-8E12 300 mg | Change From Baseline Over Time in Neuropsychiatry Inventory (NPI) Total Score | Change at Week 24 | 0.96 score on a scale | Standard Error 0.567 |
| ABBV-8E12 1000 mg | Change From Baseline Over Time in Neuropsychiatry Inventory (NPI) Total Score | Change at Week 72 | 1.80 score on a scale | Standard Error 0.745 |
| ABBV-8E12 1000 mg | Change From Baseline Over Time in Neuropsychiatry Inventory (NPI) Total Score | Change at Week 36 | 0.99 score on a scale | Standard Error 0.481 |
| ABBV-8E12 1000 mg | Change From Baseline Over Time in Neuropsychiatry Inventory (NPI) Total Score | Change at Week 96 | 2.53 score on a scale | Standard Error 0.769 |
| ABBV-8E12 1000 mg | Change From Baseline Over Time in Neuropsychiatry Inventory (NPI) Total Score | Change at Week 24 | 0.80 score on a scale | Standard Error 0.551 |
| ABBV-8E12 2000 mg | Change From Baseline Over Time in Neuropsychiatry Inventory (NPI) Total Score | Change at Week 96 | 2.94 score on a scale | Standard Error 0.804 |
| ABBV-8E12 2000 mg | Change From Baseline Over Time in Neuropsychiatry Inventory (NPI) Total Score | Change at Week 36 | 1.32 score on a scale | Standard Error 0.502 |
| ABBV-8E12 2000 mg | Change From Baseline Over Time in Neuropsychiatry Inventory (NPI) Total Score | Change at Week 24 | 1.92 score on a scale | Standard Error 0.576 |
| ABBV-8E12 2000 mg | Change From Baseline Over Time in Neuropsychiatry Inventory (NPI) Total Score | Change at Week 72 | 3.25 score on a scale | Standard Error 0.765 |
Comparison: Week 24p-value: 0.96695% CI: [-1.509, 1.577]repeated measures model
Comparison: Week 24
Comparison: Week 24p-value: 0.87495% CI: [-1.646, 1.4]repeated measures model
Comparison: Week 24
Comparison: Week 24p-value: 0.21395% CI: [-0.572, 2.551]repeated measures model
Comparison: Week 24
Comparison: Week 48p-value: 0.20895% CI: [-0.49, 2.242]repeated measures model
Comparison: Week 48
Comparison: Week 48p-value: 0.13195% CI: [-0.307, 2.365]repeated measures model
Comparison: Week 48
Comparison: Week 48p-value: 0.05295% CI: [-0.014, 2.719]repeated measures model
Comparison: Week 48
Comparison: Week 72p-value: 0.86695% CI: [-1.908, 2.268]repeated measures model
Comparison: Week 72
Comparison: Week 72p-value: 0.6695% CI: [-1.599, 2.523]repeated measures model
Comparison: Week 72
Comparison: Week 72p-value: 0.07495% CI: [-0.184, 3.995]repeated measures model
Comparison: Week 72
Comparison: Week 96p-value: 0.74795% CI: [-2.545, 1.828]repeated measures model
Comparison: Week 96
Comparison: Week 96p-value: 0.89195% CI: [-2.004, 2.304]repeated measures model
Comparison: Week 96
Comparison: Week 96p-value: 0.62195% CI: [-1.65, 2.759]repeated measures model
Comparison: Week 96
Secondary
Change From Baseline Over Time in RBANS - Coding Total Score
The RBANS is a 25-minute, standardized neurocognitive battery with North American population-based normative data. The RBANS measures five neurocognitive domains, with age-based scaling. Twelve subtests measure cognitive decline or improvement across the following domains: 1. Immediate Memory - List Learning and Story Memory, 2. Visuospatial/Constructional - Figure Copy and Line Orientation, 3. Language - Picture naming and Semantic Fluency, 4. Attention - Digit Span and Coding, and 5. Delayed Memory - List Recall, List Recognition, Story Memory, and Figure Recall. The Coding Total Score of the RBANS ranges from 0 to 89, with a higher score representing a better outcome.
Time frame: Baseline, Week 24, Week 48, Week 72, Week 96
Population: Intent-to-Treat Data Set: all randomized participants who received at least 1 dose of study drug. Participants with an assessment at given time point.
| Arm | Measure | Group | Value (LEAST_SQUARES_MEAN) | Dispersion |
|---|---|---|---|---|
| Placebo | Change From Baseline Over Time in RBANS - Coding Total Score | Change to Week 24 | -0.39 score on a scale | Standard Error 0.6 |
| Placebo | Change From Baseline Over Time in RBANS - Coding Total Score | Change to Week 48 | -1.98 score on a scale | Standard Error 0.673 |
| Placebo | Change From Baseline Over Time in RBANS - Coding Total Score | Change to Week 72 | -5.26 score on a scale | Standard Error 0.799 |
| Placebo | Change From Baseline Over Time in RBANS - Coding Total Score | Change to Week 96 | -6.12 score on a scale | Standard Error 0.957 |
| ABBV-8E12 300 mg | Change From Baseline Over Time in RBANS - Coding Total Score | Change to Week 48 | -1.17 score on a scale | Standard Error 0.694 |
| ABBV-8E12 300 mg | Change From Baseline Over Time in RBANS - Coding Total Score | Change to Week 72 | -2.80 score on a scale | Standard Error 0.819 |
| ABBV-8E12 300 mg | Change From Baseline Over Time in RBANS - Coding Total Score | Change to Week 96 | -6.95 score on a scale | Standard Error 0.97 |
| ABBV-8E12 300 mg | Change From Baseline Over Time in RBANS - Coding Total Score | Change to Week 24 | -1.29 score on a scale | Standard Error 0.611 |
| ABBV-8E12 1000 mg | Change From Baseline Over Time in RBANS - Coding Total Score | Change to Week 72 | -4.58 score on a scale | Standard Error 0.799 |
| ABBV-8E12 1000 mg | Change From Baseline Over Time in RBANS - Coding Total Score | Change to Week 48 | -2.38 score on a scale | Standard Error 0.66 |
| ABBV-8E12 1000 mg | Change From Baseline Over Time in RBANS - Coding Total Score | Change to Week 96 | -6.70 score on a scale | Standard Error 0.94 |
| ABBV-8E12 1000 mg | Change From Baseline Over Time in RBANS - Coding Total Score | Change to Week 24 | -1.40 score on a scale | Standard Error 0.595 |
| ABBV-8E12 2000 mg | Change From Baseline Over Time in RBANS - Coding Total Score | Change to Week 96 | -7.30 score on a scale | Standard Error 1.016 |
| ABBV-8E12 2000 mg | Change From Baseline Over Time in RBANS - Coding Total Score | Change to Week 48 | -3.14 score on a scale | Standard Error 0.698 |
| ABBV-8E12 2000 mg | Change From Baseline Over Time in RBANS - Coding Total Score | Change to Week 24 | -1.40 score on a scale | Standard Error 0.623 |
| ABBV-8E12 2000 mg | Change From Baseline Over Time in RBANS - Coding Total Score | Change to Week 72 | -4.53 score on a scale | Standard Error 0.828 |
Comparison: Week 24p-value: 0.28795% CI: [-2.567, 0.762]repeated measures model
Comparison: Week 24
Comparison: Week 24p-value: 0.22795% CI: [-2.661, 0.633]repeated measures model
Comparison: Week 24
Comparison: Week 24p-value: 0.24195% CI: [-2.698, 0.681]repeated measures model
Comparison: Week 24
Comparison: Week 48p-value: 0.39795% CI: [-1.073, 2.696]repeated measures model
Comparison: Week 48
Comparison: Week 48p-value: 0.67195% CI: [-2.239, 1.443]repeated measures model
Comparison: Week 48
Comparison: Week 48p-value: 0.23195% CI: [-3.052, 0.738]repeated measures model
Comparison: Week 48
Comparison: Week 72p-value: 0.03195% CI: [0.23, 4.701]repeated measures model
Comparison: Week 72
Comparison: Week 72p-value: 0.54795% CI: [-1.532, 2.888]repeated measures model
Comparison: Week 72
Comparison: Week 72p-value: 0.52495% CI: [-1.521, 2.984]repeated measures model
Comparison: Week 72
Comparison: Week 96p-value: 0.5495% CI: [-3.499, 1.836]repeated measures model
Comparison: Week 96
Comparison: Week 96p-value: 0.66495% CI: [-3.208, 2.046]repeated measures model
Comparison: Week 96
Comparison: Week 96p-value: 0.39395% CI: [-3.923, 1.546]repeated measures model
Comparison: Week 96
Secondary
Change From Baseline Over Time in RBANS - Digit Span Total Score
The RBANS is a 25-minute, standardized neurocognitive battery with North American population-based normative data. The RBANS measures five neurocognitive domains, with age-based scaling. Twelve subtests measure cognitive decline or improvement across the following domains: 1. Immediate Memory - List Learning and Story Memory, 2. Visuospatial/Constructional - Figure Copy and Line Orientation, 3. Language - Picture naming and Semantic Fluency, 4. Attention - Digit Span and Coding, and 5. Delayed Memory - List Recall, List Recognition, Story Memory, and Figure Recall. The Digit Span Total Score of the RBANS ranges from 0 to 8, with a higher score representing a better outcome.
Time frame: Baseline, Week 24, Week 48, Week 72, Week 96
Population: Intent-to-Treat Data Set: all randomized participants who received at least 1 dose of study drug. Participants with an assessment at given time point.
| Arm | Measure | Group | Value (LEAST_SQUARES_MEAN) | Dispersion |
|---|---|---|---|---|
| Placebo | Change From Baseline Over Time in RBANS - Digit Span Total Score | Change to Week 24 | -0.48 score on a scale | Standard Error 0.185 |
| Placebo | Change From Baseline Over Time in RBANS - Digit Span Total Score | Change to Week 48 | -0.75 score on a scale | Standard Error 0.207 |
| Placebo | Change From Baseline Over Time in RBANS - Digit Span Total Score | Change to Week 72 | -0.94 score on a scale | Standard Error 0.194 |
| Placebo | Change From Baseline Over Time in RBANS - Digit Span Total Score | Change to Week 96 | -1.07 score on a scale | Standard Error 0.229 |
| ABBV-8E12 300 mg | Change From Baseline Over Time in RBANS - Digit Span Total Score | Change to Week 48 | -0.65 score on a scale | Standard Error 0.217 |
| ABBV-8E12 300 mg | Change From Baseline Over Time in RBANS - Digit Span Total Score | Change to Week 72 | -0.89 score on a scale | Standard Error 0.201 |
| ABBV-8E12 300 mg | Change From Baseline Over Time in RBANS - Digit Span Total Score | Change to Week 96 | -0.81 score on a scale | Standard Error 0.232 |
| ABBV-8E12 300 mg | Change From Baseline Over Time in RBANS - Digit Span Total Score | Change to Week 24 | -0.50 score on a scale | Standard Error 0.189 |
| ABBV-8E12 1000 mg | Change From Baseline Over Time in RBANS - Digit Span Total Score | Change to Week 72 | -1.13 score on a scale | Standard Error 0.196 |
| ABBV-8E12 1000 mg | Change From Baseline Over Time in RBANS - Digit Span Total Score | Change to Week 48 | -0.41 score on a scale | Standard Error 0.204 |
| ABBV-8E12 1000 mg | Change From Baseline Over Time in RBANS - Digit Span Total Score | Change to Week 96 | -0.83 score on a scale | Standard Error 0.224 |
| ABBV-8E12 1000 mg | Change From Baseline Over Time in RBANS - Digit Span Total Score | Change to Week 24 | -0.78 score on a scale | Standard Error 0.184 |
| ABBV-8E12 2000 mg | Change From Baseline Over Time in RBANS - Digit Span Total Score | Change to Week 96 | -0.90 score on a scale | Standard Error 0.239 |
| ABBV-8E12 2000 mg | Change From Baseline Over Time in RBANS - Digit Span Total Score | Change to Week 48 | -0.65 score on a scale | Standard Error 0.216 |
| ABBV-8E12 2000 mg | Change From Baseline Over Time in RBANS - Digit Span Total Score | Change to Week 24 | -0.64 score on a scale | Standard Error 0.193 |
| ABBV-8E12 2000 mg | Change From Baseline Over Time in RBANS - Digit Span Total Score | Change to Week 72 | -0.79 score on a scale | Standard Error 0.199 |
Comparison: Week 24p-value: 0.94695% CI: [-0.534, 0.498]repeated measures model
Comparison: Week 24
Comparison: Week 24p-value: 0.24295% CI: [-0.813, 0.206]repeated measures model
Comparison: Week 24
Comparison: Week 24p-value: 0.54195% CI: [-0.685, 0.36]repeated measures model
Comparison: Week 24
Comparison: Week 48p-value: 0.72495% CI: [-0.481, 0.691]repeated measures model
Comparison: Week 48
Comparison: Week 48p-value: 0.23695% CI: [-0.226, 0.913]repeated measures model
Comparison: Week 48
Comparison: Week 48p-value: 0.71495% CI: [-0.477, 0.695]repeated measures model
Comparison: Week 48
Comparison: Week 72p-value: 0.8695% CI: [-0.496, 0.593]repeated measures model
Comparison: Week 72
Comparison: Week 72p-value: 0.47695% CI: [-0.733, 0.343]repeated measures model
Comparison: Week 72
Comparison: Week 72p-value: 0.58695% CI: [-0.393, 0.694]repeated measures model
Comparison: Week 72
Comparison: Week 96p-value: 0.41295% CI: [-0.371, 0.903]repeated measures model
Comparison: Week 96
Comparison: Week 96p-value: 0.4595% CI: [-0.386, 0.868]repeated measures model
Comparison: Week 96
Comparison: Week 96p-value: 0.61295% CI: [-0.481, 0.816]repeated measures model
Comparison: Week 96
Secondary
Change From Baseline Over Time in RBANS - Figure Copy Total Score
The RBANS is a 25-minute, standardized neurocognitive battery with North American population-based normative data. The RBANS measures five neurocognitive domains, with age-based scaling. Twelve subtests measure cognitive decline or improvement across the following domains: 1. Immediate Memory - List Learning and Story Memory, 2. Visuospatial/Constructional - Figure Copy and Line Orientation, 3. Language - Picture naming and Semantic Fluency, 4. Attention - Digit Span and Coding, and 5. Delayed Memory - List Recall, List Recognition, Story Memory, and Figure Recall. The Figure Copy Total Score of the RBANS ranges from 0 to 20, with a higher score representing a better outcome.
Time frame: Baseline, Week 24, Week 48, Week 72, Week 96
Population: Intent-to-Treat Data Set: all randomized participants who received at least 1 dose of study drug. Participants with an assessment at given time point.
| Arm | Measure | Group | Value (LEAST_SQUARES_MEAN) | Dispersion |
|---|---|---|---|---|
| Placebo | Change From Baseline Over Time in RBANS - Figure Copy Total Score | Change to Week 48 | 0.07 score on a scale | Standard Error 0.363 |
| Placebo | Change From Baseline Over Time in RBANS - Figure Copy Total Score | Change to Week 24 | 0.29 score on a scale | Standard Error 0.287 |
| Placebo | Change From Baseline Over Time in RBANS - Figure Copy Total Score | Change to Week 96 | -1.63 score on a scale | Standard Error 0.47 |
| Placebo | Change From Baseline Over Time in RBANS - Figure Copy Total Score | Change to Week 72 | -0.57 score on a scale | Standard Error 0.41 |
| ABBV-8E12 300 mg | Change From Baseline Over Time in RBANS - Figure Copy Total Score | Change to Week 24 | 0.03 score on a scale | Standard Error 0.293 |
| ABBV-8E12 300 mg | Change From Baseline Over Time in RBANS - Figure Copy Total Score | Change to Week 48 | -0.60 score on a scale | Standard Error 0.38 |
| ABBV-8E12 300 mg | Change From Baseline Over Time in RBANS - Figure Copy Total Score | Change to Week 72 | -0.77 score on a scale | Standard Error 0.426 |
| ABBV-8E12 300 mg | Change From Baseline Over Time in RBANS - Figure Copy Total Score | Change to Week 96 | -1.48 score on a scale | Standard Error 0.48 |
| ABBV-8E12 1000 mg | Change From Baseline Over Time in RBANS - Figure Copy Total Score | Change to Week 24 | -0.12 score on a scale | Standard Error 0.284 |
| ABBV-8E12 1000 mg | Change From Baseline Over Time in RBANS - Figure Copy Total Score | Change to Week 72 | -1.04 score on a scale | Standard Error 0.412 |
| ABBV-8E12 1000 mg | Change From Baseline Over Time in RBANS - Figure Copy Total Score | Change to Week 48 | -0.01 score on a scale | Standard Error 0.359 |
| ABBV-8E12 1000 mg | Change From Baseline Over Time in RBANS - Figure Copy Total Score | Change to Week 96 | -1.29 score on a scale | Standard Error 0.462 |
| ABBV-8E12 2000 mg | Change From Baseline Over Time in RBANS - Figure Copy Total Score | Change to Week 48 | -0.38 score on a scale | Standard Error 0.379 |
| ABBV-8E12 2000 mg | Change From Baseline Over Time in RBANS - Figure Copy Total Score | Change to Week 72 | -1.25 score on a scale | Standard Error 0.425 |
| ABBV-8E12 2000 mg | Change From Baseline Over Time in RBANS - Figure Copy Total Score | Change to Week 96 | -1.95 score on a scale | Standard Error 0.49 |
| ABBV-8E12 2000 mg | Change From Baseline Over Time in RBANS - Figure Copy Total Score | Change to Week 24 | -0.20 score on a scale | Standard Error 0.299 |
Comparison: Week 24p-value: 0.5295% CI: [-1.058, 0.535]repeated measures model
Comparison: Week 24
Comparison: Week 24p-value: 0.30395% CI: [-1.201, 0.374]repeated measures model
Comparison: Week 24
Comparison: Week 24p-value: 0.2395% CI: [-1.307, 0.315]repeated measures model
Comparison: Week 24
Comparison: Week 48p-value: 0.295% CI: [-1.698, 0.356]repeated measures model
Comparison: Week 48
Comparison: Week 48p-value: 0.87395% CI: [-1.08, 0.917]repeated measures model
Comparison: Week 48
Comparison: Week 48p-value: 0.38895% CI: [-1.482, 0.576]repeated measures model
Comparison: Week 48
Comparison: Week 72p-value: 0.73495% CI: [-1.355, 0.955]repeated measures model
Comparison: Week 72
Comparison: Week 72p-value: 0.41795% CI: [-1.608, 0.668]repeated measures model
Comparison: Week 72
Comparison: Week 72p-value: 0.25295% CI: [-1.836, 0.482]repeated measures model
Comparison: Week 72
Comparison: Week 96p-value: 0.82795% CI: [-1.17, 1.462]repeated measures model
Comparison: Week 96
Comparison: Week 96p-value: 0.61595% CI: [-0.962, 1.624]repeated measures model
Comparison: Week 96
Comparison: Week 96p-value: 0.63795% CI: [-1.653, 1.014]repeated measures model
Comparison: Week 96
Secondary
Change From Baseline Over Time in RBANS - Figure Recall Total Score
The RBANS is a 25-minute, standardized neurocognitive battery with North American population-based normative data. The RBANS measures five neurocognitive domains, with age-based scaling. Twelve subtests measure cognitive decline or improvement across the following domains: 1. Immediate Memory - List Learning and Story Memory, 2. Visuospatial/Constructional - Figure Copy and Line Orientation, 3. Language - Picture naming and Semantic Fluency, 4. Attention - Digit Span and Coding, and 5. Delayed Memory - List Recall, List Recognition, Story Memory, and Figure Recall. The Figure Recall Total Score of the RBANS ranges from 0 to 18, with a higher score representing a better outcome.
Time frame: Baseline, Week 24, Week 48, Week 72, Week 96
Population: Intent-to-Treat Data Set: all randomized participants who received at least 1 dose of study drug. Participants with an assessment at given time point.
| Arm | Measure | Group | Value (LEAST_SQUARES_MEAN) | Dispersion |
|---|---|---|---|---|
| Placebo | Change From Baseline Over Time in RBANS - Figure Recall Total Score | Change to Week 72 | -1.21 score on a scale | Standard Error 0.262 |
| Placebo | Change From Baseline Over Time in RBANS - Figure Recall Total Score | Change to Week 96 | -1.16 score on a scale | Standard Error 0.299 |
| Placebo | Change From Baseline Over Time in RBANS - Figure Recall Total Score | Change to Week 48 | -0.97 score on a scale | Standard Error 0.276 |
| Placebo | Change From Baseline Over Time in RBANS - Figure Recall Total Score | Change to Week 24 | -0.23 score on a scale | Standard Error 0.259 |
| ABBV-8E12 300 mg | Change From Baseline Over Time in RBANS - Figure Recall Total Score | Change to Week 48 | -0.70 score on a scale | Standard Error 0.288 |
| ABBV-8E12 300 mg | Change From Baseline Over Time in RBANS - Figure Recall Total Score | Change to Week 72 | -1.16 score on a scale | Standard Error 0.272 |
| ABBV-8E12 300 mg | Change From Baseline Over Time in RBANS - Figure Recall Total Score | Change to Week 24 | -0.65 score on a scale | Standard Error 0.264 |
| ABBV-8E12 300 mg | Change From Baseline Over Time in RBANS - Figure Recall Total Score | Change to Week 96 | -1.43 score on a scale | Standard Error 0.305 |
| ABBV-8E12 1000 mg | Change From Baseline Over Time in RBANS - Figure Recall Total Score | Change to Week 48 | -0.22 score on a scale | Standard Error 0.272 |
| ABBV-8E12 1000 mg | Change From Baseline Over Time in RBANS - Figure Recall Total Score | Change to Week 24 | 0.06 score on a scale | Standard Error 0.256 |
| ABBV-8E12 1000 mg | Change From Baseline Over Time in RBANS - Figure Recall Total Score | Change to Week 96 | -0.86 score on a scale | Standard Error 0.293 |
| ABBV-8E12 1000 mg | Change From Baseline Over Time in RBANS - Figure Recall Total Score | Change to Week 72 | -0.68 score on a scale | Standard Error 0.263 |
| ABBV-8E12 2000 mg | Change From Baseline Over Time in RBANS - Figure Recall Total Score | Change to Week 96 | -1.49 score on a scale | Standard Error 0.31 |
| ABBV-8E12 2000 mg | Change From Baseline Over Time in RBANS - Figure Recall Total Score | Change to Week 72 | -1.45 score on a scale | Standard Error 0.272 |
| ABBV-8E12 2000 mg | Change From Baseline Over Time in RBANS - Figure Recall Total Score | Change to Week 24 | -0.60 score on a scale | Standard Error 0.268 |
| ABBV-8E12 2000 mg | Change From Baseline Over Time in RBANS - Figure Recall Total Score | Change to Week 48 | -1.18 score on a scale | Standard Error 0.288 |
Comparison: Week 24p-value: 0.26195% CI: [-1.135, 0.308]repeated measures model
Comparison: Week 24
Comparison: Week 24p-value: 0.42395% CI: [-0.42, 1.001]repeated measures model
Comparison: Week 24
Comparison: Week 24p-value: 0.32295% CI: [-1.097, 0.361]repeated measures model
Comparison: Week 24
Comparison: Week 48p-value: 0.49895% CI: [-0.511, 1.049]repeated measures model
Comparison: Week 48
Comparison: Week 48p-value: 0.05295% CI: [-0.006, 1.51]repeated measures model
Comparison: Week 48
Comparison: Week 48p-value: 0.59795% CI: [-0.993, 0.572]repeated measures model
Comparison: Week 48
Comparison: Week 72p-value: 0.89695% CI: [-0.689, 0.788]repeated measures model
Comparison: Week 72
Comparison: Week 72p-value: 0.14995% CI: [-0.192, 1.258]repeated measures model
Comparison: Week 72
Comparison: Week 72p-value: 0.52295% CI: [-0.98, 0.499]repeated measures model
Comparison: Week 72
Comparison: Week 96p-value: 0.52895% CI: [-1.103, 0.567]repeated measures model
Comparison: Week 96
Comparison: Week 96p-value: 0.47495% CI: [-0.519, 1.116]repeated measures model
Comparison: Week 96
Comparison: Week 96p-value: 0.44195% CI: [-1.176, 0.513]repeated measures model
Comparison: Week 96
Secondary
Change From Baseline Over Time in RBANS - Line Orientation Total Score
The RBANS is a 25-minute, standardized neurocognitive battery with North American population-based normative data. The RBANS measures five neurocognitive domains, with age-based scaling. Twelve subtests measure cognitive decline or improvement across the following domains: 1. Immediate Memory - List Learning and Story Memory, 2. Visuospatial/Constructional - Figure Copy and Line Orientation, 3. Language - Picture naming and Semantic Fluency, 4. Attention - Digit Span and Coding, and 5. Delayed Memory - List Recall, List Recognition, Story Memory, and Figure Recall. The Line Orientation Total Score of the RBANS ranges from 0 to 20, with a higher score representing a better outcome.
Time frame: Baseline, Week 24, Week 48, Week 72, Week 96
Population: Intent-to-Treat Data Set: all randomized participants who received at least 1 dose of study drug. Participants with an assessment at given time point.
| Arm | Measure | Group | Value (LEAST_SQUARES_MEAN) | Dispersion |
|---|---|---|---|---|
| Placebo | Change From Baseline Over Time in RBANS - Line Orientation Total Score | Change to Week 24 | 0.20 score on a scale | Standard Error 0.301 |
| Placebo | Change From Baseline Over Time in RBANS - Line Orientation Total Score | Change to Week 48 | -0.84 score on a scale | Standard Error 0.348 |
| Placebo | Change From Baseline Over Time in RBANS - Line Orientation Total Score | Change to Week 72 | -0.64 score on a scale | Standard Error 0.365 |
| Placebo | Change From Baseline Over Time in RBANS - Line Orientation Total Score | Change to Week 96 | -1.33 score on a scale | Standard Error 0.404 |
| ABBV-8E12 300 mg | Change From Baseline Over Time in RBANS - Line Orientation Total Score | Change to Week 48 | 0.05 score on a scale | Standard Error 0.363 |
| ABBV-8E12 300 mg | Change From Baseline Over Time in RBANS - Line Orientation Total Score | Change to Week 72 | -0.07 score on a scale | Standard Error 0.378 |
| ABBV-8E12 300 mg | Change From Baseline Over Time in RBANS - Line Orientation Total Score | Change to Week 96 | -1.01 score on a scale | Standard Error 0.405 |
| ABBV-8E12 300 mg | Change From Baseline Over Time in RBANS - Line Orientation Total Score | Change to Week 24 | 0.24 score on a scale | Standard Error 0.308 |
| ABBV-8E12 1000 mg | Change From Baseline Over Time in RBANS - Line Orientation Total Score | Change to Week 72 | -0.60 score on a scale | Standard Error 0.369 |
| ABBV-8E12 1000 mg | Change From Baseline Over Time in RBANS - Line Orientation Total Score | Change to Week 48 | -0.53 score on a scale | Standard Error 0.344 |
| ABBV-8E12 1000 mg | Change From Baseline Over Time in RBANS - Line Orientation Total Score | Change to Week 96 | -0.99 score on a scale | Standard Error 0.392 |
| ABBV-8E12 1000 mg | Change From Baseline Over Time in RBANS - Line Orientation Total Score | Change to Week 24 | -0.05 score on a scale | Standard Error 0.301 |
| ABBV-8E12 2000 mg | Change From Baseline Over Time in RBANS - Line Orientation Total Score | Change to Week 96 | -1.88 score on a scale | Standard Error 0.424 |
| ABBV-8E12 2000 mg | Change From Baseline Over Time in RBANS - Line Orientation Total Score | Change to Week 48 | -0.47 score on a scale | Standard Error 0.363 |
| ABBV-8E12 2000 mg | Change From Baseline Over Time in RBANS - Line Orientation Total Score | Change to Week 24 | 0.03 score on a scale | Standard Error 0.313 |
| ABBV-8E12 2000 mg | Change From Baseline Over Time in RBANS - Line Orientation Total Score | Change to Week 72 | -0.60 score on a scale | Standard Error 0.377 |
Comparison: Week 24p-value: 0.92695% CI: [-0.799, 0.878]repeated measures model
Comparison: Week 24
Comparison: Week 24p-value: 0.55395% CI: [-1.082, 0.58]repeated measures model
Comparison: Week 24
Comparison: Week 24p-value: 0.6995% CI: [-1.021, 0.677]repeated measures model
Comparison: Week 24
Comparison: Week 48p-value: 0.07395% CI: [-0.085, 1.879]repeated measures model
Comparison: Week 48
Comparison: Week 48p-value: 0.51795% CI: [-0.641, 1.273]repeated measures model
Comparison: Week 48
Comparison: Week 48p-value: 0.45495% CI: [-0.609, 1.36]repeated measures model
Comparison: Week 48
Comparison: Week 72p-value: 0.27695% CI: [-0.456, 1.596]repeated measures model
Comparison: Week 72
Comparison: Week 72p-value: 0.93595% CI: [-0.973, 1.058]repeated measures model
Comparison: Week 72
Comparison: Week 72p-value: 0.94295% CI: [-0.99, 1.066]repeated measures model
Comparison: Week 72
Comparison: Week 96p-value: 0.57895% CI: [-0.802, 1.436]repeated measures model
Comparison: Week 96
Comparison: Week 96p-value: 0.54595% CI: [-0.762, 1.441]repeated measures model
Comparison: Week 96
Comparison: Week 96p-value: 0.34695% CI: [-1.697, 0.597]repeated measures model
Comparison: Week 96
Secondary
Change From Baseline Over Time in RBANS - List Learning Total Score
The RBANS is a 25-minute, standardized neurocognitive battery with North American population-based normative data. The RBANS measures five neurocognitive domains, with age-based scaling. Twelve subtests measure cognitive decline or improvement across the following domains: 1. Immediate Memory - List Learning and Story Memory, 2. Visuospatial/Constructional - Figure Copy and Line Orientation, 3. Language - Picture naming and Semantic Fluency, 4. Attention - Digit Span and Coding, and 5. Delayed Memory - List Recall, List Recognition, Story Memory, and Figure Recall. The List Learning Total Score of the RBANS ranges from 0 to 40, with a higher score representing a better outcome.
Time frame: Baseline, Week 24, Week 48, Week 72, Week 96
Population: Intent-to-Treat Data Set: all randomized participants who received at least 1 dose of study drug. Participants with an assessment at given time point.
| Arm | Measure | Group | Value (LEAST_SQUARES_MEAN) | Dispersion |
|---|---|---|---|---|
| Placebo | Change From Baseline Over Time in RBANS - List Learning Total Score | Change to Week 24 | -0.57 score on a scale | Standard Error 0.35 |
| Placebo | Change From Baseline Over Time in RBANS - List Learning Total Score | Change to Week 48 | -1.27 score on a scale | Standard Error 0.397 |
| Placebo | Change From Baseline Over Time in RBANS - List Learning Total Score | Change to Week 72 | -3.18 score on a scale | Standard Error 0.413 |
| Placebo | Change From Baseline Over Time in RBANS - List Learning Total Score | Change to Week 96 | -3.57 score on a scale | Standard Error 0.484 |
| ABBV-8E12 300 mg | Change From Baseline Over Time in RBANS - List Learning Total Score | Change to Week 48 | -0.36 score on a scale | Standard Error 0.416 |
| ABBV-8E12 300 mg | Change From Baseline Over Time in RBANS - List Learning Total Score | Change to Week 72 | -3.32 score on a scale | Standard Error 0.428 |
| ABBV-8E12 300 mg | Change From Baseline Over Time in RBANS - List Learning Total Score | Change to Week 96 | -2.93 score on a scale | Standard Error 0.496 |
| ABBV-8E12 300 mg | Change From Baseline Over Time in RBANS - List Learning Total Score | Change to Week 24 | -0.67 score on a scale | Standard Error 0.359 |
| ABBV-8E12 1000 mg | Change From Baseline Over Time in RBANS - List Learning Total Score | Change to Week 72 | -3.02 score on a scale | Standard Error 0.415 |
| ABBV-8E12 1000 mg | Change From Baseline Over Time in RBANS - List Learning Total Score | Change to Week 48 | -1.89 score on a scale | Standard Error 0.392 |
| ABBV-8E12 1000 mg | Change From Baseline Over Time in RBANS - List Learning Total Score | Change to Week 96 | -3.23 score on a scale | Standard Error 0.474 |
| ABBV-8E12 1000 mg | Change From Baseline Over Time in RBANS - List Learning Total Score | Change to Week 24 | -0.98 score on a scale | Standard Error 0.348 |
| ABBV-8E12 2000 mg | Change From Baseline Over Time in RBANS - List Learning Total Score | Change to Week 96 | -3.07 score on a scale | Standard Error 0.503 |
| ABBV-8E12 2000 mg | Change From Baseline Over Time in RBANS - List Learning Total Score | Change to Week 48 | -1.17 score on a scale | Standard Error 0.413 |
| ABBV-8E12 2000 mg | Change From Baseline Over Time in RBANS - List Learning Total Score | Change to Week 24 | -1.14 score on a scale | Standard Error 0.364 |
| ABBV-8E12 2000 mg | Change From Baseline Over Time in RBANS - List Learning Total Score | Change to Week 72 | -3.11 score on a scale | Standard Error 0.424 |
Comparison: Week 24p-value: 0.85495% CI: [-1.069, 0.885]repeated measures model
Comparison: Week 24
Comparison: Week 24p-value: 0.41295% CI: [-1.368, 0.562]repeated measures model
Comparison: Week 24
Comparison: Week 24p-value: 0.26295% CI: [-1.554, 0.424]repeated measures model
Comparison: Week 24
Comparison: Week 48p-value: 0.1195% CI: [-0.209, 2.036]repeated measures model
Comparison: Week 48
Comparison: Week 48p-value: 0.26395% CI: [-1.713, 0.469]repeated measures model
Comparison: Week 48
Comparison: Week 48p-value: 0.86895% CI: [-1.026, 1.217]repeated measures model
Comparison: Week 48
Comparison: Week 72p-value: 0.8295% CI: [-1.298, 1.029]repeated measures model
Comparison: Week 72
Comparison: Week 72p-value: 0.78195% CI: [-0.984, 1.308]repeated measures model
Comparison: Week 72
Comparison: Week 72p-value: 0.89595% CI: [-1.082, 1.238]repeated measures model
Comparison: Week 72
Comparison: Week 96p-value: 0.35995% CI: [-0.724, 1.991]repeated measures model
Comparison: Week 96
Comparison: Week 96p-value: 0.61295% CI: [-0.985, 1.67]repeated measures model
Comparison: Week 96
Comparison: Week 96p-value: 0.47595% CI: [-0.872, 1.867]repeated measures model
Comparison: Week 96
Secondary
Change From Baseline Over Time in RBANS - List Recall Total Score
The RBANS is a 25-minute, standardized neurocognitive battery with North American population-based normative data. The RBANS measures five neurocognitive domains, with age-based scaling. Twelve subtests measure cognitive decline or improvement across the following domains: 1. Immediate Memory - List Learning and Story Memory, 2. Visuospatial/Constructional - Figure Copy and Line Orientation, 3. Language - Picture naming and Semantic Fluency, 4. Attention - Digit Span and Coding, and 5. Delayed Memory - List Recall, List Recognition, Story Memory, and Figure Recall. The List Recall Total Score of the RBANS ranges from 0 to 10, with a higher score representing a better outcome.
Time frame: Baseline, Week 24, Week 48, Week 72, Week 96
Population: Intent-to-Treat Data Set: all randomized participants who received at least 1 dose of study drug. Participants with an assessment at given time point.
| Arm | Measure | Group | Value (LEAST_SQUARES_MEAN) | Dispersion |
|---|---|---|---|---|
| Placebo | Change From Baseline Over Time in RBANS - List Recall Total Score | Change to Week 24 | 0.04 score on a scale | Standard Error 0.102 |
| Placebo | Change From Baseline Over Time in RBANS - List Recall Total Score | Change to Week 48 | 0.07 score on a scale | Standard Error 0.12 |
| Placebo | Change From Baseline Over Time in RBANS - List Recall Total Score | Change to Week 72 | 0.01 score on a scale | Standard Error 0.081 |
| Placebo | Change From Baseline Over Time in RBANS - List Recall Total Score | Change to Week 96 | -0.14 score on a scale | Standard Error 0.095 |
| ABBV-8E12 300 mg | Change From Baseline Over Time in RBANS - List Recall Total Score | Change to Week 48 | 0.05 score on a scale | Standard Error 0.125 |
| ABBV-8E12 300 mg | Change From Baseline Over Time in RBANS - List Recall Total Score | Change to Week 72 | -0.29 score on a scale | Standard Error 0.084 |
| ABBV-8E12 300 mg | Change From Baseline Over Time in RBANS - List Recall Total Score | Change to Week 96 | -0.39 score on a scale | Standard Error 0.096 |
| ABBV-8E12 300 mg | Change From Baseline Over Time in RBANS - List Recall Total Score | Change to Week 24 | -0.15 score on a scale | Standard Error 0.105 |
| ABBV-8E12 1000 mg | Change From Baseline Over Time in RBANS - List Recall Total Score | Change to Week 72 | -0.24 score on a scale | Standard Error 0.082 |
| ABBV-8E12 1000 mg | Change From Baseline Over Time in RBANS - List Recall Total Score | Change to Week 48 | 0.10 score on a scale | Standard Error 0.118 |
| ABBV-8E12 1000 mg | Change From Baseline Over Time in RBANS - List Recall Total Score | Change to Week 96 | -0.35 score on a scale | Standard Error 0.092 |
| ABBV-8E12 1000 mg | Change From Baseline Over Time in RBANS - List Recall Total Score | Change to Week 24 | -0.01 score on a scale | Standard Error 0.102 |
| ABBV-8E12 2000 mg | Change From Baseline Over Time in RBANS - List Recall Total Score | Change to Week 96 | -0.31 score on a scale | Standard Error 0.098 |
| ABBV-8E12 2000 mg | Change From Baseline Over Time in RBANS - List Recall Total Score | Change to Week 48 | -0.10 score on a scale | Standard Error 0.124 |
| ABBV-8E12 2000 mg | Change From Baseline Over Time in RBANS - List Recall Total Score | Change to Week 24 | -0.08 score on a scale | Standard Error 0.106 |
| ABBV-8E12 2000 mg | Change From Baseline Over Time in RBANS - List Recall Total Score | Change to Week 72 | -0.27 score on a scale | Standard Error 0.083 |
Comparison: Week 24p-value: 0.20295% CI: [-0.473, 0.1]repeated measures model
Comparison: Week 24
Comparison: Week 24p-value: 0.7695% CI: [-0.327, 0.239]repeated measures model
Comparison: Week 24
Comparison: Week 24p-value: 0.41995% CI: [-0.409, 0.17]repeated measures model
Comparison: Week 24
Comparison: Week 48p-value: 0.89395% CI: [-0.363, 0.317]repeated measures model
Comparison: Week 48p-value: 0.88695% CI: [-0.306, 0.354]repeated measures model
Comparison: Week 48
Comparison: Week 48p-value: 0.30695% CI: [-0.515, 0.162]repeated measures model
Comparison: Week 48
Comparison: Week 72p-value: 0.00895% CI: [-0.535, -0.079]repeated measures model
Comparison: Week 72
Comparison: Week 72p-value: 0.03195% CI: [-0.474, -0.023]repeated measures model
Comparison: Week 72
Comparison: Week 72p-value: 0.01495% CI: [-0.514, -0.059]repeated measures model
Comparison: Week 96p-value: 0.06595% CI: [-0.514, 0.016]repeated measures model
Comparison: Week 96
Comparison: Week 96p-value: 0.12195% CI: [-0.465, 0.055]repeated measures model
Comparison: Week 96
Comparison: Week 96p-value: 0.2195% CI: [-0.438, 0.097]repeated measures model
Comparison: Week 96
Secondary
Change From Baseline Over Time in RBANS - List Recognition Total Score
The RBANS is a 25-minute, standardized neurocognitive battery with North American population-based normative data. The RBANS measures five neurocognitive domains, with age-based scaling. Twelve subtests measure cognitive decline or improvement across the following domains: 1. Immediate Memory - List Learning and Story Memory, 2. Visuospatial/Constructional - Figure Copy and Line Orientation, 3. Language - Picture naming and Semantic Fluency, 4. Attention - Digit Span and Coding, and 5. Delayed Memory - List Recall, List Recognition, Story Memory, and Figure Recall. The List Recognition Total Score of the RBANS ranges from 0 to 20, with a higher score representing a better outcome.
Time frame: Baseline, Week 24, Week 48, Week 72, Week 96
Population: Intent-to-Treat Data Set: all randomized participants who received at least 1 dose of study drug. Participants with an assessment at given time point.
| Arm | Measure | Group | Value (LEAST_SQUARES_MEAN) | Dispersion |
|---|---|---|---|---|
| Placebo | Change From Baseline Over Time in RBANS - List Recognition Total Score | Change to Week 72 | 0.13 score on a scale | Standard Error 0.253 |
| Placebo | Change From Baseline Over Time in RBANS - List Recognition Total Score | Change to Week 48 | 0.31 score on a scale | Standard Error 0.231 |
| Placebo | Change From Baseline Over Time in RBANS - List Recognition Total Score | Change to Week 24 | 0.09 score on a scale | Standard Error 0.233 |
| Placebo | Change From Baseline Over Time in RBANS - List Recognition Total Score | Change to Week 96 | -1.11 score on a scale | Standard Error 0.279 |
| ABBV-8E12 300 mg | Change From Baseline Over Time in RBANS - List Recognition Total Score | Change to Week 24 | -0.64 score on a scale | Standard Error 0.238 |
| ABBV-8E12 300 mg | Change From Baseline Over Time in RBANS - List Recognition Total Score | Change to Week 72 | -0.55 score on a scale | Standard Error 0.262 |
| ABBV-8E12 300 mg | Change From Baseline Over Time in RBANS - List Recognition Total Score | Change to Week 96 | -1.42 score on a scale | Standard Error 0.281 |
| ABBV-8E12 300 mg | Change From Baseline Over Time in RBANS - List Recognition Total Score | Change to Week 48 | 0.29 score on a scale | Standard Error 0.242 |
| ABBV-8E12 1000 mg | Change From Baseline Over Time in RBANS - List Recognition Total Score | Change to Week 96 | -0.90 score on a scale | Standard Error 0.271 |
| ABBV-8E12 1000 mg | Change From Baseline Over Time in RBANS - List Recognition Total Score | Change to Week 24 | -0.38 score on a scale | Standard Error 0.232 |
| ABBV-8E12 1000 mg | Change From Baseline Over Time in RBANS - List Recognition Total Score | Change to Week 48 | 0.41 score on a scale | Standard Error 0.227 |
| ABBV-8E12 1000 mg | Change From Baseline Over Time in RBANS - List Recognition Total Score | Change to Week 72 | -0.48 score on a scale | Standard Error 0.256 |
| ABBV-8E12 2000 mg | Change From Baseline Over Time in RBANS - List Recognition Total Score | Change to Week 72 | -0.43 score on a scale | Standard Error 0.26 |
| ABBV-8E12 2000 mg | Change From Baseline Over Time in RBANS - List Recognition Total Score | Change to Week 48 | -0.23 score on a scale | Standard Error 0.239 |
| ABBV-8E12 2000 mg | Change From Baseline Over Time in RBANS - List Recognition Total Score | Change to Week 24 | -0.79 score on a scale | Standard Error 0.242 |
| ABBV-8E12 2000 mg | Change From Baseline Over Time in RBANS - List Recognition Total Score | Change to Week 96 | -1.04 score on a scale | Standard Error 0.289 |
Comparison: Week 24p-value: 0.02795% CI: [-1.383, -0.082]repeated measures model
Comparison: Week 24
Comparison: Week 24p-value: 0.14695% CI: [-1.123, 0.167]repeated measures model
Comparison: Week 24
Comparison: Week 24p-value: 0.00995% CI: [-1.537, -0.22]repeated measures model
Comparison: Week 24
Comparison: Week 48p-value: 0.95295% CI: [-0.674, 0.634]repeated measures model
Comparison: Week 48
Comparison: Week 48p-value: 0.76495% CI: [-0.54, 0.734]repeated measures model
Comparison: Week 48
Comparison: Week 48p-value: 0.10395% CI: [-1.191, 0.109]repeated measures model
Comparison: Week 48
Comparison: Week 72p-value: 0.0695% CI: [-1.396, 0.028]repeated measures model
Comparison: Week 72
Comparison: Week 72p-value: 0.09195% CI: [-1.316, 0.098]repeated measures model
Comparison: Week 72
Comparison: Week 72p-value: 0.1295% CI: [-1.274, 0.147]repeated measures model
Comparison: Week 72
Comparison: Week 96p-value: 0.42995% CI: [-1.09, 0.464]repeated measures model
Comparison: Week 96
Comparison: Week 96p-value: 0.59795% CI: [-0.559, 0.97]repeated measures model
Comparison: Week 96
Comparison: Week 96p-value: 0.8695% CI: [-0.717, 0.858]repeated measures model
Comparison: Week 96
Secondary
Change From Baseline Over Time in RBANS - Picture Naming Total Score
The RBANS is a 25-minute, standardized neurocognitive battery with North American population-based normative data. The RBANS measures five neurocognitive domains, with age-based scaling. Twelve subtests measure cognitive decline or improvement across the following domains: 1. Immediate Memory - List Learning and Story Memory, 2. Visuospatial/Constructional - Figure Copy and Line Orientation, 3. Language - Picture naming and Semantic Fluency, 4. Attention - Digit Span and Coding, and 5. Delayed Memory - List Recall, List Recognition, Story Memory, and Figure Recall. The Picture Naming Total Score of the RBANS ranges from 0 to 10, with a higher score representing a better outcome.
Time frame: Baseline, Week 24, Week 48, Week 72, Week 96
Population: Intent-to-Treat Data Set: all randomized participants who received at least 1 dose of study drug. Participants with an assessment at given time point.
| Arm | Measure | Group | Value (LEAST_SQUARES_MEAN) | Dispersion |
|---|---|---|---|---|
| Placebo | Change From Baseline Over Time in RBANS - Picture Naming Total Score | Change to Week 24 | -0.68 score on a scale | Standard Error 0.132 |
| Placebo | Change From Baseline Over Time in RBANS - Picture Naming Total Score | Change to Week 48 | -0.21 score on a scale | Standard Error 0.112 |
| Placebo | Change From Baseline Over Time in RBANS - Picture Naming Total Score | Change to Week 72 | -0.91 score on a scale | Standard Error 0.162 |
| Placebo | Change From Baseline Over Time in RBANS - Picture Naming Total Score | Change to Week 96 | -0.68 score on a scale | Standard Error 0.152 |
| ABBV-8E12 300 mg | Change From Baseline Over Time in RBANS - Picture Naming Total Score | Change to Week 48 | -0.10 score on a scale | Standard Error 0.117 |
| ABBV-8E12 300 mg | Change From Baseline Over Time in RBANS - Picture Naming Total Score | Change to Week 72 | -0.81 score on a scale | Standard Error 0.168 |
| ABBV-8E12 300 mg | Change From Baseline Over Time in RBANS - Picture Naming Total Score | Change to Week 96 | -0.94 score on a scale | Standard Error 0.155 |
| ABBV-8E12 300 mg | Change From Baseline Over Time in RBANS - Picture Naming Total Score | Change to Week 24 | -0.87 score on a scale | Standard Error 0.136 |
| ABBV-8E12 1000 mg | Change From Baseline Over Time in RBANS - Picture Naming Total Score | Change to Week 72 | -0.63 score on a scale | Standard Error 0.163 |
| ABBV-8E12 1000 mg | Change From Baseline Over Time in RBANS - Picture Naming Total Score | Change to Week 48 | -0.09 score on a scale | Standard Error 0.11 |
| ABBV-8E12 1000 mg | Change From Baseline Over Time in RBANS - Picture Naming Total Score | Change to Week 96 | -0.65 score on a scale | Standard Error 0.148 |
| ABBV-8E12 1000 mg | Change From Baseline Over Time in RBANS - Picture Naming Total Score | Change to Week 24 | -0.85 score on a scale | Standard Error 0.132 |
| ABBV-8E12 2000 mg | Change From Baseline Over Time in RBANS - Picture Naming Total Score | Change to Week 96 | -0.77 score on a scale | Standard Error 0.157 |
| ABBV-8E12 2000 mg | Change From Baseline Over Time in RBANS - Picture Naming Total Score | Change to Week 48 | -0.14 score on a scale | Standard Error 0.116 |
| ABBV-8E12 2000 mg | Change From Baseline Over Time in RBANS - Picture Naming Total Score | Change to Week 24 | -0.86 score on a scale | Standard Error 0.138 |
| ABBV-8E12 2000 mg | Change From Baseline Over Time in RBANS - Picture Naming Total Score | Change to Week 72 | -0.75 score on a scale | Standard Error 0.167 |
Comparison: Week 24p-value: 0.30395% CI: [-0.564, 0.176]repeated measures model
Comparison: Week 24
Comparison: Week 24p-value: 0.35895% CI: [-0.536, 0.194]repeated measures model
Comparison: Week 24
Comparison: Week 24p-value: 0.34795% CI: [-0.553, 0.195]repeated measures model
Comparison: Week 24
Comparison: Week 48p-value: 0.49495% CI: [-0.205, 0.423]repeated measures model
Comparison: Week 48
Comparison: Week 48p-value: 0.45495% CI: [-0.189, 0.423]repeated measures model
Comparison: Week 48
Comparison: Week 48p-value: 0.64495% CI: [-0.24, 0.388]repeated measures model
Comparison: Week 48
Comparison: Week 72p-value: 0.68595% CI: [-0.363, 0.551]repeated measures model
Comparison: Week 72
Comparison: Week 72p-value: 0.21995% CI: [-0.168, 0.73]repeated measures model
Comparison: Week 72
Comparison: Week 72p-value: 0.50795% CI: [-0.302, 0.61]repeated measures model
Comparison: Week 72
Comparison: Week 96p-value: 0.23395% CI: [-0.683, 0.167]repeated measures model
Comparison: Week 96
Comparison: Week 96p-value: 0.88195% CI: [-0.383, 0.446]repeated measures model
Comparison: Week 96
Comparison: Week 96p-value: 0.67195% CI: [-0.52, 0.335]repeated measures model
Comparison: Week 96
Secondary
Change From Baseline Over Time in RBANS - Semantic Fluency Total Score
The RBANS is a 25-minute, standardized neurocognitive battery with North American population-based normative data. The RBANS measures five neurocognitive domains, with age-based scaling. Twelve subtests measure cognitive decline or improvement across the following domains: 1. Immediate Memory - List Learning and Story Memory, 2. Visuospatial/Constructional - Figure Copy and Line Orientation, 3. Language - Picture naming and Semantic Fluency, 4. Attention - Digit Span and Coding, and 5. Delayed Memory - List Recall, List Recognition, Story Memory, and Figure Recall. The Semantic Fluency Total Score of the RBANS ranges from 0 to 40, with a higher score representing a better outcome.
Time frame: Baseline, Week 24, Week 48, Week 72, Week 96
Population: Intent-to-Treat Data Set: all randomized participants who received at least 1 dose of study drug. Participants with an assessment at given time point.
| Arm | Measure | Group | Value (LEAST_SQUARES_MEAN) | Dispersion |
|---|---|---|---|---|
| Placebo | Change From Baseline Over Time in RBANS - Semantic Fluency Total Score | Change to Week 24 | -1.47 score on a scale | Standard Error 0.289 |
| Placebo | Change From Baseline Over Time in RBANS - Semantic Fluency Total Score | Change to Week 48 | -1.03 score on a scale | Standard Error 0.441 |
| Placebo | Change From Baseline Over Time in RBANS - Semantic Fluency Total Score | Change to Week 96 | -2.29 score on a scale | Standard Error 0.408 |
| Placebo | Change From Baseline Over Time in RBANS - Semantic Fluency Total Score | Change to Week 72 | -4.07 score on a scale | Standard Error 0.462 |
| ABBV-8E12 300 mg | Change From Baseline Over Time in RBANS - Semantic Fluency Total Score | Change to Week 96 | -2.87 score on a scale | Standard Error 0.415 |
| ABBV-8E12 300 mg | Change From Baseline Over Time in RBANS - Semantic Fluency Total Score | Change to Week 24 | -1.90 score on a scale | Standard Error 0.296 |
| ABBV-8E12 300 mg | Change From Baseline Over Time in RBANS - Semantic Fluency Total Score | Change to Week 72 | -4.50 score on a scale | Standard Error 0.48 |
| ABBV-8E12 300 mg | Change From Baseline Over Time in RBANS - Semantic Fluency Total Score | Change to Week 48 | -1.00 score on a scale | Standard Error 0.462 |
| ABBV-8E12 1000 mg | Change From Baseline Over Time in RBANS - Semantic Fluency Total Score | Change to Week 96 | -2.83 score on a scale | Standard Error 0.397 |
| ABBV-8E12 1000 mg | Change From Baseline Over Time in RBANS - Semantic Fluency Total Score | Change to Week 72 | -4.38 score on a scale | Standard Error 0.465 |
| ABBV-8E12 1000 mg | Change From Baseline Over Time in RBANS - Semantic Fluency Total Score | Change to Week 48 | -0.90 score on a scale | Standard Error 0.434 |
| ABBV-8E12 1000 mg | Change From Baseline Over Time in RBANS - Semantic Fluency Total Score | Change to Week 24 | -1.48 score on a scale | Standard Error 0.288 |
| ABBV-8E12 2000 mg | Change From Baseline Over Time in RBANS - Semantic Fluency Total Score | Change to Week 48 | -0.79 score on a scale | Standard Error 0.46 |
| ABBV-8E12 2000 mg | Change From Baseline Over Time in RBANS - Semantic Fluency Total Score | Change to Week 24 | -1.65 score on a scale | Standard Error 0.3 |
| ABBV-8E12 2000 mg | Change From Baseline Over Time in RBANS - Semantic Fluency Total Score | Change to Week 72 | -4.26 score on a scale | Standard Error 0.475 |
| ABBV-8E12 2000 mg | Change From Baseline Over Time in RBANS - Semantic Fluency Total Score | Change to Week 96 | -2.78 score on a scale | Standard Error 0.425 |
Comparison: Week 24p-value: 0.29795% CI: [-1.232, 0.377]repeated measures model
Comparison: Week 24
Comparison: Week 24p-value: 0.97995% CI: [-0.808, 0.786]repeated measures model
Comparison: Week 24
Comparison: Week 24p-value: 0.66395% CI: [-0.996, 0.634]repeated measures model
Comparison: Week 24
Comparison: Week 48p-value: 0.96195% CI: [-1.22, 1.282]repeated measures model
Comparison: Week 48
Comparison: Week 48p-value: 0.83395% CI: [-1.083, 1.344]repeated measures model
Comparison: Week 48
Comparison: Week 48p-value: 0.71495% CI: [-1.017, 1.484]repeated measures model
Comparison: Week 48
Comparison: Week 72p-value: 0.51895% CI: [-1.733, 0.876]repeated measures model
Comparison: Week 72
Comparison: Week 72p-value: 0.63395% CI: [-1.598, 0.973]repeated measures model
Comparison: Week 72
Comparison: Week 72p-value: 0.77695% CI: [-1.488, 1.112]repeated measures model
Comparison: Week 72
Comparison: Week 96p-value: 0.31695% CI: [-1.723, 0.558]repeated measures model
Comparison: Week 96
Comparison: Week 96p-value: 0.33695% CI: [-1.66, 0.569]repeated measures model
Comparison: Week 96
Comparison: Week 96p-value: 0.40395% CI: [-1.647, 0.663]repeated measures model
Comparison: Week 96
Secondary
Change From Baseline Over Time in RBANS - Story Memory Total Score
The RBANS is a 25-minute, standardized neurocognitive battery with North American population-based normative data. The RBANS measures five neurocognitive domains, with age-based scaling. Twelve subtests measure cognitive decline or improvement across the following domains: 1. Immediate Memory - List Learning and Story Memory, 2. Visuospatial/Constructional - Figure Copy and Line Orientation, 3. Language - Picture naming and Semantic Fluency, 4. Attention - Digit Span and Coding, and 5. Delayed Memory - List Recall, List Recognition, Story Memory, and Figure Recall. The Story Memory Total Score of the RBANS ranges from 0 to 24, with a higher score representing a better outcome.
Time frame: Baseline, Week 24, Week 48, Week 72, Week 96
Population: Intent-to-Treat Data Set: all randomized participants who received at least 1 dose of study drug. Participants with an assessment at given time point.
| Arm | Measure | Group | Value (LEAST_SQUARES_MEAN) | Dispersion |
|---|---|---|---|---|
| Placebo | Change From Baseline Over Time in RBANS - Story Memory Total Score | Change to Week 24 | -3.06 score on a scale | Standard Error 0.282 |
| Placebo | Change From Baseline Over Time in RBANS - Story Memory Total Score | Change to Week 48 | -1.62 score on a scale | Standard Error 0.324 |
| Placebo | Change From Baseline Over Time in RBANS - Story Memory Total Score | Change to Week 72 | -2.15 score on a scale | Standard Error 0.381 |
| Placebo | Change From Baseline Over Time in RBANS - Story Memory Total Score | Change to Week 96 | -3.31 score on a scale | Standard Error 0.38 |
| ABBV-8E12 300 mg | Change From Baseline Over Time in RBANS - Story Memory Total Score | Change to Week 48 | -1.07 score on a scale | Standard Error 0.341 |
| ABBV-8E12 300 mg | Change From Baseline Over Time in RBANS - Story Memory Total Score | Change to Week 72 | -2.00 score on a scale | Standard Error 0.396 |
| ABBV-8E12 300 mg | Change From Baseline Over Time in RBANS - Story Memory Total Score | Change to Week 96 | -2.67 score on a scale | Standard Error 0.388 |
| ABBV-8E12 300 mg | Change From Baseline Over Time in RBANS - Story Memory Total Score | Change to Week 24 | -3.13 score on a scale | Standard Error 0.289 |
| ABBV-8E12 1000 mg | Change From Baseline Over Time in RBANS - Story Memory Total Score | Change to Week 72 | -1.84 score on a scale | Standard Error 0.384 |
| ABBV-8E12 1000 mg | Change From Baseline Over Time in RBANS - Story Memory Total Score | Change to Week 48 | -0.70 score on a scale | Standard Error 0.32 |
| ABBV-8E12 1000 mg | Change From Baseline Over Time in RBANS - Story Memory Total Score | Change to Week 96 | -2.46 score on a scale | Standard Error 0.372 |
| ABBV-8E12 1000 mg | Change From Baseline Over Time in RBANS - Story Memory Total Score | Change to Week 24 | -2.93 score on a scale | Standard Error 0.28 |
| ABBV-8E12 2000 mg | Change From Baseline Over Time in RBANS - Story Memory Total Score | Change to Week 96 | -2.45 score on a scale | Standard Error 0.397 |
| ABBV-8E12 2000 mg | Change From Baseline Over Time in RBANS - Story Memory Total Score | Change to Week 48 | -1.01 score on a scale | Standard Error 0.338 |
| ABBV-8E12 2000 mg | Change From Baseline Over Time in RBANS - Story Memory Total Score | Change to Week 24 | -2.99 score on a scale | Standard Error 0.293 |
| ABBV-8E12 2000 mg | Change From Baseline Over Time in RBANS - Story Memory Total Score | Change to Week 72 | -2.10 score on a scale | Standard Error 0.393 |
Comparison: Week 24p-value: 0.86195% CI: [-0.856, 0.716]repeated measures model
Comparison: Week 24
Comparison: Week 24p-value: 0.74695% CI: [-0.648, 0.905]repeated measures model
Comparison: Week 24
Comparison: Week 24p-value: 0.85995% CI: [-0.724, 0.868]repeated measures model
Comparison: Week 24
Comparison: Week 48p-value: 0.2495% CI: [-0.369, 1.469]repeated measures model
Comparison: Week 48
Comparison: Week 48p-value: 0.04495% CI: [0.023, 1.087]repeated measures model
Comparison: Week 48
Comparison: Week 48p-value: 0.19595% CI: [-0.312, 1.524]repeated measures model
Comparison: Week 48
Comparison: Week 72p-value: 0.77895% CI: [-0.921, 1.229]repeated measures model
Comparison: Week 72
Comparison: Week 72p-value: 0.55895% CI: [-0.743, 1.376]repeated measures model
Comparison: Week 72
Comparison: Week 72p-value: 0.92895% CI: [-1.025, 1.124]repeated measures model
Comparison: Week 72
Comparison: Week 96p-value: 0.23895% CI: [-0.425, 1.704]repeated measures model
Comparison: Week 96
Comparison: Week 96p-value: 0.10795% CI: [-0.186, 1.898]repeated measures model
Comparison: Week 96
Comparison: Week 96p-value: 0.11695% CI: [-0.214, 1.942]repeated measures model
Comparison: Week 96
Secondary
Change From Baseline Over Time in RBANS - Story Recall Total Score
The RBANS is a 25-minute, standardized neurocognitive battery with North American population-based normative data. The RBANS measures five neurocognitive domains, with age-based scaling. Twelve subtests measure cognitive decline or improvement across the following domains: 1. Immediate Memory - List Learning and Story Memory, 2. Visuospatial/Constructional - Figure Copy and Line Orientation, 3. Language - Picture naming and Semantic Fluency, 4. Attention - Digit Span and Coding, and 5. Delayed Memory - List Recall, List Recognition, Story Memory, and Figure Recall. The Story Recall Total Score of the RBANS ranges from 0 to 12, with a higher score representing a better outcome.
Time frame: Baseline, Week 24, Week 48, Week 72, Week 96
Population: Intent-to-Treat Data Set: all randomized participants who received at least 1 dose of study drug. Participants with an assessment at given time point.
| Arm | Measure | Group | Value (LEAST_SQUARES_MEAN) | Dispersion |
|---|---|---|---|---|
| Placebo | Change From Baseline Over Time in RBANS - Story Recall Total Score | Change to Week 24 | -0.93 score on a scale | Standard Error 0.132 |
| Placebo | Change From Baseline Over Time in RBANS - Story Recall Total Score | Change to Week 48 | -0.70 score on a scale | Standard Error 0.178 |
| Placebo | Change From Baseline Over Time in RBANS - Story Recall Total Score | Change to Week 72 | -0.90 score on a scale | Standard Error 0.179 |
| Placebo | Change From Baseline Over Time in RBANS - Story Recall Total Score | Change to Week 96 | -1.28 score on a scale | Standard Error 0.197 |
| ABBV-8E12 300 mg | Change From Baseline Over Time in RBANS - Story Recall Total Score | Change to Week 48 | -0.95 score on a scale | Standard Error 0.186 |
| ABBV-8E12 300 mg | Change From Baseline Over Time in RBANS - Story Recall Total Score | Change to Week 72 | -1.12 score on a scale | Standard Error 0.186 |
| ABBV-8E12 300 mg | Change From Baseline Over Time in RBANS - Story Recall Total Score | Change to Week 96 | -1.10 score on a scale | Standard Error 0.201 |
| ABBV-8E12 300 mg | Change From Baseline Over Time in RBANS - Story Recall Total Score | Change to Week 24 | -1.01 score on a scale | Standard Error 0.135 |
| ABBV-8E12 1000 mg | Change From Baseline Over Time in RBANS - Story Recall Total Score | Change to Week 72 | -0.90 score on a scale | Standard Error 0.181 |
| ABBV-8E12 1000 mg | Change From Baseline Over Time in RBANS - Story Recall Total Score | Change to Week 48 | -0.60 score on a scale | Standard Error 0.175 |
| ABBV-8E12 1000 mg | Change From Baseline Over Time in RBANS - Story Recall Total Score | Change to Week 96 | -0.96 score on a scale | Standard Error 0.192 |
| ABBV-8E12 1000 mg | Change From Baseline Over Time in RBANS - Story Recall Total Score | Change to Week 24 | -0.93 score on a scale | Standard Error 0.131 |
| ABBV-8E12 2000 mg | Change From Baseline Over Time in RBANS - Story Recall Total Score | Change to Week 96 | -1.35 score on a scale | Standard Error 0.205 |
| ABBV-8E12 2000 mg | Change From Baseline Over Time in RBANS - Story Recall Total Score | Change to Week 48 | -0.69 score on a scale | Standard Error 0.137 |
| ABBV-8E12 2000 mg | Change From Baseline Over Time in RBANS - Story Recall Total Score | Change to Week 24 | -0.95 score on a scale | Standard Error 0.137 |
| ABBV-8E12 2000 mg | Change From Baseline Over Time in RBANS - Story Recall Total Score | Change to Week 72 | -1.38 score on a scale | Standard Error 0.185 |
Comparison: Week 24p-value: 0.68395% CI: [-0.442, 0.29]repeated measures model
Comparison: Week 24
Comparison: Week 24p-value: 0.97395% CI: [-0.356, 0.368]repeated measures model
Comparison: Week 24
Comparison: Week 24p-value: 0.92195% CI: [-0.389, 0.352]repeated measures model
Comparison: Week 24
Comparison: Week 48p-value: 0.33595% CI: [-0.751, 0.257]repeated measures model
Comparison: Week 48
Comparison: Week 48p-value: 0.6795% CI: [-0.383, 0.596]repeated measures model
Comparison: Week 48
Comparison: Week 48p-value: 0.9595% CI: [-0.486, 0.519]repeated measures model
Comparison: Week 48
Comparison: Week 72p-value: 0.38395% CI: [-0.729, 0.281]repeated measures model
Comparison: Week 24
Comparison: Week 72p-value: 0.98595% CI: [-0.504, 0.494]repeated measures model
Comparison: Week 72
Comparison: Week 72p-value: 0.06495% CI: [-0.982, 0.027]repeated measures model
Comparison: Week 72
Comparison: Week 96p-value: 0.52795% CI: [-0.374, 0.729]repeated measures model
Comparison: Week 96
Comparison: Week 96p-value: 0.25495% CI: [-0.226, 0.854]repeated measures model
Comparison: Week 96
Comparison: Week 96p-value: 0.80595% CI: [-0.628, 0.488]repeated measures model
Comparison: Week 96
Secondary
Change From Baseline Over Time in Repeatable Battery for Assessment of Neuropsychological Status (RBANS) - Total Scale Score
The RBANS is a 25-minute, standardized neurocognitive battery with North American population-based normative data. The RBANS measures five neurocognitive domains, with age-based scaling. Twelve subtests measure cognitive decline or improvement across the following domains: 1. Immediate Memory - List Learning and Story Memory, 2. Visuospatial/Constructional - Figure Copy and Line Orientation, 3. Language - Picture naming and Semantic Fluency, 4. Attention - Digit Span and Coding, and 5. Delayed Memory - List Recall, List Recognition, Story Memory, and Figure Recall. Total score can range from 40 to 160 with a higher score representing a better outcome.
Time frame: Baseline, Week 24, Week 48, Week 72, Week 96
Population: Intent-to-Treat Data Set: all randomized participants who received at least 1 dose of study drug. Participants with an assessment at baseline and given time point.
| Arm | Measure | Group | Value (LEAST_SQUARES_MEAN) | Dispersion |
|---|---|---|---|---|
| Placebo | Change From Baseline Over Time in Repeatable Battery for Assessment of Neuropsychological Status (RBANS) - Total Scale Score | Change to Week 24 | -3.52 score on a scale | Standard Error 0.64 |
| Placebo | Change From Baseline Over Time in Repeatable Battery for Assessment of Neuropsychological Status (RBANS) - Total Scale Score | Change to Week 48 | -1.85 score on a scale | Standard Error 0.757 |
| Placebo | Change From Baseline Over Time in Repeatable Battery for Assessment of Neuropsychological Status (RBANS) - Total Scale Score | Change to Week 72 | -5.27 score on a scale | Standard Error 0.861 |
| Placebo | Change From Baseline Over Time in Repeatable Battery for Assessment of Neuropsychological Status (RBANS) - Total Scale Score | Change to Week 96 | -6.79 score on a scale | Standard Error 0.923 |
| ABBV-8E12 300 mg | Change From Baseline Over Time in Repeatable Battery for Assessment of Neuropsychological Status (RBANS) - Total Scale Score | Change to Week 48 | -1.37 score on a scale | Standard Error 0.782 |
| ABBV-8E12 300 mg | Change From Baseline Over Time in Repeatable Battery for Assessment of Neuropsychological Status (RBANS) - Total Scale Score | Change to Week 72 | -5.95 score on a scale | Standard Error 0.885 |
| ABBV-8E12 300 mg | Change From Baseline Over Time in Repeatable Battery for Assessment of Neuropsychological Status (RBANS) - Total Scale Score | Change to Week 96 | -7.78 score on a scale | Standard Error 0.928 |
| ABBV-8E12 300 mg | Change From Baseline Over Time in Repeatable Battery for Assessment of Neuropsychological Status (RBANS) - Total Scale Score | Change to Week 24 | -4.83 score on a scale | Standard Error 0.649 |
| ABBV-8E12 1000 mg | Change From Baseline Over Time in Repeatable Battery for Assessment of Neuropsychological Status (RBANS) - Total Scale Score | Change to Week 72 | -6.86 score on a scale | Standard Error 0.862 |
| ABBV-8E12 1000 mg | Change From Baseline Over Time in Repeatable Battery for Assessment of Neuropsychological Status (RBANS) - Total Scale Score | Change to Week 48 | -1.86 score on a scale | Standard Error 0.746 |
| ABBV-8E12 1000 mg | Change From Baseline Over Time in Repeatable Battery for Assessment of Neuropsychological Status (RBANS) - Total Scale Score | Change to Week 96 | -6.59 score on a scale | Standard Error 0.901 |
| ABBV-8E12 1000 mg | Change From Baseline Over Time in Repeatable Battery for Assessment of Neuropsychological Status (RBANS) - Total Scale Score | Change to Week 24 | -5.04 score on a scale | Standard Error 0.637 |
| ABBV-8E12 2000 mg | Change From Baseline Over Time in Repeatable Battery for Assessment of Neuropsychological Status (RBANS) - Total Scale Score | Change to Week 96 | -7.03 score on a scale | Standard Error 0.977 |
| ABBV-8E12 2000 mg | Change From Baseline Over Time in Repeatable Battery for Assessment of Neuropsychological Status (RBANS) - Total Scale Score | Change to Week 48 | -2.67 score on a scale | Standard Error 0.792 |
| ABBV-8E12 2000 mg | Change From Baseline Over Time in Repeatable Battery for Assessment of Neuropsychological Status (RBANS) - Total Scale Score | Change to Week 24 | -5.17 score on a scale | Standard Error 0.664 |
| ABBV-8E12 2000 mg | Change From Baseline Over Time in Repeatable Battery for Assessment of Neuropsychological Status (RBANS) - Total Scale Score | Change to Week 72 | -6.38 score on a scale | Standard Error 0.897 |
Comparison: Week 24p-value: 0.14895% CI: [-3.08, 0.465]repeated measures model
Comparison: Week 24
Comparison: Week 24p-value: 0.09295% CI: [-3.278, 0.246]repeated measures model
Comparison: Week 24
Comparison: Week 24p-value: 0.07395% CI: [-3.446, 0.152]repeated measures model
Comparison: Week 24
Comparison: Week 48p-value: 0.66295% CI: [-1.652, 2.599]repeated measures model
Comparison: Week 48
Comparison: Week 48p-value: 0.99295% CI: [-2.089, 2.068]repeated measures model
Comparison: Week 48
Comparison: Week 48p-value: 0.45195% CI: [-2.961, 1.32]repeated measures model
Comparison: Week 48
Comparison: Week 72p-value: 0.58395% CI: [-3.088, 1.739]repeated measures model
Comparison: Week 72
Comparison: Week 72p-value: 0.19195% CI: [-3.975, 0.795]repeated measures model
Comparison: Week 72
Comparison: Week 72p-value: 0.37295% CI: [-3.541, 1.329]repeated measures model
Comparison: Week 72
Comparison: Week 96p-value: 0.44795% CI: [-3.553, 1.571]repeated measures model
Comparison: Week 96
Comparison: Week 96p-value: 0.88195% CI: [-2.334, 2.719]repeated measures model
Comparison: Week 96
Comparison: Week 96p-value: 0.85395% CI: [-2.881, 2.383]repeated measures model
Comparison: Week 96
Secondary
Change From Baseline Over Time in University of California's Performance Based Skills Assessment, Brief Version (UPSA-Brief) - Total Score
The UPSA-Brief is a performance-based instrument which uses a series of tasks and roleplay scenarios to evaluate a person's functional capacity in two areas of basic living skills (i.e., financial skills and communication skills). Scores range from 0 to 100; a higher score of the UPSA-Brief is desirable.
Time frame: Baseline, Week 48, Week 96
Population: Intent-to-Treat Data Set: all randomized participants who received at least 1 dose of study drug. Participants with an assessment at baseline and given time point.
| Arm | Measure | Group | Value (LEAST_SQUARES_MEAN) | Dispersion |
|---|---|---|---|---|
| Placebo | Change From Baseline Over Time in University of California's Performance Based Skills Assessment, Brief Version (UPSA-Brief) - Total Score | Change to Week 48 | -4.47 score on a scale | Standard Error 1.533 |
| Placebo | Change From Baseline Over Time in University of California's Performance Based Skills Assessment, Brief Version (UPSA-Brief) - Total Score | Change to Week 96 | -13.36 score on a scale | Standard Error 2.047 |
| ABBV-8E12 300 mg | Change From Baseline Over Time in University of California's Performance Based Skills Assessment, Brief Version (UPSA-Brief) - Total Score | Change to Week 96 | -12.74 score on a scale | Standard Error 2.037 |
| ABBV-8E12 300 mg | Change From Baseline Over Time in University of California's Performance Based Skills Assessment, Brief Version (UPSA-Brief) - Total Score | Change to Week 48 | -6.04 score on a scale | Standard Error 1.567 |
| ABBV-8E12 1000 mg | Change From Baseline Over Time in University of California's Performance Based Skills Assessment, Brief Version (UPSA-Brief) - Total Score | Change to Week 48 | -4.10 score on a scale | Standard Error 1.5 |
| ABBV-8E12 1000 mg | Change From Baseline Over Time in University of California's Performance Based Skills Assessment, Brief Version (UPSA-Brief) - Total Score | Change to Week 96 | -11.55 score on a scale | Standard Error 1.994 |
| ABBV-8E12 2000 mg | Change From Baseline Over Time in University of California's Performance Based Skills Assessment, Brief Version (UPSA-Brief) - Total Score | Change to Week 48 | -8.96 score on a scale | Standard Error 1.601 |
| ABBV-8E12 2000 mg | Change From Baseline Over Time in University of California's Performance Based Skills Assessment, Brief Version (UPSA-Brief) - Total Score | Change to Week 96 | -14.85 score on a scale | Standard Error 2.104 |
Comparison: Week 48p-value: 0.4795% CI: [-5.851, 2.703]repeated measures model
Comparison: Week 48
Comparison: Week 48p-value: 0.86495% CI: [-3.819, 4.548]repeated measures model
Comparison: Week 48
Comparison: Week 48p-value: 0.04395% CI: [-8.826, -0.15]repeated measures model
Comparison: Week 96
Comparison: Week 96p-value: 0.83195% CI: [-5.041, 6.27]repeated measures model
Comparison: Week 96
Comparison: Week 96p-value: 0.52595% CI: [-3.784, 7.404]repeated measures model
Comparison: Week 96
Comparison: Week 96p-value: 0.6195% CI: [-7.239, 4.255]repeated measures model
Comparison: Week 96
Secondary
Cmax/Dose for ABBV-8E12 Over the Dosing Interval After the First and Fourth Doses
Time frame: Day 1 (Dose 1): Pre-infusion, post-infusion (within 15 minutes), 1 and 2 hours post-infusion; Days 5 and 15. Day 85 (Dose 4): Pre-infusion (0 hour), post-infusion (within 15 minutes) and 1 and 2 hours post-infusion; Days 89 and 99.
Population: Intensive Pharmacokinetic Cohort: Among the first 48 participants enrolled in the study, those who received ABBV-8E12 and had an evaluable PK assessment at given time point.
| Arm | Measure | Group | Value (GEOMETRIC_MEAN) | Dispersion |
|---|---|---|---|---|
| Placebo | Cmax/Dose for ABBV-8E12 Over the Dosing Interval After the First and Fourth Doses | First Dosing Interval | 0.359 µg/mL/mg | Geometric Coefficient of Variation 28 |
| Placebo | Cmax/Dose for ABBV-8E12 Over the Dosing Interval After the First and Fourth Doses | Fourth Dosing Interval | 0.561 µg/mL/mg | Geometric Coefficient of Variation 23 |
| ABBV-8E12 300 mg | Cmax/Dose for ABBV-8E12 Over the Dosing Interval After the First and Fourth Doses | First Dosing Interval | 0.284 µg/mL/mg | Geometric Coefficient of Variation 21 |
| ABBV-8E12 300 mg | Cmax/Dose for ABBV-8E12 Over the Dosing Interval After the First and Fourth Doses | Fourth Dosing Interval | 0.426 µg/mL/mg | Geometric Coefficient of Variation 20 |
| ABBV-8E12 1000 mg | Cmax/Dose for ABBV-8E12 Over the Dosing Interval After the First and Fourth Doses | First Dosing Interval | 0.264 µg/mL/mg | Geometric Coefficient of Variation 27 |
| ABBV-8E12 1000 mg | Cmax/Dose for ABBV-8E12 Over the Dosing Interval After the First and Fourth Doses | Fourth Dosing Interval | 0.403 µg/mL/mg | Geometric Coefficient of Variation 37 |
Secondary
Half-Life (T1/2) for ABBV-8E12 Over the Dosing Interval After the First and Fourth Doses
Harmonic mean is presented in the data table.
Time frame: Day 1 (Dose 1): Pre-infusion, post-infusion (within 15 minutes), 1 and 2 hours post-infusion; Days 5 and 15. Day 85 (Dose 4): Pre-infusion (0 hour), post-infusion (within 15 minutes) and 1 and 2 hours post-infusion; Days 89 and 99.
Population: Intensive Pharmacokinetic Cohort: Among the first 48 participants enrolled in the study, those who received ABBV-8E12 and had an evaluable PK assessment at given time point.
| Arm | Measure | Group | Value (MEAN) | Dispersion |
|---|---|---|---|---|
| Placebo | Half-Life (T1/2) for ABBV-8E12 Over the Dosing Interval After the First and Fourth Doses | First Dosing Interval | 22.0 days | Standard Deviation 17.2 |
| Placebo | Half-Life (T1/2) for ABBV-8E12 Over the Dosing Interval After the First and Fourth Doses | Fourth Dosing Interval | 19.6 days | Standard Deviation 6.09 |
| ABBV-8E12 300 mg | Half-Life (T1/2) for ABBV-8E12 Over the Dosing Interval After the First and Fourth Doses | First Dosing Interval | 19.4 days | Standard Deviation 8.87 |
| ABBV-8E12 300 mg | Half-Life (T1/2) for ABBV-8E12 Over the Dosing Interval After the First and Fourth Doses | Fourth Dosing Interval | 24.0 days | Standard Deviation 16.6 |
| ABBV-8E12 1000 mg | Half-Life (T1/2) for ABBV-8E12 Over the Dosing Interval After the First and Fourth Doses | First Dosing Interval | 33.2 days | Standard Deviation 10.5 |
| ABBV-8E12 1000 mg | Half-Life (T1/2) for ABBV-8E12 Over the Dosing Interval After the First and Fourth Doses | Fourth Dosing Interval | 37.5 days | Standard Deviation 13.5 |
Secondary
Maximum Observed Serum Concentration (Cmax) for ABBV-8E12 Over the Dosing Interval After the First and Fourth Doses
Time frame: Day 1 (Dose 1): Pre-infusion, post-infusion (within 15 minutes), 1 and 2 hours post-infusion; Days 5 and 15. Day 85 (Dose 4): Pre-infusion (0 hour), post-infusion (within 15 minutes) and 1 and 2 hours post-infusion; Days 89 and 99.
Population: Intensive Pharmacokinetic Cohort: Among the first 48 participants enrolled in the study, those who received ABBV-8E12 and had an evaluable PK assessment at given time point.
| Arm | Measure | Group | Value (GEOMETRIC_MEAN) | Dispersion |
|---|---|---|---|---|
| Placebo | Maximum Observed Serum Concentration (Cmax) for ABBV-8E12 Over the Dosing Interval After the First and Fourth Doses | First Dosing Interval | 108 µg/mL | Geometric Coefficient of Variation 28 |
| Placebo | Maximum Observed Serum Concentration (Cmax) for ABBV-8E12 Over the Dosing Interval After the First and Fourth Doses | Fourth Dosing Interval | 168 µg/mL | Geometric Coefficient of Variation 23 |
| ABBV-8E12 300 mg | Maximum Observed Serum Concentration (Cmax) for ABBV-8E12 Over the Dosing Interval After the First and Fourth Doses | First Dosing Interval | 284 µg/mL | Geometric Coefficient of Variation 21 |
| ABBV-8E12 300 mg | Maximum Observed Serum Concentration (Cmax) for ABBV-8E12 Over the Dosing Interval After the First and Fourth Doses | Fourth Dosing Interval | 426 µg/mL | Geometric Coefficient of Variation 20 |
| ABBV-8E12 1000 mg | Maximum Observed Serum Concentration (Cmax) for ABBV-8E12 Over the Dosing Interval After the First and Fourth Doses | First Dosing Interval | 528 µg/mL | Geometric Coefficient of Variation 27 |
| ABBV-8E12 1000 mg | Maximum Observed Serum Concentration (Cmax) for ABBV-8E12 Over the Dosing Interval After the First and Fourth Doses | Fourth Dosing Interval | 806 µg/mL | Geometric Coefficient of Variation 37 |
Secondary
Serum Concentration at the End of a Dose Interval (Ctrough) for ABBV-8E12 Over the Dosing Interval After the First and Fourth Doses
Time frame: Day 1 (Dose 1): Pre-infusion, post-infusion (within 15 minutes), 1 and 2 hours post-infusion; Days 5 and 15. Day 85 (Dose 4): Pre-infusion (0 hour), post-infusion (within 15 minutes) and 1 and 2 hours post-infusion; Days 89 and 99.
Population: Intensive Pharmacokinetic Cohort: Among the first 48 participants enrolled in the study, those who received ABBV-8E12 and had an evaluable PK assessment at given time point.
| Arm | Measure | Group | Value (GEOMETRIC_MEAN) | Dispersion |
|---|---|---|---|---|
| Placebo | Serum Concentration at the End of a Dose Interval (Ctrough) for ABBV-8E12 Over the Dosing Interval After the First and Fourth Doses | First Dosing Interval | 28.6 µg/mL | Geometric Coefficient of Variation 22 |
| Placebo | Serum Concentration at the End of a Dose Interval (Ctrough) for ABBV-8E12 Over the Dosing Interval After the First and Fourth Doses | Fourth Dosing Interval | 56.4 µg/mL | Geometric Coefficient of Variation 25 |
| ABBV-8E12 300 mg | Serum Concentration at the End of a Dose Interval (Ctrough) for ABBV-8E12 Over the Dosing Interval After the First and Fourth Doses | First Dosing Interval | 75.1 µg/mL | Geometric Coefficient of Variation 33 |
| ABBV-8E12 300 mg | Serum Concentration at the End of a Dose Interval (Ctrough) for ABBV-8E12 Over the Dosing Interval After the First and Fourth Doses | Fourth Dosing Interval | 182 µg/mL | Geometric Coefficient of Variation 29 |
| ABBV-8E12 1000 mg | Serum Concentration at the End of a Dose Interval (Ctrough) for ABBV-8E12 Over the Dosing Interval After the First and Fourth Doses | First Dosing Interval | 163 µg/mL | Geometric Coefficient of Variation 26 |
| ABBV-8E12 1000 mg | Serum Concentration at the End of a Dose Interval (Ctrough) for ABBV-8E12 Over the Dosing Interval After the First and Fourth Doses | Fourth Dosing Interval | 320 µg/mL | Geometric Coefficient of Variation 36 |
Secondary
Time to Cmax (Tmax) for ABBV-8E12 Over the Dosing Interval After the First and Fourth Doses
Time frame: Day 1 (Dose 1): Pre-infusion, post-infusion (within 15 minutes), 1 and 2 hours post-infusion; Days 5 and 15. Day 85 (Dose 4): Pre-infusion (0 hour), post-infusion (within 15 minutes) and 1 and 2 hours post-infusion; Days 89 and 99.
Population: Intensive Pharmacokinetic Cohort: Among the first 48 participants enrolled in the study, those who received ABBV-8E12 and had an evaluable PK assessment at given time point.
| Arm | Measure | Group | Value (MEDIAN) |
|---|---|---|---|
| Placebo | Time to Cmax (Tmax) for ABBV-8E12 Over the Dosing Interval After the First and Fourth Doses | First Dosing Interval | 3 hours |
| Placebo | Time to Cmax (Tmax) for ABBV-8E12 Over the Dosing Interval After the First and Fourth Doses | Fourth Dosing Interval | 2.4 hours |
| ABBV-8E12 300 mg | Time to Cmax (Tmax) for ABBV-8E12 Over the Dosing Interval After the First and Fourth Doses | Fourth Dosing Interval | 2.5 hours |
| ABBV-8E12 300 mg | Time to Cmax (Tmax) for ABBV-8E12 Over the Dosing Interval After the First and Fourth Doses | First Dosing Interval | 2.5 hours |
| ABBV-8E12 1000 mg | Time to Cmax (Tmax) for ABBV-8E12 Over the Dosing Interval After the First and Fourth Doses | Fourth Dosing Interval | 2.3 hours |
| ABBV-8E12 1000 mg | Time to Cmax (Tmax) for ABBV-8E12 Over the Dosing Interval After the First and Fourth Doses | First Dosing Interval | 2.7 hours |