A Randomized, Controlled, Open-Label, Rater-Blinded, Phase 3b Study of the Efficacy, Safety, and Tolerability of 6-Week Extended Interval Dosing (EID) of Natalizumab (BG00002) in Subjects With Relapsing-Remitting Multiple Sclerosis Switching From Treatment With 4-Week Natalizumab Standard Interval Dosing (SID) in Relation to Continued SID Treatment - Followed by an Open-Label Crossover Extension Study Comprising Subcutaneous and Intravenous Natalizumab Administration
试验速览
- 阶段
- 3 期
- 状态
- 已完成
- 发起方
- Biogen
- 入组人数
- 585
- 试验地点
- 107
- 主要终点
- Part 1: Mean Number of New or Newly Enlarging T2 Hyperintense Lesions at Week 72
研究概览
简要总结
Part 1: The primary objective is to evaluate the efficacy of natalizumab extended interval dosing (EID) (every 6 weeks [Q6W]) in participants who have previously been treated with natalizumab standard interval dosing (SID) (every 4 weeks [Q4W]) for at least 12 months, in relation to continued Q4W treatment. The secondary objectives is to evaluate relapse-based clinical efficacy measures, disability worsening, additional Magnetic resonance imaging (MRI)-lesion efficacy measures and safety of Q6W in participants who have previously been treated with natalizumab Q4W for at least 12 months, in relation to continued Q4W treatment.
Part 2: The primary objective is to evaluate participant preference for subcutaneous (SC) versus intravenous (IV) route of natalizumab administration. The secondary objectives is to evaluate treatment satisfaction, drug preparation and administration time, safety and immunogenicity, efficacy and characterize pharmacokinetic (PK) and pharmacodynamic (PD) drug preparation and administration time of SC versus IV routes of natalizumab administration.
详细描述
This study will be conducted in 2 parts. At the end of part 1, participants who provide consent and are eligible, and newly enrolled participants, will enter part 2, an Open Label Extension comprising a crossover analysis.
Those participants who completed part 1 and cannot participate, or elect not to participate, in Part 2 (Open label extension) will enter a 12-week follow-up.
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
- None
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
- •For Part 1:
- •Ability of the participant to understand the purpose and risks of the study and provide signed and dated informed consent and authorization to use confidential health information in accordance with national and local participant privacy regulations.
- •Diagnosis of relapsing remitting multiple sclerosis (RRMS) according to the McDonald criteria [Thompson 2018].
- •Treatment with natalizumab as disease-modifying monotherapy for RRMS that is consistent with the approved dosing for a minimum of 12 months prior to randomization. The participant must have received at least 11 doses of natalizumab in the 12 months prior to randomization with no missed doses in the 3 months prior to randomization.
- •Expanded Disability Status Scale (EDSS) score <=5.5 at screening.
- •No relapses in the last 12 months prior to randomization, as determined by the enrolling Investigator.
- •For Part 2:
- •Ability of the participants to understand the purpose and risks of the study and provide signed and dated informed consent for Part 2 and authorization to use confidential health information in accordance with national and local participant privacy regulations.
- •Completed Part 1 Week 72 visit while remaining on their randomized treatment assignment of Q4W or Q6W.
排除标准
- •For Part 1:
- •Primary and secondary progressive multiple sclerosis (MS).
- •MRI positive for Gd-enhancing lesions at screening.
- •Participants for whom MRI is contraindicated (e.g., have a contraindicated pacemaker or other contraindicated implanted metal device, have suffered, or are at risk for, side effects from Gd, or have claustrophobia that cannot be medically managed).
- •History of any clinically significant (as determined by the Investigator) cardiac, endocrinologic, hematologic, hepatic, immunologic, metabolic (including diabetes), urologic, pulmonary, neurologic (except for RRMS), dermatologic, psychiatric, renal, or other major disease that would preclude participation in a clinical study, in the opinion of the Investigator.
- •Presence of anti-natalizumab antibodies at screening.
- •For Part 2:
- •Participants treated with natalizumab Q6W was reverted to natalizumab Q4W by choice or as rescue treatment in Part
- •Participant received treatment with any MS disease-modifying therapy other than natalizumab in Part 1 or in the period between Part 1 and Part
- •History of human immunodeficiency virus or history of other immunodeficient conditions.
- •Current enrollment or a plan to enroll in any interventional clinical study in which an investigational treatment or approved therapy for investigational use is administered within 30 days (or 5 half-lives of the agent, whichever is longer) prior to the Baseline Visit or at any time during this study.
- •Inability to comply with study requirements.
- •Other unspecified reasons that, in the opinion of the Investigator or Biogen, make the participant unsuitable for enrollment.
- •The inclusion and exclusion criteria for new participants who did not participate in Part 1 of the study are the same as those for participants who did participate in Part
- •NOTE: Other protocol defined Inclusion/Exclusion criteria may apply
研究组 & 干预措施
Part 1: IV Q4W
Participants received natalizumab 300 mg intravenous (IV) infusion once Q4W up to Week 72.
干预措施: Natalizumab (Drug)
Part 1: IV Q6W
Participants received natalizumab 300 mg IV infusion once Q6W up to Week 72.
干预措施: Natalizumab (Drug)
Part 2: Run-in Period: IV Q6W
Participants who completed Part 1 or were newly enrolled in Part 2 received natalizumab 300 mg IV infusion Q6W from Week 72 through Week 102.
干预措施: Natalizumab (Drug)
Part 2: Crossover Period: IV Q6W, then SC Q6W
Participants who completed run-in period of Part 2 were randomized to receive natalizumab 300 mg IV infusion Q6W from Week 108 through Week 126 followed by natalizumab 300 mg subcutaneous (SC) injection Q6W from Week 132 through Week 150 along with a single dose of natalizumab 300 mg SC injection or IV infusion as per participant's choice at Week 156.
干预措施: Natalizumab (Drug)
Part 2: Crossover Period: SC Q6W, then IV Q6W
Participants who completed run-in period of Part 2 were randomized to receive natalizumab 300 mg SC injection Q6W from Week 108 through Week 126 followed by natalizumab 300 mg IV infusion Q6W from Week 132 through Week 150 along with a single dose of natalizumab 300 mg SC injection or IV infusion as per participant's choice at Week 156.
干预措施: Natalizumab (Drug)
结局指标
主要结局
Part 1: Mean Number of New or Newly Enlarging T2 Hyperintense Lesions at Week 72
时间窗: Week 72
T2 hyperintense lesions were analyzed by magnetic resonance imaging (MRI) scans of brain. New MRI scans were compared with the prior MRI scans to analyze the number of new or newly enlarging T2 hyperintense lesions at Week 72 relative to baseline.
Part 2: Percentage of Participants Indicating a Preference for Natalizumab SC Administration at the End of Crossover Period of Part 2
时间窗: Week 150
次要结局
- Part 2: Change From Baseline in Cortical and Thalamic Brain Region Volume During the Crossover Period(Part 2 Baseline (Week 108) up to Week 156)
- Part 1: Percentage of Participants With Treatment-Emergent Adverse Events (TEAEs) and Serious Adverse Events (SAEs)(Baseline up to Week 84)
- Part 2: Percentage of Participants With Treatment-Emergent Adverse Events (TEAEs)(Part 2: Baseline (Week 108) up to Week 180)
- Part 2: Mean Number of New or Newly Enlarging T2 Hyperintense Lesions During the Crossover Period(Part 2 Baseline (Week 108) up to Week 156)
- Part 2: Time to First Relapse During the Crossover Period(Part 2 Baseline (Week 108) up to Week 156)
- Part 2: Annualized Relapse Rate During the Crossover Period(Part 2 Baseline (Week 108) up to Week 156)
- Part 1: Annualized Relapse Rate at Week 72(Week 72)
- Part 2: Change From Baseline in EDSS Score During the Crossover Period(Part 2 Baseline (Week 108) up to Week 156)
- Part 1: Time to Expanded Disability Status Scale (EDSS) Worsening(Up to Week 72)
- Part 1: Mean Number of New or Newly Enlarging T2 Hyperintense Lesions at Weeks 24 and 48(Weeks 24 and 48)
- Part 2: Change From Baseline in Treatment Satisfaction Questionnaire for Medication (TSQM) Scores During the Crossover Period(Part 2 Baseline (Week 108) up to Week 156)
- Part 2: Mean Number of New Gd Enhancing Lesions During the Crossover Period(Week 108 up to Week 156)
- Part 1: Time to First Relapse as Adjudicated by an Independent Neurology Evaluation Committee (INEC)(Up to Week 72)
- Part 1: Mean Number of New Gadolinium (Gd) Enhancing Lesions at Weeks 24, 48, and 72(Weeks 24, 48, and 72)
- Part 2: Percentage of Participants With Anti-Natalizumab Antibodies During the Crossover Period(Part 2 Baseline (Week 108) up to Week 156)
- Part 1: Mean Number of New T1 Hypointense Lesions at Weeks 24, 48, and 72(Weeks 24, 48, and 72)
- Part 2: Mean Time for Drug Preparation and Drug Administration During the Crossover Period(Week 108 up to Week 156)
- Part 2: Mean Percentage Change From Baseline in Brain Volume During the Crossover Period(Part 2 Baseline (Week 108) up to Week 156)
- Part 2: Mean Number of New T1 Hypointense Lesions During the Crossover Period(Week 108 up to Week 156)
- Part 2: Trough Serum Concentration of Natalizumab (Ctrough) During the Crossover Period(Pre-dose at Weeks 108, 114, 120, 126, 132, 138, 144, 150, and 156)
- Part 2: Mean Trough α4 Integrin Saturation During the Crossover Period(Pre-dose at Weeks 108, 114, 120, 126, 132, 138, 144, 150, and 156)