A Randomized, Blinded, Parallel-Group, Phase 2 Study Exploring the Safety, Tolerability, and Efficacy of Multiple Regimens of Natalizumab in Adult Subjects With Relapsing Multiple Sclerosis
试验速览
- 阶段
- 2 期
- 状态
- 已完成
- 发起方
- Biogen
- 入组人数
- 290
- 试验地点
- 1
- 主要终点
- Cumulative Number of Combined Unique Active Lesions
研究概览
简要总结
The primary objective of this study is to explore the effects of multiple regimens of natalizumab on disease activity and safety in participants with relapsing-remitting Multiple Sclerosis (RRMS).
详细描述
This is a a dose and frequency (but not route of administration) blinded, prospective, randomized, dose-ranging study in patients with RRMS who have received natalizumab for at least 12 months according to the local prescribing guidelines. The study will explore dosing of natalizumab by subcutaneous and intravenous routes. Participants will be randomly assigned to 1 of 6 dosing regimens, blinded to natalizumab dose, but not route, for 60 weeks of treatment.
研究设计
- 研究类型
- Interventional
- 分配方式
- Randomized
- 干预模型
- Parallel
- 主要目的
- Treatment
- 盲法
- Double (Participant, Investigator)
入排标准
- 年龄范围
- 18 Years 至 55 Years（Adult）
- 性别
- All
- 接受健康志愿者
- 否
入选标准
- •Ability to provide written informed consent
- •Subjects of childbearing potential must practice effective contraception during the study
- •A documented diagnosis of Relapsing Remitting Multiple Sclerosis (RRMS)
- •Free of MS relapse for 12 months prior to randomization
- •Treatment with natalizumab for a minimum of 12 months immediately prior to randomization.
- •In the 12 months prior to commencing natalizumab, subject must have experienced a minimal level of disease activity as defined by 2 or more documented clinical relapses OR 1 relapse and documented MRI activity, defined by the presence of at least 1 Gd enhancing lesion on MRI, unrelated to the relapse.
排除标准
- •Known history of Human Immunodeficiency Virus (HIV), hepatitis C and/or hepatitis B virus
- •Positive for anti-natalizumab antibodies at screening
- •MRI positive for Gd-enhancing lesions at study entry
- •Subjects for whom MRI is contraindicated
- •History of any clinically significant cardiac, endocrinologic, hematologic, hepatic, immunologic, metabolic (including diabetes), urologic, pulmonary, neurologic (except for RRMS), dermatologic, psychiatric, renal, or other major disease
- •History of malignant disease, including solid tumors and hematologic malignancies (with the exception of cured basal cell and squamous cell carcinomas of the skin)
- •History of transplantation or any anti-rejection therapy
- •History of severe allergic or anaphylactic reactions or known hypersensitivity to any drug
- •A clinically significant infectious illness within 30 days prior to screening or progressive multifocal leukoencephalopathy (PML) or other opportunistic infections at any time
- •Signs or symptoms suggestive of any serious infection, based on medical history, physical examination or laboratory testing
- •NOTE: Other protocol defined Inclusion/Exclusion criteria may apply.
研究组 & 干预措施
Natalizumab 300 mg Intravenous (IV) Every 4 Weeks
Natalizumab 300 mg IV every 4 weeks for 60 weeks. Open-label natalizumab treatment 300 mg IV at Weeks 60, 64, and 68.
干预措施: natalizumab IV (Drug)
Natalizumab 300 mg Subcutaneous (SC) Every 4 Weeks
Natalizumab 300 mg SC every 4 weeks for 60 weeks. Open-label natalizumab treatment 300 mg IV at Weeks 60, 64, and 68.
干预措施: natalizumab IV (Drug)
Natalizumab 300 mg Subcutaneous (SC) Every 4 Weeks
Natalizumab 300 mg SC every 4 weeks for 60 weeks. Open-label natalizumab treatment 300 mg IV at Weeks 60, 64, and 68.
干预措施: natalizumab SC (Drug)
Natalizumab 300 mg IV Every 12 Weeks
Natalizumab 300 mg IV every 12 weeks for 60 weeks with matching IV placebo administered during the intervening 4-week periods. Open-label natalizumab treatment 300 mg IV at Weeks 60, 64, and 68.
干预措施: natalizumab IV (Drug)
Natalizumab 300 mg IV Every 12 Weeks
Natalizumab 300 mg IV every 12 weeks for 60 weeks with matching IV placebo administered during the intervening 4-week periods. Open-label natalizumab treatment 300 mg IV at Weeks 60, 64, and 68.
干预措施: IV Placebo (Drug)
Natalizumab 300 mg SC Every 12 Weeks
Natalizumab 300 mg SC every 12 weeks for 60 weeks with matching SC placebo administered during the intervening 4-week periods. Open-label natalizumab treatment 300 mg IV at Weeks 60, 64, and 68.
干预措施: natalizumab IV (Drug)
Natalizumab 300 mg SC Every 12 Weeks
Natalizumab 300 mg SC every 12 weeks for 60 weeks with matching SC placebo administered during the intervening 4-week periods. Open-label natalizumab treatment 300 mg IV at Weeks 60, 64, and 68.
干预措施: natalizumab SC (Drug)
Natalizumab 300 mg SC Every 12 Weeks
Natalizumab 300 mg SC every 12 weeks for 60 weeks with matching SC placebo administered during the intervening 4-week periods. Open-label natalizumab treatment 300 mg IV at Weeks 60, 64, and 68.
干预措施: SC Placebo (Drug)
Natalizumab 150 mg IV Every 12 Weeks
Natalizumab 150 mg IV every 12 weeks for 60 weeks with matching IV placebo administered during the intervening 4-week periods. Open-label natalizumab treatment 300 mg IV at Weeks 60, 64, and 68.
干预措施: natalizumab IV (Drug)
Natalizumab 150 mg IV Every 12 Weeks
Natalizumab 150 mg IV every 12 weeks for 60 weeks with matching IV placebo administered during the intervening 4-week periods. Open-label natalizumab treatment 300 mg IV at Weeks 60, 64, and 68.
干预措施: IV Placebo (Drug)
Natalizumab 150 mg SC Every 12 Weeks
Natalizumab 150 mg SC every 12 weeks for 60 weeks with matching SC placebo administered during the intervening 4-week periods. Open-label natalizumab treatment 300 mg IV at Weeks 60, 64, and 68.
干预措施: natalizumab IV (Drug)
Natalizumab 150 mg SC Every 12 Weeks
Natalizumab 150 mg SC every 12 weeks for 60 weeks with matching SC placebo administered during the intervening 4-week periods. Open-label natalizumab treatment 300 mg IV at Weeks 60, 64, and 68.
干预措施: natalizumab SC (Drug)
Natalizumab 150 mg SC Every 12 Weeks
Natalizumab 150 mg SC every 12 weeks for 60 weeks with matching SC placebo administered during the intervening 4-week periods. Open-label natalizumab treatment 300 mg IV at Weeks 60, 64, and 68.
干预措施: SC Placebo (Drug)
结局指标
主要结局
Cumulative Number of Combined Unique Active Lesions
时间窗: Up to Week 60
Cumulative number of combined unique active lesions (sum of the number of new gadolinium (Gd)-enhancing lesions and new or newly enlarging T2 hyperintense lesions not associated with Gd-enhancement on T1 weighted scans) based on brain magnetic resonance imaging (MRI) scans Up to Week 60.
次要结局
未报告次要终点