Alzheimer Disease
Conditions
Brief summary
A phase 2 randomized, double blind, placebo controlled study evaluating the efficacy and safety of AL002 in participants with Early Alzheimer's Disease.
Detailed description
This is a phase 2 randomized, double blind, placebo controlled study evaluating the efficacy and safety of AL002 administered intravenously in participants with Early Alzheimer's Disease.
Interventions
DRUGAL002
Administered via intravenous (IV) infusion
DRUGPlacebo
Administered via intravenous (IV) infusion
Sponsors
Alector Inc.
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 85 Years
Healthy volunteers
No
Inclusion criteria
* Diagnosis of Early AD including evidence of brain amyloidosis by CSF or PET * MMSE score ≥ 20 points, CDR Global Score of 0.5 - 1.0, and RBANS score on the DMI ≤95. * Study partner who consents to study participation and who cares for/visits the participant at least 10 hours a week * Written informed consent must be obtained and documented (from the participant or, where jurisdictions allow it, from their legal decision maker).
Exclusion criteria
* Dementia due to a condition other than AD including, but not limited to, FTD, Parkinson's disease, dementia with Lewy bodies, Huntington disease, or vascular dementia. * Known history of severe allergic, anaphylactic, or other hypersensitivity reactions to chimeric, human, or humanized antibodies or fusion proteins. * Current uncontrolled hypertension, diabetes mellitus or thyroid disease. Clinically significant heart disease, liver disease or kidney disease. * History or evidence of clinically significant brain disease other than AD. * Females who are pregnant or breastfeeding, or planning to conceive within the study period. * Any experimental vaccine or gene therapy. * History of unresolved cancer. * Current use of anticoagulant medications. * Residence in a skilled nursing facility, convalescent home, or long term care facility at screening; or requires continuous nursing care. * Participant is positive for presence of APOE e4/e4 genotype.
Design outcomes
Primary
| Measure | Time frame | Description |
|---|---|---|
| Disease Progression as Measured by the Clinical Dementia Rating - Sum of Boxes (CDR-SB) Score | Study completion up to 96 weeks | Change from baseline in Clinical Dementia Rating - Sum of Boxes (CDR-SB) score at Weeks 24, 48, 72 and 96. The CDR-SB is a tool used to measure disease severity in Alzheimer's disease. This scale assesses three domains of cognition and three domains of function. The domains are rated on a 5 point scale in which the higher the score corresponds to greater cognitive impairment. The scale range is from 0 to 18 where 0 is considered normal and 18 indicates severe dementia. |
Secondary
| Measure | Time frame | Description |
|---|---|---|
| Change in Mini-Mental Status Examination (MMSE) Score | Study completion up to 96 weeks | Change from baseline in Mini-Mental Status Examination (MMSE) score at Weeks 24, 48, 72, and 96 The MMSE is a test that assesses orientation, registration, attention and calculation, recent memory, language and constructional praxis. There is a total possible score of 30 with a lower score correlating to a higher cognitive impairment. A score of 24 to 30 is considered normal or no cognitive impairment. A score of 18 to 24 indicates mild impairment. A score of 0 to 17 indicates a severe impairment. |
| Change in Repeatable Battery for the Assessment of Neuropsychological Status (RBANS) Score | Study completion up to 96 weeks | Change from baseline in Repeatable Battery for the Assessment of Neuropsychological Status (RBANS) score at Weeks 24, 48, 72 and 96 The RBANS test is a collection of 12 subsets representing 5 neurological domains: immediate memory, visuospatial/constructional, language, attention, and delayed memory. The scores are converted to a scale that can range from 40 to 160. The lower the score the greater the cognitive impairment. |
| Change in Alzheimer's Disease Assessment Scale - Cognitive Subscale (ADAS-Cog13) Score | Study completion up to 96 weeks | Change from baseline in Alzheimer's Disease Assessment Scale - Cognitive Subscale (ADAS-Cog13) score at Weeks 24, 48, 72, and 96 The ADAS-Cog13 is a scale that includes 13 items to assess cognitive function. These domains include memory, language, praxis, and orientation, as well as a number cancellation task and a delayed free recall task. There is a total score range of 0 to 85. A higher score on this scale indicates greater cognitive impairment. There are currently no universally accepted severity bands for ADAS-Cog13 as it is used to track changes in disease and not for severity. |
| Change in Alzheimer's Disease Cooperative Study - Activities of Daily Living - Mild Cognitive Impairment (ADCS-ADL-MCI) Score | Study completion up to 96 weeks | Change from baseline in Alzheimer's Disease Cooperative Study - Activities of Daily Living - Mild Cognitive Impairment (ADCS-ADL-MCI) score at Weeks 24, 48, 72, and 96 The ADCS-ADL-MCI is a scale for participants with mild cognitive impairment that observes their performance in completing activities associated with daily living. This scale is a multiple choice questionnaire and has a range of 0 to 53. A lower score on this scale indicates greater cognitive impairment. |
| Change in Alzheimer's Disease Composite Score (ADCOMS) Score | Study completion up to 96 weeks | Change from baseline in Alzheimer's Disease Composite Score (ADCOMS) score at Weeks 24, 48, 72, and 96 The ADCOMS scale is a composite score of 12 components that include 4 items from the ADAS-Cog13, 2 items from the MMSE, and all 6 items from the CDR-SB scales. The range of the ADCOMS is between 0 and 1.97. The higher the score the greater the cognitive impairment. |
Countries
Argentina, Australia, Canada, France, Germany, Italy, Netherlands, New Zealand, Poland, Spain, United Kingdom, United States
Participant flow
Recruitment details
Approximately 328 participants were planned to be enrolled: Part 1: Approximately 40 participants were to be randomized in a 1:1:1:1 ratio to receive either 15 mg/kg AL002, 40 mg/kg AL002, 60 mg/kg AL002, or placebo. Part 2: Approximately 288 participants were to be enrolled with the same allocation ratio (1:1:1:1) used in Part 1.
Pre-assignment details
Screening period of up to 8 weeks prior to the optional Predose Baseline Visit or to Day 1 visit.
Participants by arm
| Arm | Count |
|---|---|
| AL002 Dose 1: 15 mg/kg AL002 every 4 weeks | 97 |
| AL002 Dose 2: 40 mg/kg AL002 every 4 weeks | 94 |
| AL002 Dose 3: 60 mg/kg AL002 every 4 weeks | 77 |
| Placebo Placebo every 4 weeks | 88 |
| Total | 356 |
Baseline characteristics
| Characteristic | AL002 Dose 1: 15 mg/kg | AL002 Dose 2: 40 mg/kg | AL002 Dose 3: 60 mg/kg | Placebo | Total |
|---|---|---|---|---|---|
| Age, Categorical <=18 years | 0 Participants | 0 Participants | 0 Participants | 0 Participants | 0 Participants |
| Age, Categorical >=65 years | 73 Participants | 70 Participants | 62 Participants | 73 Participants | 278 Participants |
| Age, Categorical Between 18 and 65 years | 24 Participants | 24 Participants | 15 Participants | 15 Participants | 78 Participants |
| Ethnicity (NIH/OMB) Hispanic or Latino | 4 Participants | 5 Participants | 4 Participants | 4 Participants | 17 Participants |
| Ethnicity (NIH/OMB) Not Hispanic or Latino | 87 Participants | 86 Participants | 70 Participants | 81 Participants | 324 Participants |
| Ethnicity (NIH/OMB) Unknown or Not Reported | 6 Participants | 3 Participants | 3 Participants | 3 Participants | 15 Participants |
| Race (NIH/OMB) American Indian or Alaska Native | 0 Participants | 0 Participants | 0 Participants | 0 Participants | 0 Participants |
| Race (NIH/OMB) Asian | 0 Participants | 0 Participants | 2 Participants | 1 Participants | 3 Participants |
| Race (NIH/OMB) Black or African American | 3 Participants | 0 Participants | 0 Participants | 0 Participants | 3 Participants |
| Race (NIH/OMB) More than one race | 0 Participants | 0 Participants | 0 Participants | 1 Participants | 1 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 | 6 Participants | 2 Participants | 3 Participants | 4 Participants | 15 Participants |
| Race (NIH/OMB) White | 88 Participants | 92 Participants | 72 Participants | 82 Participants | 334 Participants |
| Sex: Female, Male Female | 45 Participants | 52 Participants | 39 Participants | 44 Participants | 180 Participants |
| Sex: Female, Male Male | 52 Participants | 42 Participants | 38 Participants | 44 Participants | 176 Participants |
Adverse events
| Event type | EG000 affected / at risk | EG001 affected / at risk | EG002 affected / at risk | EG003 affected / at risk |
|---|---|---|---|---|
| deaths Total, all-cause mortality | 1 / 97 | 1 / 94 | 1 / 77 | 1 / 88 |
| other Total, other adverse events | 66 / 97 | 75 / 94 | 59 / 77 | 64 / 88 |
| serious Total, serious adverse events | 14 / 97 | 12 / 94 | 10 / 77 | 7 / 88 |
Outcome results
Primary
Disease Progression as Measured by the Clinical Dementia Rating - Sum of Boxes (CDR-SB) Score
Change from baseline in Clinical Dementia Rating - Sum of Boxes (CDR-SB) score at Weeks 24, 48, 72 and 96. The CDR-SB is a tool used to measure disease severity in Alzheimer's disease. This scale assesses three domains of cognition and three domains of function. The domains are rated on a 5 point scale in which the higher the score corresponds to greater cognitive impairment. The scale range is from 0 to 18 where 0 is considered normal and 18 indicates severe dementia.
Time frame: Study completion up to 96 weeks
Population: Adult participants with early Alzheimer's Disease excluding apolipoprotein E homozygotes
| Arm | Measure | Group | Value (LEAST_SQUARES_MEAN) | Dispersion |
|---|---|---|---|---|
| AL002 Dose 1: 15 mg/kg | Disease Progression as Measured by the Clinical Dementia Rating - Sum of Boxes (CDR-SB) Score | Week 24 Change from Baseline | 1.02 Score on a scale | Standard Error 0.197 |
| AL002 Dose 1: 15 mg/kg | Disease Progression as Measured by the Clinical Dementia Rating - Sum of Boxes (CDR-SB) Score | Week 48 Change from Baseline | 1.68 Score on a scale | Standard Error 0.256 |
| AL002 Dose 1: 15 mg/kg | Disease Progression as Measured by the Clinical Dementia Rating - Sum of Boxes (CDR-SB) Score | Week 72 Change from Baseline | 2.61 Score on a scale | Standard Error 0.366 |
| AL002 Dose 1: 15 mg/kg | Disease Progression as Measured by the Clinical Dementia Rating - Sum of Boxes (CDR-SB) Score | Week 96 Change from Baseline | 3.17 Score on a scale | Standard Error 0.488 |
| AL002 Dose 2: 40 mg/kg | Disease Progression as Measured by the Clinical Dementia Rating - Sum of Boxes (CDR-SB) Score | Week 48 Change from Baseline | 1.61 Score on a scale | Standard Error 0.256 |
| AL002 Dose 2: 40 mg/kg | Disease Progression as Measured by the Clinical Dementia Rating - Sum of Boxes (CDR-SB) Score | Week 72 Change from Baseline | 2.93 Score on a scale | Standard Error 0.358 |
| AL002 Dose 2: 40 mg/kg | Disease Progression as Measured by the Clinical Dementia Rating - Sum of Boxes (CDR-SB) Score | Week 96 Change from Baseline | 3.61 Score on a scale | Standard Error 0.498 |
| AL002 Dose 2: 40 mg/kg | Disease Progression as Measured by the Clinical Dementia Rating - Sum of Boxes (CDR-SB) Score | Week 24 Change from Baseline | 0.80 Score on a scale | Standard Error 0.19 |
| AL002 Dose 3: 60 mg/kg | Disease Progression as Measured by the Clinical Dementia Rating - Sum of Boxes (CDR-SB) Score | Week 72 Change from Baseline | 2.12 Score on a scale | Standard Error 0.372 |
| AL002 Dose 3: 60 mg/kg | Disease Progression as Measured by the Clinical Dementia Rating - Sum of Boxes (CDR-SB) Score | Week 48 Change from Baseline | 1.95 Score on a scale | Standard Error 0.259 |
| AL002 Dose 3: 60 mg/kg | Disease Progression as Measured by the Clinical Dementia Rating - Sum of Boxes (CDR-SB) Score | Week 96 Change from Baseline | 3.31 Score on a scale | Standard Error 0.506 |
| AL002 Dose 3: 60 mg/kg | Disease Progression as Measured by the Clinical Dementia Rating - Sum of Boxes (CDR-SB) Score | Week 24 Change from Baseline | 1.07 Score on a scale | Standard Error 0.196 |
| Placebo | Disease Progression as Measured by the Clinical Dementia Rating - Sum of Boxes (CDR-SB) Score | Week 96 Change from Baseline | 3.48 Score on a scale | Standard Error 0.435 |
| Placebo | Disease Progression as Measured by the Clinical Dementia Rating - Sum of Boxes (CDR-SB) Score | Week 48 Change from Baseline | 1.68 Score on a scale | Standard Error 0.236 |
| Placebo | Disease Progression as Measured by the Clinical Dementia Rating - Sum of Boxes (CDR-SB) Score | Week 24 Change from Baseline | 1.15 Score on a scale | Standard Error 0.18 |
| Placebo | Disease Progression as Measured by the Clinical Dementia Rating - Sum of Boxes (CDR-SB) Score | Week 72 Change from Baseline | 2.25 Score on a scale | Standard Error 0.324 |
Comparison: This is using the Week 96 timepointp-value: 0.797595% CI: [-1.49, 1.15]Mixed Models Analysis
Comparison: This is using the Week 96 timepointp-value: 0.634195% CI: [-1.61, 0.98]Mixed Models Analysis
Comparison: This is using the Week 96 timepointp-value: 0.848995% CI: [-1.18, 1.43]Mixed Models Analysis
Secondary
Change in Alzheimer's Disease Assessment Scale - Cognitive Subscale (ADAS-Cog13) Score
Change from baseline in Alzheimer's Disease Assessment Scale - Cognitive Subscale (ADAS-Cog13) score at Weeks 24, 48, 72, and 96 The ADAS-Cog13 is a scale that includes 13 items to assess cognitive function. These domains include memory, language, praxis, and orientation, as well as a number cancellation task and a delayed free recall task. There is a total score range of 0 to 85. A higher score on this scale indicates greater cognitive impairment. There are currently no universally accepted severity bands for ADAS-Cog13 as it is used to track changes in disease and not for severity.
Time frame: Study completion up to 96 weeks
Population: Adult participants with early Alzheimer's Disease excluding apolipoprotein E homozygotes
| Arm | Measure | Group | Value (LEAST_SQUARES_MEAN) | Dispersion |
|---|---|---|---|---|
| AL002 Dose 1: 15 mg/kg | Change in Alzheimer's Disease Assessment Scale - Cognitive Subscale (ADAS-Cog13) Score | Week 72 Change from Baseline | 7.31 Score on a scale | Standard Error 1.325 |
| AL002 Dose 1: 15 mg/kg | Change in Alzheimer's Disease Assessment Scale - Cognitive Subscale (ADAS-Cog13) Score | Week 24 Change from Baseline | 1.09 Score on a scale | Standard Error 0.71 |
| AL002 Dose 1: 15 mg/kg | Change in Alzheimer's Disease Assessment Scale - Cognitive Subscale (ADAS-Cog13) Score | Week 96 Change from Baseline | 9.59 Score on a scale | Standard Error 1.543 |
| AL002 Dose 1: 15 mg/kg | Change in Alzheimer's Disease Assessment Scale - Cognitive Subscale (ADAS-Cog13) Score | Week 48 Change from Baseline | 3.86 Score on a scale | Standard Error 0.96 |
| AL002 Dose 2: 40 mg/kg | Change in Alzheimer's Disease Assessment Scale - Cognitive Subscale (ADAS-Cog13) Score | Week 48 Change from Baseline | 6.06 Score on a scale | Standard Error 0.95 |
| AL002 Dose 2: 40 mg/kg | Change in Alzheimer's Disease Assessment Scale - Cognitive Subscale (ADAS-Cog13) Score | Week 72 Change from Baseline | 8.30 Score on a scale | Standard Error 1.285 |
| AL002 Dose 2: 40 mg/kg | Change in Alzheimer's Disease Assessment Scale - Cognitive Subscale (ADAS-Cog13) Score | Week 96 Change from Baseline | 10.02 Score on a scale | Standard Error 1.541 |
| AL002 Dose 2: 40 mg/kg | Change in Alzheimer's Disease Assessment Scale - Cognitive Subscale (ADAS-Cog13) Score | Week 24 Change from Baseline | 3.04 Score on a scale | Standard Error 0.697 |
| AL002 Dose 3: 60 mg/kg | Change in Alzheimer's Disease Assessment Scale - Cognitive Subscale (ADAS-Cog13) Score | Week 24 Change from Baseline | 3.54 Score on a scale | Standard Error 0.717 |
| AL002 Dose 3: 60 mg/kg | Change in Alzheimer's Disease Assessment Scale - Cognitive Subscale (ADAS-Cog13) Score | Week 48 Change from Baseline | 5.67 Score on a scale | Standard Error 0.967 |
| AL002 Dose 3: 60 mg/kg | Change in Alzheimer's Disease Assessment Scale - Cognitive Subscale (ADAS-Cog13) Score | Week 72 Change from Baseline | 7.34 Score on a scale | Standard Error 1.321 |
| AL002 Dose 3: 60 mg/kg | Change in Alzheimer's Disease Assessment Scale - Cognitive Subscale (ADAS-Cog13) Score | Week 96 Change from Baseline | 11.55 Score on a scale | Standard Error 1.563 |
| Placebo | Change in Alzheimer's Disease Assessment Scale - Cognitive Subscale (ADAS-Cog13) Score | Week 24 Change from Baseline | 1.93 Score on a scale | Standard Error 0.659 |
| Placebo | Change in Alzheimer's Disease Assessment Scale - Cognitive Subscale (ADAS-Cog13) Score | Week 48 Change from Baseline | 3.79 Score on a scale | Standard Error 0.88 |
| Placebo | Change in Alzheimer's Disease Assessment Scale - Cognitive Subscale (ADAS-Cog13) Score | Week 96 Change from Baseline | 8.62 Score on a scale | Standard Error 1.397 |
| Placebo | Change in Alzheimer's Disease Assessment Scale - Cognitive Subscale (ADAS-Cog13) Score | Week 72 Change from Baseline | 6.26 Score on a scale | Standard Error 1.205 |
Comparison: This is using the Week 96 timepointp-value: 0.640395% CI: [-3.14, 5.09]Mixed Models Analysis
Comparison: This is using the Week 96 timepointp-value: 0.501695% CI: [-2.71, 5.51]Mixed Models Analysis
Comparison: This is using the Week 96 timepointp-value: 0.163195% CI: [-1.21, 7.08]Mixed Models Analysis
Secondary
Change in Alzheimer's Disease Composite Score (ADCOMS) Score
Change from baseline in Alzheimer's Disease Composite Score (ADCOMS) score at Weeks 24, 48, 72, and 96 The ADCOMS scale is a composite score of 12 components that include 4 items from the ADAS-Cog13, 2 items from the MMSE, and all 6 items from the CDR-SB scales. The range of the ADCOMS is between 0 and 1.97. The higher the score the greater the cognitive impairment.
Time frame: Study completion up to 96 weeks
Population: Adult participants with early Alzheimer's Disease excluding apolipoprotein E homozygotes
| Arm | Measure | Group | Value (LEAST_SQUARES_MEAN) | Dispersion |
|---|---|---|---|---|
| AL002 Dose 1: 15 mg/kg | Change in Alzheimer's Disease Composite Score (ADCOMS) Score | Week 24 Change from Baseline | 0.11 Score on a scale | Standard Error 0.02 |
| AL002 Dose 1: 15 mg/kg | Change in Alzheimer's Disease Composite Score (ADCOMS) Score | Week 48 Change from Baseline | 0.19 Score on a scale | Standard Error 0.027 |
| AL002 Dose 1: 15 mg/kg | Change in Alzheimer's Disease Composite Score (ADCOMS) Score | Week 72 Change from Baseline | 0.25 Score on a scale | Standard Error 0.041 |
| AL002 Dose 1: 15 mg/kg | Change in Alzheimer's Disease Composite Score (ADCOMS) Score | Week 96 Change from Baseline | 0.32 Score on a scale | Standard Error 0.052 |
| AL002 Dose 2: 40 mg/kg | Change in Alzheimer's Disease Composite Score (ADCOMS) Score | Week 48 Change from Baseline | 0.20 Score on a scale | Standard Error 0.027 |
| AL002 Dose 2: 40 mg/kg | Change in Alzheimer's Disease Composite Score (ADCOMS) Score | Week 72 Change from Baseline | 0.36 Score on a scale | Standard Error 0.039 |
| AL002 Dose 2: 40 mg/kg | Change in Alzheimer's Disease Composite Score (ADCOMS) Score | Week 96 Change from Baseline | 0.43 Score on a scale | Standard Error 0.052 |
| AL002 Dose 2: 40 mg/kg | Change in Alzheimer's Disease Composite Score (ADCOMS) Score | Week 24 Change from Baseline | 0.11 Score on a scale | Standard Error 0.019 |
| AL002 Dose 3: 60 mg/kg | Change in Alzheimer's Disease Composite Score (ADCOMS) Score | Week 72 Change from Baseline | 0.25 Score on a scale | Standard Error 0.04 |
| AL002 Dose 3: 60 mg/kg | Change in Alzheimer's Disease Composite Score (ADCOMS) Score | Week 48 Change from Baseline | 0.25 Score on a scale | Standard Error 0.027 |
| AL002 Dose 3: 60 mg/kg | Change in Alzheimer's Disease Composite Score (ADCOMS) Score | Week 96 Change from Baseline | 0.39 Score on a scale | Standard Error 0.053 |
| AL002 Dose 3: 60 mg/kg | Change in Alzheimer's Disease Composite Score (ADCOMS) Score | Week 24 Change from Baseline | 0.14 Score on a scale | Standard Error 0.02 |
| Placebo | Change in Alzheimer's Disease Composite Score (ADCOMS) Score | Week 96 Change from Baseline | 0.35 Score on a scale | Standard Error 0.047 |
| Placebo | Change in Alzheimer's Disease Composite Score (ADCOMS) Score | Week 48 Change from Baseline | 0.20 Score on a scale | Standard Error 0.024 |
| Placebo | Change in Alzheimer's Disease Composite Score (ADCOMS) Score | Week 24 Change from Baseline | 0.13 Score on a scale | Standard Error 0.018 |
| Placebo | Change in Alzheimer's Disease Composite Score (ADCOMS) Score | Week 72 Change from Baseline | 0.26 Score on a scale | Standard Error 0.036 |
Comparison: This is using the Week 96 timepointp-value: 0.645895% CI: [-0.17, 0.11]Mixed Models Analysis
Comparison: This is using the Week 96 timepointp-value: 0.277995% CI: [-0.06, 0.21]Mixed Models Analysis
Comparison: This is using the Week 96 timepointp-value: 0.535595% CI: [-0.1, 0.18]Mixed Models Analysis
Secondary
Change in Alzheimer's Disease Cooperative Study - Activities of Daily Living - Mild Cognitive Impairment (ADCS-ADL-MCI) Score
Change from baseline in Alzheimer's Disease Cooperative Study - Activities of Daily Living - Mild Cognitive Impairment (ADCS-ADL-MCI) score at Weeks 24, 48, 72, and 96 The ADCS-ADL-MCI is a scale for participants with mild cognitive impairment that observes their performance in completing activities associated with daily living. This scale is a multiple choice questionnaire and has a range of 0 to 53. A lower score on this scale indicates greater cognitive impairment.
Time frame: Study completion up to 96 weeks
Population: Adult participants with early Alzheimer's Disease excluding apolipoprotein E homozygotes
| Arm | Measure | Group | Value (LEAST_SQUARES_MEAN) | Dispersion |
|---|---|---|---|---|
| AL002 Dose 1: 15 mg/kg | Change in Alzheimer's Disease Cooperative Study - Activities of Daily Living - Mild Cognitive Impairment (ADCS-ADL-MCI) Score | Week 24 Change from Baseline | -1.60 Score on a scale | Standard Error 0.608 |
| AL002 Dose 1: 15 mg/kg | Change in Alzheimer's Disease Cooperative Study - Activities of Daily Living - Mild Cognitive Impairment (ADCS-ADL-MCI) Score | Week 96 Change from Baseline | -8.50 Score on a scale | Standard Error 1.517 |
| AL002 Dose 1: 15 mg/kg | Change in Alzheimer's Disease Cooperative Study - Activities of Daily Living - Mild Cognitive Impairment (ADCS-ADL-MCI) Score | Week 48 Change from Baseline | -2.95 Score on a scale | Standard Error 0.808 |
| AL002 Dose 1: 15 mg/kg | Change in Alzheimer's Disease Cooperative Study - Activities of Daily Living - Mild Cognitive Impairment (ADCS-ADL-MCI) Score | Week 72 Change from Baseline | -6.41 Score on a scale | Standard Error 1.183 |
| AL002 Dose 2: 40 mg/kg | Change in Alzheimer's Disease Cooperative Study - Activities of Daily Living - Mild Cognitive Impairment (ADCS-ADL-MCI) Score | Week 48 Change from Baseline | -3.11 Score on a scale | Standard Error 0.811 |
| AL002 Dose 2: 40 mg/kg | Change in Alzheimer's Disease Cooperative Study - Activities of Daily Living - Mild Cognitive Impairment (ADCS-ADL-MCI) Score | Week 24 Change from Baseline | -0.99 Score on a scale | Standard Error 0.594 |
| AL002 Dose 2: 40 mg/kg | Change in Alzheimer's Disease Cooperative Study - Activities of Daily Living - Mild Cognitive Impairment (ADCS-ADL-MCI) Score | Week 72 Change from Baseline | -6.57 Score on a scale | Standard Error 1.159 |
| AL002 Dose 2: 40 mg/kg | Change in Alzheimer's Disease Cooperative Study - Activities of Daily Living - Mild Cognitive Impairment (ADCS-ADL-MCI) Score | Week 96 Change from Baseline | -7.80 Score on a scale | Standard Error 1.549 |
| AL002 Dose 3: 60 mg/kg | Change in Alzheimer's Disease Cooperative Study - Activities of Daily Living - Mild Cognitive Impairment (ADCS-ADL-MCI) Score | Week 48 Change from Baseline | -3.46 Score on a scale | Standard Error 0.828 |
| AL002 Dose 3: 60 mg/kg | Change in Alzheimer's Disease Cooperative Study - Activities of Daily Living - Mild Cognitive Impairment (ADCS-ADL-MCI) Score | Week 72 Change from Baseline | -6.80 Score on a scale | Standard Error 1.201 |
| AL002 Dose 3: 60 mg/kg | Change in Alzheimer's Disease Cooperative Study - Activities of Daily Living - Mild Cognitive Impairment (ADCS-ADL-MCI) Score | Week 24 Change from Baseline | -2.45 Score on a scale | Standard Error 0.607 |
| AL002 Dose 3: 60 mg/kg | Change in Alzheimer's Disease Cooperative Study - Activities of Daily Living - Mild Cognitive Impairment (ADCS-ADL-MCI) Score | Week 96 Change from Baseline | -7.44 Score on a scale | Standard Error 1.57 |
| Placebo | Change in Alzheimer's Disease Cooperative Study - Activities of Daily Living - Mild Cognitive Impairment (ADCS-ADL-MCI) Score | Week 24 Change from Baseline | -0.67 Score on a scale | Standard Error 0.559 |
| Placebo | Change in Alzheimer's Disease Cooperative Study - Activities of Daily Living - Mild Cognitive Impairment (ADCS-ADL-MCI) Score | Week 72 Change from Baseline | -5.36 Score on a scale | Standard Error 1.063 |
| Placebo | Change in Alzheimer's Disease Cooperative Study - Activities of Daily Living - Mild Cognitive Impairment (ADCS-ADL-MCI) Score | Week 96 Change from Baseline | -7.97 Score on a scale | Standard Error 1.368 |
| Placebo | Change in Alzheimer's Disease Cooperative Study - Activities of Daily Living - Mild Cognitive Impairment (ADCS-ADL-MCI) Score | Week 48 Change from Baseline | -2.73 Score on a scale | Standard Error 0.744 |
Comparison: This is using the Week 96 timepointp-value: 0.794595% CI: [-4.57, 3.51]Mixed Models Analysis
Comparison: This is using the Week 96 timepointp-value: 0.937195% CI: [-3.92, 4.25]Mixed Models Analysis
Comparison: This is using the Week 96 timepointp-value: 0.799195% CI: [-3.58, 4.64]Mixed Models Analysis
Secondary
Change in Mini-Mental Status Examination (MMSE) Score
Change from baseline in Mini-Mental Status Examination (MMSE) score at Weeks 24, 48, 72, and 96 The MMSE is a test that assesses orientation, registration, attention and calculation, recent memory, language and constructional praxis. There is a total possible score of 30 with a lower score correlating to a higher cognitive impairment. A score of 24 to 30 is considered normal or no cognitive impairment. A score of 18 to 24 indicates mild impairment. A score of 0 to 17 indicates a severe impairment.
Time frame: Study completion up to 96 weeks
Population: Adult participants with early Alzheimer's Disease excluding apolipoprotein E homozygotes
| Arm | Measure | Group | Value (LEAST_SQUARES_MEAN) | Dispersion |
|---|---|---|---|---|
| AL002 Dose 1: 15 mg/kg | Change in Mini-Mental Status Examination (MMSE) Score | Week 24 Change from Baseline | -2.70 Score on a scale | Standard Error 0.396 |
| AL002 Dose 1: 15 mg/kg | Change in Mini-Mental Status Examination (MMSE) Score | Week 48 Change from Baseline | -4.06 Score on a scale | Standard Error 0.541 |
| AL002 Dose 1: 15 mg/kg | Change in Mini-Mental Status Examination (MMSE) Score | Week 72 Change from Baseline | -5.15 Score on a scale | Standard Error 0.772 |
| AL002 Dose 1: 15 mg/kg | Change in Mini-Mental Status Examination (MMSE) Score | Week 96 Change from Baseline | -5.88 Score on a scale | Standard Error 0.906 |
| AL002 Dose 2: 40 mg/kg | Change in Mini-Mental Status Examination (MMSE) Score | Week 48 Change from Baseline | -3.91 Score on a scale | Standard Error 0.535 |
| AL002 Dose 2: 40 mg/kg | Change in Mini-Mental Status Examination (MMSE) Score | Week 72 Change from Baseline | -5.47 Score on a scale | Standard Error 0.751 |
| AL002 Dose 2: 40 mg/kg | Change in Mini-Mental Status Examination (MMSE) Score | Week 96 Change from Baseline | -7.22 Score on a scale | Standard Error 0.914 |
| AL002 Dose 2: 40 mg/kg | Change in Mini-Mental Status Examination (MMSE) Score | Week 24 Change from Baseline | -3.03 Score on a scale | Standard Error 0.381 |
| AL002 Dose 3: 60 mg/kg | Change in Mini-Mental Status Examination (MMSE) Score | Week 72 Change from Baseline | -4.99 Score on a scale | Standard Error 0.78 |
| AL002 Dose 3: 60 mg/kg | Change in Mini-Mental Status Examination (MMSE) Score | Week 48 Change from Baseline | -3.74 Score on a scale | Standard Error 0.549 |
| AL002 Dose 3: 60 mg/kg | Change in Mini-Mental Status Examination (MMSE) Score | Week 96 Change from Baseline | -5.81 Score on a scale | Standard Error 0.932 |
| AL002 Dose 3: 60 mg/kg | Change in Mini-Mental Status Examination (MMSE) Score | Week 24 Change from Baseline | -2.78 Score on a scale | Standard Error 0.393 |
| Placebo | Change in Mini-Mental Status Examination (MMSE) Score | Week 96 Change from Baseline | -5.47 Score on a scale | Standard Error 0.814 |
| Placebo | Change in Mini-Mental Status Examination (MMSE) Score | Week 48 Change from Baseline | -3.33 Score on a scale | Standard Error 0.501 |
| Placebo | Change in Mini-Mental Status Examination (MMSE) Score | Week 24 Change from Baseline | -2.65 Score on a scale | Standard Error 0.364 |
| Placebo | Change in Mini-Mental Status Examination (MMSE) Score | Week 72 Change from Baseline | -4.89 Score on a scale | Standard Error 0.692 |
Comparison: This is using the Week 96 timepointp-value: 0.741795% CI: [-2.81, 2.01]Mixed Models Analysis
Comparison: This is using the Week 96 timepointp-value: 0.155995% CI: [-4.16, 0.67]Mixed Models Analysis
Comparison: This is using the Week 96 timepointp-value: 0.78595% CI: [-2.78, 2.11]Mixed Models Analysis
Secondary
Change in Repeatable Battery for the Assessment of Neuropsychological Status (RBANS) Score
Change from baseline in Repeatable Battery for the Assessment of Neuropsychological Status (RBANS) score at Weeks 24, 48, 72 and 96 The RBANS test is a collection of 12 subsets representing 5 neurological domains: immediate memory, visuospatial/constructional, language, attention, and delayed memory. The scores are converted to a scale that can range from 40 to 160. The lower the score the greater the cognitive impairment.
Time frame: Study completion up to 96 weeks
Population: Adult participants with early Alzheimer's Disease excluding apolipoprotein E homozygotes
| Arm | Measure | Group | Value (LEAST_SQUARES_MEAN) | Dispersion |
|---|---|---|---|---|
| AL002 Dose 1: 15 mg/kg | Change in Repeatable Battery for the Assessment of Neuropsychological Status (RBANS) Score | Week 48 Change from Baseline | -7.15 Score on a scale | Standard Error 0.939 |
| AL002 Dose 1: 15 mg/kg | Change in Repeatable Battery for the Assessment of Neuropsychological Status (RBANS) Score | Week 96 Change from Baseline | -8.12 Score on a scale | Standard Error 1.915 |
| AL002 Dose 1: 15 mg/kg | Change in Repeatable Battery for the Assessment of Neuropsychological Status (RBANS) Score | Week 72 Change from Baseline | -6.46 Score on a scale | Standard Error 1.339 |
| AL002 Dose 1: 15 mg/kg | Change in Repeatable Battery for the Assessment of Neuropsychological Status (RBANS) Score | Week 24 Change from Baseline | -3.37 Score on a scale | Standard Error 0.857 |
| AL002 Dose 2: 40 mg/kg | Change in Repeatable Battery for the Assessment of Neuropsychological Status (RBANS) Score | Week 72 Change from Baseline | -6.56 Score on a scale | Standard Error 1.281 |
| AL002 Dose 2: 40 mg/kg | Change in Repeatable Battery for the Assessment of Neuropsychological Status (RBANS) Score | Week 24 Change from Baseline | -2.34 Score on a scale | Standard Error 0.82 |
| AL002 Dose 2: 40 mg/kg | Change in Repeatable Battery for the Assessment of Neuropsychological Status (RBANS) Score | Week 48 Change from Baseline | -6.13 Score on a scale | Standard Error 0.921 |
| AL002 Dose 2: 40 mg/kg | Change in Repeatable Battery for the Assessment of Neuropsychological Status (RBANS) Score | Week 96 Change from Baseline | -7.23 Score on a scale | Standard Error 2.011 |
| AL002 Dose 3: 60 mg/kg | Change in Repeatable Battery for the Assessment of Neuropsychological Status (RBANS) Score | Week 24 Change from Baseline | -2.65 Score on a scale | Standard Error 0.87 |
| AL002 Dose 3: 60 mg/kg | Change in Repeatable Battery for the Assessment of Neuropsychological Status (RBANS) Score | Week 48 Change from Baseline | -5.78 Score on a scale | Standard Error 0.957 |
| AL002 Dose 3: 60 mg/kg | Change in Repeatable Battery for the Assessment of Neuropsychological Status (RBANS) Score | Week 72 Change from Baseline | -5.94 Score on a scale | Standard Error 1.357 |
| AL002 Dose 3: 60 mg/kg | Change in Repeatable Battery for the Assessment of Neuropsychological Status (RBANS) Score | Week 96 Change from Baseline | -6.56 Score on a scale | Standard Error 1.936 |
| Placebo | Change in Repeatable Battery for the Assessment of Neuropsychological Status (RBANS) Score | Week 48 Change from Baseline | -5.05 Score on a scale | Standard Error 0.844 |
| Placebo | Change in Repeatable Battery for the Assessment of Neuropsychological Status (RBANS) Score | Week 24 Change from Baseline | -3.05 Score on a scale | Standard Error 0.782 |
| Placebo | Change in Repeatable Battery for the Assessment of Neuropsychological Status (RBANS) Score | Week 96 Change from Baseline | -7.47 Score on a scale | Standard Error 1.574 |
| Placebo | Change in Repeatable Battery for the Assessment of Neuropsychological Status (RBANS) Score | Week 72 Change from Baseline | -5.86 Score on a scale | Standard Error 1.149 |
Comparison: This is using the Week 96 timepointp-value: 0.793495% CI: [-5.58, 4.28]Mixed Models Analysis
Comparison: This is using the Week 96 timepointp-value: 0.925995% CI: [-4.84, 5.32]Mixed Models Analysis
Comparison: This is using the Week 96 timepointp-value: 0.714795% CI: [-4.04, 5.87]Mixed Models Analysis