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).
Studieoversikt
Status
Intervensjon / Behandling
Detaljert beskrivelse
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
Registrering (Faktiske)
Fase
- Fase 1
Kontakter og plasseringer
Studiesteder
-
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Colorado
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Centennial, Colorado, Forente stater
- Research Site
-
-
Deltakelseskriterier
Kvalifikasjonskriterier
Alder som er kvalifisert for studier
Tar imot friske frivillige
Kjønn som er kvalifisert for studier
Beskrivelse
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.
Studieplan
Hvordan er studiet utformet?
Designdetaljer
- Tildeling: Randomisert
- Intervensjonsmodell: Enkeltgruppeoppdrag
- Masking: Trippel
Våpen og intervensjoner
Deltakergruppe / Arm |
Intervensjon / Behandling |
|---|---|
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Eksperimentell: Active study drug
Treatment
|
IV infusion of 0.3, 1, 3, 10, 30, 60 or 100 mg/kg
|
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Eksperimentell: Comparator
Dummy drug
|
IV infusion dummy drug
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Hva måler studien?
Primære resultatmål
Resultatmål |
Tidsramme |
|---|---|
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Evaluate safety and tolerability profile of two IV infusions of BIIB033 in subjects with MS
Tidsramme: For duration of study / 6 months
|
For duration of study / 6 months
|
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Identify incidence and types of adverse events
Tidsramme: For duration of study / 6 months
|
For duration of study / 6 months
|
|
The incidence of serious adverse events
Tidsramme: For duration of study / 6 months
|
For duration of study / 6 months
|
|
Changes from baseline in clinical lab assessments and vital signs
Tidsramme: For duration of study / 6 months
|
For duration of study / 6 months
|
|
Changes form baseline in other safety measures: physical and neurological examinations, brain MRIs, and ECGs
Tidsramme: For duration of study / 6 months
|
For duration of study / 6 months
|
Sekundære resultatmål
Resultatmål |
Tidsramme |
|---|---|
|
Assess the repeat-dose serum PK profile of BIIB033
Tidsramme: 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
Tidsramme: 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
Tidsramme: 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
Tidsramme: At specified timepoints in the study
|
At specified timepoints in the study
|
Samarbeidspartnere og etterforskere
Sponsor
Publikasjoner og nyttige lenker
Generelle publikasjoner
- 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.
Studierekorddatoer
Studer hoveddatoer
Studiestart
Primær fullføring (Faktiske)
Studiet fullført (Faktiske)
Datoer for studieregistrering
Først innsendt
Først innsendt som oppfylte QC-kriteriene
Først lagt ut (Anslag)
Oppdateringer av studieposter
Sist oppdatering lagt ut (Anslag)
Siste oppdatering sendt inn som oppfylte QC-kriteriene
Sist bekreftet
Mer informasjon
Begreper knyttet til denne studien
Nøkkelord
Ytterligere relevante MeSH-vilkår
Andre studie-ID-numre
- 215MS101
Legemiddel- og utstyrsinformasjon, studiedokumenter
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