Phase 2 Study of BIIB092 in Participants With Early Alzheimer's Disease

Study Overview
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Brief Summary
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The primary objective of the placebo-controlled period is to evaluate the safety and tolerability of BIIB092 in participants with mild cognitive impairment (MCI) due to Alzheimer's disease (AD) or with mild AD. The secondary objectives of the placebo-controlled period are to evaluate the efficacy of multiple doses of BIIB092 in slowing cognitive and functional impairment in participants with MCI due to AD or with mild AD, and to evaluate the immunogenicity of BIIB092 after multiple doses in participants with MCI due to AD or with mild AD. The primary objective of the long-term extension period is to evaluate the long-term safety and tolerability of BIIB092 in participants with MCI due to AD or with mild AD.

Official Title
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Randomized, Double-Blind, Placebo-Controlled, Parallel-Group Study to Assess the Safety, Tolerability, and Efficacy of BIIB092 in Subjects With Mild Cognitive Impairment Due to Alzheimer's Disease or With Mild Alzheimer's Disease

Conditions
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Alzheimer's Disease

Intervention / Treatment
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* Drug: BIIB092
* Drug: Placebo


Participation Criteria
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Eligibility Criteria
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Key Inclusion Criteria: Must have a gradual and progressive change in memory function over more than 6 months. Must meet all of the clinical criteria for mild cognitive impairment (MCI) due to Alzheimer's disease (AD) or mild AD and must have Objective evidence of cognitive impairment at Screening Clinical Dementia Rating Scale (CDR) global score of 0.5 for MCI due to AD or 0.5 or 1 for mild AD Mini-Mental State Examination (MMSE) score of 22 to 30 (inclusive) CDR Memory Box score of ≥0.5 Must consent to apolipoprotein E (ApoE) genotyping Must have 1 informant/study partner Must have amyloid beta positivity confirmed at Screening Key Exclusion Criteria: Any medical or neurological/neurodegenerative condition (other than AD) that, in the opinion of the Investigator, might be a contributing cause to the participant's cognitive impairment or could lead to discontinuation, lack of compliance, interference with study assessments, or safety concerns Clinically significant, unstable psychiatric illness Have had a stroke or Transient Ischemic Attack (TIA) or unexplained loss of consciousness in the past 1 year Relevant brain hemorrhage, bleeding disorder and cerebrovascular abnormalities History of unstable angina, myocardial infarction, chronic heart failure or clinically significant conduction abnormalities within 1 year prior to Screening Visit 1 Indication of impaired renal or liver function Alcohol or substance abuse in past 1 year Clinically significant systemic illness or serious infection within 30 days prior to or during the screening period Use of allowed medications for chronic conditions at doses that have not been stable for at least 4 weeks prior to Screening Visit 1 and during the screening period up to Study Day 1, or use of AD medications at doses that have not been stable for at least 8 weeks prior to Screening Visit 1 and during the screening period up to Study Day 1. Use of any medications that, in the opinion of the Investigator, may contribute to cognitive impairment, put the participants at higher risk for adverse events (AEs), or impair the participant's ability to perform cognitive testing or complete study procedures. Contraindications to study procedures NOTE: Other protocol defined Inclusion/Exclusion criteria may apply

Ages Eligible for Study
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Minimum Age: 50 Years
Maximum Age: 80 Years

Sexes Eligible for Study
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All

Accepts Healthy Volunteers
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No

Study Plan
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How is the study designed?
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Design Details

Primary Purpose: Treatment
Allocation: Randomized
Intervention Model: Parallel Assignment
Masking: Quadruple


Arms and Interventions

| Participant Group/Arm | Intervention/Treatment |
| --- | --- |
| Experimental: Low-dose BIIB092<br>Intravenous (IV) infusion once every 4 weeks OR once every 12 weeks and placebo at the other 4-week dosing visits to maintain the treatment blind. | Drug: BIIB092<br>* Administered as specified in treatment arm.<br>* Other names: Formally known as BMS 986168;|
| Experimental: Medium-dose BIIB092<br>Intravenous (IV) infusion once every 4 weeks. | Drug: BIIB092<br>* Administered as specified in treatment arm.<br>* Other names: Formally known as BMS 986168;|
| Experimental: High-dose BIIB092<br>Intravenous (IV) infusion once every 4 weeks. | Drug: BIIB092<br>* Administered as specified in treatment arm.<br>* Other names: Formally known as BMS 986168;|
| Placebo Comparator: Placebo<br>Intravenous (IV) infusion once every 4 weeks. | Drug: Placebo<br>* Administered as specified in treatment arm.<br>|

What is the study measuring?
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Primary Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| PC Period: Percentage of Participants With Adverse Events (AEs) and Serious Adverse Events (SAEs) | AE is any untoward medical occurrence in participant or clinical investigation participant administered pharmaceutical product and that does not necessarily have causal relationship with this treatment. AE can therefore be any unfavorable and unintended sign (including an abnormal laboratory finding), symptom, or disease temporally associated with use of medicinal (investigational) product, whether or not related to medicinal (investigational) product. SAE is any untoward medical occurrence that at any dose, results in death; in view of investigator places participant at immediate risk of death; requires inpatient hospitalization or prolongation of existing hospitalization; results in persistent or significant disability/incapacity; results in congenital anomaly/birth defect; is medically important event. Participants who completed treatment period in PC period and did not enter LTE period were to be assessed at Week 90 (14 weeks after end of treatment) as safety follow-up. | Day 1 to Week 78 (participants who entered LTE period); Day 1 up to Week 90 (participants who did not LTE period) | 
| LTE Period: Percentage of Participants With AEs and SAEs | An AE is any untoward medical occurrence in a participant or clinical investigation participant administered a pharmaceutical product and that does not necessarily have a causal relationship with this treatment. An AE can therefore be any unfavorable and unintended sign (including an abnormal laboratory finding), symptom, or disease temporally associated with the use of a medicinal (investigational) product, whether or not related to the medicinal (investigational) product. An SAE is any untoward medical occurrence that at any dose, results in death; in the view of the investigator places the participant at immediate risk of death; requires inpatient hospitalization or prolongation of existing hospitalization; results in persistent or significant disability/incapacity; results in a congenital anomaly/birth defect; is a medically important event. | From Week 80 to Week 173 | 

Secondary Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| PC Period: Change From Baseline Over Time at Week 78 on the Clinical Dementia Rating Scale - Sum of Boxes (CDR-SB) Score | The CDR-SB is a validated clinical assessment of global function in participants with AD. The CDR is comprised of 6 domains: Memory, Orientation, Judgment and Problem Solving, Community Affairs, Home and Hobbies, and Personal Care. CDR-SB is the sum of the scores for these 6 domains. Impairment is scored in each of 6 cognitive categories on a scale in which none = 0, questionable = 0.5, mild = 1, moderate = 2, and severe = 3. The 6 individual category ratings, or box scores, can be added together to give the CDR-SB score which ranges from 0 (none) to 18 (severe impairment). | Baseline, Week 78 | 
| PC Period: Percentage of Participants With Anti-BIIB092 Antibodies in Serum |  | Baseline up to Week 76 | 

 Terms related to the study
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Keywords Provided by Centre Hospitalier Valida
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Mild cognitive impairment, Alzheimer's disease