Alzheimer's Disease
Conditions
Keywords
Early Alzheimer's disease, active immunization, amyloid imaging
Brief summary
This study in individuals with early Alzheimer's disease is designed to assess:(1) safety and tolerability (2) the capacity of ACC-001 and QS-21 adjuvant to reduce brain amyloid load as measured by positron emission tomography (PET) scans.
Interventions
BIOLOGICALACC-001 3 μg/ QS-21 50 μg
ACC-001 3 μg/ QS-21 50 μg IM on day 1, month 1, month 3, month 6, month 12, and month 18
BIOLOGICALACC-001 10 μg/ QS-21 50 μg
ACC-001 10 μg/ QS-21 50 μg IM on day 1, month 1, month 3, month 6, month 12, and month 18
OTHERPlacebo- Phosphate buffered saline (PBS)
Phosphate buffered saline IM on day 1, month 1, month 3, month 6, month 12, and month 18
Sponsors
JANSSEN Alzheimer Immunotherapy Research & Development, LLC
Pfizer
Study design
Allocation
RANDOMIZED
Intervention model
PARALLEL
Primary purpose
TREATMENT
Masking
QUADRUPLE (Subject, Caregiver, Investigator, Outcomes Assessor)
Eligibility
Sex/Gender
ALL
Age
50 Years to 80 Years
Healthy volunteers
No
Inclusion criteria
* Concern about a change in cognition expressed by the subject or by an informant that knows the subject well * Mini-Mental State Examination (MMSE) score ≥ 25 * Global Clinical Dementia Rating = 0.5. * General cognition and functional performance sufficiently preserved such that a diagnosis of Alzheimer's dementia cannot not be made by the site physician at the time of screening. * Amyloid burden detected on screening brain PET scan. * Other inclusion criteria apply.
Exclusion criteria
* Significant neurological disease other than early Alzheimer's disease * Major psychiatric disorder or symptom * Contraindication to undergo brain MRI * Unstable medical conditions * Other
Design outcomes
Primary
| Measure | Time frame | Description |
|---|---|---|
| Change From Baseline in Brain Fibrillar Beta-Amyloid Protein (Aβ) at Week 104 as Measured by Standard Uptake Value Ratios (SUVRs) Over the Composite Regions of Interest (ROIs) | 104 weeks | Fibrillar brain Aβ was measured by retention of florbetapir F18 as measured by positron emission tomography (PET) scans. A positive change indicating an improvement from baseline. |
Other
| Measure | Time frame | Description |
|---|---|---|
| Change From Baseline in CSF Aβ x-42 | Week 80 or Week 104 | For the majority of the participants, the lumbar puncture for the first CSF sample was collected up to 3 days prior to injection of investigational product. For the participants who had a CSF being already drawn at week 80, no CSF sample was drawn at week 104, nor at ET visit. For those participants who early terminated the study before week 80, CSF was drawn at ET visit. |
| Change From Baseline in CSF p-Tau | Week 80 or Week 104 | For the majority of the participants, the lumbar puncture for the first CSF sample was collected up to 3 days prior to injection of investigational product. For the participants who had a CSF being already drawn at week 80, no CSF sample was drawn at week 104, nor at ET visit. For those participants who early terminated the study before week 80, CSF was drawn at ET visit. |
| Change From Baseline in CSF Total Tau | Week 80 or Week 104 | For the majority of the participants, the lumbar puncture for the first CSF sample was collected up to 3 days prior to injection of investigational product. For the participants who had a CSF being already drawn at week 80, no CSF sample was drawn at week 104, nor at ET visit. For those participants who early terminated the study before week 80, CSF was drawn at ET visit. |
| Change From Baseline in Plasma Aβ x-40 | 104 weeks | Site personnel collecting the samples for plasma Aβ (x-40) concentrations and the results were blinded to the participant treatment group assignment. |
| Change From Baseline in Volumetric Brain Magnetic Resonance Imaging (MRI) Measurements in Brain Boundary Shift Integral (BBSI) | 104 weeks | BBSI measures whole brain atrophy from registered MRI scan pairs, by subtracting the area under the intensity profile across a boundary in the repeat scans from the initial scan (baseline). |
| Change From Baseline in Volumetric Brain MRI Measurements in Ventricular Boundary Shift Integral (VBSI) | 104 weeks | VBSI measures ventricular volume change from registered MRI scan pairs, by subtracting the area under the intensity profile across a boundary in the repeat scans. |
| Change From Baseline in Volumetric Brain MRI Measurements in Hippocampal Boundary Shift Integral (HBSI), Total | 104 weeks | Left HBSI and Right HBSI respectively measure the left hippocampal atrophy and the right hippocampal atrophy from registered MRI scan pairs, by subtracting the corresponding area under the intensity profile across a boundary in the repeat scans. HBSI (Total) is defined as the summation of the left HBSI and the right HBSI. |
| Change From Baseline in Volumetric Brain MRI Measurements in HBSI, Left | 104 weeks | Left HBSI measures the left hippocampal atrophy from registered MRI scan pairs, by subtracting the corresponding area under the intensity profile across a boundary in the repeat scans. |
| Change From Baseline in Volumetric Brain MRI Measurements in HBSI, Right | 104 weeks | Right HBSI measures the right hippocampal atrophy from registered MRI scan pairs, by subtracting the corresponding area under the intensity profile across a boundary in the repeat scans. |
| Change From Baseline in Neuropsychological Test Battery (NTB) | 104 weeks | The NTB evaluated cognitive domains that are known to be affected early in the course of Alzheimer's disease (AD). The cognitive tests included in the NTB were: Rey Auditory Verbal Learning Test - Immediate recall, Detection, Identification, Go-No-Go Task, One Back Task, Controlled Oral Word Association Test, Category Fluency Test, and Rey Auditory Verbal Learning Test - delayed recall and recognition. For each of the eight NTB components, an individual z-score was derived based on the primary raw score of each test. Based on the individual z-scores, a composite z-score was derived using the formula: (z1-z2-z3-z4+z5+z6+z7+z8)/8. Positive change indicating an improvement from baseline. |
| Change From Baseline in Functional Activities Questionnaire (FAQ) Total Score | 104 weeks | FAQ is a 10-item, caregiver-based questionnaire and was administered to the study partner who was asked to rate the participant's ability to perform a variety of activities ranging from shopping, doing the laundry, simple financial transactions, comprehension of current events, some recreational or avocational activities, and reading. FAQ total score was calculated by adding the scores from each of the 10 items. A negative change indicated an improvement from baseline. FAQ Total Score is the sum of 10 items, ranging from 0 (best possible outcome) to 100 (worst possible outcome). |
| Change From Baseline in Clinical Dementia Rating Sum of Boxes (CDR-SOB) | 104 weeks | Clinical Dementia Rating (CDR) is a global clinical staging instrument that was administrated by a trained rater to assess a participant's level of impairment in six domains including: Memory, Orientation, Judgement and Problem Solving, Community Affairs, Home and Hobbies, and Personal Care, based on the CDR interview. The CDR included discussions with the participant and study partner using a structured format. A CDR-SOB score was derived based on individual scores from the six domains. A negative change indicated an improvement from baseline. The total CDR-SB score is calculated as the sum of the six clinical ratings. The CDR-SOB score range for each domain is 0 to 3. The CDR-SOB total score ranges from 0 to 18, with higher scores indicating greater dementia. If any individual item is missing, then the CDR-SB is set to missing. |
| Change From Baseline in Neuropsychiatric Inventory (NPI) Total Score | 104 weeks | The NPI scale assesses 12 domains (delusions, hallucinations, agitation, depression, anxiety, euphoria, apathy, disinhibition, irritability, aberrant motor behavior, nighttime behavior, and appetite and eating changes). The symptoms were rated on the basis of questions administered to the study partner. If a preliminary question for each domain was answered as 'Yes', each domain was rated on a 4-point frequency scale and on a 3-point severity scale. If the preliminary question was answered as 'No', the frequency, severity, and distress scales were set to zero. A negative change indicated an improvement from baseline. For each of the 12 domains, a sub-scale score is calculated as frequency\*severity and ranges from 0 to 12. The NPI total score is then calculated by summing the scores of the 12 sub-scale scores. The NPI total scores ranges from 0 to 144 with higher scores indicating greater behavioral impairment. The caregiver distress score is not included in the NPI total score. |
| Change From Baseline in NPI Distress Score (NPI-D) | 104 weeks | The NPI scale assesses 12 domains (delusions, hallucinations, agitation, depression, anxiety, euphoria, apathy, disinhibition, irritability, aberrant motor behavior, nighttime behavior, and appetite and eating changes). The symptoms were rated on the basis of questions administered to the study partner. For each domain, the study partner also rated his/her own 'emotional or psychological' distress caused by the participant's behavior on a 6-point scale. The study partner NPI-D total score was calculated by summing the scores of the 12 sub-scale distress scores. A negative change indicated an improvement from baseline. The caregiver distress (NPI-D) total score is calculated by summing the scores of the 12 sub-scale distress scores. The NPI-D total scores ranges from 0 to 60 with higher scores indicating greater distress. |
| Change From Baseline in Mini Mental State Examination (MMSE) Total Score | 104 weeks | The MMSE is a brief, structured examination of cognitive function consisting of the 11 item: Orientation-What, Orientation-Where, Registration-Objects, Attention and Calculation, Recall, Language-Naming, Language-Repetition, Language-Comprehension, Language-Reading, Language-Writing, and Language- Drawing. MMSE total score was the sum of the 11 item scores and it ranges from 0 to 30 with higher score indicating greater cognitive functioning. If any individual item is missing, then the MMSE total score is set to missing. A positive change indicating an improvement from baseline. |
| Change From Baseline in 13-item Alzheimer's Disease Assessment Scale - Cognitive (ADAS-Cog) Total Score | 104 weeks | The ADAS-Cog is a global cognitive measure. For the following 13 items, the participants were rated: Word Recall, Commands, Construction Praxis, Delayed Word Recall Task, Naming Task, Ideational Praxis, Orientation, Word Recognition Task, Remembering Test Instructions, Spoken Language Ability, Word-Finding Difficulty in Spontaneous Speech, Comprehension, and Number Cancellation. The ADAS-cog is a structured scale that evaluates memory, orientation, attention, reasoning, language and constructional praxis. The total score was the sum of the scores from the 13 individual items. This study used a modified 85 point scale with a scoring range of 0 to 85 (13 items). Higher scores of the 13 individual items indicated greater cognitive impairment. |
| Change From Baseline in Cerebrospinal Fluid (CSF) Aβ x-40 | Week 80 or Week 104 | For the majority of the participants, the lumbar puncture for the first CSF sample was collected up to 3 days prior to injection of investigational product. For the participants who had a CSF being already drawn at week 80, no CSF sample was drawn at week 104, nor at the Early termination (ET) visit. For those participants who early terminated the study before week 80, CSF was drawn at ET visit. |
| Change From Baseline in Resource Utilization in Dementia (RUD) (Abbreviated) (RUD-Lite) - Primary Caregiver | 104 weeks | An abbreviated administration of the RUD (RUD-Lite) was used. The RUD-Lite is a comprehensive tool for addressing the magnitude and nature of study partner/caregiver effort in cases of dementia. Since a significant portion of care in Alzheimer's related-dementia was performed informally by the participant's friends or family, it was desirable to measure the extent of this care for use in economic evaluations of disease. The total time spent by the primary caregiver providing support on activities of daily living (ADL), instrumental activities of daily living (IADL) and supervising, respectively, was calculated in two components. Total number of days spent during the past month on each of ADL, IADL, and supervising; and: time per day during the past month on each of ADL, IADL and supervising. The total Primary Caregiver Time per month could range from 0 - 720. This was calculated by multiplying the number of days per month (30) by the number of hours per day (24). |
| Change From Baseline in RUD (Abbreviated) (RUD-Lite) - Other Caregivers | 104 weeks | An abbreviated administration of the RUD (RUD-Lite) was used. The RUD-Lite is a comprehensive tool for addressing the magnitude and nature of study partner/caregiver effort in cases of dementia. Since a significant portion of care in Alzheimer's related-dementia was performed informally by the participant's friends or family, it was desirable to measure the extent of this care for use in economic evaluations of disease. The total time spent by the other caregivers providing support on ADL, IADL and supervising, respectively, was calculated in two components. Total number of days spent during the past month on each of ADL, IADL and supervising; and: time per day during the past month on each of ADL, IADL, and supervising. The total Other Caregiver Time per month could range from 0 - 720. This was calculated by multiplying the number of days per month (30) by the number of hours per day (24). |
| Percentage of Participants With a Global CDR Score of Equal to or Greater Than 1 for the First Time | 104 weeks | CDR is a global clinical staging instrument that was administrated by a trained rater to assess a participant's level of impairment in six domains including: Memory, Orientation, Judgement and Problem Solving, Community Affairs, Home and Hobbies, and Personal Care, based on the CDR interview. The CDR included discussions with the participant and study partner using a structured format. CDR global score was derived from the six domains according to a complex algorithm with emphasis on the Memory Domain score. Global CDR score = 0.5 with memory box score of 0.5. The total CDR-SB score is calculated as the sum of the six clinical ratings. The CDR-SOB score range for each domain is 0 to 3, with higher score indicating no significant function. If any individual item is missing, then the CDR-SB is set to missing. |
| Geometric Mean Anti-Aβ IgG Enzyme-linked Immunosorbent Assay (ELISA) Titers | 104 weeks | Site personnel collecting the samples for anti-Aβ antibody titers were blinded to the participant treatment group assignment. The lower limit of quantification (LLOQ) determined for this assay was 100 U/mL. For any anti-Aβ IgG antibody level that was below the LLOQ (100 U/mL), the lower limit of detection (LLOD) defined as 0.5\*LLOQ was imputed. |
| Geometric Mean Anti-Aβ IgM ELISA Titers | 104 weeks | Site personnel collecting the samples for anti-Aβ antibody titers were blinded to the participant treatment group assignment. The LLOQ determined for this assay was 50 U/mL. For any anti-Aβ IgM antibody level that was below the LLOQ (50 U/mL), the LLOD defined as 0.5\*LLOQ was imputed. |
| Change From Baseline in Perceived Deficits Questionnaire (PDQ) - Subject - Attention/Concentration Domain Score | 104 weeks | The PDQ is a tool consisting of 20 questions and is designed to assess perceived cognitive deficits from the participant's perspective. The instrument assessed a variety of questions in the following areas: attention/concentration, retrospective memory, prospective memory, and planning/organization. The Attention/Concentration Domain Score is the sum of the raw scores on items 1, 5, 9, 13 and 17, with a range from 0 - 4 for each of the 5 items. So the Attention/Concentration Domain Score could range from 0 - 20, with higher scores indicating greater perceived cognitive impairment. |
| Change From Baseline in PDQ - Subject - Retrospective Memory Domain Score | 104 weeks | The PDQ is a tool consisting of 20 questions and is designed to assess perceived cognitive deficits from the participant's perspective. The instrument assessed a variety of questions in the following areas: attention/concentration, retrospective memory, prospective memory, and planning/organization. The Retrospective Memory Domain Score is the sum of the raw scores on items 2, 6, 10, 14, and 18, with a range from 0 - 4 for each of the 5 items. So the Retrospective Memory Domain Score could range from 0 - 20, with higher scores indicating greater perceived cognitive impairment. |
| Change From Baseline in PDQ - Subject - Prospective Memory Domain Score | 104 weeks | The PDQ is a tool consisting of 20 questions and is designed to assess perceived cognitive deficits from the participant's perspective. The instrument assessed a variety of questions in the following areas: attention/concentration, retrospective memory, prospective memory, and planning/organization. The Prospective Memory Domain Score is the sum of the raw scores on items 3, 7, 11, 15, and 19, with a range from 0 - 4 for each of the 5 items. So the Prospective Memory Domain Score could range from 0 - 20, with higher scores indicating greater perceived cognitive impairment. |
| Change From Baseline in PDQ - Subject - Planning/Organization Domain Score | 104 weeks | The PDQ is a tool consisting of 20 questions and is designed to assess perceived cognitive deficits from the participant's perspective. The instrument assessed a variety of questions in the following areas: attention/concentration, retrospective memory, prospective memory, and planning/organization. The Planning/Organization Domain Score is the sum of the raw scores on items 4, 8, 12, 16, and 20, with a range from 0 - 4 for each of the 5 items. So the Planning/Organization Domain Score could range from 0 - 20, with higher scores indicating greater perceived cognitive impairment. |
| Change From Baseline in PDQ - Subject - Total Score | 104 weeks | The PDQ is a tool consisting of 20 questions and is designed to assess perceived cognitive deficits from the participant's perspective. The instrument assessed a variety of questions in the following areas: attention/concentration, retrospective memory, prospective memory, and planning/organization. The Total Score is computed by adding raw scores for all of the items (or all 4 domain scores) together. It could range from 0 - 80, with higher scores indicating greater perceived cognitive impairment. |
| Change From Baseline in PDQ-R - Relative - Attention/Concentration Domain Score | 104 weeks | The PDQ-R is a tool consisting of 20 questions, is designed to assess perceived cognitive deficits, and was administered to the study partner. The instrument assessed a variety of questions in the following areas: attention/concentration, retrospective memory, prospective memory, and planning/organization. The Attention/Concentration Domain Score is the sum of the raw scores on items 1, 5, 9, 13, and 17, with a range from 0 - 4 for each of the 5 items. So the Attention/Concentration Domain Score could range from 0 - 20, with higher scores indicating greater perceived cognitive impairment. |
| Change From Baseline in PDQ-R - Relative - Retrospective Memory Domain Score | 104 weeks | The PDQ-R is a tool consisting of 20 questions, is designed to assess perceived cognitive deficits, and was administered to the study partner. The instrument assessed a variety of questions in the following areas: attention/concentration, retrospective memory, prospective memory, and planning/organization. The Retrospective Memory Domain Score is the sum of the raw scores on items 2, 6, 10, 14, and 18, with a range from 0 - 4 for each of the 5 items. So the Retrospective Memory Domain Score could range from 0 - 20, with higher scores indicating greater perceived cognitive impairment. |
| Change From Baseline in PDQ-R - Relative - Prospective Memory Domain Score | 104 weeks | The PDQ-R is a tool consisting of 20 questions, is designed to assess perceived cognitive deficits, and was administered to the study partner. The instrument assessed a variety of questions in the following areas: attention/concentration, retrospective memory, prospective memory, and planning/organization. The Prospective Memory Domain Score is the sum of the raw scores on items 3, 7, 11, 15, and 19, with a range from 0 - 4 for each of the 5 items. So the Prospective Memory Domain Score could range from 0 - 20, with higher scores indicating greater perceived cognitive impairment. |
| Change From Baseline in PDQ-R - Relative - Planning/Organization Domain Score | 104 weeks | The PDQ-R is a tool consisting of 20 questions, is designed to assess perceived cognitive deficits, and was administered to the study partner. The instrument assessed a variety of questions in the following areas: attention/concentration, retrospective memory, prospective memory, and planning/organization. The Planning/Organization Domain Score is the sum of the raw scores on items 4, 8, 12, 16, and 20, with a range from 0 - 4 for each of the 5 items. So the Planning/Organization Domain Score could range from 0 - 20, with higher scores indicating greater perceived cognitive impairment. |
| Change From Baseline in PDQ-R - Relative - Total Score | 104 weeks | The PDQ-R is a tool consisting of 20 questions, is designed to assess perceived cognitive deficits, and was administered to the study partner. The instrument assessed a variety of questions in the following areas: attention/concentration, retrospective memory, prospective memory, and planning/organization. The Total Score is computed by adding raw scores for all of the items (or all 4 domain scores) together. It could range from 0 - 80, with higher scores indicating greater perceived cognitive impairment. |
| Alzheimer's Disease Medication Administration Concerns Questionnaire (AD MACQ) | 104 weeks | The AD MACQ was administered to the study partner to address preferences for medication administration by assessing: Question a: I would find it easy to give the study medication to the patient myself. Question b: The number of times the medication was given was convenient. Question c: I would prefer to have the study medication given at home by me instead of at the doctor's office by the doctor or nurse. Question d: I would prefer to have the study medication given at home by a nurse instead of at the doctor's office by the doctor or nurse. Question e: Overall, I am satisfied with the way the medication was given. |
| Change From Baseline in Dependence Scale (DS) Score | 104 weeks | An abbreviated administration (first 6 items) of the DS was used in this study. The DS is a brief study partner-completed measure which assesses the degree of support required by a subject with AD. Since the goal of treatment was to delay or arrest the processes leading to increased dependence, the DS represented a meaningful endpoint for clinical studies in AD. The dependence score was derived by summing the first 6 items of the DS. Item 1 and 2 ranged from 0 - 2 and item 3 - 6 ranged from 0 - 1. The total score was calculated by summing the score from each of the 6 items. So the total score could range from 0 - 8, with higher scores indicating greater dependence. |
Countries
United States
Participant flow
Recruitment details
Twenty study centers in the United States of America participated. One of these did not enroll any participants.
Pre-assignment details
Participants, who were found eligible, were randomized to 1 of 3 groups in a 1:1:1 ratio between ACC-001 3 μg+QS-21, or ACC-001 10 μg+QS-21, or placebo (which was administrated as phosphate buffered saline \[PBS\]). The study randomization was stratified based on apolipoprotein E (Apo E) genotype (E4 carrier or non-carrier).
Participants by arm
| Arm | Count |
|---|---|
| ACC 3 μg+QS-21 Participants received 3 μg of ACC-001 and 50 μg of QS-21. Investigational product was administered by intramuscular injection into the deltoid muscle at 0, 1, 3, 6, 12, and 18 months. | 22 |
| ACC 10 μg+QS-21 Participants received 10 μg of ACC-001 and 50 μg of QS-21. Investigational product was administered by intramuscular injection into the deltoid muscle at 0, 1, 3, 6, 12, and 18 months. | 20 |
| Placebo Participants received PBS. Investigational product was administered by intramuscular injection into the deltoid muscle at 0, 1, 3, 6, 12, and 18 months. | 21 |
| Total | 63 |
Withdrawals & dropouts
| Period | Reason | FG000 | FG001 | FG002 |
|---|---|---|---|---|
| Overall Study | No Longer Willing to Participate | 4 | 2 | 5 |
| Overall Study | Participant moved to another town | 0 | 0 | 1 |
Baseline characteristics
| Characteristic | ACC 3 μg+QS-21 | ACC 10 μg+QS-21 | Placebo | Total |
|---|---|---|---|---|
| Age, Continuous | 66.8 years STANDARD_DEVIATION 7.31 | 68.5 years STANDARD_DEVIATION 7.02 | 69.6 years STANDARD_DEVIATION 6.82 | 68.3 years STANDARD_DEVIATION 7.04 |
| MMSE Score | 27.3 score STANDARD_DEVIATION 1.64 | 27.7 score STANDARD_DEVIATION 1.63 | 28.0 score STANDARD_DEVIATION 1.47 | 27.6 score STANDARD_DEVIATION 1.58 |
| Sex: Female, Male Female | 11 Participants | 13 Participants | 9 Participants | 33 Participants |
| Sex: Female, Male Male | 11 Participants | 7 Participants | 12 Participants | 30 Participants |
Adverse events
| Event type | EG000 affected / at risk | EG001 affected / at risk | EG002 affected / at risk |
|---|---|---|---|
| deaths Total, all-cause mortality | — / — | — / — | — / — |
| other Total, other adverse events | 20 / 22 | 19 / 20 | 17 / 21 |
| serious Total, serious adverse events | 1 / 22 | 6 / 20 | 6 / 21 |
Outcome results
Primary
Change From Baseline in Brain Fibrillar Beta-Amyloid Protein (Aβ) at Week 104 as Measured by Standard Uptake Value Ratios (SUVRs) Over the Composite Regions of Interest (ROIs)
Fibrillar brain Aβ was measured by retention of florbetapir F18 as measured by positron emission tomography (PET) scans. A positive change indicating an improvement from baseline.
Time frame: 104 weeks
Population: The full analysis set (FAS) population included all randomized participants who had at least one dose of investigational product.
| Arm | Measure | Group | Value (LEAST_SQUARES_MEAN) |
|---|---|---|---|
| ACC 3 μg+QS-21 | Change From Baseline in Brain Fibrillar Beta-Amyloid Protein (Aβ) at Week 104 as Measured by Standard Uptake Value Ratios (SUVRs) Over the Composite Regions of Interest (ROIs) | Week 52 (N: 22, 19, 41, 20) | 0.009 ratio |
| ACC 3 μg+QS-21 | Change From Baseline in Brain Fibrillar Beta-Amyloid Protein (Aβ) at Week 104 as Measured by Standard Uptake Value Ratios (SUVRs) Over the Composite Regions of Interest (ROIs) | Week 104 (N: 14, 15, 29, 13) | -0.018 ratio |
| ACC 3 μg+QS-21 | Change From Baseline in Brain Fibrillar Beta-Amyloid Protein (Aβ) at Week 104 as Measured by Standard Uptake Value Ratios (SUVRs) Over the Composite Regions of Interest (ROIs) | Week 78 (N: 21, 18, 39, 16) | -0.011 ratio |
| ACC 10 μg+QS-21 | Change From Baseline in Brain Fibrillar Beta-Amyloid Protein (Aβ) at Week 104 as Measured by Standard Uptake Value Ratios (SUVRs) Over the Composite Regions of Interest (ROIs) | Week 52 (N: 22, 19, 41, 20) | 0.017 ratio |
| ACC 10 μg+QS-21 | Change From Baseline in Brain Fibrillar Beta-Amyloid Protein (Aβ) at Week 104 as Measured by Standard Uptake Value Ratios (SUVRs) Over the Composite Regions of Interest (ROIs) | Week 104 (N: 14, 15, 29, 13) | -0.018 ratio |
| ACC 10 μg+QS-21 | Change From Baseline in Brain Fibrillar Beta-Amyloid Protein (Aβ) at Week 104 as Measured by Standard Uptake Value Ratios (SUVRs) Over the Composite Regions of Interest (ROIs) | Week 78 (N: 21, 18, 39, 16) | -0.022 ratio |
| Overall ACC + QS21 | Change From Baseline in Brain Fibrillar Beta-Amyloid Protein (Aβ) at Week 104 as Measured by Standard Uptake Value Ratios (SUVRs) Over the Composite Regions of Interest (ROIs) | Week 78 (N: 21, 18, 39, 16) | -0.017 ratio |
| Overall ACC + QS21 | Change From Baseline in Brain Fibrillar Beta-Amyloid Protein (Aβ) at Week 104 as Measured by Standard Uptake Value Ratios (SUVRs) Over the Composite Regions of Interest (ROIs) | Week 52 (N: 22, 19, 41, 20) | 0.013 ratio |
| Overall ACC + QS21 | Change From Baseline in Brain Fibrillar Beta-Amyloid Protein (Aβ) at Week 104 as Measured by Standard Uptake Value Ratios (SUVRs) Over the Composite Regions of Interest (ROIs) | Week 104 (N: 14, 15, 29, 13) | -0.018 ratio |
| Placebo | Change From Baseline in Brain Fibrillar Beta-Amyloid Protein (Aβ) at Week 104 as Measured by Standard Uptake Value Ratios (SUVRs) Over the Composite Regions of Interest (ROIs) | Week 52 (N: 22, 19, 41, 20) | 0.011 ratio |
| Placebo | Change From Baseline in Brain Fibrillar Beta-Amyloid Protein (Aβ) at Week 104 as Measured by Standard Uptake Value Ratios (SUVRs) Over the Composite Regions of Interest (ROIs) | Week 104 (N: 14, 15, 29, 13) | 0.032 ratio |
| Placebo | Change From Baseline in Brain Fibrillar Beta-Amyloid Protein (Aβ) at Week 104 as Measured by Standard Uptake Value Ratios (SUVRs) Over the Composite Regions of Interest (ROIs) | Week 78 (N: 21, 18, 39, 16) | -0.014 ratio |
Comparison: A mixed-effect model repeated measures was used, with the baseline measure of average SUVRs over ROIs and Apo E4 Status (Carrier or Non-carrier) as covariates, time, treatment, and treatment\*time as fixed effects. Estimates of the adjusted mean differences (test-reference) and corresponding 95% confidence intervals were obtained from the model. ACC 3 µg+QS-21 50 µg was the test treatment and placebo was the reference treatment. Statistical analysis presented above for Week 52.p-value: 0.953895% CI: [-0.075, 0.071]Mixed-Effects Model Repeated Measures
Comparison: A mixed-effect model repeated measures was used, with the baseline measure of average SUVRs over ROIs and Apo E4 Status (Carrier or Non-carrier) as covariates, time, treatment, and treatment\*time as fixed effects. Estimates of the adjusted mean differences (test-reference) and corresponding 95% confidence intervals were obtained from the model. ACC 10 µg+QS-21 50 µg was the test treatment and placebo was the reference treatment. Statistical analysis presented above for Week 52.p-value: 0.878795% CI: [-0.07, 0.081]Mixed-Effects Model Repeated Measures
Comparison: A mixed-effect model repeated measures was used, with the baseline measure of average SUVRs over ROIs and Apo E4 Status (Carrier or Non-carrier) as covariates, time, treatment, and treatment\*time as fixed effects. Estimates of the adjusted mean differences (test-reference) and corresponding 95% confidence intervals were obtained from the model. ACC 3 µg or ACC 10 µg + QS-21 50 µg was the test treatment and placebo was the reference treatment. Statistical analysis presented above for Week 52.p-value: 0.954495% CI: [-0.062, 0.066]Mixed-Effects Model Repeated Measures
Comparison: A mixed-effect model repeated measures was used, with the baseline measure of average SUVRs over ROIs and Apo E4 Status (Carrier or Non-carrier) as covariates, time, treatment, and treatment\*time as fixed effects. Estimates of the adjusted mean differences (test-reference) and corresponding 95% confidence intervals were obtained from the model. ACC 3 µg+QS-21 50 µg was the test treatment and placebo was the reference treatment. Statistical analysis presented above for Week 78.p-value: 0.95595% CI: [-0.106, 0.112]Mixed-Effects Model Repeated Measures
Comparison: A mixed-effect model repeated measures was used, with the baseline measure of average SUVRs over ROIs and Apo E4 Status (Carrier or Non-carrier) as covariates, time, treatment, and treatment\*time as fixed effects. Estimates of the adjusted mean differences (test-reference) and corresponding 95% confidence intervals were obtained from the model. ACC 10 µg+QS-21 50 µg was the test treatment and placebo was the reference treatment. Statistical analysis presented above for Week 78.p-value: 0.887495% CI: [-0.121, 0.105]Mixed-Effects Model Repeated Measures
Comparison: A mixed-effect model repeated measures was used, with the baseline measure of average SUVRs over ROIs and Apo E4 Status (Carrier or Non-carrier) as covariates, time, treatment, and treatment\*time as fixed effects. Estimates of the adjusted mean differences (test-reference) and corresponding 95% confidence intervals were obtained from the model. ACC 3 µg or ACC 10 µg + QS-21 50 µg was the test treatment and placebo was the reference treatment. Statistical analysis presented above for Week 78.p-value: 0.959595% CI: [-0.099, 0.095]Mixed-Effects Model Repeated Measures
Comparison: A mixed-effect model repeated measures was used, with the baseline measure of average SUVRs over ROIs and Apo E4 Status (Carrier or Non-carrier) as covariates, time, treatment, and treatment\*time as fixed effects. Estimates of the adjusted mean differences (test-reference) and corresponding 95% confidence intervals were obtained from the model. ACC 3 µg+QS-21 50 µg was the test treatment and placebo was the reference treatment. Statistical analysis presented above for Week 104.p-value: 0.382695% CI: [-0.164, 0.064]Mixed-Effects Model Repeated Measures
Comparison: A mixed-effect model repeated measures was used, with the baseline measure of average SUVRs over ROIs and Apo E4 Status (Carrier or Non-carrier) as covariates, time, treatment, and treatment\*time as fixed effects. Estimates of the adjusted mean differences (test-reference) and corresponding 95% confidence intervals were obtained from the model. ACC 10 µg+QS-21 50 µg was the test treatment and placebo was the reference treatment. Statistical analysis presented above for Week 104.p-value: 0.391295% CI: [-0.164, 0.065]Mixed-Effects Model Repeated Measures
Comparison: A mixed-effect model repeated measures was used, with the baseline measure of average SUVRs over ROIs and Apo E4 Status (Carrier or Non-carrier) as covariates, time, treatment, and treatment\*time as fixed effects. Estimates of the adjusted mean differences (test-reference) and corresponding 95% confidence intervals were obtained from the model. ACC 3 µg or ACC 10 µg + QS-21 50 µg was the test treatment and placebo was the reference treatment. Statistical analysis presented above for Week 104.p-value: 0.322195% CI: [-0.149, 0.05]Mixed-Effects Model Repeated Measures
Other Pre-specified
Alzheimer's Disease Medication Administration Concerns Questionnaire (AD MACQ)
The AD MACQ was administered to the study partner to address preferences for medication administration by assessing: Question a: I would find it easy to give the study medication to the patient myself. Question b: The number of times the medication was given was convenient. Question c: I would prefer to have the study medication given at home by me instead of at the doctor's office by the doctor or nurse. Question d: I would prefer to have the study medication given at home by a nurse instead of at the doctor's office by the doctor or nurse. Question e: Overall, I am satisfied with the way the medication was given.
Time frame: 104 weeks
Population: FAS population included all randomized participants who had at least one dose of investigational product.
| Arm | Measure | Group | Value (NUMBER) |
|---|---|---|---|
| ACC 3 μg+QS-21 | Alzheimer's Disease Medication Administration Concerns Questionnaire (AD MACQ) | Question a: Slightly Disagree | 9.1 percentage of participants |
| ACC 3 μg+QS-21 | Alzheimer's Disease Medication Administration Concerns Questionnaire (AD MACQ) | Question d: Slightly Agree | 4.5 percentage of participants |
| ACC 3 μg+QS-21 | Alzheimer's Disease Medication Administration Concerns Questionnaire (AD MACQ) | Question b: Disagree | 0 percentage of participants |
| ACC 3 μg+QS-21 | Alzheimer's Disease Medication Administration Concerns Questionnaire (AD MACQ) | Question e: Disagree | 0 percentage of participants |
| ACC 3 μg+QS-21 | Alzheimer's Disease Medication Administration Concerns Questionnaire (AD MACQ) | Question a: Agree | 40.9 percentage of participants |
| ACC 3 μg+QS-21 | Alzheimer's Disease Medication Administration Concerns Questionnaire (AD MACQ) | Question c: Agree | 4.5 percentage of participants |
| ACC 3 μg+QS-21 | Alzheimer's Disease Medication Administration Concerns Questionnaire (AD MACQ) | Question e: Slightly Agree | 13.6 percentage of participants |
| ACC 3 μg+QS-21 | Alzheimer's Disease Medication Administration Concerns Questionnaire (AD MACQ) | Question d: Agree | 27.3 percentage of participants |
| ACC 3 μg+QS-21 | Alzheimer's Disease Medication Administration Concerns Questionnaire (AD MACQ) | Question c: Slightly Agree | 13.6 percentage of participants |
| ACC 3 μg+QS-21 | Alzheimer's Disease Medication Administration Concerns Questionnaire (AD MACQ) | Question a: Disagree | 22.7 percentage of participants |
| ACC 3 μg+QS-21 | Alzheimer's Disease Medication Administration Concerns Questionnaire (AD MACQ) | Question c: Disagree | 54.5 percentage of participants |
| ACC 3 μg+QS-21 | Alzheimer's Disease Medication Administration Concerns Questionnaire (AD MACQ) | Question c: Neither Agree Nor Disagree | 22.7 percentage of participants |
| ACC 3 μg+QS-21 | Alzheimer's Disease Medication Administration Concerns Questionnaire (AD MACQ) | Question e: Slightly Disagree | 0 percentage of participants |
| ACC 3 μg+QS-21 | Alzheimer's Disease Medication Administration Concerns Questionnaire (AD MACQ) | Question c: Slightly Disagree | 4.5 percentage of participants |
| ACC 3 μg+QS-21 | Alzheimer's Disease Medication Administration Concerns Questionnaire (AD MACQ) | Question e: Agree | 63.6 percentage of participants |
| ACC 3 μg+QS-21 | Alzheimer's Disease Medication Administration Concerns Questionnaire (AD MACQ) | Question b: Agree | 68.2 percentage of participants |
| ACC 3 μg+QS-21 | Alzheimer's Disease Medication Administration Concerns Questionnaire (AD MACQ) | Question a: Neither Agree Nor Disagree | 13.6 percentage of participants |
| ACC 3 μg+QS-21 | Alzheimer's Disease Medication Administration Concerns Questionnaire (AD MACQ) | Question d: Disagree | 27.3 percentage of participants |
| ACC 3 μg+QS-21 | Alzheimer's Disease Medication Administration Concerns Questionnaire (AD MACQ) | Question b: Slightly Agree | 9.1 percentage of participants |
| ACC 3 μg+QS-21 | Alzheimer's Disease Medication Administration Concerns Questionnaire (AD MACQ) | Question a: Slightly Agree | 13.6 percentage of participants |
| ACC 3 μg+QS-21 | Alzheimer's Disease Medication Administration Concerns Questionnaire (AD MACQ) | Question d: Slightly Disagree | 0 percentage of participants |
| ACC 3 μg+QS-21 | Alzheimer's Disease Medication Administration Concerns Questionnaire (AD MACQ) | Question b: Neither Agree Nor Disagree | 22.7 percentage of participants |
| ACC 3 μg+QS-21 | Alzheimer's Disease Medication Administration Concerns Questionnaire (AD MACQ) | Question e: Neither Agree Nor Disagree | 22.7 percentage of participants |
| ACC 3 μg+QS-21 | Alzheimer's Disease Medication Administration Concerns Questionnaire (AD MACQ) | Question d: Neither Agree Nor Disagree | 40.9 percentage of participants |
| ACC 3 μg+QS-21 | Alzheimer's Disease Medication Administration Concerns Questionnaire (AD MACQ) | Question b: Slightly Disagree | 0 percentage of participants |
| ACC 10 μg+QS-21 | Alzheimer's Disease Medication Administration Concerns Questionnaire (AD MACQ) | Question d: Agree | 21.1 percentage of participants |
| ACC 10 μg+QS-21 | Alzheimer's Disease Medication Administration Concerns Questionnaire (AD MACQ) | Question a: Agree | 42.1 percentage of participants |
| ACC 10 μg+QS-21 | Alzheimer's Disease Medication Administration Concerns Questionnaire (AD MACQ) | Question a: Slightly Agree | 0 percentage of participants |
| ACC 10 μg+QS-21 | Alzheimer's Disease Medication Administration Concerns Questionnaire (AD MACQ) | Question a: Neither Agree Nor Disagree | 21.1 percentage of participants |
| ACC 10 μg+QS-21 | Alzheimer's Disease Medication Administration Concerns Questionnaire (AD MACQ) | Question a: Slightly Disagree | 0 percentage of participants |
| ACC 10 μg+QS-21 | Alzheimer's Disease Medication Administration Concerns Questionnaire (AD MACQ) | Question a: Disagree | 36.8 percentage of participants |
| ACC 10 μg+QS-21 | Alzheimer's Disease Medication Administration Concerns Questionnaire (AD MACQ) | Question b: Agree | 68.4 percentage of participants |
| ACC 10 μg+QS-21 | Alzheimer's Disease Medication Administration Concerns Questionnaire (AD MACQ) | Question b: Slightly Agree | 10.5 percentage of participants |
| ACC 10 μg+QS-21 | Alzheimer's Disease Medication Administration Concerns Questionnaire (AD MACQ) | Question b: Neither Agree Nor Disagree | 21.1 percentage of participants |
| ACC 10 μg+QS-21 | Alzheimer's Disease Medication Administration Concerns Questionnaire (AD MACQ) | Question b: Slightly Disagree | 0 percentage of participants |
| ACC 10 μg+QS-21 | Alzheimer's Disease Medication Administration Concerns Questionnaire (AD MACQ) | Question b: Disagree | 0 percentage of participants |
| ACC 10 μg+QS-21 | Alzheimer's Disease Medication Administration Concerns Questionnaire (AD MACQ) | Question c: Agree | 26.3 percentage of participants |
| ACC 10 μg+QS-21 | Alzheimer's Disease Medication Administration Concerns Questionnaire (AD MACQ) | Question c: Slightly Agree | 5.3 percentage of participants |
| ACC 10 μg+QS-21 | Alzheimer's Disease Medication Administration Concerns Questionnaire (AD MACQ) | Question c: Neither Agree Nor Disagree | 26.3 percentage of participants |
| ACC 10 μg+QS-21 | Alzheimer's Disease Medication Administration Concerns Questionnaire (AD MACQ) | Question c: Slightly Disagree | 0 percentage of participants |
| ACC 10 μg+QS-21 | Alzheimer's Disease Medication Administration Concerns Questionnaire (AD MACQ) | Question c: Disagree | 42.1 percentage of participants |
| ACC 10 μg+QS-21 | Alzheimer's Disease Medication Administration Concerns Questionnaire (AD MACQ) | Question d: Slightly Agree | 10.5 percentage of participants |
| ACC 10 μg+QS-21 | Alzheimer's Disease Medication Administration Concerns Questionnaire (AD MACQ) | Question d: Neither Agree Nor Disagree | 31.6 percentage of participants |
| ACC 10 μg+QS-21 | Alzheimer's Disease Medication Administration Concerns Questionnaire (AD MACQ) | Question d: Slightly Disagree | 5.3 percentage of participants |
| ACC 10 μg+QS-21 | Alzheimer's Disease Medication Administration Concerns Questionnaire (AD MACQ) | Question d: Disagree | 31.6 percentage of participants |
| ACC 10 μg+QS-21 | Alzheimer's Disease Medication Administration Concerns Questionnaire (AD MACQ) | Question e: Agree | 84.2 percentage of participants |
| ACC 10 μg+QS-21 | Alzheimer's Disease Medication Administration Concerns Questionnaire (AD MACQ) | Question e: Slightly Agree | 0 percentage of participants |
| ACC 10 μg+QS-21 | Alzheimer's Disease Medication Administration Concerns Questionnaire (AD MACQ) | Question e: Neither Agree Nor Disagree | 15.8 percentage of participants |
| ACC 10 μg+QS-21 | Alzheimer's Disease Medication Administration Concerns Questionnaire (AD MACQ) | Question e: Slightly Disagree | 0 percentage of participants |
| ACC 10 μg+QS-21 | Alzheimer's Disease Medication Administration Concerns Questionnaire (AD MACQ) | Question e: Disagree | 0 percentage of participants |
| Overall ACC + QS21 | Alzheimer's Disease Medication Administration Concerns Questionnaire (AD MACQ) | Question d: Slightly Agree | 0 percentage of participants |
| Overall ACC + QS21 | Alzheimer's Disease Medication Administration Concerns Questionnaire (AD MACQ) | Question b: Neither Agree Nor Disagree | 15 percentage of participants |
| Overall ACC + QS21 | Alzheimer's Disease Medication Administration Concerns Questionnaire (AD MACQ) | Question a: Agree | 25 percentage of participants |
| Overall ACC + QS21 | Alzheimer's Disease Medication Administration Concerns Questionnaire (AD MACQ) | Question d: Neither Agree Nor Disagree | 25 percentage of participants |
| Overall ACC + QS21 | Alzheimer's Disease Medication Administration Concerns Questionnaire (AD MACQ) | Question b: Slightly Agree | 15 percentage of participants |
| Overall ACC + QS21 | Alzheimer's Disease Medication Administration Concerns Questionnaire (AD MACQ) | Question e: Neither Agree Nor Disagree | 15 percentage of participants |
| Overall ACC + QS21 | Alzheimer's Disease Medication Administration Concerns Questionnaire (AD MACQ) | Question d: Slightly Disagree | 15 percentage of participants |
| Overall ACC + QS21 | Alzheimer's Disease Medication Administration Concerns Questionnaire (AD MACQ) | Question b: Agree | 70 percentage of participants |
| Overall ACC + QS21 | Alzheimer's Disease Medication Administration Concerns Questionnaire (AD MACQ) | Question a: Slightly Agree | 0 percentage of participants |
| Overall ACC + QS21 | Alzheimer's Disease Medication Administration Concerns Questionnaire (AD MACQ) | Question d: Disagree | 40 percentage of participants |
| Overall ACC + QS21 | Alzheimer's Disease Medication Administration Concerns Questionnaire (AD MACQ) | Question a: Disagree | 65 percentage of participants |
| Overall ACC + QS21 | Alzheimer's Disease Medication Administration Concerns Questionnaire (AD MACQ) | Question e: Disagree | 0 percentage of participants |
| Overall ACC + QS21 | Alzheimer's Disease Medication Administration Concerns Questionnaire (AD MACQ) | Question e: Agree | 80 percentage of participants |
| Overall ACC + QS21 | Alzheimer's Disease Medication Administration Concerns Questionnaire (AD MACQ) | Question a: Slightly Disagree | 10 percentage of participants |
| Overall ACC + QS21 | Alzheimer's Disease Medication Administration Concerns Questionnaire (AD MACQ) | Question c: Neither Agree Nor Disagree | 10 percentage of participants |
| Overall ACC + QS21 | Alzheimer's Disease Medication Administration Concerns Questionnaire (AD MACQ) | Question e: Slightly Disagree | 0 percentage of participants |
| Overall ACC + QS21 | Alzheimer's Disease Medication Administration Concerns Questionnaire (AD MACQ) | Question c: Slightly Disagree | 10 percentage of participants |
| Overall ACC + QS21 | Alzheimer's Disease Medication Administration Concerns Questionnaire (AD MACQ) | Question c: Slightly Agree | 0 percentage of participants |
| Overall ACC + QS21 | Alzheimer's Disease Medication Administration Concerns Questionnaire (AD MACQ) | Question e: Slightly Agree | 5 percentage of participants |
| Overall ACC + QS21 | Alzheimer's Disease Medication Administration Concerns Questionnaire (AD MACQ) | Question c: Disagree | 60 percentage of participants |
| Overall ACC + QS21 | Alzheimer's Disease Medication Administration Concerns Questionnaire (AD MACQ) | Question c: Agree | 20 percentage of participants |
| Overall ACC + QS21 | Alzheimer's Disease Medication Administration Concerns Questionnaire (AD MACQ) | Question b: Disagree | 0 percentage of participants |
| Overall ACC + QS21 | Alzheimer's Disease Medication Administration Concerns Questionnaire (AD MACQ) | Question d: Agree | 20 percentage of participants |
| Overall ACC + QS21 | Alzheimer's Disease Medication Administration Concerns Questionnaire (AD MACQ) | Question b: Slightly Disagree | 0 percentage of participants |
| Overall ACC + QS21 | Alzheimer's Disease Medication Administration Concerns Questionnaire (AD MACQ) | Question a: Neither Agree Nor Disagree | 0 percentage of participants |
Other Pre-specified
Change From Baseline in 13-item Alzheimer's Disease Assessment Scale - Cognitive (ADAS-Cog) Total Score
The ADAS-Cog is a global cognitive measure. For the following 13 items, the participants were rated: Word Recall, Commands, Construction Praxis, Delayed Word Recall Task, Naming Task, Ideational Praxis, Orientation, Word Recognition Task, Remembering Test Instructions, Spoken Language Ability, Word-Finding Difficulty in Spontaneous Speech, Comprehension, and Number Cancellation. The ADAS-cog is a structured scale that evaluates memory, orientation, attention, reasoning, language and constructional praxis. The total score was the sum of the scores from the 13 individual items. This study used a modified 85 point scale with a scoring range of 0 to 85 (13 items). Higher scores of the 13 individual items indicated greater cognitive impairment.
Time frame: 104 weeks
Population: FAS population included all randomized participants who had at least one dose of investigational product.
| Arm | Measure | Group | Value (LEAST_SQUARES_MEAN) |
|---|---|---|---|
| ACC 3 μg+QS-21 | Change From Baseline in 13-item Alzheimer's Disease Assessment Scale - Cognitive (ADAS-Cog) Total Score | Week 54 (N: 22, 19, 41, 29) | -5.58 score |
| ACC 3 μg+QS-21 | Change From Baseline in 13-item Alzheimer's Disease Assessment Scale - Cognitive (ADAS-Cog) Total Score | Week 86 (N: 19, 18, 37, 17) | 1.80 score |
| ACC 10 μg+QS-21 | Change From Baseline in 13-item Alzheimer's Disease Assessment Scale - Cognitive (ADAS-Cog) Total Score | Week 86 (N: 19, 18, 37, 17) | 0.28 score |
| ACC 10 μg+QS-21 | Change From Baseline in 13-item Alzheimer's Disease Assessment Scale - Cognitive (ADAS-Cog) Total Score | Week 54 (N: 22, 19, 41, 29) | -6.69 score |
| Overall ACC + QS21 | Change From Baseline in 13-item Alzheimer's Disease Assessment Scale - Cognitive (ADAS-Cog) Total Score | Week 54 (N: 22, 19, 41, 29) | -6.14 score |
| Overall ACC + QS21 | Change From Baseline in 13-item Alzheimer's Disease Assessment Scale - Cognitive (ADAS-Cog) Total Score | Week 86 (N: 19, 18, 37, 17) | 1.04 score |
| Placebo | Change From Baseline in 13-item Alzheimer's Disease Assessment Scale - Cognitive (ADAS-Cog) Total Score | Week 54 (N: 22, 19, 41, 29) | -5.05 score |
| Placebo | Change From Baseline in 13-item Alzheimer's Disease Assessment Scale - Cognitive (ADAS-Cog) Total Score | Week 86 (N: 19, 18, 37, 17) | 1.56 score |
Comparison: A mixed effects model for repeated measures analysis was used, with the baseline assessment and ApoE4 status as covariates, and visit, treatment and visit by treatment interaction as fixed effects, with variance-covariance structure set to unstructured. Statistical analysis presented above for Week 54.p-value: 0.714695% CI: [-3.4, 2.35]Mixed-Effects Model Repeated Measures
Comparison: A mixed effects model for repeated measures analysis was used, with the baseline assessment and ApoE4 status as covariates, and visit, treatment and visit by treatment interaction as fixed effects, with variance-covariance structure set to unstructured. Statistical analysis presented above for Week 54.p-value: 0.273395% CI: [-4.6, 1.33]Mixed-Effects Model Repeated Measures
Comparison: A mixed effects model for repeated measures analysis was used, with the baseline assessment and ApoE4 status as covariates, and visit, treatment and visit by treatment interaction as fixed effects, with variance-covariance structure set to unstructured. Statistical analysis presented above for Week 54.p-value: 0.396995% CI: [-3.62, 1.46]Mixed-Effects Model Repeated Measures
Comparison: A mixed effects model for repeated measures analysis was used, with the baseline assessment and ApoE4 status as covariates, and visit, treatment and visit by treatment interaction as fixed effects, with variance-covariance structure set to unstructured. Statistical analysis presented above for Week 86.p-value: 0.856695% CI: [-2.43, 2.92]Mixed-Effects Model Repeated Measures
Comparison: A mixed effects model for repeated measures analysis was used, with the baseline assessment and ApoE4 status as covariates, and visit, treatment and visit by treatment interaction as fixed effects, with variance-covariance structure set to unstructured. Statistical analysis presented above for Week 86.p-value: 0.34695% CI: [-3.98, 1.42]Mixed-Effects Model Repeated Measures
Comparison: A mixed effects model for repeated measures analysis was used, with the baseline assessment and ApoE4 status as covariates, and visit, treatment and visit by treatment interaction as fixed effects, with variance-covariance structure set to unstructured. Statistical analysis presented above for Week 86.p-value: 0.658295% CI: [-2.86, 1.82]Mixed-Effects Model Repeated Measures
Other Pre-specified
Change From Baseline in Cerebrospinal Fluid (CSF) Aβ x-40
For the majority of the participants, the lumbar puncture for the first CSF sample was collected up to 3 days prior to injection of investigational product. For the participants who had a CSF being already drawn at week 80, no CSF sample was drawn at week 104, nor at the Early termination (ET) visit. For those participants who early terminated the study before week 80, CSF was drawn at ET visit.
Time frame: Week 80 or Week 104
Population: FAS population included all randomized participants who had at least one dose of investigational product.
| Arm | Measure | Value (LEAST_SQUARES_MEAN) |
|---|---|---|
| ACC 3 μg+QS-21 | Change From Baseline in Cerebrospinal Fluid (CSF) Aβ x-40 | 192.93 μg/ml |
| ACC 10 μg+QS-21 | Change From Baseline in Cerebrospinal Fluid (CSF) Aβ x-40 | 726.74 μg/ml |
| Overall ACC + QS21 | Change From Baseline in Cerebrospinal Fluid (CSF) Aβ x-40 | 459.83 μg/ml |
| Placebo | Change From Baseline in Cerebrospinal Fluid (CSF) Aβ x-40 | 144.76 μg/ml |
Comparison: Analysis of Covariance (ANCOVA) was used with baseline assessment and ApoE4 status as covariates, in addition to treatment included in the ANCOVA model.p-value: 0.938495% CI: [-1197.07, 1293.42]ANCOVA
Comparison: ANCOVA was used with baseline assessment and ApoE4 status as covariates, in addition to treatment included in the ANCOVA model.p-value: 0.394595% CI: [-778.17, 1942.13]ANCOVA
Comparison: ANCOVA was used with baseline assessment and ApoE4 status as covariates, in addition to treatment included in the ANCOVA model.p-value: 0.577395% CI: [-812.15, 1442.3]ANCOVA
Other Pre-specified
Change From Baseline in Clinical Dementia Rating Sum of Boxes (CDR-SOB)
Clinical Dementia Rating (CDR) is a global clinical staging instrument that was administrated by a trained rater to assess a participant's level of impairment in six domains including: Memory, Orientation, Judgement and Problem Solving, Community Affairs, Home and Hobbies, and Personal Care, based on the CDR interview. The CDR included discussions with the participant and study partner using a structured format. A CDR-SOB score was derived based on individual scores from the six domains. A negative change indicated an improvement from baseline. The total CDR-SB score is calculated as the sum of the six clinical ratings. The CDR-SOB score range for each domain is 0 to 3. The CDR-SOB total score ranges from 0 to 18, with higher scores indicating greater dementia. If any individual item is missing, then the CDR-SB is set to missing.
Time frame: 104 weeks
Population: FAS population included all randomized participants who had at least one dose of investigational product.
| Arm | Measure | Group | Value (LEAST_SQUARES_MEAN) |
|---|---|---|---|
| ACC 3 μg+QS-21 | Change From Baseline in Clinical Dementia Rating Sum of Boxes (CDR-SOB) | Week 26 (N: 22, 20, 42, 20) | 0.60 score |
| ACC 3 μg+QS-21 | Change From Baseline in Clinical Dementia Rating Sum of Boxes (CDR-SOB) | Week 52 (N: 22, 19, 41, 20) | 1.10 score |
| ACC 3 μg+QS-21 | Change From Baseline in Clinical Dementia Rating Sum of Boxes (CDR-SOB) | Week 78 (N: 22, 18, 40, 18) | 1.71 score |
| ACC 3 μg+QS-21 | Change From Baseline in Clinical Dementia Rating Sum of Boxes (CDR-SOB) | Week 104 (N: 17, 18, 35, 14) | 2.15 score |
| ACC 10 μg+QS-21 | Change From Baseline in Clinical Dementia Rating Sum of Boxes (CDR-SOB) | Week 52 (N: 22, 19, 41, 20) | 0.39 score |
| ACC 10 μg+QS-21 | Change From Baseline in Clinical Dementia Rating Sum of Boxes (CDR-SOB) | Week 78 (N: 22, 18, 40, 18) | 0.69 score |
| ACC 10 μg+QS-21 | Change From Baseline in Clinical Dementia Rating Sum of Boxes (CDR-SOB) | Week 104 (N: 17, 18, 35, 14) | 1.23 score |
| ACC 10 μg+QS-21 | Change From Baseline in Clinical Dementia Rating Sum of Boxes (CDR-SOB) | Week 26 (N: 22, 20, 42, 20) | 0.31 score |
| Overall ACC + QS21 | Change From Baseline in Clinical Dementia Rating Sum of Boxes (CDR-SOB) | Week 78 (N: 22, 18, 40, 18) | 1.20 score |
| Overall ACC + QS21 | Change From Baseline in Clinical Dementia Rating Sum of Boxes (CDR-SOB) | Week 52 (N: 22, 19, 41, 20) | 0.74 score |
| Overall ACC + QS21 | Change From Baseline in Clinical Dementia Rating Sum of Boxes (CDR-SOB) | Week 104 (N: 17, 18, 35, 14) | 1.69 score |
| Overall ACC + QS21 | Change From Baseline in Clinical Dementia Rating Sum of Boxes (CDR-SOB) | Week 26 (N: 22, 20, 42, 20) | 0.46 score |
| Placebo | Change From Baseline in Clinical Dementia Rating Sum of Boxes (CDR-SOB) | Week 104 (N: 17, 18, 35, 14) | 1.11 score |
| Placebo | Change From Baseline in Clinical Dementia Rating Sum of Boxes (CDR-SOB) | Week 52 (N: 22, 19, 41, 20) | 0.71 score |
| Placebo | Change From Baseline in Clinical Dementia Rating Sum of Boxes (CDR-SOB) | Week 26 (N: 22, 20, 42, 20) | 0.21 score |
| Placebo | Change From Baseline in Clinical Dementia Rating Sum of Boxes (CDR-SOB) | Week 78 (N: 22, 18, 40, 18) | 1.25 score |
Comparison: A mixed effects model for repeated measures analysis was used, with the baseline assessment and ApoE4 status as covariates, and visit, treatment and visit by treatment interaction as fixed effects, with variance-covariance structure set to unstructured. Statistical analysis presented above for Week 26.p-value: 0.179695% CI: [-0.18, 0.96]Mixed-Effects Model Repeated Measures
Comparison: A mixed effects model for repeated measures analysis was used, with the baseline assessment and ApoE4 status as covariates, and visit, treatment and visit by treatment interaction as fixed effects, with variance-covariance structure set to unstructured. Statistical analysis presented above for Week 26.p-value: 0.728195% CI: [-0.49, 0.69]Mixed-Effects Model Repeated Measures
Comparison: A mixed effects model for repeated measures analysis was used, with the baseline assessment and ApoE4 status as covariates, and visit, treatment and visit by treatment interaction as fixed effects, with variance-covariance structure set to unstructured. Statistical analysis presented above for Week 26.p-value: 0.334795% CI: [-0.26, 0.75]Mixed-Effects Model Repeated Measures
Comparison: A mixed effects model for repeated measures analysis was used, with the baseline assessment and ApoE4 status as covariates, and visit, treatment and visit by treatment interaction as fixed effects, with variance-covariance structure set to unstructured. Statistical analysis presented above for Week 52.p-value: 0.342595% CI: [-0.43, 1.2]Mixed-Effects Model Repeated Measures
Comparison: A mixed effects model for repeated measures analysis was used, with the baseline assessment and ApoE4 status as covariates, and visit, treatment and visit by treatment interaction as fixed effects, with variance-covariance structure set to unstructured. Statistical analysis presented above for Week 52.p-value: 0.450195% CI: [-1.16, 0.52]Mixed-Effects Model Repeated Measures
Comparison: A mixed effects model for repeated measures analysis was used, with the baseline assessment and ApoE4 status as covariates, and visit, treatment and visit by treatment interaction as fixed effects, with variance-covariance structure set to unstructured. Statistical analysis presented above for Week 52.p-value: 0.922795% CI: [-0.68, 0.75]Mixed-Effects Model Repeated Measures
Comparison: A mixed effects model for repeated measures analysis was used, with the baseline assessment and ApoE4 status as covariates, and visit, treatment and visit by treatment interaction as fixed effects, with variance-covariance structure set to unstructured. Statistical analysis presented above for Week 78.p-value: 0.34595% CI: [-0.51, 1.45]Mixed-Effects Model Repeated Measures
Comparison: A mixed effects model for repeated measures analysis was used, with the baseline assessment and ApoE4 status as covariates, and visit, treatment and visit by treatment interaction as fixed effects, with variance-covariance structure set to unstructured. Statistical analysis presented above for Week 78.p-value: 0.27495% CI: [-1.58, 0.45]Mixed-Effects Model Repeated Measures
Comparison: A mixed effects model for repeated measures analysis was used, with the baseline assessment and ApoE4 status as covariates, and visit, treatment and visit by treatment interaction as fixed effects, with variance-covariance structure set to unstructured. Statistical analysis presented above for Week 78.p-value: 0.91495% CI: [-0.92, 0.82]Mixed-Effects Model Repeated Measures
Comparison: A mixed effects model for repeated measures analysis was used, with the baseline assessment and ApoE4 status as covariates, and visit, treatment and visit by treatment interaction as fixed effects, with variance-covariance structure set to unstructured. Statistical analysis presented above for Week 104.p-value: 0.092395% CI: [-0.18, 2.24]Mixed-Effects Model Repeated Measures
Comparison: A mixed effects model for repeated measures analysis was used, with the baseline assessment and ApoE4 status as covariates, and visit, treatment and visit by treatment interaction as fixed effects, with variance-covariance structure set to unstructured. Statistical analysis presented above for Week 104.p-value: 0.848295% CI: [-1.11, 1.35]Mixed-Effects Model Repeated Measures
Comparison: A mixed effects model for repeated measures analysis was used, with the baseline assessment and ApoE4 status as covariates, and visit, treatment and visit by treatment interaction as fixed effects, with variance-covariance structure set to unstructured. Statistical analysis presented above for Week 104.p-value: 0.28495% CI: [-0.49, 1.64]Mixed-Effects Model Repeated Measures
Other Pre-specified
Change From Baseline in CSF Aβ x-42
For the majority of the participants, the lumbar puncture for the first CSF sample was collected up to 3 days prior to injection of investigational product. For the participants who had a CSF being already drawn at week 80, no CSF sample was drawn at week 104, nor at ET visit. For those participants who early terminated the study before week 80, CSF was drawn at ET visit.
Time frame: Week 80 or Week 104
Population: FAS population included all randomized participants who had at least one dose of investigational product.
| Arm | Measure | Value (LEAST_SQUARES_MEAN) |
|---|---|---|
| ACC 3 μg+QS-21 | Change From Baseline in CSF Aβ x-42 | 15.29 μg/ml |
| ACC 10 μg+QS-21 | Change From Baseline in CSF Aβ x-42 | 75.55 μg/ml |
| Overall ACC + QS21 | Change From Baseline in CSF Aβ x-42 | 45.42 μg/ml |
| Placebo | Change From Baseline in CSF Aβ x-42 | -8.87 μg/ml |
Comparison: ANCOVA was used with baseline assessment and ApoE4 status as covariates, in addition to treatment included in the ANCOVA model.p-value: 0.581895% CI: [-63.31, 111.62]ANCOVA
Comparison: ANCOVA was used with baseline assessment and ApoE4 status as covariates, in addition to treatment included in the ANCOVA model.p-value: 0.064895% CI: [-5.37, 174.21]ANCOVA
Comparison: ANCOVA was used with baseline assessment and ApoE4 status as covariates, in addition to treatment included in the ANCOVA model.p-value: 0.167295% CI: [-23.47, 132.05]ANCOVA
Other Pre-specified
Change From Baseline in CSF p-Tau
For the majority of the participants, the lumbar puncture for the first CSF sample was collected up to 3 days prior to injection of investigational product. For the participants who had a CSF being already drawn at week 80, no CSF sample was drawn at week 104, nor at ET visit. For those participants who early terminated the study before week 80, CSF was drawn at ET visit.
Time frame: Week 80 or Week 104
Population: FAS population included all randomized participants who had at least one dose of investigational product.
| Arm | Measure | Value (LEAST_SQUARES_MEAN) |
|---|---|---|
| ACC 3 μg+QS-21 | Change From Baseline in CSF p-Tau | -2.32 μg/ml |
| ACC 10 μg+QS-21 | Change From Baseline in CSF p-Tau | -3.47 μg/ml |
| Overall ACC + QS21 | Change From Baseline in CSF p-Tau | -2.90 μg/ml |
| Placebo | Change From Baseline in CSF p-Tau | 1.03 μg/ml |
Comparison: ANCOVA was used with baseline assessment and ApoE4 status as covariates, in addition to treatment included in the ANCOVA model.p-value: 0.310695% CI: [-9.94, 3.22]ANCOVA
Comparison: ANCOVA was used with baseline assessment and ApoE4 status as covariates, in addition to treatment included in the ANCOVA model.p-value: 0.187695% CI: [-11.28, 2.27]ANCOVA
Comparison: ANCOVA was used with baseline assessment and ApoE4 status as covariates, in addition to treatment included in the ANCOVA model.p-value: 0.174295% CI: [-9.66, 1.79]ANCOVA
Other Pre-specified
Change From Baseline in CSF Total Tau
For the majority of the participants, the lumbar puncture for the first CSF sample was collected up to 3 days prior to injection of investigational product. For the participants who had a CSF being already drawn at week 80, no CSF sample was drawn at week 104, nor at ET visit. For those participants who early terminated the study before week 80, CSF was drawn at ET visit.
Time frame: Week 80 or Week 104
Population: FAS population included all randomized participants who had at least one dose of investigational product.
| Arm | Measure | Value (LEAST_SQUARES_MEAN) |
|---|---|---|
| ACC 3 μg+QS-21 | Change From Baseline in CSF Total Tau | 25.56 μg/ml |
| ACC 10 μg+QS-21 | Change From Baseline in CSF Total Tau | -27.48 μg/ml |
| Overall ACC + QS21 | Change From Baseline in CSF Total Tau | -0.96 μg/ml |
| Placebo | Change From Baseline in CSF Total Tau | 55.92 μg/ml |
Comparison: ANCOVA was used with baseline assessment and ApoE4 status as covariates, in addition to treatment included in the ANCOVA model.p-value: 0.408995% CI: [-103.52, 42.81]ANCOVA
Comparison: ANCOVA was used with baseline assessment and ApoE4 status as covariates, in addition to treatment included in the ANCOVA model.p-value: 0.032795% CI: [-159.69, -7.11]ANCOVA
Comparison: ANCOVA was used with baseline assessment and ApoE4 status as covariates, in addition to treatment included in the ANCOVA model.p-value: 0.080195% CI: [-120.82, 7.06]ANCOVA
Other Pre-specified
Change From Baseline in Dependence Scale (DS) Score
An abbreviated administration (first 6 items) of the DS was used in this study. The DS is a brief study partner-completed measure which assesses the degree of support required by a subject with AD. Since the goal of treatment was to delay or arrest the processes leading to increased dependence, the DS represented a meaningful endpoint for clinical studies in AD. The dependence score was derived by summing the first 6 items of the DS. Item 1 and 2 ranged from 0 - 2 and item 3 - 6 ranged from 0 - 1. The total score was calculated by summing the score from each of the 6 items. So the total score could range from 0 - 8, with higher scores indicating greater dependence.
Time frame: 104 weeks
Population: FAS population included all randomized participants who had at least one dose of investigational product.
| Arm | Measure | Group | Value (MEAN) | Dispersion |
|---|---|---|---|---|
| ACC 3 μg+QS-21 | Change From Baseline in Dependence Scale (DS) Score | Week 26 (N: 22, 20 , 20) | 0.1 score | Standard Deviation 1.44 |
| ACC 3 μg+QS-21 | Change From Baseline in Dependence Scale (DS) Score | Week 52 (N: 22, 19 , 20) | -0.2 score | Standard Deviation 1.6 |
| ACC 3 μg+QS-21 | Change From Baseline in Dependence Scale (DS) Score | Week 78 (22, 18, 18) | 0.2 score | Standard Deviation 1.07 |
| ACC 3 μg+QS-21 | Change From Baseline in Dependence Scale (DS) Score | Week 104 (N: 18, 18,15) | 0.9 score | Standard Deviation 2.21 |
| ACC 10 μg+QS-21 | Change From Baseline in Dependence Scale (DS) Score | Week 104 (N: 18, 18,15) | 0.6 score | Standard Deviation 1.58 |
| ACC 10 μg+QS-21 | Change From Baseline in Dependence Scale (DS) Score | Week 26 (N: 22, 20 , 20) | -0.4 score | Standard Deviation 1.39 |
| ACC 10 μg+QS-21 | Change From Baseline in Dependence Scale (DS) Score | Week 78 (22, 18, 18) | 0.3 score | Standard Deviation 1.41 |
| ACC 10 μg+QS-21 | Change From Baseline in Dependence Scale (DS) Score | Week 52 (N: 22, 19 , 20) | 0.2 score | Standard Deviation 1.96 |
| Overall ACC + QS21 | Change From Baseline in Dependence Scale (DS) Score | Week 104 (N: 18, 18,15) | -0.1 score | Standard Deviation 2.07 |
| Overall ACC + QS21 | Change From Baseline in Dependence Scale (DS) Score | Week 52 (N: 22, 19 , 20) | 0.1 score | Standard Deviation 1.86 |
| Overall ACC + QS21 | Change From Baseline in Dependence Scale (DS) Score | Week 78 (22, 18, 18) | -0.2 score | Standard Deviation 1.93 |
| Overall ACC + QS21 | Change From Baseline in Dependence Scale (DS) Score | Week 26 (N: 22, 20 , 20) | 0.0 score | Standard Deviation 1.65 |
Other Pre-specified
Change From Baseline in Functional Activities Questionnaire (FAQ) Total Score
FAQ is a 10-item, caregiver-based questionnaire and was administered to the study partner who was asked to rate the participant's ability to perform a variety of activities ranging from shopping, doing the laundry, simple financial transactions, comprehension of current events, some recreational or avocational activities, and reading. FAQ total score was calculated by adding the scores from each of the 10 items. A negative change indicated an improvement from baseline. FAQ Total Score is the sum of 10 items, ranging from 0 (best possible outcome) to 100 (worst possible outcome).
Time frame: 104 weeks
Population: FAS population included all randomized participants who had at least one dose of investigational product.
| Arm | Measure | Group | Value (LEAST_SQUARES_MEAN) |
|---|---|---|---|
| ACC 3 μg+QS-21 | Change From Baseline in Functional Activities Questionnaire (FAQ) Total Score | Week 26 (N: 22, 20, 42, 19) | 3.45 score |
| ACC 3 μg+QS-21 | Change From Baseline in Functional Activities Questionnaire (FAQ) Total Score | Week 52 (N: 22, 19, 41, 19) | 4.63 score |
| ACC 3 μg+QS-21 | Change From Baseline in Functional Activities Questionnaire (FAQ) Total Score | Week 78 (N: 22, 18, 40, 17) | 5.36 score |
| ACC 3 μg+QS-21 | Change From Baseline in Functional Activities Questionnaire (FAQ) Total Score | Week 104 (N: 18, 18, 36, 14) | 6.90 score |
| ACC 10 μg+QS-21 | Change From Baseline in Functional Activities Questionnaire (FAQ) Total Score | Week 52 (N: 22, 19, 41, 19) | 0.98 score |
| ACC 10 μg+QS-21 | Change From Baseline in Functional Activities Questionnaire (FAQ) Total Score | Week 78 (N: 22, 18, 40, 17) | 2.09 score |
| ACC 10 μg+QS-21 | Change From Baseline in Functional Activities Questionnaire (FAQ) Total Score | Week 104 (N: 18, 18, 36, 14) | 3.11 score |
| ACC 10 μg+QS-21 | Change From Baseline in Functional Activities Questionnaire (FAQ) Total Score | Week 26 (N: 22, 20, 42, 19) | 0.25 score |
| Overall ACC + QS21 | Change From Baseline in Functional Activities Questionnaire (FAQ) Total Score | Week 78 (N: 22, 18, 40, 17) | 3.73 score |
| Overall ACC + QS21 | Change From Baseline in Functional Activities Questionnaire (FAQ) Total Score | Week 52 (N: 22, 19, 41, 19) | 2.81 score |
| Overall ACC + QS21 | Change From Baseline in Functional Activities Questionnaire (FAQ) Total Score | Week 104 (N: 18, 18, 36, 14) | 5.01 score |
| Overall ACC + QS21 | Change From Baseline in Functional Activities Questionnaire (FAQ) Total Score | Week 26 (N: 22, 20, 42, 19) | 1.85 score |
| Placebo | Change From Baseline in Functional Activities Questionnaire (FAQ) Total Score | Week 104 (N: 18, 18, 36, 14) | 4.66 score |
| Placebo | Change From Baseline in Functional Activities Questionnaire (FAQ) Total Score | Week 52 (N: 22, 19, 41, 19) | 2.85 score |
| Placebo | Change From Baseline in Functional Activities Questionnaire (FAQ) Total Score | Week 26 (N: 22, 20, 42, 19) | 1.80 score |
| Placebo | Change From Baseline in Functional Activities Questionnaire (FAQ) Total Score | Week 78 (N: 22, 18, 40, 17) | 4.89 score |
Comparison: A mixed effects model for repeated measures analysis was used, with the baseline assessment and ApoE4 status as covariates, and visit, treatment and visit by treatment interaction as fixed effects, with variance-covariance structure set to unstructured. Statistical analysis presented above for Week 26.p-value: 0.159795% CI: [-0.67, 3.97]Mixed-Effects Model Repeated Measures
Comparison: A mixed effects model for repeated measures analysis was used, with the baseline assessment and ApoE4 status as covariates, and visit, treatment and visit by treatment interaction as fixed effects, with variance-covariance structure set to unstructured. Statistical analysis presented above for Week 26.p-value: 0.21395% CI: [-4.01, 0.91]Mixed-Effects Model Repeated Measures
Comparison: A mixed effects model for repeated measures analysis was used, with the baseline assessment and ApoE4 status as covariates, and visit, treatment and visit by treatment interaction as fixed effects, with variance-covariance structure set to unstructured. Statistical analysis presented above for Week 26.p-value: 0.961695% CI: [-2.06, 2.16]Mixed-Effects Model Repeated Measures
Comparison: A mixed effects model for repeated measures analysis was used, with the baseline assessment and ApoE4 status as covariates, and visit, treatment and visit by treatment interaction as fixed effects, with variance-covariance structure set to unstructured. Statistical analysis presented above for Week 52.p-value: 0.214395% CI: [-1.06, 4.62]Mixed-Effects Model Repeated Measures
Comparison: A mixed effects model for repeated measures analysis was used, with the baseline assessment and ApoE4 status as covariates, and visit, treatment and visit by treatment interaction as fixed effects, with variance-covariance structure set to unstructured. Statistical analysis presented above for Week 52.p-value: 0.215195% CI: [-4.87, 1.12]Mixed-Effects Model Repeated Measures
Comparison: A mixed effects model for repeated measures analysis was used, with the baseline assessment and ApoE4 status as covariates, and visit, treatment and visit by treatment interaction as fixed effects, with variance-covariance structure set to unstructured. Statistical analysis presented above for Week 52.p-value: 0.970495% CI: [-2.61, 2.51]Mixed-Effects Model Repeated Measures
Comparison: A mixed effects model for repeated measures analysis was used, with the baseline assessment and ApoE4 status as covariates, and visit, treatment and visit by treatment interaction as fixed effects, with variance-covariance structure set to unstructured. Statistical analysis presented above for Week 78.p-value: 0.785795% CI: [-3, 3.95]Mixed-Effects Model Repeated Measures
Comparison: A mixed effects model for repeated measures analysis was used, with the baseline assessment and ApoE4 status as covariates, and visit, treatment and visit by treatment interaction as fixed effects, with variance-covariance structure set to unstructured. Statistical analysis presented above for Week 78.p-value: 0.132395% CI: [-6.45, 0.87]Mixed-Effects Model Repeated Measures
Comparison: A mixed effects model for repeated measures analysis was used, with the baseline assessment and ApoE4 status as covariates, and visit, treatment and visit by treatment interaction as fixed effects, with variance-covariance structure set to unstructured. Statistical analysis presented above for Week 78.p-value: 0.461895% CI: [-4.29, 1.97]Mixed-Effects Model Repeated Measures
Comparison: A mixed effects model for repeated measures analysis was used, with the baseline assessment and ApoE4 status as covariates, and visit, treatment and visit by treatment interaction as fixed effects, with variance-covariance structure set to unstructured. Statistical analysis presented above for Week 104.p-value: 0.262295% CI: [-1.74, 6.22]Mixed-Effects Model Repeated Measures
Comparison: A mixed effects model for repeated measures analysis was used, with the baseline assessment and ApoE4 status as covariates, and visit, treatment and visit by treatment interaction as fixed effects, with variance-covariance structure set to unstructured. Statistical analysis presented above for Week 104.p-value: 0.449995% CI: [-5.64, 2.55]Mixed-Effects Model Repeated Measures
Comparison: A mixed effects model for repeated measures analysis was used, with the baseline assessment and ApoE4 status as covariates, and visit, treatment and visit by treatment interaction as fixed effects, with variance-covariance structure set to unstructured. Statistical analysis presented above for Week 104.p-value: 0.845495% CI: [-3.21, 3.91]Mixed-Effects Model Repeated Measures
Other Pre-specified
Change From Baseline in Mini Mental State Examination (MMSE) Total Score
The MMSE is a brief, structured examination of cognitive function consisting of the 11 item: Orientation-What, Orientation-Where, Registration-Objects, Attention and Calculation, Recall, Language-Naming, Language-Repetition, Language-Comprehension, Language-Reading, Language-Writing, and Language- Drawing. MMSE total score was the sum of the 11 item scores and it ranges from 0 to 30 with higher score indicating greater cognitive functioning. If any individual item is missing, then the MMSE total score is set to missing. A positive change indicating an improvement from baseline.
Time frame: 104 weeks
Population: FAS population included all randomized participants who had at least one dose of investigational product.
| Arm | Measure | Group | Value (LEAST_SQUARES_MEAN) |
|---|---|---|---|
| ACC 3 μg+QS-21 | Change From Baseline in Mini Mental State Examination (MMSE) Total Score | Week 26 (N: 22, 20, 42, 20) | -1.06 score |
| ACC 3 μg+QS-21 | Change From Baseline in Mini Mental State Examination (MMSE) Total Score | Week 52 (N: 22, 19, 41, 20) | -2.46 score |
| ACC 3 μg+QS-21 | Change From Baseline in Mini Mental State Examination (MMSE) Total Score | Week 78 (N: 22, 18, 40, 18) | -2.28 score |
| ACC 3 μg+QS-21 | Change From Baseline in Mini Mental State Examination (MMSE) Total Score | Week 104 (N: 19, 18, 37, 15) | -3.55 score |
| ACC 10 μg+QS-21 | Change From Baseline in Mini Mental State Examination (MMSE) Total Score | Week 104 (N: 19, 18, 37, 15) | -1.34 score |
| ACC 10 μg+QS-21 | Change From Baseline in Mini Mental State Examination (MMSE) Total Score | Week 78 (N: 22, 18, 40, 18) | -1.92 score |
| ACC 10 μg+QS-21 | Change From Baseline in Mini Mental State Examination (MMSE) Total Score | Week 52 (N: 22, 19, 41, 20) | -1.54 score |
| ACC 10 μg+QS-21 | Change From Baseline in Mini Mental State Examination (MMSE) Total Score | Week 26 (N: 22, 20, 42, 20) | -1.09 score |
| Overall ACC + QS21 | Change From Baseline in Mini Mental State Examination (MMSE) Total Score | Week 78 (N: 22, 18, 40, 18) | -2.10 score |
| Overall ACC + QS21 | Change From Baseline in Mini Mental State Examination (MMSE) Total Score | Week 104 (N: 19, 18, 37, 15) | -2.45 score |
| Overall ACC + QS21 | Change From Baseline in Mini Mental State Examination (MMSE) Total Score | Week 52 (N: 22, 19, 41, 20) | -2.00 score |
| Overall ACC + QS21 | Change From Baseline in Mini Mental State Examination (MMSE) Total Score | Week 26 (N: 22, 20, 42, 20) | -1.08 score |
| Placebo | Change From Baseline in Mini Mental State Examination (MMSE) Total Score | Week 104 (N: 19, 18, 37, 15) | -2.53 score |
| Placebo | Change From Baseline in Mini Mental State Examination (MMSE) Total Score | Week 26 (N: 22, 20, 42, 20) | -1.10 score |
| Placebo | Change From Baseline in Mini Mental State Examination (MMSE) Total Score | Week 52 (N: 22, 19, 41, 20) | -1.30 score |
| Placebo | Change From Baseline in Mini Mental State Examination (MMSE) Total Score | Week 78 (N: 22, 18, 40, 18) | -1.42 score |
Comparison: A mixed effects model for repeated measures analysis was used, with the baseline assessment and ApoE4 status as covariates, and visit, treatment and visit by treatment interaction as fixed effects, with variance-covariance structure set to unstructured. Statistical analysis presented above for Week 26.p-value: 0.953595% CI: [-1.58, 1.68]Mixed-Effects Model Repeated Measures
Comparison: A mixed effects model for repeated measures analysis was used, with the baseline assessment and ApoE4 status as covariates, and visit, treatment and visit by treatment interaction as fixed effects, with variance-covariance structure set to unstructured. Statistical analysis presented above for Week 26.p-value: 0.991495% CI: [-1.63, 1.65]Mixed-Effects Model Repeated Measures
Comparison: A mixed effects model for repeated measures analysis was used, with the baseline assessment and ApoE4 status as covariates, and visit, treatment and visit by treatment interaction as fixed effects, with variance-covariance structure set to unstructured. Statistical analysis presented above for Week 26.p-value: 0.968295% CI: [-1.39, 1.44]Mixed-Effects Model Repeated Measures
Comparison: A mixed effects model for repeated measures analysis was used, with the baseline assessment and ApoE4 status as covariates, and visit, treatment and visit by treatment interaction as fixed effects, with variance-covariance structure set to unstructured. Statistical analysis presented above for Week 52.p-value: 0.200895% CI: [-2.96, 0.64]Mixed-Effects Model Repeated Measures
Comparison: A mixed effects model for repeated measures analysis was used, with the baseline assessment and ApoE4 status as covariates, and visit, treatment and visit by treatment interaction as fixed effects, with variance-covariance structure set to unstructured. Statistical analysis presented above for Week 52.p-value: 0.798895% CI: [-2.07, 1.6]Mixed-Effects Model Repeated Measures
Comparison: A mixed effects model for repeated measures analysis was used, with the baseline assessment and ApoE4 status as covariates, and visit, treatment and visit by treatment interaction as fixed effects, with variance-covariance structure set to unstructured. Statistical analysis presented above for Week 52.p-value: 0.376495% CI: [-2.27, 0.87]Mixed-Effects Model Repeated Measures
Comparison: A mixed effects model for repeated measures analysis was used, with the baseline assessment and ApoE4 status as covariates, and visit, treatment and visit by treatment interaction as fixed effects, with variance-covariance structure set to unstructured. Statistical analysis presented above for Week 78.p-value: 0.417795% CI: [-2.98, 1.25]Mixed-Effects Model Repeated Measures
Comparison: A mixed effects model for repeated measures analysis was used, with the baseline assessment and ApoE4 status as covariates, and visit, treatment and visit by treatment interaction as fixed effects, with variance-covariance structure set to unstructured. Statistical analysis presented above for Week 78.p-value: 0.649495% CI: [-2.67, 1.68]Mixed-Effects Model Repeated Measures
Comparison: A mixed effects model for repeated measures analysis was used, with the baseline assessment and ApoE4 status as covariates, and visit, treatment and visit by treatment interaction as fixed effects, with variance-covariance structure set to unstructured. Statistical analysis presented above for Week 78.p-value: 0.467495% CI: [-2.54, 1.18]Mixed-Effects Model Repeated Measures
Comparison: A mixed effects model for repeated measures analysis was used, with the baseline assessment and ApoE4 status as covariates, and visit, treatment and visit by treatment interaction as fixed effects, with variance-covariance structure set to unstructured. Statistical analysis presented above for Week 104.p-value: 0.470995% CI: [-3.85, 1.81]Mixed-Effects Model Repeated Measures
Comparison: A mixed effects model for repeated measures analysis was used, with the baseline assessment and ApoE4 status as covariates, and visit, treatment and visit by treatment interaction as fixed effects, with variance-covariance structure set to unstructured. Statistical analysis presented above for Week 104.p-value: 0.412895% CI: [-1.7, 4.07]Mixed-Effects Model Repeated Measures
Comparison: A mixed effects model for repeated measures analysis was used, with the baseline assessment and ApoE4 status as covariates, and visit, treatment and visit by treatment interaction as fixed effects, with variance-covariance structure set to unstructured. Statistical analysis presented above for Week 104.p-value: 0.947895% CI: [-2.41, 2.58]Mixed-Effects Model Repeated Measures
Other Pre-specified
Change From Baseline in Neuropsychiatric Inventory (NPI) Total Score
The NPI scale assesses 12 domains (delusions, hallucinations, agitation, depression, anxiety, euphoria, apathy, disinhibition, irritability, aberrant motor behavior, nighttime behavior, and appetite and eating changes). The symptoms were rated on the basis of questions administered to the study partner. If a preliminary question for each domain was answered as 'Yes', each domain was rated on a 4-point frequency scale and on a 3-point severity scale. If the preliminary question was answered as 'No', the frequency, severity, and distress scales were set to zero. A negative change indicated an improvement from baseline. For each of the 12 domains, a sub-scale score is calculated as frequency\*severity and ranges from 0 to 12. The NPI total score is then calculated by summing the scores of the 12 sub-scale scores. The NPI total scores ranges from 0 to 144 with higher scores indicating greater behavioral impairment. The caregiver distress score is not included in the NPI total score.
Time frame: 104 weeks
Population: FAS population included all randomized participants who had at least one dose of investigational product.
| Arm | Measure | Group | Value (LEAST_SQUARES_MEAN) |
|---|---|---|---|
| ACC 3 μg+QS-21 | Change From Baseline in Neuropsychiatric Inventory (NPI) Total Score | Week 26 (N: 22, 20, 42, 20) | 1.51 score |
| ACC 3 μg+QS-21 | Change From Baseline in Neuropsychiatric Inventory (NPI) Total Score | Week 78 (N: 22, 18, 40, 18) | 2.01 score |
| ACC 3 μg+QS-21 | Change From Baseline in Neuropsychiatric Inventory (NPI) Total Score | Week 104 (N: 18, 18, 36, 15) | 1.38 score |
| ACC 3 μg+QS-21 | Change From Baseline in Neuropsychiatric Inventory (NPI) Total Score | Week 52 (N: 22, 19, 41, 20) | 1.97 score |
| ACC 10 μg+QS-21 | Change From Baseline in Neuropsychiatric Inventory (NPI) Total Score | Week 78 (N: 22, 18, 40, 18) | 1.17 score |
| ACC 10 μg+QS-21 | Change From Baseline in Neuropsychiatric Inventory (NPI) Total Score | Week 52 (N: 22, 19, 41, 20) | 2.44 score |
| ACC 10 μg+QS-21 | Change From Baseline in Neuropsychiatric Inventory (NPI) Total Score | Week 26 (N: 22, 20, 42, 20) | -0.76 score |
| ACC 10 μg+QS-21 | Change From Baseline in Neuropsychiatric Inventory (NPI) Total Score | Week 104 (N: 18, 18, 36, 15) | 1.31 score |
| Overall ACC + QS21 | Change From Baseline in Neuropsychiatric Inventory (NPI) Total Score | Week 52 (N: 22, 19, 41, 20) | 2.21 score |
| Overall ACC + QS21 | Change From Baseline in Neuropsychiatric Inventory (NPI) Total Score | Week 78 (N: 22, 18, 40, 18) | 1.59 score |
| Overall ACC + QS21 | Change From Baseline in Neuropsychiatric Inventory (NPI) Total Score | Week 26 (N: 22, 20, 42, 20) | 0.38 score |
| Overall ACC + QS21 | Change From Baseline in Neuropsychiatric Inventory (NPI) Total Score | Week 104 (N: 18, 18, 36, 15) | 1.34 score |
| Placebo | Change From Baseline in Neuropsychiatric Inventory (NPI) Total Score | Week 52 (N: 22, 19, 41, 20) | 2.65 score |
| Placebo | Change From Baseline in Neuropsychiatric Inventory (NPI) Total Score | Week 104 (N: 18, 18, 36, 15) | 2.08 score |
| Placebo | Change From Baseline in Neuropsychiatric Inventory (NPI) Total Score | Week 78 (N: 22, 18, 40, 18) | 3.34 score |
| Placebo | Change From Baseline in Neuropsychiatric Inventory (NPI) Total Score | Week 26 (N: 22, 20, 42, 20) | 3.50 score |
Comparison: A mixed effects model for repeated measures analysis was used, with the baseline assessment and ApoE4 status as covariates, and visit, treatment and visit by treatment interaction as fixed effects, with variance-covariance structure set to unstructured. Statistical analysis presented above for Week 26.p-value: 0.176795% CI: [-4.9, 0.92]Mixed-Effects Model Repeated Measures
Comparison: A mixed effects model for repeated measures analysis was used, with the baseline assessment and ApoE4 status as covariates, and visit, treatment and visit by treatment interaction as fixed effects, with variance-covariance structure set to unstructured. Statistical analysis presented above for Week 26.p-value: 0.005795% CI: [-7.23, -1.29]Mixed-Effects Model Repeated Measures
Comparison: A mixed effects model for repeated measures analysis was used, with the baseline assessment and ApoE4 status as covariates, and visit, treatment and visit by treatment interaction as fixed effects, with variance-covariance structure set to unstructured. Statistical analysis presented above for Week 26.p-value: 0.017695% CI: [-5.69, -0.57]Mixed-Effects Model Repeated Measures
Comparison: A mixed effects model for repeated measures analysis was used, with the baseline assessment and ApoE4 status as covariates, and visit, treatment and visit by treatment interaction as fixed effects, with variance-covariance structure set to unstructured. Statistical analysis presented above for Week 52.p-value: 0.67995% CI: [-3.98, 2.61]Mixed-Effects Model Repeated Measures
Comparison: A mixed effects model for repeated measures analysis was used, with the baseline assessment and ApoE4 status as covariates, and visit, treatment and visit by treatment interaction as fixed effects, with variance-covariance structure set to unstructured. Statistical analysis presented above for Week 52.p-value: 0.902895% CI: [-3.62, 3.2]Mixed-Effects Model Repeated Measures
Comparison: A mixed effects model for repeated measures analysis was used, with the baseline assessment and ApoE4 status as covariates, and visit, treatment and visit by treatment interaction as fixed effects, with variance-covariance structure set to unstructured. Statistical analysis presented above for Week 52.p-value: 0.7695% CI: [-3.36, 2.47]Mixed-Effects Model Repeated Measures
Comparison: A mixed effects model for repeated measures analysis was used, with the baseline assessment and ApoE4 status as covariates, and visit, treatment and visit by treatment interaction as fixed effects, with variance-covariance structure set to unstructured. Statistical analysis presented above for Week 78.p-value: 0.408995% CI: [-4.51, 1.86]Mixed-Effects Model Repeated Measures
Comparison: A mixed effects model for repeated measures analysis was used, with the baseline assessment and ApoE4 status as covariates, and visit, treatment and visit by treatment interaction as fixed effects, with variance-covariance structure set to unstructured. Statistical analysis presented above for Week 78.p-value: 0.196495% CI: [-5.49, 1.15]Mixed-Effects Model Repeated Measures
Comparison: A mixed effects model for repeated measures analysis was used, with the baseline assessment and ApoE4 status as covariates, and visit, treatment and visit by treatment interaction as fixed effects, with variance-covariance structure set to unstructured. Statistical analysis presented above for Week 78.p-value: 0.223495% CI: [-4.58, 1.09]Mixed-Effects Model Repeated Measures
Comparison: A mixed effects model for repeated measures analysis was used, with the baseline assessment and ApoE4 status as covariates, and visit, treatment and visit by treatment interaction as fixed effects, with variance-covariance structure set to unstructured. Statistical analysis presented above for Week 104.p-value: 0.618695% CI: [-3.52, 2.12]Mixed-Effects Model Repeated Measures
Comparison: A mixed effects model for repeated measures analysis was used, with the baseline assessment and ApoE4 status as covariates, and visit, treatment and visit by treatment interaction as fixed effects, with variance-covariance structure set to unstructured. Statistical analysis presented above for Week 104.p-value: 0.585395% CI: [-3.6, 2.06]Mixed-Effects Model Repeated Measures
Comparison: A mixed effects model for repeated measures analysis was used, with the baseline assessment and ApoE4 status as covariates, and visit, treatment and visit by treatment interaction as fixed effects, with variance-covariance structure set to unstructured. Statistical analysis presented above for Week 104.p-value: 0.554195% CI: [-3.23, 1.75]Mixed-Effects Model Repeated Measures
Other Pre-specified
Change From Baseline in Neuropsychological Test Battery (NTB)
The NTB evaluated cognitive domains that are known to be affected early in the course of Alzheimer's disease (AD). The cognitive tests included in the NTB were: Rey Auditory Verbal Learning Test - Immediate recall, Detection, Identification, Go-No-Go Task, One Back Task, Controlled Oral Word Association Test, Category Fluency Test, and Rey Auditory Verbal Learning Test - delayed recall and recognition. For each of the eight NTB components, an individual z-score was derived based on the primary raw score of each test. Based on the individual z-scores, a composite z-score was derived using the formula: (z1-z2-z3-z4+z5+z6+z7+z8)/8. Positive change indicating an improvement from baseline.
Time frame: 104 weeks
Population: FAS population included all randomized participants who had at least one dose of investigational product.
| Arm | Measure | Group | Value (LEAST_SQUARES_MEAN) |
|---|---|---|---|
| ACC 3 μg+QS-21 | Change From Baseline in Neuropsychological Test Battery (NTB) | Week 26 (N: 20, 20, 40, 19) | -0.14 z-scores |
| ACC 3 μg+QS-21 | Change From Baseline in Neuropsychological Test Battery (NTB) | Week 52 (N: 22, 19, 41, 20) | -0.08 z-scores |
| ACC 3 μg+QS-21 | Change From Baseline in Neuropsychological Test Battery (NTB) | Week 78 (N: 22, 18, 40, 18) | -0.31 z-scores |
| ACC 3 μg+QS-21 | Change From Baseline in Neuropsychological Test Battery (NTB) | Week 104 (N: 18, 18, 36, 15) | -0.42 z-scores |
| ACC 10 μg+QS-21 | Change From Baseline in Neuropsychological Test Battery (NTB) | Week 52 (N: 22, 19, 41, 20) | -0.08 z-scores |
| ACC 10 μg+QS-21 | Change From Baseline in Neuropsychological Test Battery (NTB) | Week 78 (N: 22, 18, 40, 18) | 0.01 z-scores |
| ACC 10 μg+QS-21 | Change From Baseline in Neuropsychological Test Battery (NTB) | Week 104 (N: 18, 18, 36, 15) | -0.12 z-scores |
| ACC 10 μg+QS-21 | Change From Baseline in Neuropsychological Test Battery (NTB) | Week 26 (N: 20, 20, 40, 19) | -0.07 z-scores |
| Overall ACC + QS21 | Change From Baseline in Neuropsychological Test Battery (NTB) | Week 78 (N: 22, 18, 40, 18) | -0.15 z-scores |
| Overall ACC + QS21 | Change From Baseline in Neuropsychological Test Battery (NTB) | Week 52 (N: 22, 19, 41, 20) | -0.08 z-scores |
| Overall ACC + QS21 | Change From Baseline in Neuropsychological Test Battery (NTB) | Week 104 (N: 18, 18, 36, 15) | -0.27 z-scores |
| Overall ACC + QS21 | Change From Baseline in Neuropsychological Test Battery (NTB) | Week 26 (N: 20, 20, 40, 19) | -0.10 z-scores |
| Placebo | Change From Baseline in Neuropsychological Test Battery (NTB) | Week 104 (N: 18, 18, 36, 15) | -0.45 z-scores |
| Placebo | Change From Baseline in Neuropsychological Test Battery (NTB) | Week 52 (N: 22, 19, 41, 20) | -0.06 z-scores |
| Placebo | Change From Baseline in Neuropsychological Test Battery (NTB) | Week 26 (N: 20, 20, 40, 19) | -0.11 z-scores |
| Placebo | Change From Baseline in Neuropsychological Test Battery (NTB) | Week 78 (N: 22, 18, 40, 18) | -0.27 z-scores |
Comparison: A mixed effects model for repeated measures analysis was used, with the baseline assessment and ApoE4 status as covariates, and visit, treatment and visit by treatment interaction as fixed effects, with variance-covariance structure set to unstructured. Statistical analysis presented above for Week 26.p-value: 0.768795% CI: [-0.23, 0.17]Mixed-Effects Model Repeated Measures
Comparison: A mixed effects model for repeated measures analysis was used, with the baseline assessment and ApoE4 status as covariates, and visit, treatment and visit by treatment interaction as fixed effects, with variance-covariance structure set to unstructured. Statistical analysis presented above for Week 26.p-value: 0.680495% CI: [-0.16, 0.24]Mixed-Effects Model Repeated Measures
Comparison: A mixed effects model for repeated measures analysis was used, with the baseline assessment and ApoE4 status as covariates, and visit, treatment and visit by treatment interaction as fixed effects, with variance-covariance structure set to unstructured. Statistical analysis presented above for Week 26.p-value: 0.945295% CI: [-0.17, 0.18]Mixed-Effects Model Repeated Measures
Comparison: A mixed effects model for repeated measures analysis was used, with the baseline assessment and ApoE4 status as covariates, and visit, treatment and visit by treatment interaction as fixed effects, with variance-covariance structure set to unstructured. Statistical analysis presented above for Week 52.p-value: 0.882595% CI: [-0.27, 0.23]Mixed-Effects Model Repeated Measures
Comparison: A mixed effects model for repeated measures analysis was used, with the baseline assessment and ApoE4 status as covariates, and visit, treatment and visit by treatment interaction as fixed effects, with variance-covariance structure set to unstructured. Statistical analysis presented above for Week 52.p-value: 0.879195% CI: [-0.28, 0.24]Mixed-Effects Model Repeated Measures
Comparison: A mixed effects model for repeated measures analysis was used, with the baseline assessment and ApoE4 status as covariates, and visit, treatment and visit by treatment interaction as fixed effects, with variance-covariance structure set to unstructured. Statistical analysis presented above for Week 52.p-value: 0.862895% CI: [-0.24, 0.2]Mixed-Effects Model Repeated Measures
Comparison: A mixed effects model for repeated measures analysis was used, with the baseline assessment and ApoE4 status as covariates, and visit, treatment and visit by treatment interaction as fixed effects, with variance-covariance structure set to unstructured. Statistical analysis presented above for Week 78.p-value: 0.784395% CI: [-0.35, 0.26]Mixed-Effects Model Repeated Measures
Comparison: A mixed effects model for repeated measures analysis was used, with the baseline assessment and ApoE4 status as covariates, and visit, treatment and visit by treatment interaction as fixed effects, with variance-covariance structure set to unstructured. Statistical analysis presented above for Week 78.p-value: 0.085795% CI: [-0.04, 0.6]Mixed-Effects Model Repeated Measures
Comparison: A mixed effects model for repeated measures analysis was used, with the baseline assessment and ApoE4 status as covariates, and visit, treatment and visit by treatment interaction as fixed effects, with variance-covariance structure set to unstructured. Statistical analysis presented above for Week 78.p-value: 0.387895% CI: [-0.15, 0.39]Mixed-Effects Model Repeated Measures
Comparison: A mixed effects model for repeated measures analysis was used, with the baseline assessment and ApoE4 status as covariates, and visit, treatment and visit by treatment interaction as fixed effects, with variance-covariance structure set to unstructured. Statistical analysis presented above for Week 104.p-value: 0.891895% CI: [-0.39, 0.45]Mixed-Effects Model Repeated Measures
Comparison: A mixed effects model for repeated measures analysis was used, with the baseline assessment and ApoE4 status as covariates, and visit, treatment and visit by treatment interaction as fixed effects, with variance-covariance structure set to unstructured. Statistical analysis presented above for Week 104.p-value: 0.123395% CI: [-0.09, 0.76]Mixed-Effects Model Repeated Measures
Comparison: A mixed effects model for repeated measures analysis was used, with the baseline assessment and ApoE4 status as covariates, and visit, treatment and visit by treatment interaction as fixed effects, with variance-covariance structure set to unstructured. Statistical analysis presented above for Week 104.p-value: 0.330295% CI: [-0.19, 0.55]Mixed-Effects Model Repeated Measures
Other Pre-specified
Change From Baseline in NPI Distress Score (NPI-D)
The NPI scale assesses 12 domains (delusions, hallucinations, agitation, depression, anxiety, euphoria, apathy, disinhibition, irritability, aberrant motor behavior, nighttime behavior, and appetite and eating changes). The symptoms were rated on the basis of questions administered to the study partner. For each domain, the study partner also rated his/her own 'emotional or psychological' distress caused by the participant's behavior on a 6-point scale. The study partner NPI-D total score was calculated by summing the scores of the 12 sub-scale distress scores. A negative change indicated an improvement from baseline. The caregiver distress (NPI-D) total score is calculated by summing the scores of the 12 sub-scale distress scores. The NPI-D total scores ranges from 0 to 60 with higher scores indicating greater distress.
Time frame: 104 weeks
Population: FAS population included all randomized participants who had at least one dose of investigational product.
| Arm | Measure | Group | Value (LEAST_SQUARES_MEAN) |
|---|---|---|---|
| ACC 3 μg+QS-21 | Change From Baseline in NPI Distress Score (NPI-D) | Week 26 (N: 22, 20, 42, 20) | 1.49 score |
| ACC 3 μg+QS-21 | Change From Baseline in NPI Distress Score (NPI-D) | Week 52 (N: 22, 19, 41, 20) | 1.54 score |
| ACC 3 μg+QS-21 | Change From Baseline in NPI Distress Score (NPI-D) | Week 78 (N: 22, 18, 40, 18) | 1.45 score |
| ACC 3 μg+QS-21 | Change From Baseline in NPI Distress Score (NPI-D) | Week 104 (N: 18, 18, 36, 15) | 1.73 score |
| ACC 10 μg+QS-21 | Change From Baseline in NPI Distress Score (NPI-D) | Week 52 (N: 22, 19, 41, 20) | 1.24 score |
| ACC 10 μg+QS-21 | Change From Baseline in NPI Distress Score (NPI-D) | Week 78 (N: 22, 18, 40, 18) | 0.44 score |
| ACC 10 μg+QS-21 | Change From Baseline in NPI Distress Score (NPI-D) | Week 104 (N: 18, 18, 36, 15) | 1.76 score |
| ACC 10 μg+QS-21 | Change From Baseline in NPI Distress Score (NPI-D) | Week 26 (N: 22, 20, 42, 20) | 0.42 score |
| Overall ACC + QS21 | Change From Baseline in NPI Distress Score (NPI-D) | Week 78 (N: 22, 18, 40, 18) | 0.95 score |
| Overall ACC + QS21 | Change From Baseline in NPI Distress Score (NPI-D) | Week 52 (N: 22, 19, 41, 20) | 1.39 score |
| Overall ACC + QS21 | Change From Baseline in NPI Distress Score (NPI-D) | Week 104 (N: 18, 18, 36, 15) | 1.74 score |
| Overall ACC + QS21 | Change From Baseline in NPI Distress Score (NPI-D) | Week 26 (N: 22, 20, 42, 20) | 0.95 score |
| Placebo | Change From Baseline in NPI Distress Score (NPI-D) | Week 104 (N: 18, 18, 36, 15) | 1.27 score |
| Placebo | Change From Baseline in NPI Distress Score (NPI-D) | Week 52 (N: 22, 19, 41, 20) | 2.27 score |
| Placebo | Change From Baseline in NPI Distress Score (NPI-D) | Week 26 (N: 22, 20, 42, 20) | 1.57 score |
| Placebo | Change From Baseline in NPI Distress Score (NPI-D) | Week 78 (N: 22, 18, 40, 18) | 2.56 score |
Comparison: A mixed effects model for repeated measures analysis was used, with the baseline assessment and ApoE4 status as covariates, and visit, treatment and visit by treatment interaction as fixed effects, with variance-covariance structure set to unstructured. Statistical analysis presented above for Week 26.p-value: 0.93795% CI: [-2.09, 1.93]Mixed-Effects Model Repeated Measures
Comparison: A mixed effects model for repeated measures analysis was used, with the baseline assessment and ApoE4 status as covariates, and visit, treatment and visit by treatment interaction as fixed effects, with variance-covariance structure set to unstructured. Statistical analysis presented above for Week 26.p-value: 0.259795% CI: [-3.19, 0.88]Mixed-Effects Model Repeated Measures
Comparison: A mixed effects model for repeated measures analysis was used, with the baseline assessment and ApoE4 status as covariates, and visit, treatment and visit by treatment interaction as fixed effects, with variance-covariance structure set to unstructured. Statistical analysis presented above for Week 26.p-value: 0.485295% CI: [-2.38, 1.14]Mixed-Effects Model Repeated Measures
Comparison: A mixed effects model for repeated measures analysis was used, with the baseline assessment and ApoE4 status as covariates, and visit, treatment and visit by treatment interaction as fixed effects, with variance-covariance structure set to unstructured. Statistical analysis presented above for Week 52.p-value: 0.454295% CI: [-2.69, 1.22]Mixed-Effects Model Repeated Measures
Comparison: A mixed effects model for repeated measures analysis was used, with the baseline assessment and ApoE4 status as covariates, and visit, treatment and visit by treatment interaction as fixed effects, with variance-covariance structure set to unstructured. Statistical analysis presented above for Week 52.p-value: 0.306195% CI: [-3.04, 0.97]Mixed-Effects Model Repeated Measures
Comparison: A mixed effects model for repeated measures analysis was used, with the baseline assessment and ApoE4 status as covariates, and visit, treatment and visit by treatment interaction as fixed effects, with variance-covariance structure set to unstructured. Statistical analysis presented above for Week 52.p-value: 0.308295% CI: [-2.61, 0.84]Mixed-Effects Model Repeated Measures
Comparison: A mixed effects model for repeated measures analysis was used, with the baseline assessment and ApoE4 status as covariates, and visit, treatment and visit by treatment interaction as fixed effects, with variance-covariance structure set to unstructured. Statistical analysis presented above for Week 78.p-value: 0.267295% CI: [-3.09, 0.87]Mixed-Effects Model Repeated Measures
Comparison: A mixed effects model for repeated measures analysis was used, with the baseline assessment and ApoE4 status as covariates, and visit, treatment and visit by treatment interaction as fixed effects, with variance-covariance structure set to unstructured. Statistical analysis presented above for Week 78.p-value: 0.042795% CI: [-4.15, -0.07]Mixed-Effects Model Repeated Measures
Comparison: A mixed effects model for repeated measures analysis was used, with the baseline assessment and ApoE4 status as covariates, and visit, treatment and visit by treatment interaction as fixed effects, with variance-covariance structure set to unstructured. Statistical analysis presented above for Week 78.p-value: 0.071695% CI: [-3.37, 0.15]Mixed-Effects Model Repeated Measures
Comparison: A mixed effects model for repeated measures analysis was used, with the baseline assessment and ApoE4 status as covariates, and visit, treatment and visit by treatment interaction as fixed effects, with variance-covariance structure set to unstructured. Statistical analysis presented above for Week 104.p-value: 0.718495% CI: [-2.09, 3]Mixed-Effects Model Repeated Measures
Comparison: A mixed effects model for repeated measures analysis was used, with the baseline assessment and ApoE4 status as covariates, and visit, treatment and visit by treatment interaction as fixed effects, with variance-covariance structure set to unstructured. Statistical analysis presented above for Week 104.p-value: 0.700495% CI: [-2.06, 3.03]Mixed-Effects Model Repeated Measures
Comparison: A mixed effects model for repeated measures analysis was used, with the baseline assessment and ApoE4 status as covariates, and visit, treatment and visit by treatment interaction as fixed effects, with variance-covariance structure set to unstructured. Statistical analysis presented above for Week 104.p-value: 0.672395% CI: [-1.77, 2.71]Mixed-Effects Model Repeated Measures
Other Pre-specified
Change From Baseline in PDQ-R - Relative - Attention/Concentration Domain Score
The PDQ-R is a tool consisting of 20 questions, is designed to assess perceived cognitive deficits, and was administered to the study partner. The instrument assessed a variety of questions in the following areas: attention/concentration, retrospective memory, prospective memory, and planning/organization. The Attention/Concentration Domain Score is the sum of the raw scores on items 1, 5, 9, 13, and 17, with a range from 0 - 4 for each of the 5 items. So the Attention/Concentration Domain Score could range from 0 - 20, with higher scores indicating greater perceived cognitive impairment.
Time frame: 104 weeks
Population: FAS population included all randomized participants who had at least one dose of investigational product.
| Arm | Measure | Group | Value (MEAN) | Dispersion |
|---|---|---|---|---|
| ACC 3 μg+QS-21 | Change From Baseline in PDQ-R - Relative - Attention/Concentration Domain Score | Week 26 (N: 22, 20 , 20) | 2.0 score | Standard Deviation 3.37 |
| ACC 3 μg+QS-21 | Change From Baseline in PDQ-R - Relative - Attention/Concentration Domain Score | Week 52 (N: 22, 19 , 20) | 2.0 score | Standard Deviation 3.43 |
| ACC 3 μg+QS-21 | Change From Baseline in PDQ-R - Relative - Attention/Concentration Domain Score | Week 78 (N: 22, 18, 18) | 2.9 score | Standard Deviation 3.38 |
| ACC 3 μg+QS-21 | Change From Baseline in PDQ-R - Relative - Attention/Concentration Domain Score | Week 104 (N: 17, 18,15) | 3.9 score | Standard Deviation 3.52 |
| ACC 10 μg+QS-21 | Change From Baseline in PDQ-R - Relative - Attention/Concentration Domain Score | Week 104 (N: 17, 18,15) | 1.1 score | Standard Deviation 3.16 |
| ACC 10 μg+QS-21 | Change From Baseline in PDQ-R - Relative - Attention/Concentration Domain Score | Week 26 (N: 22, 20 , 20) | -0.1 score | Standard Deviation 3.85 |
| ACC 10 μg+QS-21 | Change From Baseline in PDQ-R - Relative - Attention/Concentration Domain Score | Week 78 (N: 22, 18, 18) | 0.9 score | Standard Deviation 3.77 |
| ACC 10 μg+QS-21 | Change From Baseline in PDQ-R - Relative - Attention/Concentration Domain Score | Week 52 (N: 22, 19 , 20) | -0.1 score | Standard Deviation 3.85 |
| Overall ACC + QS21 | Change From Baseline in PDQ-R - Relative - Attention/Concentration Domain Score | Week 104 (N: 17, 18,15) | 1.1 score | Standard Deviation 4.16 |
| Overall ACC + QS21 | Change From Baseline in PDQ-R - Relative - Attention/Concentration Domain Score | Week 52 (N: 22, 19 , 20) | 1.8 score | Standard Deviation 2.75 |
| Overall ACC + QS21 | Change From Baseline in PDQ-R - Relative - Attention/Concentration Domain Score | Week 78 (N: 22, 18, 18) | 2.0 score | Standard Deviation 3.14 |
| Overall ACC + QS21 | Change From Baseline in PDQ-R - Relative - Attention/Concentration Domain Score | Week 26 (N: 22, 20 , 20) | 0.9 score | Standard Deviation 2.83 |
Other Pre-specified
Change From Baseline in PDQ-R - Relative - Planning/Organization Domain Score
The PDQ-R is a tool consisting of 20 questions, is designed to assess perceived cognitive deficits, and was administered to the study partner. The instrument assessed a variety of questions in the following areas: attention/concentration, retrospective memory, prospective memory, and planning/organization. The Planning/Organization Domain Score is the sum of the raw scores on items 4, 8, 12, 16, and 20, with a range from 0 - 4 for each of the 5 items. So the Planning/Organization Domain Score could range from 0 - 20, with higher scores indicating greater perceived cognitive impairment.
Time frame: 104 weeks
Population: FAS population included all randomized participants who had at least one dose of investigational product.
| Arm | Measure | Group | Value (MEAN) | Dispersion |
|---|---|---|---|---|
| ACC 3 μg+QS-21 | Change From Baseline in PDQ-R - Relative - Planning/Organization Domain Score | Week 26 (N: 22, 20 , 20) | 1.9 score | Standard Deviation 3.07 |
| ACC 3 μg+QS-21 | Change From Baseline in PDQ-R - Relative - Planning/Organization Domain Score | Week 52 (N: 22, 19 , 20) | 1.7 score | Standard Deviation 3.28 |
| ACC 3 μg+QS-21 | Change From Baseline in PDQ-R - Relative - Planning/Organization Domain Score | Week 78 (N: 22, 18, 18) | 2.5 score | Standard Deviation 0.36 |
| ACC 3 μg+QS-21 | Change From Baseline in PDQ-R - Relative - Planning/Organization Domain Score | Week 104 (N: 18, 18,15) | 2.7 score | Standard Deviation 3.87 |
| ACC 10 μg+QS-21 | Change From Baseline in PDQ-R - Relative - Planning/Organization Domain Score | Week 104 (N: 18, 18,15) | 1.1 score | Standard Deviation 3.9 |
| ACC 10 μg+QS-21 | Change From Baseline in PDQ-R - Relative - Planning/Organization Domain Score | Week 26 (N: 22, 20 , 20) | -0.2 score | Standard Deviation 2.76 |
| ACC 10 μg+QS-21 | Change From Baseline in PDQ-R - Relative - Planning/Organization Domain Score | Week 78 (N: 22, 18, 18) | -0.1 score | Standard Deviation 3.39 |
| ACC 10 μg+QS-21 | Change From Baseline in PDQ-R - Relative - Planning/Organization Domain Score | Week 52 (N: 22, 19 , 20) | 0.3 score | Standard Deviation 4.27 |
| Overall ACC + QS21 | Change From Baseline in PDQ-R - Relative - Planning/Organization Domain Score | Week 104 (N: 18, 18,15) | 1.0 score | Standard Deviation 3.63 |
| Overall ACC + QS21 | Change From Baseline in PDQ-R - Relative - Planning/Organization Domain Score | Week 52 (N: 22, 19 , 20) | 1.7 score | Standard Deviation 2.74 |
| Overall ACC + QS21 | Change From Baseline in PDQ-R - Relative - Planning/Organization Domain Score | Week 78 (N: 22, 18, 18) | 1.9 score | Standard Deviation 2.91 |
| Overall ACC + QS21 | Change From Baseline in PDQ-R - Relative - Planning/Organization Domain Score | Week 26 (N: 22, 20 , 20) | 1.7 score | Standard Deviation 2.8 |
Other Pre-specified
Change From Baseline in PDQ-R - Relative - Prospective Memory Domain Score
The PDQ-R is a tool consisting of 20 questions, is designed to assess perceived cognitive deficits, and was administered to the study partner. The instrument assessed a variety of questions in the following areas: attention/concentration, retrospective memory, prospective memory, and planning/organization. The Prospective Memory Domain Score is the sum of the raw scores on items 3, 7, 11, 15, and 19, with a range from 0 - 4 for each of the 5 items. So the Prospective Memory Domain Score could range from 0 - 20, with higher scores indicating greater perceived cognitive impairment.
Time frame: 104 weeks
Population: FAS population included all randomized participants who had at least one dose of investigational product.
| Arm | Measure | Group | Value (MEAN) | Dispersion |
|---|---|---|---|---|
| ACC 3 μg+QS-21 | Change From Baseline in PDQ-R - Relative - Prospective Memory Domain Score | Week 26 (N: 22, 20 , 20) | 1.0 score | Standard Deviation 2.13 |
| ACC 3 μg+QS-21 | Change From Baseline in PDQ-R - Relative - Prospective Memory Domain Score | Week 52 (N: 22, 19 , 20) | 0.6 score | Standard Deviation 2.22 |
| ACC 3 μg+QS-21 | Change From Baseline in PDQ-R - Relative - Prospective Memory Domain Score | Week 78 (N: 22, 18, 18) | 1.5 score | Standard Deviation 2.37 |
| ACC 3 μg+QS-21 | Change From Baseline in PDQ-R - Relative - Prospective Memory Domain Score | Week 104 (N: 18, 18,15) | 2.6 score | Standard Deviation 2.48 |
| ACC 10 μg+QS-21 | Change From Baseline in PDQ-R - Relative - Prospective Memory Domain Score | Week 104 (N: 18, 18,15) | 0.9 score | Standard Deviation 2.31 |
| ACC 10 μg+QS-21 | Change From Baseline in PDQ-R - Relative - Prospective Memory Domain Score | Week 26 (N: 22, 20 , 20) | -0.4 score | Standard Deviation 2.08 |
| ACC 10 μg+QS-21 | Change From Baseline in PDQ-R - Relative - Prospective Memory Domain Score | Week 78 (N: 22, 18, 18) | 0.2 score | Standard Deviation 2.53 |
| ACC 10 μg+QS-21 | Change From Baseline in PDQ-R - Relative - Prospective Memory Domain Score | Week 52 (N: 22, 19 , 20) | 0.3 score | Standard Deviation 2.51 |
| Overall ACC + QS21 | Change From Baseline in PDQ-R - Relative - Prospective Memory Domain Score | Week 104 (N: 18, 18,15) | 0.5 score | Standard Deviation 3.76 |
| Overall ACC + QS21 | Change From Baseline in PDQ-R - Relative - Prospective Memory Domain Score | Week 52 (N: 22, 19 , 20) | 1.0 score | Standard Deviation 2.86 |
| Overall ACC + QS21 | Change From Baseline in PDQ-R - Relative - Prospective Memory Domain Score | Week 78 (N: 22, 18, 18) | 0.8 score | Standard Deviation 2.92 |
| Overall ACC + QS21 | Change From Baseline in PDQ-R - Relative - Prospective Memory Domain Score | Week 26 (N: 22, 20 , 20) | 1.1 score | Standard Deviation 2.19 |
Other Pre-specified
Change From Baseline in PDQ-R - Relative - Retrospective Memory Domain Score
The PDQ-R is a tool consisting of 20 questions, is designed to assess perceived cognitive deficits, and was administered to the study partner. The instrument assessed a variety of questions in the following areas: attention/concentration, retrospective memory, prospective memory, and planning/organization. The Retrospective Memory Domain Score is the sum of the raw scores on items 2, 6, 10, 14, and 18, with a range from 0 - 4 for each of the 5 items. So the Retrospective Memory Domain Score could range from 0 - 20, with higher scores indicating greater perceived cognitive impairment.
Time frame: 104 weeks
Population: FAS population included all randomized participants who had at least one dose of investigational product.
| Arm | Measure | Group | Value (MEAN) | Dispersion |
|---|---|---|---|---|
| ACC 3 μg+QS-21 | Change From Baseline in PDQ-R - Relative - Retrospective Memory Domain Score | Week 26 (N: 22, 20 , 20) | 1.3 score | Standard Deviation 3.49 |
| ACC 3 μg+QS-21 | Change From Baseline in PDQ-R - Relative - Retrospective Memory Domain Score | Week 52 (N: 22, 19 , 20) | 1.7 score | Standard Deviation 2.95 |
| ACC 3 μg+QS-21 | Change From Baseline in PDQ-R - Relative - Retrospective Memory Domain Score | Week 78 (N: 22, 18, 18) | 2.3 score | Standard Deviation 2.55 |
| ACC 3 μg+QS-21 | Change From Baseline in PDQ-R - Relative - Retrospective Memory Domain Score | Week 104 (N: 18, 18,15) | 3.1 score | Standard Deviation 3.03 |
| ACC 10 μg+QS-21 | Change From Baseline in PDQ-R - Relative - Retrospective Memory Domain Score | Week 104 (N: 18, 18,15) | 1.7 score | Standard Deviation 2.89 |
| ACC 10 μg+QS-21 | Change From Baseline in PDQ-R - Relative - Retrospective Memory Domain Score | Week 26 (N: 22, 20 , 20) | 0.0 score | Standard Deviation 2.83 |
| ACC 10 μg+QS-21 | Change From Baseline in PDQ-R - Relative - Retrospective Memory Domain Score | Week 78 (N: 22, 18, 18) | 1.2 score | Standard Deviation 2.57 |
| ACC 10 μg+QS-21 | Change From Baseline in PDQ-R - Relative - Retrospective Memory Domain Score | Week 52 (N: 22, 19 , 20) | 0.4 score | Standard Deviation 2.55 |
| Overall ACC + QS21 | Change From Baseline in PDQ-R - Relative - Retrospective Memory Domain Score | Week 104 (N: 18, 18,15) | 1.7 score | Standard Deviation 3.99 |
| Overall ACC + QS21 | Change From Baseline in PDQ-R - Relative - Retrospective Memory Domain Score | Week 52 (N: 22, 19 , 20) | 1.4 score | Standard Deviation 2.41 |
| Overall ACC + QS21 | Change From Baseline in PDQ-R - Relative - Retrospective Memory Domain Score | Week 78 (N: 22, 18, 18) | 2.2 score | Standard Deviation 2.09 |
| Overall ACC + QS21 | Change From Baseline in PDQ-R - Relative - Retrospective Memory Domain Score | Week 26 (N: 22, 20 , 20) | 1.8 score | Standard Deviation 2.57 |
Other Pre-specified
Change From Baseline in PDQ-R - Relative - Total Score
The PDQ-R is a tool consisting of 20 questions, is designed to assess perceived cognitive deficits, and was administered to the study partner. The instrument assessed a variety of questions in the following areas: attention/concentration, retrospective memory, prospective memory, and planning/organization. The Total Score is computed by adding raw scores for all of the items (or all 4 domain scores) together. It could range from 0 - 80, with higher scores indicating greater perceived cognitive impairment.
Time frame: 104 weeks
Population: FAS population included all randomized participants who had at least one dose of investigational product.
| Arm | Measure | Group | Value (MEAN) | Dispersion |
|---|---|---|---|---|
| ACC 3 μg+QS-21 | Change From Baseline in PDQ-R - Relative - Total Score | Week 26 (N: 22, 20 , 20) | 6.2 score | Standard Deviation 10.69 |
| ACC 3 μg+QS-21 | Change From Baseline in PDQ-R - Relative - Total Score | Week 52 (N: 22, 19 , 20) | 6.0 score | Standard Deviation 9.91 |
| ACC 3 μg+QS-21 | Change From Baseline in PDQ-R - Relative - Total Score | Week 78 (N: 22, 18, 18) | 9.2 score | Standard Deviation 9.5 |
| ACC 3 μg+QS-21 | Change From Baseline in PDQ-R - Relative - Total Score | Week 104 (N: 17, 18,15) | 12.8 score | Standard Deviation 10.59 |
| ACC 10 μg+QS-21 | Change From Baseline in PDQ-R - Relative - Total Score | Week 104 (N: 17, 18,15) | 4.8 score | Standard Deviation 9.98 |
| ACC 10 μg+QS-21 | Change From Baseline in PDQ-R - Relative - Total Score | Week 26 (N: 22, 20 , 20) | -0.6 score | Standard Deviation 10.37 |
| ACC 10 μg+QS-21 | Change From Baseline in PDQ-R - Relative - Total Score | Week 78 (N: 22, 18, 18) | 2.2 score | Standard Deviation 10.3 |
| ACC 10 μg+QS-21 | Change From Baseline in PDQ-R - Relative - Total Score | Week 52 (N: 22, 19 , 20) | 0.9 score | Standard Deviation 11.65 |
| Overall ACC + QS21 | Change From Baseline in PDQ-R - Relative - Total Score | Week 104 (N: 17, 18,15) | 4.3 score | Standard Deviation 13.68 |
| Overall ACC + QS21 | Change From Baseline in PDQ-R - Relative - Total Score | Week 52 (N: 22, 19 , 20) | 5.7 score | Standard Deviation 7.89 |
| Overall ACC + QS21 | Change From Baseline in PDQ-R - Relative - Total Score | Week 78 (N: 22, 18, 18) | 6.9 score | Standard Deviation 8.9 |
| Overall ACC + QS21 | Change From Baseline in PDQ-R - Relative - Total Score | Week 26 (N: 22, 20 , 20) | 5.4 score | Standard Deviation 8.03 |
Other Pre-specified
Change From Baseline in PDQ - Subject - Planning/Organization Domain Score
The PDQ is a tool consisting of 20 questions and is designed to assess perceived cognitive deficits from the participant's perspective. The instrument assessed a variety of questions in the following areas: attention/concentration, retrospective memory, prospective memory, and planning/organization. The Planning/Organization Domain Score is the sum of the raw scores on items 4, 8, 12, 16, and 20, with a range from 0 - 4 for each of the 5 items. So the Planning/Organization Domain Score could range from 0 - 20, with higher scores indicating greater perceived cognitive impairment.
Time frame: 104 weeks
Population: FAS population included all randomized participants who had at least one dose of investigational product.
| Arm | Measure | Group | Value (MEAN) | Dispersion |
|---|---|---|---|---|
| ACC 3 μg+QS-21 | Change From Baseline in PDQ - Subject - Planning/Organization Domain Score | Week 26 (N: 22, 20 , 20) | 0.3 score | Standard Deviation 3.39 |
| ACC 3 μg+QS-21 | Change From Baseline in PDQ - Subject - Planning/Organization Domain Score | Week 52 (N: 22, 19 , 20) | 0.3 score | Standard Deviation 2.91 |
| ACC 3 μg+QS-21 | Change From Baseline in PDQ - Subject - Planning/Organization Domain Score | Week 78 (N: 22, 18, 18) | 1.0 score | Standard Deviation 3.73 |
| ACC 3 μg+QS-21 | Change From Baseline in PDQ - Subject - Planning/Organization Domain Score | Week 104 (N: 18, 18,15) | 1.6 score | Standard Deviation 3.35 |
| ACC 10 μg+QS-21 | Change From Baseline in PDQ - Subject - Planning/Organization Domain Score | Week 104 (N: 18, 18,15) | 1.0 score | Standard Deviation 2.45 |
| ACC 10 μg+QS-21 | Change From Baseline in PDQ - Subject - Planning/Organization Domain Score | Week 26 (N: 22, 20 , 20) | -0.4 score | Standard Deviation 2.08 |
| ACC 10 μg+QS-21 | Change From Baseline in PDQ - Subject - Planning/Organization Domain Score | Week 78 (N: 22, 18, 18) | 1.2 score | Standard Deviation 1.8 |
| ACC 10 μg+QS-21 | Change From Baseline in PDQ - Subject - Planning/Organization Domain Score | Week 52 (N: 22, 19 , 20) | -0.1 score | Standard Deviation 2.53 |
| Overall ACC + QS21 | Change From Baseline in PDQ - Subject - Planning/Organization Domain Score | Week 104 (N: 18, 18,15) | 1.3 score | Standard Deviation 3.79 |
| Overall ACC + QS21 | Change From Baseline in PDQ - Subject - Planning/Organization Domain Score | Week 52 (N: 22, 19 , 20) | 0.3 score | Standard Deviation 3.26 |
| Overall ACC + QS21 | Change From Baseline in PDQ - Subject - Planning/Organization Domain Score | Week 78 (N: 22, 18, 18) | 0.9 score | Standard Deviation 4.34 |
| Overall ACC + QS21 | Change From Baseline in PDQ - Subject - Planning/Organization Domain Score | Week 26 (N: 22, 20 , 20) | -0.4 score | Standard Deviation 3.05 |
Other Pre-specified
Change From Baseline in PDQ - Subject - Prospective Memory Domain Score
The PDQ is a tool consisting of 20 questions and is designed to assess perceived cognitive deficits from the participant's perspective. The instrument assessed a variety of questions in the following areas: attention/concentration, retrospective memory, prospective memory, and planning/organization. The Prospective Memory Domain Score is the sum of the raw scores on items 3, 7, 11, 15, and 19, with a range from 0 - 4 for each of the 5 items. So the Prospective Memory Domain Score could range from 0 - 20, with higher scores indicating greater perceived cognitive impairment.
Time frame: 104 weeks
Population: FAS population included all randomized participants who had at least one dose of investigational product.
| Arm | Measure | Group | Value (MEAN) | Dispersion |
|---|---|---|---|---|
| ACC 3 μg+QS-21 | Change From Baseline in PDQ - Subject - Prospective Memory Domain Score | Week 26 (N: 22, 20 , 20) | 0.1 score | Standard Deviation 2.65 |
| ACC 3 μg+QS-21 | Change From Baseline in PDQ - Subject - Prospective Memory Domain Score | Week 52 (N: 22, 19 , 20) | 0.4 score | Standard Deviation 2.94 |
| ACC 3 μg+QS-21 | Change From Baseline in PDQ - Subject - Prospective Memory Domain Score | Week 78 (N: 22, 18, 18) | 0.3 score | Standard Deviation 2.51 |
| ACC 3 μg+QS-21 | Change From Baseline in PDQ - Subject - Prospective Memory Domain Score | Week 104 (N: 18, 18,15) | 0.5 score | Standard Deviation 2.66 |
| ACC 10 μg+QS-21 | Change From Baseline in PDQ - Subject - Prospective Memory Domain Score | Week 104 (N: 18, 18,15) | 0.6 score | Standard Deviation 1.94 |
| ACC 10 μg+QS-21 | Change From Baseline in PDQ - Subject - Prospective Memory Domain Score | Week 26 (N: 22, 20 , 20) | -0.1 score | Standard Deviation 2.17 |
| ACC 10 μg+QS-21 | Change From Baseline in PDQ - Subject - Prospective Memory Domain Score | Week 78 (N: 22, 18, 18) | -0.1 score | Standard Deviation 1.43 |
| ACC 10 μg+QS-21 | Change From Baseline in PDQ - Subject - Prospective Memory Domain Score | Week 52 (N: 22, 19 , 20) | 0.1 score | Standard Deviation 1.73 |
| Overall ACC + QS21 | Change From Baseline in PDQ - Subject - Prospective Memory Domain Score | Week 104 (N: 18, 18,15) | 1.3 score | Standard Deviation 3.88 |
| Overall ACC + QS21 | Change From Baseline in PDQ - Subject - Prospective Memory Domain Score | Week 52 (N: 22, 19 , 20) | -0.1 score | Standard Deviation 2.7 |
| Overall ACC + QS21 | Change From Baseline in PDQ - Subject - Prospective Memory Domain Score | Week 78 (N: 22, 18, 18) | 0.9 score | Standard Deviation 2.8 |
| Overall ACC + QS21 | Change From Baseline in PDQ - Subject - Prospective Memory Domain Score | Week 26 (N: 22, 20 , 20) | -0.7 score | Standard Deviation 3.48 |
Other Pre-specified
Change From Baseline in PDQ - Subject - Retrospective Memory Domain Score
The PDQ is a tool consisting of 20 questions and is designed to assess perceived cognitive deficits from the participant's perspective. The instrument assessed a variety of questions in the following areas: attention/concentration, retrospective memory, prospective memory, and planning/organization. The Retrospective Memory Domain Score is the sum of the raw scores on items 2, 6, 10, 14, and 18, with a range from 0 - 4 for each of the 5 items. So the Retrospective Memory Domain Score could range from 0 - 20, with higher scores indicating greater perceived cognitive impairment.
Time frame: 104 weeks
Population: FAS population included all randomized participants who had at least one dose of investigational product.
| Arm | Measure | Group | Value (MEAN) | Dispersion |
|---|---|---|---|---|
| ACC 3 μg+QS-21 | Change From Baseline in PDQ - Subject - Retrospective Memory Domain Score | Week 26 (N: 22, 20 , 20) | 0.5 score | Standard Deviation 3.11 |
| ACC 3 μg+QS-21 | Change From Baseline in PDQ - Subject - Retrospective Memory Domain Score | Week 52 (N: 22, 19 , 20) | 0.0 score | Standard Deviation 2.82 |
| ACC 3 μg+QS-21 | Change From Baseline in PDQ - Subject - Retrospective Memory Domain Score | Week 78 (N: 22, 18, 18) | 1.0 score | Standard Deviation 3.78 |
| ACC 3 μg+QS-21 | Change From Baseline in PDQ - Subject - Retrospective Memory Domain Score | Week 104 (N: 18, 18,15) | 1.6 score | Standard Deviation 3.47 |
| ACC 10 μg+QS-21 | Change From Baseline in PDQ - Subject - Retrospective Memory Domain Score | Week 104 (N: 18, 18,15) | -0.3 score | Standard Deviation 2.59 |
| ACC 10 μg+QS-21 | Change From Baseline in PDQ - Subject - Retrospective Memory Domain Score | Week 26 (N: 22, 20 , 20) | -1.2 score | Standard Deviation 2.89 |
| ACC 10 μg+QS-21 | Change From Baseline in PDQ - Subject - Retrospective Memory Domain Score | Week 78 (N: 22, 18, 18) | 0.1 score | Standard Deviation 2.61 |
| ACC 10 μg+QS-21 | Change From Baseline in PDQ - Subject - Retrospective Memory Domain Score | Week 52 (N: 22, 19 , 20) | 0.2 score | Standard Deviation 2.52 |
| Overall ACC + QS21 | Change From Baseline in PDQ - Subject - Retrospective Memory Domain Score | Week 104 (N: 18, 18,15) | 1.4 score | Standard Deviation 5.03 |
| Overall ACC + QS21 | Change From Baseline in PDQ - Subject - Retrospective Memory Domain Score | Week 52 (N: 22, 19 , 20) | 0.5 score | Standard Deviation 4.12 |
| Overall ACC + QS21 | Change From Baseline in PDQ - Subject - Retrospective Memory Domain Score | Week 78 (N: 22, 18, 18) | 1.2 score | Standard Deviation 4.14 |
| Overall ACC + QS21 | Change From Baseline in PDQ - Subject - Retrospective Memory Domain Score | Week 26 (N: 22, 20 , 20) | 0.4 score | Standard Deviation 4.21 |
Other Pre-specified
Change From Baseline in PDQ - Subject - Total Score
The PDQ is a tool consisting of 20 questions and is designed to assess perceived cognitive deficits from the participant's perspective. The instrument assessed a variety of questions in the following areas: attention/concentration, retrospective memory, prospective memory, and planning/organization. The Total Score is computed by adding raw scores for all of the items (or all 4 domain scores) together. It could range from 0 - 80, with higher scores indicating greater perceived cognitive impairment.
Time frame: 104 weeks
Population: FAS population included all randomized participants who had at least one dose of investigational product.
| Arm | Measure | Group | Value (MEAN) | Dispersion |
|---|---|---|---|---|
| ACC 3 μg+QS-21 | Change From Baseline in PDQ - Subject - Total Score | Week 26 (N: 22, 20 , 20) | 1.4 score | Standard Deviation 10.72 |
| ACC 3 μg+QS-21 | Change From Baseline in PDQ - Subject - Total Score | Week 52 (N: 22, 19 , 20) | 1.5 score | Standard Deviation 8.6 |
| ACC 3 μg+QS-21 | Change From Baseline in PDQ - Subject - Total Score | Week 78 (N: 22, 18, 18) | 3.0 score | Standard Deviation 11.03 |
| ACC 3 μg+QS-21 | Change From Baseline in PDQ - Subject - Total Score | Week 104 (N: 18, 18,15) | 5.2 score | Standard Deviation 10.76 |
| ACC 10 μg+QS-21 | Change From Baseline in PDQ - Subject - Total Score | Week 104 (N: 18, 18,15) | 2.4 score | Standard Deviation 8.36 |
| ACC 10 μg+QS-21 | Change From Baseline in PDQ - Subject - Total Score | Week 26 (N: 22, 20 , 20) | -1.6 score | Standard Deviation 7.54 |
| ACC 10 μg+QS-21 | Change From Baseline in PDQ - Subject - Total Score | Week 78 (N: 22, 18, 18) | 1.2 score | Standard Deviation 6.53 |
| ACC 10 μg+QS-21 | Change From Baseline in PDQ - Subject - Total Score | Week 52 (N: 22, 19 , 20) | 0.2 score | Standard Deviation 7.83 |
| Overall ACC + QS21 | Change From Baseline in PDQ - Subject - Total Score | Week 104 (N: 18, 18,15) | 5.3 score | Standard Deviation 15.63 |
| Overall ACC + QS21 | Change From Baseline in PDQ - Subject - Total Score | Week 52 (N: 22, 19 , 20) | 1.5 score | Standard Deviation 11.6 |
| Overall ACC + QS21 | Change From Baseline in PDQ - Subject - Total Score | Week 78 (N: 22, 18, 18) | 4.4 score | Standard Deviation 13.74 |
| Overall ACC + QS21 | Change From Baseline in PDQ - Subject - Total Score | Week 26 (N: 22, 20 , 20) | -0.3 score | Standard Deviation 12.95 |
Other Pre-specified
Change From Baseline in Perceived Deficits Questionnaire (PDQ) - Subject - Attention/Concentration Domain Score
The PDQ is a tool consisting of 20 questions and is designed to assess perceived cognitive deficits from the participant's perspective. The instrument assessed a variety of questions in the following areas: attention/concentration, retrospective memory, prospective memory, and planning/organization. The Attention/Concentration Domain Score is the sum of the raw scores on items 1, 5, 9, 13 and 17, with a range from 0 - 4 for each of the 5 items. So the Attention/Concentration Domain Score could range from 0 - 20, with higher scores indicating greater perceived cognitive impairment.
Time frame: 104 weeks
Population: FAS population included all randomized participants who had at least one dose of investigational product.
| Arm | Measure | Group | Value (MEAN) | Dispersion |
|---|---|---|---|---|
| ACC 3 μg+QS-21 | Change From Baseline in Perceived Deficits Questionnaire (PDQ) - Subject - Attention/Concentration Domain Score | Week 26 (N: 22, 20 , 20) | 0.5 score | Standard Deviation 3.07 |
| ACC 3 μg+QS-21 | Change From Baseline in Perceived Deficits Questionnaire (PDQ) - Subject - Attention/Concentration Domain Score | Week 52 (N: 22, 19 , 20) | 0.7 score | Standard Deviation 2.41 |
| ACC 3 μg+QS-21 | Change From Baseline in Perceived Deficits Questionnaire (PDQ) - Subject - Attention/Concentration Domain Score | Week 78 (N: 22, 18, 18) | 0.7 score | Standard Deviation 3.27 |
| ACC 3 μg+QS-21 | Change From Baseline in Perceived Deficits Questionnaire (PDQ) - Subject - Attention/Concentration Domain Score | Week 104 (N: 18, 18,15) | 1.6 score | Standard Deviation 3.54 |
| ACC 10 μg+QS-21 | Change From Baseline in Perceived Deficits Questionnaire (PDQ) - Subject - Attention/Concentration Domain Score | Week 104 (N: 18, 18,15) | 1.1 score | Standard Deviation 3.14 |
| ACC 10 μg+QS-21 | Change From Baseline in Perceived Deficits Questionnaire (PDQ) - Subject - Attention/Concentration Domain Score | Week 26 (N: 22, 20 , 20) | 0.1 score | Standard Deviation 2.95 |
| ACC 10 μg+QS-21 | Change From Baseline in Perceived Deficits Questionnaire (PDQ) - Subject - Attention/Concentration Domain Score | Week 78 (N: 22, 18, 18) | -0.1 score | Standard Deviation 2.83 |
| ACC 10 μg+QS-21 | Change From Baseline in Perceived Deficits Questionnaire (PDQ) - Subject - Attention/Concentration Domain Score | Week 52 (N: 22, 19 , 20) | -0.1 score | Standard Deviation 2.91 |
| Overall ACC + QS21 | Change From Baseline in Perceived Deficits Questionnaire (PDQ) - Subject - Attention/Concentration Domain Score | Week 104 (N: 18, 18,15) | 1.3 score | Standard Deviation 3.79 |
| Overall ACC + QS21 | Change From Baseline in Perceived Deficits Questionnaire (PDQ) - Subject - Attention/Concentration Domain Score | Week 52 (N: 22, 19 , 20) | 0.7 score | Standard Deviation 3.34 |
| Overall ACC + QS21 | Change From Baseline in Perceived Deficits Questionnaire (PDQ) - Subject - Attention/Concentration Domain Score | Week 78 (N: 22, 18, 18) | 1.4 score | Standard Deviation 3.66 |
| Overall ACC + QS21 | Change From Baseline in Perceived Deficits Questionnaire (PDQ) - Subject - Attention/Concentration Domain Score | Week 26 (N: 22, 20 , 20) | 0.5 score | Standard Deviation 3.49 |
Other Pre-specified
Change From Baseline in Plasma Aβ x-40
Site personnel collecting the samples for plasma Aβ (x-40) concentrations and the results were blinded to the participant treatment group assignment.
Time frame: 104 weeks
Population: FAS population included all randomized participants who had at least one dose of investigational product.
| Arm | Measure | Group | Value (LEAST_SQUARES_MEAN) |
|---|---|---|---|
| ACC 3 μg+QS-21 | Change From Baseline in Plasma Aβ x-40 | Week 26 (N: 22, 18, 40, 19) | 150.51 pg/mL |
| ACC 3 μg+QS-21 | Change From Baseline in Plasma Aβ x-40 | Week 12 (N: 22, 19, 41, 20) | 30.42 pg/mL |
| ACC 3 μg+QS-21 | Change From Baseline in Plasma Aβ x-40 | Week 52 (N: 22, 18, 40, 19) | 252.87 pg/mL |
| ACC 3 μg+QS-21 | Change From Baseline in Plasma Aβ x-40 | Week 104 (N: 18, 17, 35, 13) | 216.51 pg/mL |
| ACC 3 μg+QS-21 | Change From Baseline in Plasma Aβ x-40 | Week 78 (N: 22, 17, 39, 17) | 225.15 pg/mL |
| ACC 10 μg+QS-21 | Change From Baseline in Plasma Aβ x-40 | Week 78 (N: 22, 17, 39, 17) | 344.13 pg/mL |
| ACC 10 μg+QS-21 | Change From Baseline in Plasma Aβ x-40 | Week 12 (N: 22, 19, 41, 20) | 61.70 pg/mL |
| ACC 10 μg+QS-21 | Change From Baseline in Plasma Aβ x-40 | Week 26 (N: 22, 18, 40, 19) | 276.86 pg/mL |
| ACC 10 μg+QS-21 | Change From Baseline in Plasma Aβ x-40 | Week 52 (N: 22, 18, 40, 19) | 313.34 pg/mL |
| ACC 10 μg+QS-21 | Change From Baseline in Plasma Aβ x-40 | Week 104 (N: 18, 17, 35, 13) | 279.00 pg/mL |
| Overall ACC + QS21 | Change From Baseline in Plasma Aβ x-40 | Week 104 (N: 18, 17, 35, 13) | 247.76 pg/mL |
| Overall ACC + QS21 | Change From Baseline in Plasma Aβ x-40 | Week 52 (N: 22, 18, 40, 19) | 283.11 pg/mL |
| Overall ACC + QS21 | Change From Baseline in Plasma Aβ x-40 | Week 78 (N: 22, 17, 39, 17) | 284.64 pg/mL |
| Overall ACC + QS21 | Change From Baseline in Plasma Aβ x-40 | Week 12 (N: 22, 19, 41, 20) | 46.06 pg/mL |
| Overall ACC + QS21 | Change From Baseline in Plasma Aβ x-40 | Week 26 (N: 22, 18, 40, 19) | 213.68 pg/mL |
| Placebo | Change From Baseline in Plasma Aβ x-40 | Week 78 (N: 22, 17, 39, 17) | 117.31 pg/mL |
| Placebo | Change From Baseline in Plasma Aβ x-40 | Week 26 (N: 22, 18, 40, 19) | 51.22 pg/mL |
| Placebo | Change From Baseline in Plasma Aβ x-40 | Week 52 (N: 22, 18, 40, 19) | 138.74 pg/mL |
| Placebo | Change From Baseline in Plasma Aβ x-40 | Week 12 (N: 22, 19, 41, 20) | 10.64 pg/mL |
| Placebo | Change From Baseline in Plasma Aβ x-40 | Week 104 (N: 18, 17, 35, 13) | 74.60 pg/mL |
Comparison: A mixed effects model for repeated measures analysis was used, with the baseline assessment and ApoE4 status as covariates, and visit, treatment and visit by treatment interaction as fixed effects, with variance-covariance structure set to unstructured. Statistical analysis presented above for Week 12.p-value: 0.489295% CI: [-37.15, 76.71]Mixed-Effects Model Repeated Measures
Comparison: A mixed effects model for repeated measures analysis was used, with the baseline assessment and ApoE4 status as covariates, and visit, treatment and visit by treatment interaction as fixed effects, with variance-covariance structure set to unstructured. Statistical analysis presented above for Week 12.p-value: 0.091595% CI: [-8.51, 110.63]Mixed-Effects Model Repeated Measures
Comparison: A mixed effects model for repeated measures analysis was used, with the baseline assessment and ApoE4 status as covariates, and visit, treatment and visit by treatment interaction as fixed effects, with variance-covariance structure set to unstructured. Statistical analysis presented above for Week 12.p-value: 0.163895% CI: [-14.88, 85.72]Mixed-Effects Model Repeated Measures
Comparison: A mixed effects model for repeated measures analysis was used, with the baseline assessment and ApoE4 status as covariates, and visit, treatment and visit by treatment interaction as fixed effects, with variance-covariance structure set to unstructured. Statistical analysis presented above for Week 26.p-value: 0.200695% CI: [-54.28, 252.86]Mixed-Effects Model Repeated Measures
Comparison: A mixed effects model for repeated measures analysis was used, with the baseline assessment and ApoE4 status as covariates, and visit, treatment and visit by treatment interaction as fixed effects, with variance-covariance structure set to unstructured. Statistical analysis presented above for Week 26.p-value: 0.006795% CI: [65.18, 386.09]Mixed-Effects Model Repeated Measures
Comparison: A mixed effects model for repeated measures analysis was used, with the baseline assessment and ApoE4 status as covariates, and visit, treatment and visit by treatment interaction as fixed effects, with variance-covariance structure set to unstructured. Statistical analysis presented above for Week 26.p-value: 0.020495% CI: [26.05, 298.87]Mixed-Effects Model Repeated Measures
Comparison: A mixed effects model for repeated measures analysis was used, with the baseline assessment and ApoE4 status as covariates, and visit, treatment and visit by treatment interaction as fixed effects, with variance-covariance structure set to unstructured. Statistical analysis presented above for Week 52.p-value: 0.076695% CI: [-12.63, 240.89]Mixed-Effects Model Repeated Measures
Comparison: A mixed effects model for repeated measures analysis was used, with the baseline assessment and ApoE4 status as covariates, and visit, treatment and visit by treatment interaction as fixed effects, with variance-covariance structure set to unstructured. Statistical analysis presented above for Week 52.p-value: 0.018195% CI: [40.23, 413.41]Mixed-Effects Model Repeated Measures
Comparison: A mixed effects model for repeated measures analysis was used, with the baseline assessment and ApoE4 status as covariates, and visit, treatment and visit by treatment interaction as fixed effects, with variance-covariance structure set to unstructured. Statistical analysis presented above for Week 52.p-value: 0.038795% CI: [9.03, 325.63]Mixed-Effects Model Repeated Measures
Comparison: A mixed effects model for repeated measures analysis was used, with the baseline assessment and ApoE4 status as covariates, and visit, treatment and visit by treatment interaction as fixed effects, with variance-covariance structure set to unstructured. Statistical analysis presented above for Week 78.p-value: 0.227795% CI: [-69.29, 284.97]Mixed-Effects Model Repeated Measures
Comparison: A mixed effects model for repeated measures analysis was used, with the baseline assessment and ApoE4 status as covariates, and visit, treatment and visit by treatment interaction as fixed effects, with variance-covariance structure set to unstructured. Statistical analysis presented above for Week 78.p-value: 0.018195% CI: [40.23, 413.41]Mixed-Effects Model Repeated Measures
Comparison: A mixed effects model for repeated measures analysis was used, with the baseline assessment and ApoE4 status as covariates, and visit, treatment and visit by treatment interaction as fixed effects, with variance-covariance structure set to unstructured. Statistical analysis presented above for Week 78.p-value: 0.038795% CI: [9.03, 325.63]Mixed-Effects Model Repeated Measures
Comparison: A mixed effects model for repeated measures analysis was used, with the baseline assessment and ApoE4 status as covariates, and visit, treatment and visit by treatment interaction as fixed effects, with variance-covariance structure set to unstructured. Statistical analysis presented above for Week 104.p-value: 0.074795% CI: [-14.62, 298.45]Mixed-Effects Model Repeated Measures
Comparison: A mixed effects model for repeated measures analysis was used, with the baseline assessment and ApoE4 status as covariates, and visit, treatment and visit by treatment interaction as fixed effects, with variance-covariance structure set to unstructured. Statistical analysis presented above for Week 104.p-value: 0.015195% CI: [41.02, 367.79]Mixed-Effects Model Repeated Measures
Comparison: A mixed effects model for repeated measures analysis was used, with the baseline assessment and ApoE4 status as covariates, and visit, treatment and visit by treatment interaction as fixed effects, with variance-covariance structure set to unstructured. Statistical analysis presented above for Week 104.p-value: 0.016195% CI: [33.25, 313.07]Mixed-Effects Model Repeated Measures
Other Pre-specified
Change From Baseline in Resource Utilization in Dementia (RUD) (Abbreviated) (RUD-Lite) - Primary Caregiver
An abbreviated administration of the RUD (RUD-Lite) was used. The RUD-Lite is a comprehensive tool for addressing the magnitude and nature of study partner/caregiver effort in cases of dementia. Since a significant portion of care in Alzheimer's related-dementia was performed informally by the participant's friends or family, it was desirable to measure the extent of this care for use in economic evaluations of disease. The total time spent by the primary caregiver providing support on activities of daily living (ADL), instrumental activities of daily living (IADL) and supervising, respectively, was calculated in two components. Total number of days spent during the past month on each of ADL, IADL, and supervising; and: time per day during the past month on each of ADL, IADL and supervising. The total Primary Caregiver Time per month could range from 0 - 720. This was calculated by multiplying the number of days per month (30) by the number of hours per day (24).
Time frame: 104 weeks
Population: FAS population included all randomized participants who had at least one dose of investigational product.
| Arm | Measure | Group | Value (LEAST_SQUARES_MEAN) |
|---|---|---|---|
| ACC 3 μg+QS-21 | Change From Baseline in Resource Utilization in Dementia (RUD) (Abbreviated) (RUD-Lite) - Primary Caregiver | Week 26 (N: 22, 20, 20) | 3.97 hours |
| ACC 3 μg+QS-21 | Change From Baseline in Resource Utilization in Dementia (RUD) (Abbreviated) (RUD-Lite) - Primary Caregiver | Week 52 (N: 22, 19, 20) | 16.76 hours |
| ACC 3 μg+QS-21 | Change From Baseline in Resource Utilization in Dementia (RUD) (Abbreviated) (RUD-Lite) - Primary Caregiver | Week 78 (N: 22, 18, 18) | 30.80 hours |
| ACC 3 μg+QS-21 | Change From Baseline in Resource Utilization in Dementia (RUD) (Abbreviated) (RUD-Lite) - Primary Caregiver | Week 104 (N: 18, 18, 15) | 36.36 hours |
| ACC 10 μg+QS-21 | Change From Baseline in Resource Utilization in Dementia (RUD) (Abbreviated) (RUD-Lite) - Primary Caregiver | Week 104 (N: 18, 18, 15) | -5.88 hours |
| ACC 10 μg+QS-21 | Change From Baseline in Resource Utilization in Dementia (RUD) (Abbreviated) (RUD-Lite) - Primary Caregiver | Week 26 (N: 22, 20, 20) | -6.05 hours |
| ACC 10 μg+QS-21 | Change From Baseline in Resource Utilization in Dementia (RUD) (Abbreviated) (RUD-Lite) - Primary Caregiver | Week 78 (N: 22, 18, 18) | -3.23 hours |
| ACC 10 μg+QS-21 | Change From Baseline in Resource Utilization in Dementia (RUD) (Abbreviated) (RUD-Lite) - Primary Caregiver | Week 52 (N: 22, 19, 20) | -7.97 hours |
| Overall ACC + QS21 | Change From Baseline in Resource Utilization in Dementia (RUD) (Abbreviated) (RUD-Lite) - Primary Caregiver | Week 104 (N: 18, 18, 15) | 20.31 hours |
| Overall ACC + QS21 | Change From Baseline in Resource Utilization in Dementia (RUD) (Abbreviated) (RUD-Lite) - Primary Caregiver | Week 52 (N: 22, 19, 20) | 21.73 hours |
| Overall ACC + QS21 | Change From Baseline in Resource Utilization in Dementia (RUD) (Abbreviated) (RUD-Lite) - Primary Caregiver | Week 78 (N: 22, 18, 18) | 61.74 hours |
| Overall ACC + QS21 | Change From Baseline in Resource Utilization in Dementia (RUD) (Abbreviated) (RUD-Lite) - Primary Caregiver | Week 26 (N: 22, 20, 20) | 6.47 hours |
Comparison: A mixed effects model for repeated measures analysis was used, with the baseline assessment and ApoE4 status as covariates, and visit, treatment and visit by treatment interaction as fixed effects, with variance-covariance structure set to unstructured. Statistical analysis presented above for Week 26.p-value: 0.753795% CI: [-18.36, 13.36]Mixed-Effects Model Repeated Measures
Comparison: A mixed effects model for repeated measures analysis was used, with the baseline assessment and ApoE4 status as covariates, and visit, treatment and visit by treatment interaction as fixed effects, with variance-covariance structure set to unstructured. Statistical analysis presented above for Week 26.p-value: 0.126695% CI: [-28.86, 3.65]Mixed-Effects Model Repeated Measures
Comparison: A mixed effects model for repeated measures analysis was used, with the baseline assessment and ApoE4 status as covariates, and visit, treatment and visit by treatment interaction as fixed effects, with variance-covariance structure set to unstructured. Statistical analysis presented above for Week 52.p-value: 0.672495% CI: [-28.34, 18.41]Mixed-Effects Model Repeated Measures
Comparison: A mixed effects model for repeated measures analysis was used, with the baseline assessment and ApoE4 status as covariates, and visit, treatment and visit by treatment interaction as fixed effects, with variance-covariance structure set to unstructured. Statistical analysis presented above for Week 52.p-value: 0.01795% CI: [-53.89, -5.5]Mixed-Effects Model Repeated Measures
Comparison: A mixed effects model for repeated measures analysis was used, with the baseline assessment and ApoE4 status as covariates, and visit, treatment and visit by treatment interaction as fixed effects, with variance-covariance structure set to unstructured. Statistical analysis presented above for Week 78.p-value: 0.319695% CI: [-92.67, 30.78]Mixed-Effects Model Repeated Measures
Comparison: A mixed effects model for repeated measures analysis was used, with the baseline assessment and ApoE4 status as covariates, and visit, treatment and visit by treatment interaction as fixed effects, with variance-covariance structure set to unstructured. Statistical analysis presented above for Week 78.p-value: 0.04995% CI: [-129.64, -0.31]Mixed-Effects Model Repeated Measures
Comparison: A mixed effects model for repeated measures analysis was used, with the baseline assessment and ApoE4 status as covariates, and visit, treatment and visit by treatment interaction as fixed effects, with variance-covariance structure set to unstructured. Statistical analysis presented above for Week 104.p-value: 0.296995% CI: [-14.7, 46.79]Mixed-Effects Model Repeated Measures
Comparison: A mixed effects model for repeated measures analysis was used, with the baseline assessment and ApoE4 status as covariates, and visit, treatment and visit by treatment interaction as fixed effects, with variance-covariance structure set to unstructured. Statistical analysis presented above for Week 104.p-value: 0.097395% CI: [-57.42, 5.03]Mixed-Effects Model Repeated Measures
Other Pre-specified
Change From Baseline in RUD (Abbreviated) (RUD-Lite) - Other Caregivers
An abbreviated administration of the RUD (RUD-Lite) was used. The RUD-Lite is a comprehensive tool for addressing the magnitude and nature of study partner/caregiver effort in cases of dementia. Since a significant portion of care in Alzheimer's related-dementia was performed informally by the participant's friends or family, it was desirable to measure the extent of this care for use in economic evaluations of disease. The total time spent by the other caregivers providing support on ADL, IADL and supervising, respectively, was calculated in two components. Total number of days spent during the past month on each of ADL, IADL and supervising; and: time per day during the past month on each of ADL, IADL, and supervising. The total Other Caregiver Time per month could range from 0 - 720. This was calculated by multiplying the number of days per month (30) by the number of hours per day (24).
Time frame: 104 weeks
Population: FAS population included all randomized participants who had at least one dose of investigational product.
| Arm | Measure | Group | Value (LEAST_SQUARES_MEAN) |
|---|---|---|---|
| ACC 3 μg+QS-21 | Change From Baseline in RUD (Abbreviated) (RUD-Lite) - Other Caregivers | Week 26 (N: 22, 20, 20) | 0.14 hours |
| ACC 3 μg+QS-21 | Change From Baseline in RUD (Abbreviated) (RUD-Lite) - Other Caregivers | Week 52 (N: 22, 19, 20) | 0.72 hours |
| ACC 3 μg+QS-21 | Change From Baseline in RUD (Abbreviated) (RUD-Lite) - Other Caregivers | Week 78 (N: 22, 18, 18) | 0.86 hours |
| ACC 3 μg+QS-21 | Change From Baseline in RUD (Abbreviated) (RUD-Lite) - Other Caregivers | Week 104 (N: 18, 18, 15) | 2.13 hours |
| ACC 10 μg+QS-21 | Change From Baseline in RUD (Abbreviated) (RUD-Lite) - Other Caregivers | Week 104 (N: 18, 18, 15) | 1.58 hours |
| ACC 10 μg+QS-21 | Change From Baseline in RUD (Abbreviated) (RUD-Lite) - Other Caregivers | Week 26 (N: 22, 20, 20) | 4.03 hours |
| ACC 10 μg+QS-21 | Change From Baseline in RUD (Abbreviated) (RUD-Lite) - Other Caregivers | Week 78 (N: 22, 18, 18) | 0.79 hours |
| ACC 10 μg+QS-21 | Change From Baseline in RUD (Abbreviated) (RUD-Lite) - Other Caregivers | Week 52 (N: 22, 19, 20) | 3.03 hours |
| Overall ACC + QS21 | Change From Baseline in RUD (Abbreviated) (RUD-Lite) - Other Caregivers | Week 104 (N: 18, 18, 15) | 9.64 hours |
| Overall ACC + QS21 | Change From Baseline in RUD (Abbreviated) (RUD-Lite) - Other Caregivers | Week 52 (N: 22, 19, 20) | 0.01 hours |
| Overall ACC + QS21 | Change From Baseline in RUD (Abbreviated) (RUD-Lite) - Other Caregivers | Week 78 (N: 22, 18, 18) | 0.06 hours |
| Overall ACC + QS21 | Change From Baseline in RUD (Abbreviated) (RUD-Lite) - Other Caregivers | Week 26 (N: 22, 20, 20) | 1.56 hours |
Comparison: A mixed effects model for repeated measures analysis was used, with the baseline assessment and ApoE4 status as covariates, and visit, treatment and visit by treatment interaction as fixed effects, with variance-covariance structure set to unstructured. Statistical analysis presented above for Week 26.p-value: 0.665395% CI: [-7.94, 5.1]Mixed-Effects Model Repeated Measures
Comparison: A mixed effects model for repeated measures analysis was used, with the baseline assessment and ApoE4 status as covariates, and visit, treatment and visit by treatment interaction as fixed effects, with variance-covariance structure set to unstructured. Statistical analysis presented above for Week 26.p-value: 0.461395% CI: [-4.2, 9.15]Mixed-Effects Model Repeated Measures
Comparison: A mixed effects model for repeated measures analysis was used, with the baseline assessment and ApoE4 status as covariates, and visit, treatment and visit by treatment interaction as fixed effects, with variance-covariance structure set to unstructured. Statistical analysis presented above for Week 52.p-value: 0.77195% CI: [-4.18, 5.61]Mixed-Effects Model Repeated Measures
Comparison: A mixed effects model for repeated measures analysis was used, with the baseline assessment and ApoE4 status as covariates, and visit, treatment and visit by treatment interaction as fixed effects, with variance-covariance structure set to unstructured. Statistical analysis presented above for Week 52.p-value: 0.232895% CI: [-1.99, 8.04]Mixed-Effects Model Repeated Measures
Comparison: A mixed effects model for repeated measures analysis was used, with the baseline assessment and ApoE4 status as covariates, and visit, treatment and visit by treatment interaction as fixed effects, with variance-covariance structure set to unstructured. Statistical analysis presented above for Week 78.p-value: 0.369395% CI: [-0.97, 2.58]Mixed-Effects Model Repeated Measures
Comparison: A mixed effects model for repeated measures analysis was used, with the baseline assessment and ApoE4 status as covariates, and visit, treatment and visit by treatment interaction as fixed effects, with variance-covariance structure set to unstructured. Statistical analysis presented above for Week 78.p-value: 0.42295% CI: [-1.09, 2.56]Mixed-Effects Model Repeated Measures
Comparison: A mixed effects model for repeated measures analysis was used, with the baseline assessment and ApoE4 status as covariates, and visit, treatment and visit by treatment interaction as fixed effects, with variance-covariance structure set to unstructured. Statistical analysis presented above for Week 104.p-value: 0.372895% CI: [-24.25, 9.23]Mixed-Effects Model Repeated Measures
Comparison: A mixed effects model for repeated measures analysis was used, with the baseline assessment and ApoE4 status as covariates, and visit, treatment and visit by treatment interaction as fixed effects, with variance-covariance structure set to unstructured. Statistical analysis presented above for Week 104.p-value: 0.345295% CI: [-25.05, 8.91]Mixed-Effects Model Repeated Measures
Other Pre-specified
Change From Baseline in Volumetric Brain Magnetic Resonance Imaging (MRI) Measurements in Brain Boundary Shift Integral (BBSI)
BBSI measures whole brain atrophy from registered MRI scan pairs, by subtracting the area under the intensity profile across a boundary in the repeat scans from the initial scan (baseline).
Time frame: 104 weeks
Population: FAS population included all randomized participants who had at least one dose of investigational product.
| Arm | Measure | Group | Value (LEAST_SQUARES_MEAN) |
|---|---|---|---|
| ACC 3 μg+QS-21 | Change From Baseline in Volumetric Brain Magnetic Resonance Imaging (MRI) Measurements in Brain Boundary Shift Integral (BBSI) | Week 76 (N: 21, 17, 38, 15) | -16.579 mL |
| ACC 3 μg+QS-21 | Change From Baseline in Volumetric Brain Magnetic Resonance Imaging (MRI) Measurements in Brain Boundary Shift Integral (BBSI) | Week 24 (N: 22, 20, 42, 21) | -6.080 mL |
| ACC 3 μg+QS-21 | Change From Baseline in Volumetric Brain Magnetic Resonance Imaging (MRI) Measurements in Brain Boundary Shift Integral (BBSI) | Week 104 (N: 18, 16, 34, 14) | -20.982 mL |
| ACC 3 μg+QS-21 | Change From Baseline in Volumetric Brain Magnetic Resonance Imaging (MRI) Measurements in Brain Boundary Shift Integral (BBSI) | Week 50 (N: 22, 19, 41, 18) | -12.329 mL |
| ACC 3 μg+QS-21 | Change From Baseline in Volumetric Brain Magnetic Resonance Imaging (MRI) Measurements in Brain Boundary Shift Integral (BBSI) | Week 10 (N: 22, 20, 42, 20) | -4.100 mL |
| ACC 10 μg+QS-21 | Change From Baseline in Volumetric Brain Magnetic Resonance Imaging (MRI) Measurements in Brain Boundary Shift Integral (BBSI) | Week 50 (N: 22, 19, 41, 18) | -5.926 mL |
| ACC 10 μg+QS-21 | Change From Baseline in Volumetric Brain Magnetic Resonance Imaging (MRI) Measurements in Brain Boundary Shift Integral (BBSI) | Week 76 (N: 21, 17, 38, 15) | -10.802 mL |
| ACC 10 μg+QS-21 | Change From Baseline in Volumetric Brain Magnetic Resonance Imaging (MRI) Measurements in Brain Boundary Shift Integral (BBSI) | Week 104 (N: 18, 16, 34, 14) | -12.662 mL |
| ACC 10 μg+QS-21 | Change From Baseline in Volumetric Brain Magnetic Resonance Imaging (MRI) Measurements in Brain Boundary Shift Integral (BBSI) | Week 24 (N: 22, 20, 42, 21) | -2.357 mL |
| ACC 10 μg+QS-21 | Change From Baseline in Volumetric Brain Magnetic Resonance Imaging (MRI) Measurements in Brain Boundary Shift Integral (BBSI) | Week 10 (N: 22, 20, 42, 20) | -0.952 mL |
| Overall ACC + QS21 | Change From Baseline in Volumetric Brain Magnetic Resonance Imaging (MRI) Measurements in Brain Boundary Shift Integral (BBSI) | Week 50 (N: 22, 19, 41, 18) | -9.128 mL |
| Overall ACC + QS21 | Change From Baseline in Volumetric Brain Magnetic Resonance Imaging (MRI) Measurements in Brain Boundary Shift Integral (BBSI) | Week 10 (N: 22, 20, 42, 20) | -2.526 mL |
| Overall ACC + QS21 | Change From Baseline in Volumetric Brain Magnetic Resonance Imaging (MRI) Measurements in Brain Boundary Shift Integral (BBSI) | Week 24 (N: 22, 20, 42, 21) | -4.218 mL |
| Overall ACC + QS21 | Change From Baseline in Volumetric Brain Magnetic Resonance Imaging (MRI) Measurements in Brain Boundary Shift Integral (BBSI) | Week 76 (N: 21, 17, 38, 15) | -13.690 mL |
| Overall ACC + QS21 | Change From Baseline in Volumetric Brain Magnetic Resonance Imaging (MRI) Measurements in Brain Boundary Shift Integral (BBSI) | Week 104 (N: 18, 16, 34, 14) | -16.822 mL |
| Placebo | Change From Baseline in Volumetric Brain Magnetic Resonance Imaging (MRI) Measurements in Brain Boundary Shift Integral (BBSI) | Week 76 (N: 21, 17, 38, 15) | -16.196 mL |
| Placebo | Change From Baseline in Volumetric Brain Magnetic Resonance Imaging (MRI) Measurements in Brain Boundary Shift Integral (BBSI) | Week 24 (N: 22, 20, 42, 21) | -5.906 mL |
| Placebo | Change From Baseline in Volumetric Brain Magnetic Resonance Imaging (MRI) Measurements in Brain Boundary Shift Integral (BBSI) | Week 10 (N: 22, 20, 42, 20) | -1.449 mL |
| Placebo | Change From Baseline in Volumetric Brain Magnetic Resonance Imaging (MRI) Measurements in Brain Boundary Shift Integral (BBSI) | Week 50 (N: 22, 19, 41, 18) | -10.684 mL |
| Placebo | Change From Baseline in Volumetric Brain Magnetic Resonance Imaging (MRI) Measurements in Brain Boundary Shift Integral (BBSI) | Week 104 (N: 18, 16, 34, 14) | -18.772 mL |
Comparison: A mixed effects model for repeated measures analysis was used, with baseline total brain volume and ApoE4 status as covariates, and visit, treatment and visit by treatment interaction as fixed effects, with variance-covariance structure set to unstructured. Statistical analysis presented above for Week 10.p-value: 0.180795% CI: [-6.57, 1.267]Mixed-Effects Model Repeated Measures
Comparison: A mixed effects model for repeated measures analysis was used, with baseline total brain volume and ApoE4 status as covariates, and visit, treatment and visit by treatment interaction as fixed effects, with variance-covariance structure set to unstructured. Statistical analysis presented above for Week 10.p-value: 0.805195% CI: [-3.515, 4.508]Mixed-Effects Model Repeated Measures
Comparison: A mixed effects model for repeated measures analysis was used, with baseline total brain volume and ApoE4 status as covariates, and visit, treatment and visit by treatment interaction as fixed effects, with variance-covariance structure set to unstructured. Statistical analysis presented above for Week 10.p-value: 0.533195% CI: [-4.519, 2.364]Mixed-Effects Model Repeated Measures
Comparison: A mixed effects model for repeated measures analysis was used, with baseline total brain volume and ApoE4 status as covariates, and visit, treatment and visit by treatment interaction as fixed effects, with variance-covariance structure set to unstructured. Statistical analysis presented above for Week 24.p-value: 0.927495% CI: [-3.99, 3.641]Mixed-Effects Model Repeated Measures
Comparison: A mixed effects model for repeated measures analysis was used, with baseline total brain volume and ApoE4 status as covariates, and visit, treatment and visit by treatment interaction as fixed effects, with variance-covariance structure set to unstructured. Statistical analysis presented above for Week 24.p-value: 0.074395% CI: [-0.36, 7.458]Mixed-Effects Model Repeated Measures
Comparison: A mixed effects model for repeated measures analysis was used, with baseline total brain volume and ApoE4 status as covariates, and visit, treatment and visit by treatment interaction as fixed effects, with variance-covariance structure set to unstructured. Statistical analysis presented above for Week 24.p-value: 0.316395% CI: [-1.656, 5.031]Mixed-Effects Model Repeated Measures
Comparison: A mixed effects model for repeated measures analysis was used, with baseline total brain volume and ApoE4 status as covariates, and visit, treatment and visit by treatment interaction as fixed effects, with variance-covariance structure set to unstructured. Statistical analysis presented above for Week 50.p-value: 0.51995% CI: [-6.721, 3.43]Mixed-Effects Model Repeated Measures
Comparison: A mixed effects model for repeated measures analysis was used, with baseline total brain volume and ApoE4 status as covariates, and visit, treatment and visit by treatment interaction as fixed effects, with variance-covariance structure set to unstructured. Statistical analysis presented above for Week 50.p-value: 0.07495% CI: [-0.476, 9.991]Mixed-Effects Model Repeated Measures
Comparison: A mixed effects model for repeated measures analysis was used, with baseline total brain volume and ApoE4 status as covariates, and visit, treatment and visit by treatment interaction as fixed effects, with variance-covariance structure set to unstructured. Statistical analysis presented above for Week 50.p-value: 0.490995% CI: [-2.937, 6.049]Mixed-Effects Model Repeated Measures
Comparison: A mixed effects model for repeated measures analysis was used, with baseline total brain volume and ApoE4 status as covariates, and visit, treatment and visit by treatment interaction as fixed effects, with variance-covariance structure set to unstructured. Statistical analysis presented above for Week 76.p-value: 0.915195% CI: [-7.549, 6.783]Mixed-Effects Model Repeated Measures
Comparison: A mixed effects model for repeated measures analysis was used, with baseline total brain volume and ApoE4 status as covariates, and visit, treatment and visit by treatment interaction as fixed effects, with variance-covariance structure set to unstructured. Statistical analysis presented above for Week 76.p-value: 0.153395% CI: [-2.069, 12.857]Mixed-Effects Model Repeated Measures
Comparison: A mixed effects model for repeated measures analysis was used, with baseline total brain volume and ApoE4 status as covariates, and visit, treatment and visit by treatment interaction as fixed effects, with variance-covariance structure set to unstructured. Statistical analysis presented above for Week 76.p-value: 0.437195% CI: [-3.904, 8.915]Mixed-Effects Model Repeated Measures
Comparison: A mixed effects model for repeated measures analysis was used, with baseline total brain volume and ApoE4 status as covariates, and visit, treatment and visit by treatment interaction as fixed effects, with variance-covariance structure set to unstructured. Statistical analysis presented above for Week 104.p-value: 0.616795% CI: [-10.999, 6.579]Mixed-Effects Model Repeated Measures
Comparison: A mixed effects model for repeated measures analysis was used, with baseline total brain volume and ApoE4 status as covariates, and visit, treatment and visit by treatment interaction as fixed effects, with variance-covariance structure set to unstructured. Statistical analysis presented above for Week 104.p-value: 0.184495% CI: [-2.993, 15.212]Mixed-Effects Model Repeated Measures
Comparison: A mixed effects model for repeated measures analysis was used, with baseline total brain volume and ApoE4 status as covariates, and visit, treatment and visit by treatment interaction as fixed effects, with variance-covariance structure set to unstructured. Statistical analysis presented above for Week 104.p-value: 0.620595% CI: [-5.888, 9.878]Mixed-Effects Model Repeated Measures
Other Pre-specified
Change From Baseline in Volumetric Brain MRI Measurements in HBSI, Left
Left HBSI measures the left hippocampal atrophy from registered MRI scan pairs, by subtracting the corresponding area under the intensity profile across a boundary in the repeat scans.
Time frame: 104 weeks
Population: FAS population included all randomized participants who had at least one dose of investigational product.
| Arm | Measure | Group | Value (LEAST_SQUARES_MEAN) |
|---|---|---|---|
| ACC 3 μg+QS-21 | Change From Baseline in Volumetric Brain MRI Measurements in HBSI, Left | Week 76 (N: 22, 17, 39, 16) | -0.163 mL |
| ACC 3 μg+QS-21 | Change From Baseline in Volumetric Brain MRI Measurements in HBSI, Left | Week 24 (N: 22, 20, 42, 21) | -0.057 mL |
| ACC 3 μg+QS-21 | Change From Baseline in Volumetric Brain MRI Measurements in HBSI, Left | Week 104 (N: 18, 16, 34, 14) | -0.222 mL |
| ACC 3 μg+QS-21 | Change From Baseline in Volumetric Brain MRI Measurements in HBSI, Left | Week 50 (N: 22, 19, 41, 18) | -0.119 mL |
| ACC 3 μg+QS-21 | Change From Baseline in Volumetric Brain MRI Measurements in HBSI, Left | Week 10 (N: 22, 20, 42, 20) | -0.029 mL |
| ACC 10 μg+QS-21 | Change From Baseline in Volumetric Brain MRI Measurements in HBSI, Left | Week 50 (N: 22, 19, 41, 18) | -0.080 mL |
| ACC 10 μg+QS-21 | Change From Baseline in Volumetric Brain MRI Measurements in HBSI, Left | Week 76 (N: 22, 17, 39, 16) | -0.117 mL |
| ACC 10 μg+QS-21 | Change From Baseline in Volumetric Brain MRI Measurements in HBSI, Left | Week 104 (N: 18, 16, 34, 14) | -0.158 mL |
| ACC 10 μg+QS-21 | Change From Baseline in Volumetric Brain MRI Measurements in HBSI, Left | Week 24 (N: 22, 20, 42, 21) | -0.037 mL |
| ACC 10 μg+QS-21 | Change From Baseline in Volumetric Brain MRI Measurements in HBSI, Left | Week 10 (N: 22, 20, 42, 20) | -0.010 mL |
| Overall ACC + QS21 | Change From Baseline in Volumetric Brain MRI Measurements in HBSI, Left | Week 50 (N: 22, 19, 41, 18) | -0.099 mL |
| Overall ACC + QS21 | Change From Baseline in Volumetric Brain MRI Measurements in HBSI, Left | Week 10 (N: 22, 20, 42, 20) | -0.020 mL |
| Overall ACC + QS21 | Change From Baseline in Volumetric Brain MRI Measurements in HBSI, Left | Week 24 (N: 22, 20, 42, 21) | -0.047 mL |
| Overall ACC + QS21 | Change From Baseline in Volumetric Brain MRI Measurements in HBSI, Left | Week 76 (N: 22, 17, 39, 16) | -0.140 mL |
| Overall ACC + QS21 | Change From Baseline in Volumetric Brain MRI Measurements in HBSI, Left | Week 104 (N: 18, 16, 34, 14) | -0.190 mL |
| Placebo | Change From Baseline in Volumetric Brain MRI Measurements in HBSI, Left | Week 76 (N: 22, 17, 39, 16) | -0.157 mL |
| Placebo | Change From Baseline in Volumetric Brain MRI Measurements in HBSI, Left | Week 24 (N: 22, 20, 42, 21) | -0.040 mL |
| Placebo | Change From Baseline in Volumetric Brain MRI Measurements in HBSI, Left | Week 10 (N: 22, 20, 42, 20) | -0.019 mL |
| Placebo | Change From Baseline in Volumetric Brain MRI Measurements in HBSI, Left | Week 50 (N: 22, 19, 41, 18) | -0.107 mL |
| Placebo | Change From Baseline in Volumetric Brain MRI Measurements in HBSI, Left | Week 104 (N: 18, 16, 34, 14) | -0.230 mL |
Comparison: A mixed effects model for repeated measures analysis was used, with baseline left hippocampal volume and ApoE4 status as covariates, and visit, treatment and visit by treatment interaction as fixed effects, with variance-covariance structure set to unstructured. Statistical analysis presented above for Week 10.p-value: 0.513495% CI: [-0.043, 0.022]Mixed-Effects Model Repeated Measures
Comparison: A mixed effects model for repeated measures analysis was used, with baseline left hippocampal volume and ApoE4 status as covariates, and visit, treatment and visit by treatment interaction as fixed effects, with variance-covariance structure set to unstructured. Statistical analysis presented above for Week 10.p-value: 0.608395% CI: [-0.024, 0.041]Mixed-Effects Model Repeated Measures
Comparison: A mixed effects model for repeated measures analysis was used, with baseline left hippocampal volume and ApoE4 status as covariates, and visit, treatment and visit by treatment interaction as fixed effects, with variance-covariance structure set to unstructured. Statistical analysis presented above for Week 10.p-value: 0.940195% CI: [-0.029, 0.027]Mixed-Effects Model Repeated Measures
Comparison: A mixed effects model for repeated measures analysis was used, with baseline left hippocampal volume and ApoE4 status as covariates, and visit, treatment and visit by treatment interaction as fixed effects, with variance-covariance structure set to unstructured. Statistical analysis presented above for Week 24.p-value: 0.29595% CI: [-0.051, 0.016]Mixed-Effects Model Repeated Measures
Comparison: A mixed effects model for repeated measures analysis was used, with baseline left hippocampal volume and ApoE4 status as covariates, and visit, treatment and visit by treatment interaction as fixed effects, with variance-covariance structure set to unstructured. Statistical analysis presented above for Week 24.p-value: 0.881795% CI: [-0.031, 0.037]Mixed-Effects Model Repeated Measures
Comparison: A mixed effects model for repeated measures analysis was used, with baseline left hippocampal volume and ApoE4 status as covariates, and visit, treatment and visit by treatment interaction as fixed effects, with variance-covariance structure set to unstructured. Statistical analysis presented above for Week 24.p-value: 0.607295% CI: [-0.037, 0.022]Mixed-Effects Model Repeated Measures
Comparison: A mixed effects model for repeated measures analysis was used, with baseline left hippocampal volume and ApoE4 status as covariates, and visit, treatment and visit by treatment interaction as fixed effects, with variance-covariance structure set to unstructured. Statistical analysis presented above for Week 50.p-value: 0.625995% CI: [-0.06, 0.036]Mixed-Effects Model Repeated Measures
Comparison: A mixed effects model for repeated measures analysis was used, with baseline left hippocampal volume and ApoE4 status as covariates, and visit, treatment and visit by treatment interaction as fixed effects, with variance-covariance structure set to unstructured. Statistical analysis presented above for Week 50.p-value: 0.280795% CI: [-0.023, 0.076]Mixed-Effects Model Repeated Measures
Comparison: A mixed effects model for repeated measures analysis was used, with baseline left hippocampal volume and ApoE4 status as covariates, and visit, treatment and visit by treatment interaction as fixed effects, with variance-covariance structure set to unstructured. Statistical analysis presented above for Week 50.p-value: 0.722495% CI: [-0.035, 0.05]Mixed-Effects Model Repeated Measures
Comparison: A mixed effects model for repeated measures analysis was used, with baseline left hippocampal volume and ApoE4 status as covariates, and visit, treatment and visit by treatment interaction as fixed effects, with variance-covariance structure set to unstructured. Statistical analysis presented above for Week 76.p-value: 0.853295% CI: [-0.08, 0.067]Mixed-Effects Model Repeated Measures
Comparison: A mixed effects model for repeated measures analysis was used, with baseline left hippocampal volume and ApoE4 status as covariates, and visit, treatment and visit by treatment interaction as fixed effects, with variance-covariance structure set to unstructured. Statistical analysis presented above for Week 76.p-value: 0.311695% CI: [-0.038, 0.116]Mixed-Effects Model Repeated Measures
Comparison: A mixed effects model for repeated measures analysis was used, with baseline left hippocampal volume and ApoE4 status as covariates, and visit, treatment and visit by treatment interaction as fixed effects, with variance-covariance structure set to unstructured. Statistical analysis presented above for Week 76.p-value: 0.624695% CI: [-0.049, 0.082]Mixed-Effects Model Repeated Measures
Comparison: A mixed effects model for repeated measures analysis was used, with baseline left hippocampal volume and ApoE4 status as covariates, and visit, treatment and visit by treatment interaction as fixed effects, with variance-covariance structure set to unstructured. Statistical analysis presented above for Week 104.p-value: 0.869795% CI: [-0.092, 0.108]Mixed-Effects Model Repeated Measures
Comparison: A mixed effects model for repeated measures analysis was used, with baseline left hippocampal volume and ApoE4 status as covariates, and visit, treatment and visit by treatment interaction as fixed effects, with variance-covariance structure set to unstructured. Statistical analysis presented above for Week 104.p-value: 0.170795% CI: [-0.032, 0.176]Mixed-Effects Model Repeated Measures
Comparison: A mixed effects model for repeated measures analysis was used, with baseline left hippocampal volume and ApoE4 status as covariates, and visit, treatment and visit by treatment interaction as fixed effects, with variance-covariance structure set to unstructured. Statistical analysis presented above for Week 104.p-value: 0.373295% CI: [-0.049, 0.129]Mixed-Effects Model Repeated Measures
Other Pre-specified
Change From Baseline in Volumetric Brain MRI Measurements in HBSI, Right
Right HBSI measures the right hippocampal atrophy from registered MRI scan pairs, by subtracting the corresponding area under the intensity profile across a boundary in the repeat scans.
Time frame: 104 weeks
Population: FAS population included all randomized participants who had at least one dose of investigational product.
| Arm | Measure | Group | Value (LEAST_SQUARES_MEAN) |
|---|---|---|---|
| ACC 3 μg+QS-21 | Change From Baseline in Volumetric Brain MRI Measurements in HBSI, Right | Week 76 (N: 22, 17, 39, 16) | -0.194 mL |
| ACC 3 μg+QS-21 | Change From Baseline in Volumetric Brain MRI Measurements in HBSI, Right | Week 24 (N: 22, 20, 42, 21) | -0.067 mL |
| ACC 3 μg+QS-21 | Change From Baseline in Volumetric Brain MRI Measurements in HBSI, Right | Week 104 (N: 18, 16, 34, 14) | -0.247 mL |
| ACC 3 μg+QS-21 | Change From Baseline in Volumetric Brain MRI Measurements in HBSI, Right | Week 50 (N: 22, 19, 41, 18) | -0.133 mL |
| ACC 3 μg+QS-21 | Change From Baseline in Volumetric Brain MRI Measurements in HBSI, Right | Week 10 (N: 22, 20, 42, 20) | -0.027 mL |
| ACC 10 μg+QS-21 | Change From Baseline in Volumetric Brain MRI Measurements in HBSI, Right | Week 50 (N: 22, 19, 41, 18) | -0.078 mL |
| ACC 10 μg+QS-21 | Change From Baseline in Volumetric Brain MRI Measurements in HBSI, Right | Week 76 (N: 22, 17, 39, 16) | -0.136 mL |
| ACC 10 μg+QS-21 | Change From Baseline in Volumetric Brain MRI Measurements in HBSI, Right | Week 104 (N: 18, 16, 34, 14) | -0.170 mL |
| ACC 10 μg+QS-21 | Change From Baseline in Volumetric Brain MRI Measurements in HBSI, Right | Week 24 (N: 22, 20, 42, 21) | -0.027 mL |
| ACC 10 μg+QS-21 | Change From Baseline in Volumetric Brain MRI Measurements in HBSI, Right | Week 10 (N: 22, 20, 42, 20) | -0.005 mL |
| Overall ACC + QS21 | Change From Baseline in Volumetric Brain MRI Measurements in HBSI, Right | Week 50 (N: 22, 19, 41, 18) | -0.106 mL |
| Overall ACC + QS21 | Change From Baseline in Volumetric Brain MRI Measurements in HBSI, Right | Week 10 (N: 22, 20, 42, 20) | -0.016 mL |
| Overall ACC + QS21 | Change From Baseline in Volumetric Brain MRI Measurements in HBSI, Right | Week 24 (N: 22, 20, 42, 21) | -0.047 mL |
| Overall ACC + QS21 | Change From Baseline in Volumetric Brain MRI Measurements in HBSI, Right | Week 76 (N: 22, 17, 39, 16) | -0.165 mL |
| Overall ACC + QS21 | Change From Baseline in Volumetric Brain MRI Measurements in HBSI, Right | Week 104 (N: 18, 16, 34, 14) | -0.208 mL |
| Placebo | Change From Baseline in Volumetric Brain MRI Measurements in HBSI, Right | Week 76 (N: 22, 17, 39, 16) | -0.177 mL |
| Placebo | Change From Baseline in Volumetric Brain MRI Measurements in HBSI, Right | Week 24 (N: 22, 20, 42, 21) | -0.059 mL |
| Placebo | Change From Baseline in Volumetric Brain MRI Measurements in HBSI, Right | Week 10 (N: 22, 20, 42, 20) | -0.021 mL |
| Placebo | Change From Baseline in Volumetric Brain MRI Measurements in HBSI, Right | Week 50 (N: 22, 19, 41, 18) | -0.119 mL |
| Placebo | Change From Baseline in Volumetric Brain MRI Measurements in HBSI, Right | Week 104 (N: 18, 16, 34, 14) | -0.240 mL |
Comparison: A mixed effects model for repeated measures analysis was used, with baseline right hippocampal volume and ApoE4 status as covariates, and visit, treatment and visit by treatment interaction as fixed effects, with variance-covariance structure set to unstructured. Statistical analysis presented above for Week 10.p-value: 0.725995% CI: [-0.04, 0.028]Mixed-Effects Model Repeated Measures
Comparison: A mixed effects model for repeated measures analysis was used, with baseline right hippocampal volume and ApoE4 status as covariates, and visit, treatment and visit by treatment interaction as fixed effects, with variance-covariance structure set to unstructured. Statistical analysis presented above for Week 10.p-value: 0.351795% CI: [-0.018, 0.051]Mixed-Effects Model Repeated Measures
Comparison: A mixed effects model for repeated measures analysis was used, with baseline right hippocampal volume and ApoE4 status as covariates, and visit, treatment and visit by treatment interaction as fixed effects, with variance-covariance structure set to unstructured. Statistical analysis presented above for Week 10.p-value: 0.731195% CI: [-0.024, 0.035]Mixed-Effects Model Repeated Measures
Comparison: A mixed effects model for repeated measures analysis was used, with baseline right hippocampal volume and ApoE4 status as covariates, and visit, treatment and visit by treatment interaction as fixed effects, with variance-covariance structure set to unstructured. Statistical analysis presented above for Week 24.p-value: 0.644695% CI: [-0.041, 0.026]Mixed-Effects Model Repeated Measures
Comparison: A mixed effects model for repeated measures analysis was used, with baseline right hippocampal volume and ApoE4 status as covariates, and visit, treatment and visit by treatment interaction as fixed effects, with variance-covariance structure set to unstructured. Statistical analysis presented above for Week 24.p-value: 0.06495% CI: [-0.002, 0.066]Mixed-Effects Model Repeated Measures
Comparison: A mixed effects model for repeated measures analysis was used, with baseline right hippocampal volume and ApoE4 status as covariates, and visit, treatment and visit by treatment interaction as fixed effects, with variance-covariance structure set to unstructured. Statistical analysis presented above for Week 24.p-value: 0.405795% CI: [-0.017, 0.041]Mixed-Effects Model Repeated Measures
Comparison: A mixed effects model for repeated measures analysis was used, with baseline right hippocampal volume and ApoE4 status as covariates, and visit, treatment and visit by treatment interaction as fixed effects, with variance-covariance structure set to unstructured. Statistical analysis presented above for Week 50.p-value: 0.574295% CI: [-0.066, 0.037]Mixed-Effects Model Repeated Measures
Comparison: A mixed effects model for repeated measures analysis was used, with baseline right hippocampal volume and ApoE4 status as covariates, and visit, treatment and visit by treatment interaction as fixed effects, with variance-covariance structure set to unstructured. Statistical analysis presented above for Week 50.p-value: 0.133695% CI: [-0.013, 0.093]Mixed-Effects Model Repeated Measures
Comparison: A mixed effects model for repeated measures analysis was used, with baseline right hippocampal volume and ApoE4 status as covariates, and visit, treatment and visit by treatment interaction as fixed effects, with variance-covariance structure set to unstructured. Statistical analysis presented above for Week 50.p-value: 0.573495% CI: [-0.033, 0.058]Mixed-Effects Model Repeated Measures
Comparison: A mixed effects model for repeated measures analysis was used, with baseline right hippocampal volume and ApoE4 status as covariates, and visit, treatment and visit by treatment interaction as fixed effects, with variance-covariance structure set to unstructured. Statistical analysis presented above for Week 76.p-value: 0.706795% CI: [-0.104, 0.071]Mixed-Effects Model Repeated Measures
Comparison: A mixed effects model for repeated measures analysis was used, with baseline right hippocampal volume and ApoE4 status as covariates, and visit, treatment and visit by treatment interaction as fixed effects, with variance-covariance structure set to unstructured. Statistical analysis presented above for Week 76.p-value: 0.3695% CI: [-0.049, 0.132]Mixed-Effects Model Repeated Measures
Comparison: A mixed effects model for repeated measures analysis was used, with baseline right hippocampal volume and ApoE4 status as covariates, and visit, treatment and visit by treatment interaction as fixed effects, with variance-covariance structure set to unstructured. Statistical analysis presented above for Week 76.p-value: 0.745495% CI: [-0.065, 0.09]Mixed-Effects Model Repeated Measures
Comparison: A mixed effects model for repeated measures analysis was used, with baseline right hippocampal volume and ApoE4 status as covariates, and visit, treatment and visit by treatment interaction as fixed effects, with variance-covariance structure set to unstructured. Statistical analysis presented above for Week 104.p-value: 0.903795% CI: [-0.113, 0.1]Mixed-Effects Model Repeated Measures
Comparison: A mixed effects model for repeated measures analysis was used, with baseline right hippocampal volume and ApoE4 status as covariates, and visit, treatment and visit by treatment interaction as fixed effects, with variance-covariance structure set to unstructured. Statistical analysis presented above for Week 104.p-value: 0.208295% CI: [-0.04, 0.181]Mixed-Effects Model Repeated Measures
Comparison: A mixed effects model for repeated measures analysis was used, with baseline right hippocampal volume and ApoE4 status as covariates, and visit, treatment and visit by treatment interaction as fixed effects, with variance-covariance structure set to unstructured. Statistical analysis presented above for Week 104.p-value: 0.504495% CI: [-0.063, 0.127]Mixed-Effects Model Repeated Measures
Other Pre-specified
Change From Baseline in Volumetric Brain MRI Measurements in Hippocampal Boundary Shift Integral (HBSI), Total
Left HBSI and Right HBSI respectively measure the left hippocampal atrophy and the right hippocampal atrophy from registered MRI scan pairs, by subtracting the corresponding area under the intensity profile across a boundary in the repeat scans. HBSI (Total) is defined as the summation of the left HBSI and the right HBSI.
Time frame: 104 weeks
Population: FAS population included all randomized participants who had at least one dose of investigational product.
| Arm | Measure | Group | Value (LEAST_SQUARES_MEAN) |
|---|---|---|---|
| ACC 3 μg+QS-21 | Change From Baseline in Volumetric Brain MRI Measurements in Hippocampal Boundary Shift Integral (HBSI), Total | Week 76 (N: 22, 17, 39, 16) | -0.357 mL |
| ACC 3 μg+QS-21 | Change From Baseline in Volumetric Brain MRI Measurements in Hippocampal Boundary Shift Integral (HBSI), Total | Week 24 (N: 22, 20, 42, 21) | -0.124 mL |
| ACC 3 μg+QS-21 | Change From Baseline in Volumetric Brain MRI Measurements in Hippocampal Boundary Shift Integral (HBSI), Total | Week 104 (N: 18, 16, 34, 14) | -0.468 mL |
| ACC 3 μg+QS-21 | Change From Baseline in Volumetric Brain MRI Measurements in Hippocampal Boundary Shift Integral (HBSI), Total | Week 50 (N: 22, 19, 41, 18) | -0.251 mL |
| ACC 3 μg+QS-21 | Change From Baseline in Volumetric Brain MRI Measurements in Hippocampal Boundary Shift Integral (HBSI), Total | Week 10 (N: 22, 20, 42, 20) | -0.056 mL |
| ACC 10 μg+QS-21 | Change From Baseline in Volumetric Brain MRI Measurements in Hippocampal Boundary Shift Integral (HBSI), Total | Week 50 (N: 22, 19, 41, 18) | -0.159 mL |
| ACC 10 μg+QS-21 | Change From Baseline in Volumetric Brain MRI Measurements in Hippocampal Boundary Shift Integral (HBSI), Total | Week 76 (N: 22, 17, 39, 16) | -0.255 mL |
| ACC 10 μg+QS-21 | Change From Baseline in Volumetric Brain MRI Measurements in Hippocampal Boundary Shift Integral (HBSI), Total | Week 104 (N: 18, 16, 34, 14) | -0.329 mL |
| ACC 10 μg+QS-21 | Change From Baseline in Volumetric Brain MRI Measurements in Hippocampal Boundary Shift Integral (HBSI), Total | Week 24 (N: 22, 20, 42, 21) | -0.065 mL |
| ACC 10 μg+QS-21 | Change From Baseline in Volumetric Brain MRI Measurements in Hippocampal Boundary Shift Integral (HBSI), Total | Week 10 (N: 22, 20, 42, 20) | -0.016 mL |
| Overall ACC + QS21 | Change From Baseline in Volumetric Brain MRI Measurements in Hippocampal Boundary Shift Integral (HBSI), Total | Week 50 (N: 22, 19, 41, 18) | -0.205 mL |
| Overall ACC + QS21 | Change From Baseline in Volumetric Brain MRI Measurements in Hippocampal Boundary Shift Integral (HBSI), Total | Week 10 (N: 22, 20, 42, 20) | -0.036 mL |
| Overall ACC + QS21 | Change From Baseline in Volumetric Brain MRI Measurements in Hippocampal Boundary Shift Integral (HBSI), Total | Week 24 (N: 22, 20, 42, 21) | -0.094 mL |
| Overall ACC + QS21 | Change From Baseline in Volumetric Brain MRI Measurements in Hippocampal Boundary Shift Integral (HBSI), Total | Week 76 (N: 22, 17, 39, 16) | -0.306 mL |
| Overall ACC + QS21 | Change From Baseline in Volumetric Brain MRI Measurements in Hippocampal Boundary Shift Integral (HBSI), Total | Week 104 (N: 18, 16, 34, 14) | -0.398 mL |
| Placebo | Change From Baseline in Volumetric Brain MRI Measurements in Hippocampal Boundary Shift Integral (HBSI), Total | Week 76 (N: 22, 17, 39, 16) | -0.334 mL |
| Placebo | Change From Baseline in Volumetric Brain MRI Measurements in Hippocampal Boundary Shift Integral (HBSI), Total | Week 24 (N: 22, 20, 42, 21) | -0.099 mL |
| Placebo | Change From Baseline in Volumetric Brain MRI Measurements in Hippocampal Boundary Shift Integral (HBSI), Total | Week 10 (N: 22, 20, 42, 20) | -0.041 mL |
| Placebo | Change From Baseline in Volumetric Brain MRI Measurements in Hippocampal Boundary Shift Integral (HBSI), Total | Week 50 (N: 22, 19, 41, 18) | -0.226 mL |
| Placebo | Change From Baseline in Volumetric Brain MRI Measurements in Hippocampal Boundary Shift Integral (HBSI), Total | Week 104 (N: 18, 16, 34, 14) | -0.471 mL |
Comparison: A mixed effects model for repeated measures analysis was used, with baseline hippocampal volume and ApoE4 status as covariates, and visit, treatment and visit by treatment interaction as fixed effects, with variance-covariance structure set to unstructured. Statistical analysis presented above for Week 10.p-value: 0.605495% CI: [-0.074, 0.043]Mixed-Effects Model Repeated Measures
Comparison: A mixed effects model for repeated measures analysis was used, with baseline hippocampal volume and ApoE4 status as covariates, and visit, treatment and visit by treatment interaction as fixed effects, with variance-covariance structure set to unstructured. Statistical analysis presented above for Week 10.p-value: 0.408795% CI: [-0.035, 0.084]Mixed-Effects Model Repeated Measures
Comparison: A mixed effects model for repeated measures analysis was used, with baseline hippocampal volume and ApoE4 status as covariates, and visit, treatment and visit by treatment interaction as fixed effects, with variance-covariance structure set to unstructured. Statistical analysis presented above for Week 10.p-value: 0.851895% CI: [-0.046, 0.056]Mixed-Effects Model Repeated Measures
Comparison: A mixed effects model for repeated measures analysis was used, with baseline hippocampal volume and ApoE4 status as covariates, and visit, treatment and visit by treatment interaction as fixed effects, with variance-covariance structure set to unstructured. Statistical analysis presented above for Week 24.p-value: 0.421695% CI: [-0.085, 0.036]Mixed-Effects Model Repeated Measures
Comparison: A mixed effects model for repeated measures analysis was used, with baseline hippocampal volume and ApoE4 status as covariates, and visit, treatment and visit by treatment interaction as fixed effects, with variance-covariance structure set to unstructured. Statistical analysis presented above for Week 24.p-value: 0.27395% CI: [-0.028, 0.097]Mixed-Effects Model Repeated Measures
Comparison: A mixed effects model for repeated measures analysis was used, with baseline hippocampal volume and ApoE4 status as covariates, and visit, treatment and visit by treatment interaction as fixed effects, with variance-covariance structure set to unstructured. Statistical analysis presented above for Week 24.p-value: 0.854995% CI: [-0.048, 0.058]Mixed-Effects Model Repeated Measures
Comparison: A mixed effects model for repeated measures analysis was used, with baseline hippocampal volume and ApoE4 status as covariates, and visit, treatment and visit by treatment interaction as fixed effects, with variance-covariance structure set to unstructured. Statistical analysis presented above for Week 50.p-value: 0.584795% CI: [-0.12, 0.068]Mixed-Effects Model Repeated Measures
Comparison: A mixed effects model for repeated measures analysis was used, with baseline hippocampal volume and ApoE4 status as covariates, and visit, treatment and visit by treatment interaction as fixed effects, with variance-covariance structure set to unstructured. Statistical analysis presented above for Week 50.p-value: 0.17495% CI: [-0.03, 0.163]Mixed-Effects Model Repeated Measures
Comparison: A mixed effects model for repeated measures analysis was used, with baseline hippocampal volume and ApoE4 status as covariates, and visit, treatment and visit by treatment interaction as fixed effects, with variance-covariance structure set to unstructured. Statistical analysis presented above for Week 50.p-value: 0.625595% CI: [-0.063, 0.103]Mixed-Effects Model Repeated Measures
Comparison: A mixed effects model for repeated measures analysis was used, with baseline hippocampal volume and ApoE4 status as covariates, and visit, treatment and visit by treatment interaction as fixed effects, with variance-covariance structure set to unstructured. Statistical analysis presented above for Week 76.p-value: 0.765895% CI: [-0.177, 0.131]Mixed-Effects Model Repeated Measures
Comparison: A mixed effects model for repeated measures analysis was used, with baseline hippocampal volume and ApoE4 status as covariates, and visit, treatment and visit by treatment interaction as fixed effects, with variance-covariance structure set to unstructured. Statistical analysis presented above for Week 76.p-value: 0.330995% CI: [-0.082, 0.24]Mixed-Effects Model Repeated Measures
Comparison: A mixed effects model for repeated measures analysis was used, with baseline hippocampal volume and ApoE4 status as covariates, and visit, treatment and visit by treatment interaction as fixed effects, with variance-covariance structure set to unstructured. Statistical analysis presented above for Week 76.p-value: 0.687295% CI: [-0.11, 0.166]Mixed-Effects Model Repeated Measures
Comparison: A mixed effects model for repeated measures analysis was used, with baseline hippocampal volume and ApoE4 status as covariates, and visit, treatment and visit by treatment interaction as fixed effects, with variance-covariance structure set to unstructured. Statistical analysis presented above for Week 104.p-value: 0.975295% CI: [-0.196, 0.202]Mixed-Effects Model Repeated Measures
Comparison: A mixed effects model for repeated measures analysis was used, with baseline hippocampal volume and ApoE4 status as covariates, and visit, treatment and visit by treatment interaction as fixed effects, with variance-covariance structure set to unstructured. Statistical analysis presented above for Week 104.p-value: 0.171595% CI: [-0.064, 0.349]Mixed-Effects Model Repeated Measures
Comparison: A mixed effects model for repeated measures analysis was used, with baseline hippocampal volume and ApoE4 status as covariates, and visit, treatment and visit by treatment interaction as fixed effects, with variance-covariance structure set to unstructured. Statistical analysis presented above for Week 104.p-value: 0.414595% CI: [-0.105, 0.25]Mixed-Effects Model Repeated Measures
Other Pre-specified
Change From Baseline in Volumetric Brain MRI Measurements in Ventricular Boundary Shift Integral (VBSI)
VBSI measures ventricular volume change from registered MRI scan pairs, by subtracting the area under the intensity profile across a boundary in the repeat scans.
Time frame: 104 weeks
Population: FAS population included all randomized participants who had at least one dose of investigational product.
| Arm | Measure | Group | Value (LEAST_SQUARES_MEAN) |
|---|---|---|---|
| ACC 3 μg+QS-21 | Change From Baseline in Volumetric Brain MRI Measurements in Ventricular Boundary Shift Integral (VBSI) | Week 24 (N: 22, 20, 42, 21) | 1.540 mL |
| ACC 3 μg+QS-21 | Change From Baseline in Volumetric Brain MRI Measurements in Ventricular Boundary Shift Integral (VBSI) | Week 10 (N: 22, 20, 42, 20) | 0.913 mL |
| ACC 3 μg+QS-21 | Change From Baseline in Volumetric Brain MRI Measurements in Ventricular Boundary Shift Integral (VBSI) | Week 104 (N: 18, 16, 34, 14) | 6.422 mL |
| ACC 3 μg+QS-21 | Change From Baseline in Volumetric Brain MRI Measurements in Ventricular Boundary Shift Integral (VBSI) | Week 50 (N: 22, 19, 41, 18) | 3.023 mL |
| ACC 3 μg+QS-21 | Change From Baseline in Volumetric Brain MRI Measurements in Ventricular Boundary Shift Integral (VBSI) | Week 76 (N: 22, 17, 39, 16) | 4.729 mL |
| ACC 10 μg+QS-21 | Change From Baseline in Volumetric Brain MRI Measurements in Ventricular Boundary Shift Integral (VBSI) | Week 50 (N: 22, 19, 41, 18) | 2.242 mL |
| ACC 10 μg+QS-21 | Change From Baseline in Volumetric Brain MRI Measurements in Ventricular Boundary Shift Integral (VBSI) | Week 76 (N: 22, 17, 39, 16) | 3.445 mL |
| ACC 10 μg+QS-21 | Change From Baseline in Volumetric Brain MRI Measurements in Ventricular Boundary Shift Integral (VBSI) | Week 104 (N: 18, 16, 34, 14) | 4.970 mL |
| ACC 10 μg+QS-21 | Change From Baseline in Volumetric Brain MRI Measurements in Ventricular Boundary Shift Integral (VBSI) | Week 24 (N: 22, 20, 42, 21) | 1.229 mL |
| ACC 10 μg+QS-21 | Change From Baseline in Volumetric Brain MRI Measurements in Ventricular Boundary Shift Integral (VBSI) | Week 10 (N: 22, 20, 42, 20) | 0.643 mL |
| Overall ACC + QS21 | Change From Baseline in Volumetric Brain MRI Measurements in Ventricular Boundary Shift Integral (VBSI) | Week 24 (N: 22, 20, 42, 21) | 1.385 mL |
| Overall ACC + QS21 | Change From Baseline in Volumetric Brain MRI Measurements in Ventricular Boundary Shift Integral (VBSI) | Week 10 (N: 22, 20, 42, 20) | 0.778 mL |
| Overall ACC + QS21 | Change From Baseline in Volumetric Brain MRI Measurements in Ventricular Boundary Shift Integral (VBSI) | Week 50 (N: 22, 19, 41, 18) | 2.632 mL |
| Overall ACC + QS21 | Change From Baseline in Volumetric Brain MRI Measurements in Ventricular Boundary Shift Integral (VBSI) | Week 76 (N: 22, 17, 39, 16) | 4.087 mL |
| Overall ACC + QS21 | Change From Baseline in Volumetric Brain MRI Measurements in Ventricular Boundary Shift Integral (VBSI) | Week 104 (N: 18, 16, 34, 14) | 5.696 mL |
| Placebo | Change From Baseline in Volumetric Brain MRI Measurements in Ventricular Boundary Shift Integral (VBSI) | Week 76 (N: 22, 17, 39, 16) | 4.474 mL |
| Placebo | Change From Baseline in Volumetric Brain MRI Measurements in Ventricular Boundary Shift Integral (VBSI) | Week 24 (N: 22, 20, 42, 21) | 1.533 mL |
| Placebo | Change From Baseline in Volumetric Brain MRI Measurements in Ventricular Boundary Shift Integral (VBSI) | Week 10 (N: 22, 20, 42, 20) | 0.496 mL |
| Placebo | Change From Baseline in Volumetric Brain MRI Measurements in Ventricular Boundary Shift Integral (VBSI) | Week 50 (N: 22, 19, 41, 18) | 3.038 mL |
| Placebo | Change From Baseline in Volumetric Brain MRI Measurements in Ventricular Boundary Shift Integral (VBSI) | Week 104 (N: 18, 16, 34, 14) | 5.770 mL |
Comparison: A mixed effects model for repeated measures analysis was used, with baseline ventricular volume and ApoE4 status as covariates, and visit, treatment and visit by treatment interaction as fixed effects, with variance-covariance structure set to unstructured. Statistical analysis presented above for Week 10.p-value: 0.169595% CI: [-0.183, 1.018]Mixed-Effects Model Repeated Measures
Comparison: A mixed effects model for repeated measures analysis was used, with baseline ventricular volume and ApoE4 status as covariates, and visit, treatment and visit by treatment interaction as fixed effects, with variance-covariance structure set to unstructured. Statistical analysis presented above for Week 10.p-value: 0.633195% CI: [-0.465, 0.759]Mixed-Effects Model Repeated Measures
Comparison: A mixed effects model for repeated measures analysis was used, with baseline ventricular volume and ApoE4 status as covariates, and visit, treatment and visit by treatment interaction as fixed effects, with variance-covariance structure set to unstructured. Statistical analysis presented above for Week 10.p-value: 0.290795% CI: [-0.247, 0.812]Mixed-Effects Model Repeated Measures
Comparison: A mixed effects model for repeated measures analysis was used, with baseline ventricular volume and ApoE4 status as covariates, and visit, treatment and visit by treatment interaction as fixed effects, with variance-covariance structure set to unstructured. Statistical analysis presented above for Week 24.p-value: 0.984695% CI: [-0.675, 0.688]Mixed-Effects Model Repeated Measures
Comparison: A mixed effects model for repeated measures analysis was used, with baseline ventricular volume and ApoE4 status as covariates, and visit, treatment and visit by treatment interaction as fixed effects, with variance-covariance structure set to unstructured. Statistical analysis presented above for Week 24.p-value: 0.384595% CI: [-1, 0.392]Mixed-Effects Model Repeated Measures
Comparison: A mixed effects model for repeated measures analysis was used, with baseline ventricular volume and ApoE4 status as covariates, and visit, treatment and visit by treatment interaction as fixed effects, with variance-covariance structure set to unstructured. Statistical analysis presented above for Week 24.p-value: 0.620495% CI: [-0.748, 0.45]Mixed-Effects Model Repeated Measures
Comparison: A mixed effects model for repeated measures analysis was used, with baseline ventricular volume and ApoE4 status as covariates, and visit, treatment and visit by treatment interaction as fixed effects, with variance-covariance structure set to unstructured. Statistical analysis presented above for Week 50.p-value: 0.98195% CI: [-1.221, 1.192]Mixed-Effects Model Repeated Measures
Comparison: A mixed effects model for repeated measures analysis was used, with baseline ventricular volume and ApoE4 status as covariates, and visit, treatment and visit by treatment interaction as fixed effects, with variance-covariance structure set to unstructured. Statistical analysis presented above for Week 50.p-value: 0.203495% CI: [-2.034, 0.443]Mixed-Effects Model Repeated Measures
Comparison: A mixed effects model for repeated measures analysis was used, with baseline ventricular volume and ApoE4 status as covariates, and visit, treatment and visit by treatment interaction as fixed effects, with variance-covariance structure set to unstructured. Statistical analysis presented above for Week 50.p-value: 0.449195% CI: [-1.469, 0.659]Mixed-Effects Model Repeated Measures
Comparison: A mixed effects model for repeated measures analysis was used, with baseline ventricular volume and ApoE4 status as covariates, and visit, treatment and visit by treatment interaction as fixed effects, with variance-covariance structure set to unstructured. Statistical analysis presented above for Week 76.p-value: 0.807495% CI: [-1.827, 2.337]Mixed-Effects Model Repeated Measures
Comparison: A mixed effects model for repeated measures analysis was used, with baseline ventricular volume and ApoE4 status as covariates, and visit, treatment and visit by treatment interaction as fixed effects, with variance-covariance structure set to unstructured. Statistical analysis presented above for Week 76.p-value: 0.344495% CI: [-3.189, 1.131]Mixed-Effects Model Repeated Measures
Comparison: A mixed effects model for repeated measures analysis was used, with baseline ventricular volume and ApoE4 status as covariates, and visit, treatment and visit by treatment interaction as fixed effects, with variance-covariance structure set to unstructured. Statistical analysis presented above for Week 76.p-value: 0.677295% CI: [-2.239, 1.464]Mixed-Effects Model Repeated Measures
Comparison: A mixed effects model for repeated measures analysis was used, with baseline ventricular volume and ApoE4 status as covariates, and visit, treatment and visit by treatment interaction as fixed effects, with variance-covariance structure set to unstructured. Statistical analysis presented above for Week 104.p-value: 0.632595% CI: [-2.063, 3.367]Mixed-Effects Model Repeated Measures
Comparison: A mixed effects model for repeated measures analysis was used, with baseline ventricular volume and ApoE4 status as covariates, and visit, treatment and visit by treatment interaction as fixed effects, with variance-covariance structure set to unstructured. Statistical analysis presented above for Week 104.p-value: 0.570695% CI: [-3.606, 2.007]Mixed-Effects Model Repeated Measures
Comparison: A mixed effects model for repeated measures analysis was used, with baseline ventricular volume and ApoE4 status as covariates, and visit, treatment and visit by treatment interaction as fixed effects, with variance-covariance structure set to unstructured. Statistical analysis presented above for Week 104.p-value: 0.951395% CI: [-2.485, 2.337]Mixed-Effects Model Repeated Measures
Other Pre-specified
Geometric Mean Anti-Aβ IgG Enzyme-linked Immunosorbent Assay (ELISA) Titers
Site personnel collecting the samples for anti-Aβ antibody titers were blinded to the participant treatment group assignment. The lower limit of quantification (LLOQ) determined for this assay was 100 U/mL. For any anti-Aβ IgG antibody level that was below the LLOQ (100 U/mL), the lower limit of detection (LLOD) defined as 0.5\*LLOQ was imputed.
Time frame: 104 weeks
Population: FAS population included all randomized participants who had at least one dose of investigational product.
| Arm | Measure | Group | Value (GEOMETRIC_MEAN) |
|---|---|---|---|
| ACC 3 μg+QS-21 | Geometric Mean Anti-Aβ IgG Enzyme-linked Immunosorbent Assay (ELISA) Titers | Week 28 (N: 22, 20, 42, 20) | 6482.5 U/ml |
| ACC 3 μg+QS-21 | Geometric Mean Anti-Aβ IgG Enzyme-linked Immunosorbent Assay (ELISA) Titers | Week 26 (N: 22, 19, 41, 20) | 1657.0 U/ml |
| ACC 3 μg+QS-21 | Geometric Mean Anti-Aβ IgG Enzyme-linked Immunosorbent Assay (ELISA) Titers | Week 12 (N: 22, 18, 40, 20) | 566.4 U/ml |
| ACC 3 μg+QS-21 | Geometric Mean Anti-Aβ IgG Enzyme-linked Immunosorbent Assay (ELISA) Titers | Week 104 (N: 11, 9, 20, 9) | 3960.8 U/ml |
| ACC 3 μg+QS-21 | Geometric Mean Anti-Aβ IgG Enzyme-linked Immunosorbent Assay (ELISA) Titers | Week 20 (N: 21, 20, 41, 21) | 3320.9 U/ml |
| ACC 3 μg+QS-21 | Geometric Mean Anti-Aβ IgG Enzyme-linked Immunosorbent Assay (ELISA) Titers | Week 14 (N: 22, 20, 42, 20) | 5997.5 U/ml |
| ACC 3 μg+QS-21 | Geometric Mean Anti-Aβ IgG Enzyme-linked Immunosorbent Assay (ELISA) Titers | Week 80 (N: 19, 14, 33, 16) | 8006.3 U/ml |
| ACC 3 μg+QS-21 | Geometric Mean Anti-Aβ IgG Enzyme-linked Immunosorbent Assay (ELISA) Titers | Week 78 (N: 19, 14, 33, 14) | 2007.1 U/ml |
| ACC 3 μg+QS-21 | Geometric Mean Anti-Aβ IgG Enzyme-linked Immunosorbent Assay (ELISA) Titers | Week 4 (N: 21, 17, 38, 21) | 59.0 U/ml |
| ACC 3 μg+QS-21 | Geometric Mean Anti-Aβ IgG Enzyme-linked Immunosorbent Assay (ELISA) Titers | Baseline (N: 21, 18, 39, 21) | 50.0 U/ml |
| ACC 3 μg+QS-21 | Geometric Mean Anti-Aβ IgG Enzyme-linked Immunosorbent Assay (ELISA) Titers | Week 60 (N: 21, 19, 40, 19) | 4130.7 U/ml |
| ACC 3 μg+QS-21 | Geometric Mean Anti-Aβ IgG Enzyme-linked Immunosorbent Assay (ELISA) Titers | Week 54 (N: 20, 19, 39, 19) | 6787.7 U/ml |
| ACC 3 μg+QS-21 | Geometric Mean Anti-Aβ IgG Enzyme-linked Immunosorbent Assay (ELISA) Titers | Week 6 (N: 22, 20, 42, 21) | 1490.0 U/ml |
| ACC 3 μg+QS-21 | Geometric Mean Anti-Aβ IgG Enzyme-linked Immunosorbent Assay (ELISA) Titers | Week 86 (N: 15, 17, 32, 14) | 6584.2 U/ml |
| ACC 3 μg+QS-21 | Geometric Mean Anti-Aβ IgG Enzyme-linked Immunosorbent Assay (ELISA) Titers | Week 52 (N: 20, 18, 38, 19) | 1322.6 U/ml |
| ACC 3 μg+QS-21 | Geometric Mean Anti-Aβ IgG Enzyme-linked Immunosorbent Assay (ELISA) Titers | Week 34 (N: 22, 20, 42, 20) | 3731.9 U/ml |
| ACC 3 μg+QS-21 | Geometric Mean Anti-Aβ IgG Enzyme-linked Immunosorbent Assay (ELISA) Titers | Week 10 (N:22, 20, 42, 20) | 774.8 U/ml |
| ACC 3 μg+QS-21 | Geometric Mean Anti-Aβ IgG Enzyme-linked Immunosorbent Assay (ELISA) Titers | Week 2 (N: 20, 20, 40, 21) | 61.5 U/ml |
| ACC 10 μg+QS-21 | Geometric Mean Anti-Aβ IgG Enzyme-linked Immunosorbent Assay (ELISA) Titers | Week 4 (N: 21, 17, 38, 21) | 86.3 U/ml |
| ACC 10 μg+QS-21 | Geometric Mean Anti-Aβ IgG Enzyme-linked Immunosorbent Assay (ELISA) Titers | Baseline (N: 21, 18, 39, 21) | 50.0 U/ml |
| ACC 10 μg+QS-21 | Geometric Mean Anti-Aβ IgG Enzyme-linked Immunosorbent Assay (ELISA) Titers | Week 2 (N: 20, 20, 40, 21) | 81.4 U/ml |
| ACC 10 μg+QS-21 | Geometric Mean Anti-Aβ IgG Enzyme-linked Immunosorbent Assay (ELISA) Titers | Week 6 (N: 22, 20, 42, 21) | 1485.3 U/ml |
| ACC 10 μg+QS-21 | Geometric Mean Anti-Aβ IgG Enzyme-linked Immunosorbent Assay (ELISA) Titers | Week 10 (N:22, 20, 42, 20) | 960.3 U/ml |
| ACC 10 μg+QS-21 | Geometric Mean Anti-Aβ IgG Enzyme-linked Immunosorbent Assay (ELISA) Titers | Week 12 (N: 22, 18, 40, 20) | 536.0 U/ml |
| ACC 10 μg+QS-21 | Geometric Mean Anti-Aβ IgG Enzyme-linked Immunosorbent Assay (ELISA) Titers | Week 14 (N: 22, 20, 42, 20) | 2796.3 U/ml |
| ACC 10 μg+QS-21 | Geometric Mean Anti-Aβ IgG Enzyme-linked Immunosorbent Assay (ELISA) Titers | Week 20 (N: 21, 20, 41, 21) | 2172.9 U/ml |
| ACC 10 μg+QS-21 | Geometric Mean Anti-Aβ IgG Enzyme-linked Immunosorbent Assay (ELISA) Titers | Week 26 (N: 22, 19, 41, 20) | 1739.1 U/ml |
| ACC 10 μg+QS-21 | Geometric Mean Anti-Aβ IgG Enzyme-linked Immunosorbent Assay (ELISA) Titers | Week 28 (N: 22, 20, 42, 20) | 4668.3 U/ml |
| ACC 10 μg+QS-21 | Geometric Mean Anti-Aβ IgG Enzyme-linked Immunosorbent Assay (ELISA) Titers | Week 34 (N: 22, 20, 42, 20) | 5329.0 U/ml |
| ACC 10 μg+QS-21 | Geometric Mean Anti-Aβ IgG Enzyme-linked Immunosorbent Assay (ELISA) Titers | Week 52 (N: 20, 18, 38, 19) | 1920.8 U/ml |
| ACC 10 μg+QS-21 | Geometric Mean Anti-Aβ IgG Enzyme-linked Immunosorbent Assay (ELISA) Titers | Week 54 (N: 20, 19, 39, 19) | 12064.7 U/ml |
| ACC 10 μg+QS-21 | Geometric Mean Anti-Aβ IgG Enzyme-linked Immunosorbent Assay (ELISA) Titers | Week 60 (N: 21, 19, 40, 19) | 9665.3 U/ml |
| ACC 10 μg+QS-21 | Geometric Mean Anti-Aβ IgG Enzyme-linked Immunosorbent Assay (ELISA) Titers | Week 78 (N: 19, 14, 33, 14) | 2973.5 U/ml |
| ACC 10 μg+QS-21 | Geometric Mean Anti-Aβ IgG Enzyme-linked Immunosorbent Assay (ELISA) Titers | Week 80 (N: 19, 14, 33, 16) | 11086.8 U/ml |
| ACC 10 μg+QS-21 | Geometric Mean Anti-Aβ IgG Enzyme-linked Immunosorbent Assay (ELISA) Titers | Week 86 (N: 15, 17, 32, 14) | 10125.5 U/ml |
| ACC 10 μg+QS-21 | Geometric Mean Anti-Aβ IgG Enzyme-linked Immunosorbent Assay (ELISA) Titers | Week 104 (N: 11, 9, 20, 9) | 3513.9 U/ml |
| Overall ACC + QS21 | Geometric Mean Anti-Aβ IgG Enzyme-linked Immunosorbent Assay (ELISA) Titers | Week 10 (N:22, 20, 42, 20) | 858.1 U/ml |
| Overall ACC + QS21 | Geometric Mean Anti-Aβ IgG Enzyme-linked Immunosorbent Assay (ELISA) Titers | Week 28 (N: 22, 20, 42, 20) | 5544.3 U/ml |
| Overall ACC + QS21 | Geometric Mean Anti-Aβ IgG Enzyme-linked Immunosorbent Assay (ELISA) Titers | Week 34 (N: 22, 20, 42, 20) | 4421.9 U/ml |
| Overall ACC + QS21 | Geometric Mean Anti-Aβ IgG Enzyme-linked Immunosorbent Assay (ELISA) Titers | Week 6 (N: 22, 20, 42, 21) | 1487.7 U/ml |
| Overall ACC + QS21 | Geometric Mean Anti-Aβ IgG Enzyme-linked Immunosorbent Assay (ELISA) Titers | Week 104 (N: 11, 9, 20, 9) | 3753.1 U/ml |
| Overall ACC + QS21 | Geometric Mean Anti-Aβ IgG Enzyme-linked Immunosorbent Assay (ELISA) Titers | Week 52 (N: 20, 18, 38, 19) | 1578.3 U/ml |
| Overall ACC + QS21 | Geometric Mean Anti-Aβ IgG Enzyme-linked Immunosorbent Assay (ELISA) Titers | Week 86 (N: 15, 17, 32, 14) | 8275.6 U/ml |
| Overall ACC + QS21 | Geometric Mean Anti-Aβ IgG Enzyme-linked Immunosorbent Assay (ELISA) Titers | Week 54 (N: 20, 19, 39, 19) | 8982.9 U/ml |
| Overall ACC + QS21 | Geometric Mean Anti-Aβ IgG Enzyme-linked Immunosorbent Assay (ELISA) Titers | Week 4 (N: 21, 17, 38, 21) | 70.0 U/ml |
| Overall ACC + QS21 | Geometric Mean Anti-Aβ IgG Enzyme-linked Immunosorbent Assay (ELISA) Titers | Week 60 (N: 21, 19, 40, 19) | 6185.7 U/ml |
| Overall ACC + QS21 | Geometric Mean Anti-Aβ IgG Enzyme-linked Immunosorbent Assay (ELISA) Titers | Baseline (N: 21, 18, 39, 21) | 50.0 U/ml |
| Overall ACC + QS21 | Geometric Mean Anti-Aβ IgG Enzyme-linked Immunosorbent Assay (ELISA) Titers | Week 78 (N: 19, 14, 33, 14) | 2371.3 U/ml |
| Overall ACC + QS21 | Geometric Mean Anti-Aβ IgG Enzyme-linked Immunosorbent Assay (ELISA) Titers | Week 2 (N: 20, 20, 40, 21) | 70.7 U/ml |
| Overall ACC + QS21 | Geometric Mean Anti-Aβ IgG Enzyme-linked Immunosorbent Assay (ELISA) Titers | Week 14 (N: 22, 20, 42, 20) | 4170.3 U/ml |
| Overall ACC + QS21 | Geometric Mean Anti-Aβ IgG Enzyme-linked Immunosorbent Assay (ELISA) Titers | Week 12 (N: 22, 18, 40, 20) | 552.5 U/ml |
| Overall ACC + QS21 | Geometric Mean Anti-Aβ IgG Enzyme-linked Immunosorbent Assay (ELISA) Titers | Week 20 (N: 21, 20, 41, 21) | 2700.2 U/ml |
| Overall ACC + QS21 | Geometric Mean Anti-Aβ IgG Enzyme-linked Immunosorbent Assay (ELISA) Titers | Week 80 (N: 19, 14, 33, 16) | 9192.0 U/ml |
| Overall ACC + QS21 | Geometric Mean Anti-Aβ IgG Enzyme-linked Immunosorbent Assay (ELISA) Titers | Week 26 (N: 22, 19, 41, 20) | 1694.6 U/ml |
| Placebo | Geometric Mean Anti-Aβ IgG Enzyme-linked Immunosorbent Assay (ELISA) Titers | Week 14 (N: 22, 20, 42, 20) | 50.0 U/ml |
| Placebo | Geometric Mean Anti-Aβ IgG Enzyme-linked Immunosorbent Assay (ELISA) Titers | Week 80 (N: 19, 14, 33, 16) | 50.0 U/ml |
| Placebo | Geometric Mean Anti-Aβ IgG Enzyme-linked Immunosorbent Assay (ELISA) Titers | Week 60 (N: 21, 19, 40, 19) | 50.0 U/ml |
| Placebo | Geometric Mean Anti-Aβ IgG Enzyme-linked Immunosorbent Assay (ELISA) Titers | Week 28 (N: 22, 20, 42, 20) | 50.0 U/ml |
| Placebo | Geometric Mean Anti-Aβ IgG Enzyme-linked Immunosorbent Assay (ELISA) Titers | Week 6 (N: 22, 20, 42, 21) | 50.0 U/ml |
| Placebo | Geometric Mean Anti-Aβ IgG Enzyme-linked Immunosorbent Assay (ELISA) Titers | Baseline (N: 21, 18, 39, 21) | 53.5 U/ml |
| Placebo | Geometric Mean Anti-Aβ IgG Enzyme-linked Immunosorbent Assay (ELISA) Titers | Week 2 (N: 20, 20, 40, 21) | 50.0 U/ml |
| Placebo | Geometric Mean Anti-Aβ IgG Enzyme-linked Immunosorbent Assay (ELISA) Titers | Week 34 (N: 22, 20, 42, 20) | 50.0 U/ml |
| Placebo | Geometric Mean Anti-Aβ IgG Enzyme-linked Immunosorbent Assay (ELISA) Titers | Week 10 (N:22, 20, 42, 20) | 50.0 U/ml |
| Placebo | Geometric Mean Anti-Aβ IgG Enzyme-linked Immunosorbent Assay (ELISA) Titers | Week 104 (N: 11, 9, 20, 9) | 50.0 U/ml |
| Placebo | Geometric Mean Anti-Aβ IgG Enzyme-linked Immunosorbent Assay (ELISA) Titers | Week 78 (N: 19, 14, 33, 14) | 50.0 U/ml |
| Placebo | Geometric Mean Anti-Aβ IgG Enzyme-linked Immunosorbent Assay (ELISA) Titers | Week 52 (N: 20, 18, 38, 19) | 50.0 U/ml |
| Placebo | Geometric Mean Anti-Aβ IgG Enzyme-linked Immunosorbent Assay (ELISA) Titers | Week 4 (N: 21, 17, 38, 21) | 50.0 U/ml |
| Placebo | Geometric Mean Anti-Aβ IgG Enzyme-linked Immunosorbent Assay (ELISA) Titers | Week 12 (N: 22, 18, 40, 20) | 50.0 U/ml |
| Placebo | Geometric Mean Anti-Aβ IgG Enzyme-linked Immunosorbent Assay (ELISA) Titers | Week 26 (N: 22, 19, 41, 20) | 60.7 U/ml |
| Placebo | Geometric Mean Anti-Aβ IgG Enzyme-linked Immunosorbent Assay (ELISA) Titers | Week 54 (N: 20, 19, 39, 19) | 50.0 U/ml |
| Placebo | Geometric Mean Anti-Aβ IgG Enzyme-linked Immunosorbent Assay (ELISA) Titers | Week 20 (N: 21, 20, 41, 21) | 50.0 U/ml |
| Placebo | Geometric Mean Anti-Aβ IgG Enzyme-linked Immunosorbent Assay (ELISA) Titers | Week 86 (N: 15, 17, 32, 14) | 50.0 U/ml |
Other Pre-specified
Geometric Mean Anti-Aβ IgM ELISA Titers
Site personnel collecting the samples for anti-Aβ antibody titers were blinded to the participant treatment group assignment. The LLOQ determined for this assay was 50 U/mL. For any anti-Aβ IgM antibody level that was below the LLOQ (50 U/mL), the LLOD defined as 0.5\*LLOQ was imputed.
Time frame: 104 weeks
Population: FAS population included all randomized participants who had at least one dose of investigational product.
| Arm | Measure | Group | Value (GEOMETRIC_MEAN) |
|---|---|---|---|
| ACC 3 μg+QS-21 | Geometric Mean Anti-Aβ IgM ELISA Titers | Week 52 (N: 20, 18, 38, 19) | 493.8 U/ml |
| ACC 3 μg+QS-21 | Geometric Mean Anti-Aβ IgM ELISA Titers | Week 2 (N: 20, 20, 40, 21) | 69.7 U/ml |
| ACC 3 μg+QS-21 | Geometric Mean Anti-Aβ IgM ELISA Titers | Week 80 (N: 19, 14, 33, 16) | 744.8 U/ml |
| ACC 3 μg+QS-21 | Geometric Mean Anti-Aβ IgM ELISA Titers | Week 12 (N: 22, 18, 40, 19) | 604.2 U/ml |
| ACC 3 μg+QS-21 | Geometric Mean Anti-Aβ IgM ELISA Titers | Week 34 (N: 22, 20, 42, 20) | 953.6 U/ml |
| ACC 3 μg+QS-21 | Geometric Mean Anti-Aβ IgM ELISA Titers | Week 28 (N: 22, 20, 42, 20) | 1241.6 U/ml |
| ACC 3 μg+QS-21 | Geometric Mean Anti-Aβ IgM ELISA Titers | Week 54 (N: 20, 19, 39, 19) | 776.5 U/ml |
| ACC 3 μg+QS-21 | Geometric Mean Anti-Aβ IgM ELISA Titers | Week 14 (N: 22, 20, 42, 20) | 1232.4 U/ml |
| ACC 3 μg+QS-21 | Geometric Mean Anti-Aβ IgM ELISA Titers | Week 6 (N: 22, 20, 42, 21) | 840.8 U/ml |
| ACC 3 μg+QS-21 | Geometric Mean Anti-Aβ IgM ELISA Titers | Baseline (N: 21, 18, 39, 21) | 31.8 U/ml |
| ACC 3 μg+QS-21 | Geometric Mean Anti-Aβ IgM ELISA Titers | Week 60 (N: 21, 19, 40, 19) | 782.2 U/ml |
| ACC 3 μg+QS-21 | Geometric Mean Anti-Aβ IgM ELISA Titers | Week 20 (N: 21, 20, 41, 21) | 1060.2 U/ml |
| ACC 3 μg+QS-21 | Geometric Mean Anti-Aβ IgM ELISA Titers | Week 86 (N: 15, 17, 32, 14) | 768.1 U/ml |
| ACC 3 μg+QS-21 | Geometric Mean Anti-Aβ IgM ELISA Titers | Week 104 (N: 11, 9, 20, 9) | 602.7 U/ml |
| ACC 3 μg+QS-21 | Geometric Mean Anti-Aβ IgM ELISA Titers | Week 78 (N: 19, 14, 33, 14) | 635.3 U/ml |
| ACC 3 μg+QS-21 | Geometric Mean Anti-Aβ IgM ELISA Titers | Week 26 (N: 22, 19, 41, 20) | 684.8 U/ml |
| ACC 3 μg+QS-21 | Geometric Mean Anti-Aβ IgM ELISA Titers | Week 10 (N:22, 20, 42, 20) | 723.6 U/ml |
| ACC 3 μg+QS-21 | Geometric Mean Anti-Aβ IgM ELISA Titers | Week 4 (N: 21, 17, 38, 21) | 75.0 U/ml |
| ACC 10 μg+QS-21 | Geometric Mean Anti-Aβ IgM ELISA Titers | Week 10 (N:22, 20, 42, 20) | 967.3 U/ml |
| ACC 10 μg+QS-21 | Geometric Mean Anti-Aβ IgM ELISA Titers | Week 28 (N: 22, 20, 42, 20) | 1117.1 U/ml |
| ACC 10 μg+QS-21 | Geometric Mean Anti-Aβ IgM ELISA Titers | Week 4 (N: 21, 17, 38, 21) | 141.3 U/ml |
| ACC 10 μg+QS-21 | Geometric Mean Anti-Aβ IgM ELISA Titers | Week 34 (N: 22, 20, 42, 20) | 1084.5 U/ml |
| ACC 10 μg+QS-21 | Geometric Mean Anti-Aβ IgM ELISA Titers | Week 54 (N: 20, 19, 39, 19) | 1176.0 U/ml |
| ACC 10 μg+QS-21 | Geometric Mean Anti-Aβ IgM ELISA Titers | Week 52 (N: 20, 18, 38, 19) | 522.9 U/ml |
| ACC 10 μg+QS-21 | Geometric Mean Anti-Aβ IgM ELISA Titers | Week 86 (N: 15, 17, 32, 14) | 1023.7 U/ml |
| ACC 10 μg+QS-21 | Geometric Mean Anti-Aβ IgM ELISA Titers | Week 6 (N: 22, 20, 42, 21) | 975.8 U/ml |
| ACC 10 μg+QS-21 | Geometric Mean Anti-Aβ IgM ELISA Titers | Week 104 (N: 11, 9, 20, 9) | 287.8 U/ml |
| ACC 10 μg+QS-21 | Geometric Mean Anti-Aβ IgM ELISA Titers | Week 60 (N: 21, 19, 40, 19) | 1228.4 U/ml |
| ACC 10 μg+QS-21 | Geometric Mean Anti-Aβ IgM ELISA Titers | Week 12 (N: 22, 18, 40, 19) | 611.5 U/ml |
| ACC 10 μg+QS-21 | Geometric Mean Anti-Aβ IgM ELISA Titers | Week 2 (N: 20, 20, 40, 21) | 121.0 U/ml |
| ACC 10 μg+QS-21 | Geometric Mean Anti-Aβ IgM ELISA Titers | Week 80 (N: 19, 14, 33, 16) | 677.0 U/ml |
| ACC 10 μg+QS-21 | Geometric Mean Anti-Aβ IgM ELISA Titers | Week 14 (N: 22, 20, 42, 20) | 1194.6 U/ml |
| ACC 10 μg+QS-21 | Geometric Mean Anti-Aβ IgM ELISA Titers | Baseline (N: 21, 18, 39, 21) | 33.9 U/ml |
| ACC 10 μg+QS-21 | Geometric Mean Anti-Aβ IgM ELISA Titers | Week 78 (N: 19, 14, 33, 14) | 321.4 U/ml |
| ACC 10 μg+QS-21 | Geometric Mean Anti-Aβ IgM ELISA Titers | Week 20 (N: 21, 20, 41, 21) | 1070.5 U/ml |
| ACC 10 μg+QS-21 | Geometric Mean Anti-Aβ IgM ELISA Titers | Week 26 (N: 22, 19, 41, 20) | 939.4 U/ml |
| Overall ACC + QS21 | Geometric Mean Anti-Aβ IgM ELISA Titers | Week 80 (N: 19, 14, 33, 16) | 715.2 U/ml |
| Overall ACC + QS21 | Geometric Mean Anti-Aβ IgM ELISA Titers | Baseline (N: 21, 18, 39, 21) | 32.7 U/ml |
| Overall ACC + QS21 | Geometric Mean Anti-Aβ IgM ELISA Titers | Week 2 (N: 20, 20, 40, 21) | 91.8 U/ml |
| Overall ACC + QS21 | Geometric Mean Anti-Aβ IgM ELISA Titers | Week 4 (N: 21, 17, 38, 21) | 99.6 U/ml |
| Overall ACC + QS21 | Geometric Mean Anti-Aβ IgM ELISA Titers | Week 6 (N: 22, 20, 42, 21) | 902.6 U/ml |
| Overall ACC + QS21 | Geometric Mean Anti-Aβ IgM ELISA Titers | Week 10 (N:22, 20, 42, 20) | 830.8 U/ml |
| Overall ACC + QS21 | Geometric Mean Anti-Aβ IgM ELISA Titers | Week 12 (N: 22, 18, 40, 19) | 607.5 U/ml |
| Overall ACC + QS21 | Geometric Mean Anti-Aβ IgM ELISA Titers | Week 14 (N: 22, 20, 42, 20) | 1214.2 U/ml |
| Overall ACC + QS21 | Geometric Mean Anti-Aβ IgM ELISA Titers | Week 20 (N: 21, 20, 41, 21) | 1065.2 U/ml |
| Overall ACC + QS21 | Geometric Mean Anti-Aβ IgM ELISA Titers | Week 26 (N: 22, 19, 41, 20) | 792.9 U/ml |
| Overall ACC + QS21 | Geometric Mean Anti-Aβ IgM ELISA Titers | Week 28 (N: 22, 20, 42, 20) | 1180.6 U/ml |
| Overall ACC + QS21 | Geometric Mean Anti-Aβ IgM ELISA Titers | Week 34 (N: 22, 20, 42, 20) | 1013.9 U/ml |
| Overall ACC + QS21 | Geometric Mean Anti-Aβ IgM ELISA Titers | Week 52 (N: 20, 18, 38, 19) | 507.4 U/ml |
| Overall ACC + QS21 | Geometric Mean Anti-Aβ IgM ELISA Titers | Week 54 (N: 20, 19, 39, 19) | 950.5 U/ml |
| Overall ACC + QS21 | Geometric Mean Anti-Aβ IgM ELISA Titers | Week 60 (N: 21, 19, 40, 19) | 969.2 U/ml |
| Overall ACC + QS21 | Geometric Mean Anti-Aβ IgM ELISA Titers | Week 78 (N: 19, 14, 33, 14) | 475.8 U/ml |
| Overall ACC + QS21 | Geometric Mean Anti-Aβ IgM ELISA Titers | Week 86 (N: 15, 17, 32, 14) | 894.7 U/ml |
| Overall ACC + QS21 | Geometric Mean Anti-Aβ IgM ELISA Titers | Week 104 (N: 11, 9, 20, 9) | 432.2 U/ml |
| Placebo | Geometric Mean Anti-Aβ IgM ELISA Titers | Week 26 (N: 22, 19, 41, 20) | 32.6 U/ml |
| Placebo | Geometric Mean Anti-Aβ IgM ELISA Titers | Week 2 (N: 20, 20, 40, 21) | 30.2 U/ml |
| Placebo | Geometric Mean Anti-Aβ IgM ELISA Titers | Week 60 (N: 21, 19, 40, 19) | 31.0 U/ml |
| Placebo | Geometric Mean Anti-Aβ IgM ELISA Titers | Week 20 (N: 21, 20, 41, 21) | 31.6 U/ml |
| Placebo | Geometric Mean Anti-Aβ IgM ELISA Titers | Week 14 (N: 22, 20, 42, 20) | 32.6 U/ml |
| Placebo | Geometric Mean Anti-Aβ IgM ELISA Titers | Baseline (N: 21, 18, 39, 21) | 31.6 U/ml |
| Placebo | Geometric Mean Anti-Aβ IgM ELISA Titers | Week 78 (N: 19, 14, 33, 14) | 28.5 U/ml |
| Placebo | Geometric Mean Anti-Aβ IgM ELISA Titers | Week 12 (N: 22, 18, 40, 19) | 32.6 U/ml |
| Placebo | Geometric Mean Anti-Aβ IgM ELISA Titers | Week 10 (N:22, 20, 42, 20) | 32.1 U/ml |
| Placebo | Geometric Mean Anti-Aβ IgM ELISA Titers | Week 80 (N: 19, 14, 33, 16) | 30.7 U/ml |
| Placebo | Geometric Mean Anti-Aβ IgM ELISA Titers | Week 6 (N: 22, 20, 42, 21) | 31.5 U/ml |
| Placebo | Geometric Mean Anti-Aβ IgM ELISA Titers | Week 4 (N: 21, 17, 38, 21) | 31.0 U/ml |
| Placebo | Geometric Mean Anti-Aβ IgM ELISA Titers | Week 104 (N: 11, 9, 20, 9) | 29.2 U/ml |
| Placebo | Geometric Mean Anti-Aβ IgM ELISA Titers | Week 52 (N: 20, 18, 38, 19) | 29.2 U/ml |
| Placebo | Geometric Mean Anti-Aβ IgM ELISA Titers | Week 34 (N: 22, 20, 42, 20) | 32.0 U/ml |
| Placebo | Geometric Mean Anti-Aβ IgM ELISA Titers | Week 86 (N: 15, 17, 32, 14) | 32.2 U/ml |
| Placebo | Geometric Mean Anti-Aβ IgM ELISA Titers | Week 54 (N: 20, 19, 39, 19) | 29.8 U/ml |
| Placebo | Geometric Mean Anti-Aβ IgM ELISA Titers | Week 28 (N: 22, 20, 42, 20) | 31.9 U/ml |
Other Pre-specified
Percentage of Participants With a Global CDR Score of Equal to or Greater Than 1 for the First Time
CDR is a global clinical staging instrument that was administrated by a trained rater to assess a participant's level of impairment in six domains including: Memory, Orientation, Judgement and Problem Solving, Community Affairs, Home and Hobbies, and Personal Care, based on the CDR interview. The CDR included discussions with the participant and study partner using a structured format. CDR global score was derived from the six domains according to a complex algorithm with emphasis on the Memory Domain score. Global CDR score = 0.5 with memory box score of 0.5. The total CDR-SB score is calculated as the sum of the six clinical ratings. The CDR-SOB score range for each domain is 0 to 3, with higher score indicating no significant function. If any individual item is missing, then the CDR-SB is set to missing.
Time frame: 104 weeks
Population: FAS population included all randomized participants who had at least one dose of investigational product.
| Arm | Measure | Group | Value (NUMBER) |
|---|---|---|---|
| ACC 3 μg+QS-21 | Percentage of Participants With a Global CDR Score of Equal to or Greater Than 1 for the First Time | Week 26 | 86.4 percentage of participants |
| ACC 3 μg+QS-21 | Percentage of Participants With a Global CDR Score of Equal to or Greater Than 1 for the First Time | Week 52 | 0.0 percentage of participants |
| ACC 3 μg+QS-21 | Percentage of Participants With a Global CDR Score of Equal to or Greater Than 1 for the First Time | Week 78 | 13.6 percentage of participants |
| ACC 3 μg+QS-21 | Percentage of Participants With a Global CDR Score of Equal to or Greater Than 1 for the First Time | Week 104 | 0.0 percentage of participants |
| ACC 10 μg+QS-21 | Percentage of Participants With a Global CDR Score of Equal to or Greater Than 1 for the First Time | Week 104 | 10.0 percentage of participants |
| ACC 10 μg+QS-21 | Percentage of Participants With a Global CDR Score of Equal to or Greater Than 1 for the First Time | Week 78 | 0.0 percentage of participants |
| ACC 10 μg+QS-21 | Percentage of Participants With a Global CDR Score of Equal to or Greater Than 1 for the First Time | Week 52 | 15.0 percentage of participants |
| ACC 10 μg+QS-21 | Percentage of Participants With a Global CDR Score of Equal to or Greater Than 1 for the First Time | Week 26 | 70.0 percentage of participants |
| Overall ACC + QS21 | Percentage of Participants With a Global CDR Score of Equal to or Greater Than 1 for the First Time | Week 78 | 7.1 percentage of participants |
| Overall ACC + QS21 | Percentage of Participants With a Global CDR Score of Equal to or Greater Than 1 for the First Time | Week 104 | 4.8 percentage of participants |
| Overall ACC + QS21 | Percentage of Participants With a Global CDR Score of Equal to or Greater Than 1 for the First Time | Week 52 | 7.1 percentage of participants |
| Overall ACC + QS21 | Percentage of Participants With a Global CDR Score of Equal to or Greater Than 1 for the First Time | Week 26 | 78.6 percentage of participants |
| Placebo | Percentage of Participants With a Global CDR Score of Equal to or Greater Than 1 for the First Time | Week 52 | 10.0 percentage of participants |
| Placebo | Percentage of Participants With a Global CDR Score of Equal to or Greater Than 1 for the First Time | Week 26 | 80.0 percentage of participants |
| Placebo | Percentage of Participants With a Global CDR Score of Equal to or Greater Than 1 for the First Time | Week 104 | 0.0 percentage of participants |
| Placebo | Percentage of Participants With a Global CDR Score of Equal to or Greater Than 1 for the First Time | Week 78 | 0.0 percentage of participants |