A Phase II, Multicenter, Randomized, Double-Blind, Placebo-Controlled, Parallel-Group, Efficacy, and Safety Study of MTAU9937A in Patients With Moderate Alzheimer's Disease
Overview
- Phase
- Phase 2
- Intervention
- Semorinemab
- Conditions
- Alzheimer's Disease
- Sponsor
- Genentech, Inc.
- Enrollment
- 272
- Locations
- 49
- Primary Endpoint
- Change From Baseline to Last Visit of Double-Blind Treatment Period in Functional Capacities as Measured by the Alzheimer's Disease Cooperative Study-Daily Living Inventory (ADCS-ADL)
- Status
- Completed
- Last Updated
- 2 years ago
Overview
Brief Summary
This Phase II, multicenter, randomized, double-blind, placebo-controlled, parallel-group study will evaluate the clinical efficacy, safety, pharmacokinetics, and pharmacodynamics of semorinemab in patients with moderate AD. The study consists of a screening period, a double-blind treatment period, an optional open-label extension (OLE) period, and a safety follow-up period. There may be up to two study cohorts.
Investigators
Eligibility Criteria
Inclusion Criteria
- •National Institute on Aging/Alzheimer's Association core clinical criteria for probable AD dementia
- •Evidence of the AD pathological process, by a positive amyloid assessment either on CSF Aβ1-42 as measured on Elecsys β-Amyloid(1-42) Test System OR amyloid PET scan
- •AD dementia of moderate severity, as defined by a screening MMSE score of 16-21 points, inclusive, and a CDR-GS of 1 or 2
- •Availability of a person with sufficient contact with the participant to be able to provide accurate information on the participant's cognitive, behavioral and functional ability
Exclusion Criteria
- •Pregnant or breastfeeding
- •Inability to tolerate MRI procedures or contraindication to MRI
- •Contraindication to PET imaging
- •Residence in a skilled nursing facility
- •Any serious medical condition or abnormality in clinical laboratory tests that, in the investigator's judgment, precludes the patient's safe participation in and completion of the study, or bias the assessment of the clinical or mental status of the participant to a significant degree
- •Any evidence of a condition other than AD that may affect cognition
- •Substance abuse within the past 2 years
- •Use of any experimental therapy within 90 days or 5 half-lives prior to screening, whichever is greater, or any passive immunotherapy against tau
- •Use of any passive immunotherapy (immunoglobulin) against Aβ, unless the last dose was at least 1 year prior to screening or any active immunotherapy (vaccine) that is under evaluation to prevent or postpone cognitive decline
- •Any other biologic therapy or previous treatment with medications specifically intended to treat Parkinsonian symptoms or any other non-AD neurodegenerative disorder within 1 year of screening
Arms & Interventions
Semorinemab
Semorinemab will be administered intravenously in the double-blind treatment period, and semorinemab will be administered intravenously in the optional open-label extension period.
Intervention: Semorinemab
Semorinemab
Semorinemab will be administered intravenously in the double-blind treatment period, and semorinemab will be administered intravenously in the optional open-label extension period.
Intervention: [18F]GTP1
Placebo
Placebo will be administered intravenously in the double-blind treatment period and semorinemab will be administered intravenously in the optional open-label extension.
Intervention: Placebo
Placebo
Placebo will be administered intravenously in the double-blind treatment period and semorinemab will be administered intravenously in the optional open-label extension.
Intervention: [18F]GTP1
Outcomes
Primary Outcomes
Change From Baseline to Last Visit of Double-Blind Treatment Period in Functional Capacities as Measured by the Alzheimer's Disease Cooperative Study-Daily Living Inventory (ADCS-ADL)
Time Frame: Baseline to Week 49 for Cohorts 1 and 2, and Baseline to Week 61 for Cohort 2
The Alzheimer's Disease Cooperative Study-Daily Living Inventory (ADCS-ADL) is a scale used to quantify performance of activities of daily living (ADL). Scores on the ADCS-ADL range from 0-78, with higher scores indicating better ADL function.
Change From Baseline to Last Visit of Double-Blind Treatment Period in Cognitive Function as Measured by the Alzheimer's Disease Assessment Scale, Cognitive Subscale, 11-Item Version (ADAS-Cog11)
Time Frame: Baseline to Week 49 for Cohorts 1 and 2, and Baseline to Week 61 for Cohort 2
The Alzheimer's Disease Assessment Scale, Cognitive Subscale, 11-Item Version (ADAS-Cog11) is an 11 item cognitive subscale used to quantify the areas of cognitive function most often affected in Alzheimer's disease. The total score ranges from 0-70 with lower scores indicating better cognitive function.
Secondary Outcomes
- Change From Baseline to Last Visit of Double-Blind Treatment Period on the Clinical Dementia Rating-Sum of Boxes (CDR-SB)(Baseline to Week 49 for Cohorts 1 and 2, and Baseline to Week 61 for Cohort 2)
- Change From Baseline to Last Visit of Double-Blind Treatment Period on the Mini-Mental State Examination (MMSE)(Baseline to Week 49 for Cohorts 1 and 2, and Baseline to Week 61 for Cohort 2)
- Percentage of Participants With Adverse Events(Baseline up to end of study (approximately 4 years and 7 months))
- Serum Concentration of RO7105705 at Specified Timepoints(Weeks 1,3,5,9,13,25,37,49, and at treatment discontinuation (up to Week 48) for Cohort 1. Weeks 1,3,5,9,13,25,37,49,61, and at treatment discontinuation (up to Week 60) for Cohort 2.)
- Incidence of Anti-drug Antibodies (ADAs) During the Study Relative to the Prevalence of ADAs at Baseline(Weeks 1,13,25,37,49, and at treatment discontinuation (up to Week 48) for Cohort 1. Weeks 1,13,25,37,49,61, and at treatment discontinuation (up to Week 60) for Cohort 2.)
- Relationship Between ADA Status and Percentage of Participants With Adverse Events(Up to 57 weeks for Cohort 1, and up to 69 weeks for Cohort 2.)
- Relationship Between ADA Status and Change From Baseline to Last Visit of Double-Blind Treatment Period in Cognitive Function as Measured by the Alzheimer's Disease Assessment Scale, Cognitive Subscale, 11-Item Version (ADAS-Cog11)(Baseline to Week 49 for Cohorts 1 and 2, and Baseline to Week 61 for Cohort 2)
- Relationship Between ADA Status and Change From Baseline to Last Visit of Double-Blind Treatment Period in Functional Capacities as Measured by the Alzheimer's Disease Cooperative Study-Daily Living Inventory (ADCS-ADL)(Baseline to Week 49 for Cohorts 1 and 2, and Baseline to Week 61 for Cohort 2)
- Relationship Between ADA Status and Change From Baseline to Last Visit of Double-Blind Treatment Period on the Clinical Dementia Rating-Sum of Boxes (CDR-SB)(Baseline to Week 49 for Cohorts 1 and 2, and Baseline to Week 61 for Cohort 2)
- Relationship Between ADA Status and Change From Baseline to Last Visit of Double-Blind Treatment Period on the Mini-Mental State Examination (MMSE)(Baseline to Week 49 for Cohorts 1 and 2, and Baseline to Week 61 for Cohort 2)
- Relationship Between ADA Status and Serum Concentration of RO7105705 at Specified Timepoints(Weeks 1,13,25,37,49, and at treatment discontinuation (up to Week 48) for Cohort 1. Weeks 1,13,25,37,49,61, and at treatment discontinuation (up to Week 60) for Cohort 2.)
- Relationship Between ADA Status and Incidence of Anti-Drug Antibodies (ADAs) During the Study Relative to the Prevalence of ADAs at Baseline(Weeks 1,13,25,37,49, and at treatment discontinuation (up to Week 48) for Cohort 1. Weeks 1,13,25,37,49,61, and at treatment discontinuation (up to Week 60) for Cohort 2.)