Safety Study of BIIB033 in Subjects With Multiple Sclerosis

Sponsor

Biogen (Industry)

Overall Status

Completed

CT.gov ID

NCT01244139

Collaborator

(none)

Enrollment

Location

Arms

Duration (Months)

2.6

Patients Per Site Per Month

Study Details

Study Description

Brief Summary

The main purpose of the study is to evaluate the safety, tolerability, and pharmacokinetic profile of two intravenous infusions of BIIB033 administered two weeks apart in subjects with MS.

Approximately 42 MS subjects are planned to be enrolled in the study in 7 separate groups (i.e., 6 subjects per group). Each subsequent group will be administered a higher dose of BIIB033. Before a higher dose group is allowed to start, a Drug Safety Review Committee will review all safety data from previous groups enrolled, as well as data from another study where BIIB033 is being administered to healthy volunteers (215HV101).

Condition or Disease	Intervention/Treatment	Phase
Relapsing-Remitting Multiple Sclerosis Multiple Sclerosis	Drug: BIIB033 Drug: Placebo	Phase 1

Detailed Description

BIIB033 is a protein that acts on certain types of brain cells by blocking the function of another protein called LINGO-1. It is believed that LINGO-1 is one of the reasons why nerves in the brain of patients with MS do not repair well. It is thought BIIB033 may improve MS by repairing damaged nerve tissue. LINGO-1 is also present in the brain of healthy people.

Subjects will take part in the 215MS101 study for up to 28 weeks. This includes a 4-week screening period, a 2 week treatment period in which 2 doses of BIIB033 are given, and a post-dosing safety follow up period of up to 22 weeks (depending on dose cohort).

The study tests vary at each of the individual visits and may include:

medical history evaluation, height and weight assessment, physical examination, neurological examination, vital signs assessment (pulse, respiratory rate, blood pressure, and temperature), MS performance score, electrocardiogram, cardiac monitoring, routine blood and urine tests, drug concentration testing of the blood, hepatitis and HIV tests, blood clotting tests, brain MRI scan, lumbar puncture, and drugs of abuse screen and pregnancy test.

Study Design

Study Type:

Interventional

Actual Enrollment :

47 participants

Allocation:

Randomized

Intervention Model:

Single Group Assignment

Masking:

Triple (Participant, Care Provider, Investigator)

Official Title:

A Randomized, Blinded, Placebo-Controlled, Serial-Cohort, Multiple Ascending Dose Study of the Safety, Tolerability, and Pharmacokinetics of BIIB033 in Subjects With Multiple Sclerosis

Study Start Date :

Oct 1, 2010

Actual Primary Completion Date :

Apr 1, 2012

Actual Study Completion Date :

Apr 1, 2012

Arms and Interventions

Arm	Intervention/Treatment
Experimental: Active study drug Treatment	Drug: BIIB033 IV infusion of 0.3, 1, 3, 10, 30, 60 or 100 mg/kg
Experimental: Comparator Dummy drug	Drug: Placebo IV infusion dummy drug

Arm

Intervention/Treatment

Experimental: Active study drug

Treatment

Drug: BIIB033

IV infusion of 0.3, 1, 3, 10, 30, 60 or 100 mg/kg

Experimental: Comparator

Dummy drug

Drug: Placebo

IV infusion dummy drug

Outcome Measures

Primary Outcome Measures

Evaluate safety and tolerability profile of two IV infusions of BIIB033 in subjects with MS [For duration of study / 6 months]
Identify incidence and types of adverse events [For duration of study / 6 months]
The incidence of serious adverse events [For duration of study / 6 months]
Changes from baseline in clinical lab assessments and vital signs [For duration of study / 6 months]
Changes form baseline in other safety measures: physical and neurological examinations, brain MRIs, and ECGs [For duration of study / 6 months]

Secondary Outcome Measures

Assess the repeat-dose serum PK profile of BIIB033 [For duration of study / 6 months]
Assess the repeat-dose immunogenicity of BIIB033 [For duration of study / 6 months]
Measure the concentration of BIIB033 in the cerebrospinal fluid [At specified timepoints in the study]
Explore potential biomarkers of BIIB033 activity in the periphery and in the central nervous system [At specified timepoints in the study]

Eligibility Criteria

Criteria

Ages Eligible for Study:

18 Years to 60 Years

Sexes Eligible for Study:

All

Accepts Healthy Volunteers:

Inclusion Criteria:

Give informed consnet
Aged 18 to 60 years
Have relapsing remitting MS or secondary progressive MS
EDSS score of 1 to 6 inclusive
Body mass index of 18 to 30 kg/m2
Commitment to use effective contraception 6 months after last dose of study drug Treatment with any interferon beta or glatiramer acetate is allowed to continue during the study as long as the initiation of treatment was at least 3 months and the dose is stable.

Key Exclusion Criteria:

Primary progressive MS
Any significant cardiac, endocrinologic, hematologic, hepatic, immunologic, metabolic, urologic, pulmonary, neurologic, dermatologic, psychiatric, renal, allergic or anaphylactic reactions or other major disease
Clinically significant lab value at screening outside of normal range
Clinically significant ECG abnormality
Contraindication to MRI scans or lumbar punctures
Plans to undergo elective surgery during study
An MS relapse that has not resolved within 30 days before screening
History or postive test result for Hepatitis B, C and HIV
Serious infections within 3 months prior to Day -1
Treatment with MS medication within 12 months prior to Day -1: natalizumab, daclizumab, azathioprine, methotrexate, iV immunoglobulin, plasmapheresis or mycophenolate motefil
Prior treatment with total lymphoid irradiation, T cell or T-cell receptor vaccination, alemtuzumab, mitoxantone, cyclophosphamide, rituximab, fingolimod.