Alzheimer's Disease (AD)
Conditions
Keywords
Alzheimer's disease (AD), Dementia, ABBV-552
Brief summary
Alzheimer's disease (AD) is a progressive, irreversible neurological disorder and is the most common cause of dementia in the elderly population. Clinical symptoms of the disease may begin with occasional forgetfulness such as misplacement of items, forgetting important dates or events, and may progress to noticeable memory loss, increased confusion and agitation, and eventually, loss of independence and non-responsiveness. This study will assess how safe and effective ABBV-552 is in treating symptoms of early AD. Adverse events, change in disease activity, how ABBV-552 moves through body of participants and the body response to ABBV-552 will be assessed. ABBV-552 is an investigational drug being developed for the treatment of Alzheimer's disease (AD). Study doctors put the participants in 1 of 4 groups (3 active dose groups and a placebo group), called treatment arms. Each group receives a different treatment. There is a 1 in 4 chance that participants will be assigned to placebo. Approximately 240 participants aged 50-90 years with mild AD will be enrolled in approximately 60 sites across the world. Participants will receive oral ABBV-552 or placebo capsules once daily for 12 weeks and followed for 30 days after the last dose of study drug. There may be higher treatment burden for participants in this trial compared to their standard of care. Participants will attend regular visits during the study at a hospital or clinic. The effect of the treatment will be checked by medical assessments, blood tests, checking for side effects and completing questionnaires.
Interventions
DRUGABBV-552
Oral Capsule
DRUGPlacebo for ABBV-552
Oral Capsule
Sponsors
AbbVie
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 90 Years
Healthy volunteers
No
Inclusion criteria
* Diagnosis of probable Alzheimer's disease according to the National Institute of Aging-Alzheimer's Association (NIA-AA) (2011) criteria. * Mini-Mental State Examination (MMSE) score of 20 to 26, a Clinical Dementia Rating (CDR) global score of 0.5 or 1.0, with a CDR memory score of 0.5 or higher, and at least 1 CDR functional domain (community affairs, home and hobbies, or personal care) score of 0.5 or higher at Screening Visit 1.
Exclusion criteria
\- Clinically significant and/or unstable medical conditions or any other reason that the investigator determines would interfere with participation in this study (e.g., unlikely to adhere to the study or procedures, keep appointments, or is planning to relocate during the study) or would make the participant an unsuitable candidate to receive ABBV-552.
Design outcomes
Primary
| Measure | Time frame | Description |
|---|---|---|
| Change From Baseline in the Alzheimer's Disease Assessment Scale-Cognitive Subscale (ADAS-Cog 14) Score at Week 12 | Week 12 | The ADAS-Cog was designed to assess the cognitive impairments most common in AD. The ADAS-Cog-14 includes the original 11 items from the ADAS-Cog-11 \[1. Spoken language ability, 2. Comprehension of spoken language, 3. Recall of test instructions, 4. Word-findings difficulty in spontaneous speech, 5. Following commands, 6. Naming objects and fingers, 7. Constructional praxis, 8. Ideational praxis, 9. Orientation, 10. Word-recall task, 11. Word-recognition task\] and includes 3 additional tasks \[12. Number cancellation task, 13. Delayed word recall task, 14. Executive functioning\], for increased sensitivity in mild cognitive impairment (MCI) patients. The Total Score of the ADAS-Cog-14 ranges from 0 to 90, with a higher score representing greater impairment. |
Countries
Australia, Germany, Japan, New Zealand, Spain, United Kingdom, United States
Participant flow
Participants by arm
| Arm | Count |
|---|---|
| Placebo Participants received placebo for ABBV-552 once daily (QD) for 12 weeks. | 66 |
| ABBV-552: 1 mg Participants received 1 mg of ABBV-552 QD for 12 weeks. | 65 |
| ABBV-552: 5 mg Participants received 5 mg of ABBV-552 QD for 12 weeks. | 65 |
| ABBV-552: 15 mg Participants received 5 mg of ABBV-552 QD for 12 weeks. | 66 |
| Total | 262 |
Withdrawals & dropouts
| Period | Reason | FG000 | FG001 | FG002 | FG003 |
|---|---|---|---|---|---|
| Overall Study | Adverse Event | 0 | 1 | 1 | 1 |
| Overall Study | Other | 0 | 1 | 2 | 1 |
| Overall Study | Randomized but Not Treated | 0 | 0 | 1 | 0 |
| Overall Study | Withdrawal by Subject | 3 | 2 | 1 | 4 |
Baseline characteristics
| Characteristic | Placebo | Total | ABBV-552: 15 mg | ABBV-552: 5 mg | ABBV-552: 1 mg |
|---|---|---|---|---|---|
| ADAS-Cog 14 Score at Baseline | 24.10 units on a scale STANDARD_DEVIATION 8.26 | 23.54 units on a scale STANDARD_DEVIATION 8.188 | 23.82 units on a scale STANDARD_DEVIATION 8.273 | 23.24 units on a scale STANDARD_DEVIATION 7.78 | 22.99 units on a scale STANDARD_DEVIATION 8.573 |
| Age, Continuous | 72.7 years STANDARD_DEVIATION 9.19 | 73.1 years STANDARD_DEVIATION 7.97 | 73.1 years STANDARD_DEVIATION 7.6 | 73.2 years STANDARD_DEVIATION 7.78 | 73.5 years STANDARD_DEVIATION 7.33 |
| Ethnicity (NIH/OMB) Hispanic or Latino | 20 Participants | 94 Participants | 22 Participants | 27 Participants | 25 Participants |
| Ethnicity (NIH/OMB) Not Hispanic or Latino | 46 Participants | 168 Participants | 44 Participants | 38 Participants | 40 Participants |
| Ethnicity (NIH/OMB) Unknown or Not Reported | 0 Participants | 0 Participants | 0 Participants | 0 Participants | 0 Participants |
| Race (NIH/OMB) American Indian or Alaska Native | 0 Participants | 1 Participants | 0 Participants | 0 Participants | 1 Participants |
| Race (NIH/OMB) Asian | 6 Participants | 26 Participants | 10 Participants | 7 Participants | 3 Participants |
| Race (NIH/OMB) Black or African American | 8 Participants | 27 Participants | 7 Participants | 7 Participants | 5 Participants |
| Race (NIH/OMB) More than one race | 0 Participants | 1 Participants | 1 Participants | 0 Participants | 0 Participants |
| Race (NIH/OMB) Native Hawaiian or Other Pacific Islander | 0 Participants | 0 Participants | 0 Participants | 0 Participants | 0 Participants |
| Race (NIH/OMB) Unknown or Not Reported | 0 Participants | 2 Participants | 1 Participants | 0 Participants | 1 Participants |
| Race (NIH/OMB) White | 52 Participants | 205 Participants | 47 Participants | 51 Participants | 55 Participants |
| Sex: Female, Male Female | 30 Participants | 146 Participants | 33 Participants | 43 Participants | 40 Participants |
| Sex: Female, Male Male | 36 Participants | 116 Participants | 33 Participants | 22 Participants | 25 Participants |
Adverse events
| Event type | EG000 affected / at risk | EG001 affected / at risk | EG002 affected / at risk | EG003 affected / at risk |
|---|---|---|---|---|
| deaths Total, all-cause mortality | 0 / 66 | 0 / 65 | 1 / 66 | 0 / 66 |
| other Total, other adverse events | 15 / 66 | 16 / 65 | 19 / 66 | 20 / 66 |
| serious Total, serious adverse events | 3 / 66 | 3 / 65 | 2 / 66 | 2 / 66 |
Outcome results
Primary
Change From Baseline in the Alzheimer's Disease Assessment Scale-Cognitive Subscale (ADAS-Cog 14) Score at Week 12
The ADAS-Cog was designed to assess the cognitive impairments most common in AD. The ADAS-Cog-14 includes the original 11 items from the ADAS-Cog-11 \[1. Spoken language ability, 2. Comprehension of spoken language, 3. Recall of test instructions, 4. Word-findings difficulty in spontaneous speech, 5. Following commands, 6. Naming objects and fingers, 7. Constructional praxis, 8. Ideational praxis, 9. Orientation, 10. Word-recall task, 11. Word-recognition task\] and includes 3 additional tasks \[12. Number cancellation task, 13. Delayed word recall task, 14. Executive functioning\], for increased sensitivity in mild cognitive impairment (MCI) patients. The Total Score of the ADAS-Cog-14 ranges from 0 to 90, with a higher score representing greater impairment.
Time frame: Week 12
Population: mITT population includes participants who received at least 1 dose of study drug, have at least 1 post baseline assessment of ADAS-Cog 14, and have data available for analysis.
| Arm | Measure | Value (LEAST_SQUARES_MEAN) | Dispersion |
|---|---|---|---|
| Placebo | Change From Baseline in the Alzheimer's Disease Assessment Scale-Cognitive Subscale (ADAS-Cog 14) Score at Week 12 | -1.26 score on a scale | Standard Error 0.66 |
| ABBV-552: 1 mg | Change From Baseline in the Alzheimer's Disease Assessment Scale-Cognitive Subscale (ADAS-Cog 14) Score at Week 12 | -1.28 score on a scale | Standard Error 0.668 |
| ABBV-552: 5 mg | Change From Baseline in the Alzheimer's Disease Assessment Scale-Cognitive Subscale (ADAS-Cog 14) Score at Week 12 | -1.68 score on a scale | Standard Error 0.658 |
| ABBV-552: 15 mg | Change From Baseline in the Alzheimer's Disease Assessment Scale-Cognitive Subscale (ADAS-Cog 14) Score at Week 12 | -1.01 score on a scale | Standard Error 0.655 |
p-value: 0.981995% CI: [-1.87, 1.83]Mixed-effect Model Repeated Measurement
p-value: 0.654595% CI: [-2.25, 1.42]Mixed-effect Model Repeated Measurement
p-value: 0.78695% CI: [-1.58, 2.08]Mixed-effect Model Repeated Measurement