Single Ascending Dose Study of BIIB037 in Participants With Alzheimer's Disease

Study Overview
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Brief Summary
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The primary objective of the study is to evaluate the safety and tolerability of a range of BIIB037 doses administered as single intravenous (IV) infusions in participants with mild to moderate Alzheimer's Disease (AD). Secondary objectives of this study in this study population are to assess the pharmacokinetics(PK) and to evaluate the immunogenicity of BIIB037 after single-dose administration.

Detailed Description
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BIIB037 is an investigational product being developed as a treatment for Alzheimer's disease (AD). BIIB037 is a fully human immunoglobulin gamma 1 (IgG1) monoclonal antibody that is selective for the fibrillar form of beta amyloid (Aß).

Official Title
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A Randomized, Blinded, Placebo-Controlled Single Ascending Dose Study of the Safety, Tolerability, and Pharmacokinetics of BIIB037 in Subjects With Mild to Moderate Alzheimer's Disease

Conditions
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Alzheimer's Disease

Intervention / Treatment
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* Drug: BIIB037
* Other: Placebo


Participation Criteria
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Eligibility Criteria
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Key Inclusion Criteria: Must be ambulatory Must have a clinical diagnosis of Alzheimer's Disease (AD) consistent with the following: Probable Alzheimer's Disease (AD), according to National Institute of Neurological and Communicative Disease and Stroke and Alzheimer's Disease and Related Disorders Association (NINCDS-ADRDA) criteria [McKhann et al. 1984]. Dementia of Alzheimer's type, according to Diagnostic and Statistical Manual of Mental Disorders-Text Revision (DSM IV TR) criteria [American Psychiatric Association 2000] Subject (or subject's permanent caregiver) has the ability to understand the purpose and risks of the study and provide signed and dated informed consent (or assent) and authorization to use protected health information (PHI) in accordance with national and local subject privacy regulations. Must have a Mini Mental State Examination (MMSE) score of 14 to 26 inclusive. Key Exclusion Criteria: Any medical or neurological condition other than Alzheimer's Disease (AD) that in the opinion of the Investigator could be a contributing cause of the subject's dementia (e.g., medication use, vitamin B12 deficiency, abnormal thyroid function, stroke or other cerebrovascular condition, diffuse Lewy body disease, head trauma). History within the past 6 months or evidence of clinically significant psychiatric illness (e.g., major depression, schizophrenia, or bipolar affective disorder). Subject currently lives in a nursing home. Blood donation (1 unit or more) within the 1 month prior to Screening Participation in any other drug, biologic, device, or clinical study or treatment with any investigational drug or approved therapy for investigational use within 30 days (or 5 half lives, whichever is longer) prior to Screening, and/or participation in any other clinical study involving experimental medications for AD within the 60 days (or 5 half lives, whichever is longer) prior to Screening. Any contraindications to having a brain Magnetic Resonance Imaging (MRI) e.g., pacemaker; Non-Magnetic Resonance Imaging (MRI)-compatible aneurysm clips, artificial heart valves, or other metal foreign body; claustrophobia). NOTE: Other protocol defined Inclusion/Exclusion criteria may apply.

Ages Eligible for Study
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Minimum Age: 55 Years
Maximum Age: 85 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: Single Group Assignment
Masking: Double


Arms and Interventions

| Participant Group/Arm | Intervention/Treatment |
| --- | --- |
| Experimental: BIIB037<br>A single dose of BIIB037 by intravenous infusion. | Drug: BIIB037<br>* Participants receive a single dose of BIIB037 by intravenous (IV) infusion in cohorts assigned to the following ascending doses: .03 mg/kg, 1 mg/kg, 3 mg/kg, 10 mg/kg, 20 mg/kg, 30 mg/kg, and 60 mg/kg.<br>* Other names: fully human IgG1 anti-Aβ mAb;|
| Placebo Comparator: Placebo<br>A single dose of placebo matching BIIB037 by intravenous infusion. | Other: Placebo<br>* Participants receive a single dose of matching BIIB037 placebo by intravenous (IV) infusion.<br>|

What is the study measuring?
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Primary Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| Number of Participants with Adverse Events as a Measure of Safety and Tolerability | Incidence and nature of adverse events (AEs) and serious adverse events (SAEs). Significant assessments reported as AEs or SAEs include clinical laboratory assessments and vital signs, physical and neurological examination, 12-lead electrocardiogram (ECG), and brain MRI findings (including the occurrence of vasogenic edema and incident hemorrhage). | 6 months | 

Secondary Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| Area Under the Curve from Time Zero Extrapolated to Infinity [AUC0-∞] |  | 6 months | 
| Area Under the Curve from Time 0 to Time of the Last Measurable Concentration [AUC0-tlast] |  | 6 months | 
| Maximum Concentration [Cmax] of BIIB037 |  | 6 Months | 
| Time to Cmax [Tmax] |  | 6 Months | 
| Elimination Half-life [t1/2] |  | 6 Months | 
| Clearance [Cl] |  | 6 Months | 
| Incidence of Anti-BIIB037 Antibodies in Serum |  | 6 Months |