A Randomized, Blinded, Placebo-Controlled, Serial-Cohort, Multiple Ascending Dose Study of the Safety, Tolerability, and Pharmacokinetics of BIIB033 in Subjects With Multiple Sclerosis
试验速览
- 阶段
- 1 期
- 状态
- 已完成
- 发起方
- Biogen
- 入组人数
- 47
- 试验地点
- 1
- 主要终点
- The incidence of serious adverse events
研究概览
简要总结
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).
详细描述
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.
研究设计
- 研究类型
- Interventional
- 分配方式
- Randomized
- 干预模型
- Single Group
- 盲法
- Triple (Participant, Care Provider, Investigator)
入排标准
- 年龄范围
- 18 Years 至 60 Years（Adult）
- 性别
- All
- 接受健康志愿者
- 否
入选标准
- •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.
排除标准
- •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.
研究组 & 干预措施
Active study drug
Treatment
干预措施: BIIB033 (Drug)
Comparator
Dummy drug
干预措施: Placebo (Drug)
结局指标
主要结局
The incidence of serious adverse events
时间窗: For duration of study / 6 months
Changes form baseline in other safety measures: physical and neurological examinations, brain MRIs, and ECGs
时间窗: For duration of study / 6 months
Changes from baseline in clinical lab assessments and vital signs
时间窗: For duration of study / 6 months
Identify incidence and types of adverse events
时间窗: For duration of study / 6 months
Evaluate safety and tolerability profile of two IV infusions of BIIB033 in subjects with MS
时间窗: For duration of study / 6 months
次要结局
- Assess the repeat-dose serum PK profile of BIIB033(For duration of study / 6 months)
- Explore potential biomarkers of BIIB033 activity in the periphery and in the central nervous system(At specified timepoints in the study)
- 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)