Safety, Tolerability, and Pharmacokinetics of Single and Multiple Doses of BIIB033 in Healthy Japanese Participants

Study Overview
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Brief Summary
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The primary objective of this study is to assess the safety and tolerability of a single dose and multiple doses of BIIB033 administered to healthy adult Japanese participants. The secondary objectives of this study are to evaluate the pharmacokinetics (PK) profile of BIIB033 administered as single and multiple doses in healthy adult Japanese participants and to assess the single-dose and multiple-dose immunogenicity of BIIB033.

Official Title
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A Randomized, Blinded, Placebo-Controlled, Single- and Multiple-Dose Study of the Safety, Tolerability, and Pharmacokinetics of BIIB033 in Healthy Japanese Subjects

Conditions
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Central Nervous System (CNS) Demyelinating Disease, Multiple Sclerosis

Intervention / Treatment
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* Biological: BIIB033
* Other: Placebo


Participation Criteria
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Eligibility Criteria
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Key Inclusion Criteria: Japanese subjects must have been born in Japan, and their biological parents and grandparents must all have been of Japanese origin. Subjects who have lived out of Japan for more than 5 years must not have significantly modified their diets since leaving Japan. Must be a nonsmoker or light smoker (<10 cigarettes per day) and be willing to abstain from using tobacco and tobacco-containing products during the Inpatient Period and for at least 48 hours prior to Day -1, Day 14 (for Cohort 3), and all outpatient visits. Must have a body mass index of 18 to 32 kg/m2, inclusive. Key Exclusion Criteria: History of any clinically significant cardiac, endocrine, hematologic, hepatic, immunologic, metabolic, urologic, pulmonary, neurologic, dermatologic, psychiatric, renal, or other major disease, as determined by the Investigator. Serious infection (e.g., pneumonia, septicemia) as determined by the Investigator within the 3 months prior to Day -1. Fever or bacterial or viral infection (including upper respiratory tract infection) within 2 weeks prior to Day -1. History of severe allergic or anaphylactic reactions. NOTE: Other protocol defined Inclusion/Exclusion criteria may apply.

Ages Eligible for Study
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Minimum Age: 20 Years
Maximum Age: 55 Years

Sexes Eligible for Study
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All

Accepts Healthy Volunteers
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Accepts Healthy Volunteers

Study Plan
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How is the study designed?
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Design Details

Primary Purpose: Basic Science
Allocation: Randomized
Intervention Model: Parallel Assignment
Masking: Quadruple


Arms and Interventions

| Participant Group/Arm | Intervention/Treatment |
| --- | --- |
| Experimental: Cohort 1<br>A single IV dose of 10 mg/kg BIIB033 or placebo given on Day 1 | Biological: BIIB033<br>* single or multiple dose<br>Other: Placebo<br>* single or multiple dose<br>|
| Experimental: Cohort 2<br>A single IV dose of 30 mg/kg BIIB033 or placebo given on Day 1 | Biological: BIIB033<br>* single or multiple dose<br>Other: Placebo<br>* single or multiple dose<br>|
| Experimental: Cohort 3<br>One IV dose of 100 mg/kg BIIB033 or placebo given on Days 1 and 15 | Biological: BIIB033<br>* single or multiple dose<br>Other: Placebo<br>* single or multiple dose<br>|

What is the study measuring?
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Primary Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| Number of participants experiencing Adverse Events (AEs) and Serious Adverse Events (SAEs) |  | Up to day 113 | 
| Number of participants with clinically significant laboratory parameters |  | Up to day 113 | 
| Number of participants with clinically significant vital sign abnormalities |  | Up to day 113 | 
| Number of participants with clinically significant electrocardiograms (ECGs) abnormalities |  | Up to day 113 | 
| Number of participants with clinically significant physical examination abnormalities |  | Up to day 113 | 
| Number of participants with clinically significant neurological examination abnormalities |  | Up to day 113 | 

Secondary Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| PK parameter of BIIB033: Area under the concentration-time curve from time zero to infinity (AUCinf) |  | Up to day 113 | 
| PK parameter of BIIB033: Area under the concentration-time curve from time zero to the time of the last measurable sample (AUClast) |  | Up to day 113 | 
| PK parameter of BIIB033: AUC over a given dosing interval |  | Up to day 113 | 
| PK parameter of BIIB033: Maximum observed concentration (Cmax) |  | Up to day 113 | 
| PK parameter of BIIB033: Time to reach maximum observed concentration (Tmax) |  | Up to day 113 | 
| PK parameter of BIIB033: Terminal elimination half-life (t1/2) |  | Up to day 113 | 
| PK parameter of BIIB033: Volume of distribution at steady state (Vss) |  | Up to day 113 | 
| PK parameter of BIIB033: Clearance (CL) |  | Up to day 113 | 
| PK parameter of BIIB033: accumulation ratio (RAC) |  | Up to day 113 | 
| Number of participants with positive serum BIIB033 antibodies |  | Up to day 113 | 

 Terms related to the study
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Keywords Provided by Centre Hospitalier Valida
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Japanese, Single Ascending Dose (SAD), Multiple Ascending Dose (MAD)