Single Ascending Doses of BIIB063 in Healthy Volunteers

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 single ascending intravenous (IV) doses and a single subcutaneous (SC) dose of BIIB063 in healthy volunteers. The secondary objectives of the study are to estimate the PK parameters of single ascending IV doses of BIIB063; to estimate the PK parameters and absolute bioavailability (F) of a single SC dose of BIIB063; and to evaluate the immunogenicity of single ascending doses of BIIB063.

Official Title
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Phase 1 Randomized, Blinded, Placebo-Controlled Study of Single Ascending Doses of BIIB063 in Healthy Volunteers

Conditions
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Healthy

Intervention / Treatment
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* Biological: BIIB063
* Other: Placebo


Participation Criteria
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Eligibility Criteria
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Key Inclusion Criteria: All male subjects and all female subjects of childbearing potential must practice at least 1 highly effective method of contraception (i.e., contraceptive measure with a failure rate of <1% per year; estrogen-containing contraceptives are prohibited) during the study and be willing and able to continue contraception for 4 months after being dosed with study treatment. Male subjects must also be willing to refrain from sperm donation for at least 4 months after the last dose of study treatment. Male subjects must not have unprotected sexual intercourse with a female who is pregnant or breastfeeding during the study. Must have a body mass index between 18 and 30 kg/m2, inclusive. Must be in good health as determined by the Investigator, based on medical history, physical examination, and 12-lead ECG. Key Exclusion Criteria: History of or positive test result at screening for human immunodeficiency virus, hepatitis C virus antibody, or hepatitis B virus (defined as positive for hepatitis B surface antigen [HBsAg] or hepatitis B core antibody [HBcAb]). 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. Personal or family history of cardiovascular disease under the age of 50 years, inherited disorder of coagulation (e.g., Factor V Leiden, protein C or S deficiency), or anti-phospholipid Ab syndrome (APS). History of meningococcal vaccination or meningococcal meningitis, or history of hypersensitivity to single components of meningococcal vaccines (including MENVEO), any other CRM197, diphtheria toxoid, or meningococcal-containing vaccine. History of tuberculosis (TB) or positive QuantiFERON®-TB Gold test Personal history of thromboembolic events Treatment with any prescription or over-the-counter medication within 14 days prior to randomization (excluding vitamins, dietary supplements, herbal preparations, progestin-only birth control, and paracetamol up to 4 g/day for no more than 5 consecutive days). Current enrollment or a plan to enroll in any interventional clinical study in which an investigational treatment or approved therapy for investigational use is administered within 3 months Current enrollment or a plan to enroll in any other drug, biologic or device clinical study, or treatment with an investigational drug or approved therapy for investigational use within 3 months Blood donation (1 unit or more) within 3 months prior to randomization. NOTE: Other protocol defined Inclusion/Exclusion criteria may apply

Ages Eligible for Study
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Minimum Age: 18 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: Treatment
Allocation: Randomized
Intervention Model: Parallel Assignment
Masking: Quadruple


Arms and Interventions

| Participant Group/Arm | Intervention/Treatment |
| --- | --- |
| Experimental: IV Dose 1<br>Single ascending IV dose or matching placebo based on body weight recorded on Day 1 | Biological: BIIB063<br>* Single ascending IV dose<br>Other: Placebo<br>* Single dose<br>|
| Experimental: IV Dose 2<br>Single ascending IV dose or matching placebo based on body weight recorded on Day 1 | Biological: BIIB063<br>* Single ascending IV dose<br>Other: Placebo<br>* Single dose<br>|
| Experimental: IV Dose 3<br>Single ascending IV dose or matching placebo based on body weight recorded on Day 1 | Biological: BIIB063<br>* Single ascending IV dose<br>Other: Placebo<br>* Single dose<br>|
| Experimental: IV Dose 4<br>Single ascending IV dose or matching placebo based on body weight recorded on Day 1 | Biological: BIIB063<br>* Single ascending IV dose<br>Other: Placebo<br>* Single dose<br>|
| Experimental: IV Dose 5<br>Single ascending IV dose or matching placebo based on body weight recorded on Day 1 | Biological: BIIB063<br>* Single ascending IV dose<br>Other: Placebo<br>* Single dose<br>|
| Experimental: IV Dose 6<br>Single ascending IV dose or matching placebo based on body weight recorded on Day 1 | Biological: BIIB063<br>* Single ascending IV dose<br>Other: Placebo<br>* Single dose<br>|
| Experimental: IV Dose 7<br>Single ascending IV dose or matching placebo based on body weight recorded on Day 1 | Biological: BIIB063<br>* Single ascending IV dose<br>Other: Placebo<br>* Single dose<br>|
| Experimental: SC Dose<br>Single SC dose or matching placebo | Biological: BIIB063<br>* Single ascending IV dose<br>Other: Placebo<br>* Single 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 week 12 | 
| Number of participants with clinically significant laboratory assessment abnormalities |  | Up to week 12 | 
| Number of participants with clinically significant Vital sign abnormalities |  | Up to week 12 | 
| Number of participants with clinically significant 12-lead electrocardiograms (ECGs) abnormalities |  | Up to week 12 | 
| Number of participants with clinically significant physical examination abnormalities |  | Up to week 12 | 
| Change in antibody titers of vaccine immunization for tetanus |  | Up to week 12 | 
| Change in antibody titers of vaccine immunization for diphtheria |  | Up to week 12 | 
| Change in antibody titers of vaccine immunization for pneumococcus |  | Up to week 12 | 

Secondary Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| PK parameter of single-ascending IV doses of BIIB063: Area under the concentration-time curve from time zero to the time of the last measurable sample (AUClast) |  | Up to week 12 | 
| PK parameter of single-ascending IV doses of BIIB063: Area under the concentration-time curve from time zero to infinity (AUCinf) |  | Up to week 12 | 
| PK parameter of single-ascending IV doses of BIIB063: Maximum observed concentration (Cmax) |  | Up to week 12 | 
| PK parameter of single-ascending IV doses of BIIB063: Time to reach maximum observed concentration (Tmax) |  | Up to week 12 | 
| PK parameter of single-ascending IV doses of BIIB063: Terminal elimination half-life (t1/2) |  | Up to week 12 | 
| PK parameter of single-ascending IV doses of BIIB063: Clearance (CL) |  | Up to week 12 | 
| PK parameter of single-ascending IV doses of BIIB063: Volume of distribution at steady state (Vss) |  | Up to week 12 | 
| PK parameter of a single SC dose of BIIB063: Area under the concentration-time curve from time zero to the time of the last measurable sample (AUClast) |  | Up to week 12 | 
| PK parameter of a single SC dose of BIIB063: Area under the concentration-time curve from time zero to infinity (AUCinf) |  | Up to week 12 | 
| PK parameter of a single SC dose of BIIB063: Maximum observed concentration (Cmax) |  | Up to week 12 | 
| PK parameter of a single SC dose of BIIB063: Time to reach maximum observed concentration (Tmax) |  | Up to week 12 | 
| PK parameter of a single SC dose of BIIB063: Terminal elimination half-life (t1/2) |  | Up to week 12 | 
| PK parameter of a single SC dose of BIIB063 Apparent total body clearance (CL/F) |  | Up to week 12 | 
| PK parameter of a single SC dose of BIIB063: Apparent volume of distribution during terminal elimination phase (Vz/F) |  | Up to week 12 | 
| PK parameter of a single SC dose of BIIB063: Absolute Bioavailability (F) |  | Up to week 12 | 
| Number of participants with positive serum anti-BIIB063 antibodies |  | Up to week 12 | 
| Percentage of participants with positive anti-BIIB063 titers within 12 weeks after administration of BIIB063 |  | Up to 12 weeks |