Safety Study of BIIB033 in Subjects With Multiple Sclerosis

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

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).

Study Overview

• Status: Completed
• Conditions: Multiple Sclerosis; Relapsing-Remitting Multiple Sclerosis
• Intervention / Treatment: Drug: BIIB033; Drug: Placebo

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 Type: Interventional
• Enrollment (Actual): 47
• Phase: Phase 1

Contacts and Locations

Study Locations

• United States
  • Colorado
    • Centennial, Colorado, United States
      • Research Site

Participation Criteria

Eligibility Criteria

• Ages Eligible for Study: 18 years to 60 years (Adult)
• Accepts Healthy Volunteers: No
• Genders Eligible for Study: All

Description

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.

Study Plan

How is the study designed?

Design Details

• Allocation: Randomized
• Interventional Model: Single Group Assignment
• Masking: Triple

Number of Arms

2

Arms and Interventions

Participant Group / 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

What is the study measuring?

Primary Outcome Measures

Outcome Measure	Time Frame
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

Outcome Measure	Time Frame
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

Collaborators and Investigators

• Sponsor: Biogen

Publications and helpful links

General Publications

• Tran JQ, Rana J, Barkhof F, Melamed I, Gevorkyan H, Wattjes MP, de Jong R, Brosofsky K, Ray S, Xu L, Zhao J, Parr E, Cadavid D. Randomized phase I trials of the safety/tolerability of anti-LINGO-1 monoclonal antibody BIIB033. Neurol Neuroimmunol Neuroinflamm. 2014 Aug 21;1(2):e18. doi: 10.1212/NXI.0000000000000018. eCollection 2014 Aug.
• Boyd A, Zhang H, Williams A. Insufficient OPC migration into demyelinated lesions is a cause of poor remyelination in MS and mouse models. Acta Neuropathol. 2013 Jun;125(6):841-59. doi: 10.1007/s00401-013-1112-y. Epub 2013 Apr 18.

Study record dates

Study Major Dates

• Study Start: October 1, 2010
• Primary Completion (Actual): April 1, 2012
• Study Completion (Actual): April 1, 2012

Study Registration Dates

• First Submitted: November 18, 2010
• First Submitted That Met QC Criteria: November 18, 2010
• First Posted (Estimate): November 19, 2010

Study Record Updates

• Last Update Posted (Estimate): January 9, 2017
• Last Update Submitted That Met QC Criteria: January 5, 2017
• Last Verified: January 1, 2017

More Information

Terms related to this study

• Keywords: Multiple Sclerosis; BIIB033; anti-LINGO-1 antibody; Relapsing Remitting MS; remyelination; myelin repair; Multiple ascending dose; Secondary progessive MS
• Additional Relevant MeSH Terms: Pathologic Processes; Nervous System Diseases; Immune System Diseases; Demyelinating Autoimmune Diseases, CNS; Autoimmune Diseases of the Nervous System; Demyelinating Diseases; Autoimmune Diseases; Multiple Sclerosis; Sclerosis; Multiple Sclerosis, Relapsing-Remitting
• Other Study ID Numbers: 215MS101

Drug and device information, study documents

• Studies a U.S. FDA-regulated drug product: No
• Studies a U.S. FDA-regulated device product: No
• product manufactured in and exported from the U.S.: No