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).
Studie Overzicht
Toestand
Interventie / Behandeling
Gedetailleerde beschrijving
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.
Studietype
Inschrijving (Werkelijk)
Fase
- Fase 1
Contacten en locaties
Studie Locaties
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Colorado
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Centennial, Colorado, Verenigde Staten
- Research Site
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Deelname Criteria
Geschiktheidscriteria
Leeftijden die in aanmerking komen voor studie
Accepteert gezonde vrijwilligers
Geslachten die in aanmerking komen voor studie
Beschrijving
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.
Studie plan
Hoe is de studie opgezet?
Ontwerpdetails
- Toewijzing: Gerandomiseerd
- Interventioneel model: Opdracht voor een enkele groep
- Masker: Verdrievoudigen
Wapens en interventies
Deelnemersgroep / Arm |
Interventie / Behandeling |
|---|---|
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Experimenteel: Active study drug
Treatment
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IV infusion of 0.3, 1, 3, 10, 30, 60 or 100 mg/kg
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Experimenteel: Comparator
Dummy drug
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IV infusion dummy drug
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Wat meet het onderzoek?
Primaire uitkomstmaten
Uitkomstmaat |
Tijdsspanne |
|---|---|
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Evaluate safety and tolerability profile of two IV infusions of BIIB033 in subjects with MS
Tijdsspanne: For duration of study / 6 months
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For duration of study / 6 months
|
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Identify incidence and types of adverse events
Tijdsspanne: For duration of study / 6 months
|
For duration of study / 6 months
|
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The incidence of serious adverse events
Tijdsspanne: For duration of study / 6 months
|
For duration of study / 6 months
|
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Changes from baseline in clinical lab assessments and vital signs
Tijdsspanne: For duration of study / 6 months
|
For duration of study / 6 months
|
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Changes form baseline in other safety measures: physical and neurological examinations, brain MRIs, and ECGs
Tijdsspanne: For duration of study / 6 months
|
For duration of study / 6 months
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Secundaire uitkomstmaten
Uitkomstmaat |
Tijdsspanne |
|---|---|
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Assess the repeat-dose serum PK profile of BIIB033
Tijdsspanne: For duration of study / 6 months
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For duration of study / 6 months
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Assess the repeat-dose immunogenicity of BIIB033
Tijdsspanne: For duration of study / 6 months
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For duration of study / 6 months
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Measure the concentration of BIIB033 in the cerebrospinal fluid
Tijdsspanne: At specified timepoints in the study
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At specified timepoints in the study
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Explore potential biomarkers of BIIB033 activity in the periphery and in the central nervous system
Tijdsspanne: At specified timepoints in the study
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At specified timepoints in the study
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Medewerkers en onderzoekers
Sponsor
Publicaties en nuttige links
Algemene publicaties
- 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.
Studie record data
Bestudeer belangrijke data
Studie start
Primaire voltooiing (Werkelijk)
Studie voltooiing (Werkelijk)
Studieregistratiedata
Eerst ingediend
Eerst ingediend dat voldeed aan de QC-criteria
Eerst geplaatst (Schatting)
Updates van studierecords
Laatste update geplaatst (Schatting)
Laatste update ingediend die voldeed aan QC-criteria
Laatst geverifieerd
Meer informatie
Termen gerelateerd aan deze studie
Trefwoorden
Aanvullende relevante MeSH-voorwaarden
Andere studie-ID-nummers
- 215MS101
Informatie over medicijnen en apparaten, studiedocumenten
Bestudeert een door de Amerikaanse FDA gereguleerd geneesmiddel
Bestudeert een door de Amerikaanse FDA gereguleerd apparaatproduct
product vervaardigd in en geëxporteerd uit de V.S.
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