A Multicenter, Randomized, Double-Blind, Placebo-Controlled Study of the Efficacy of Natalizumab on Reducing Disability Progression in Subjects With Secondary Progressive Multiple Sclerosis, With Optional Open-Label Extension
试验速览
- 阶段
- 3 期
- 状态
- 终止
- 发起方
- Biogen
- 入组人数
- 889
- 试验地点
- 1
- 主要终点
- Number of Participants With Treatment-Emergent Adverse Events (AEs) and Serious Adverse Events (SAEs)
研究概览
简要总结
This is a Phase 3b, multicenter, international study conducted in 2 parts. Upon completion of the placebo-controlled period (Part 1), participants will have the option of enrolling in a 2-year open-label extension (Part 2).
Part 1: The primary objective of the study is to investigate whether treatment with natalizumab slows the accumulation of disability not related to relapses in participants with secondary progressive multiple sclerosis (SPMS).
The secondary objectives of Part 1 of this study are to determine the proportion of participants with consistent improvement in Timed 25-Foot Walk (T25FW), the change in participant-reported ambulatory status as measured by the 12-item MS Walking Scale (MSWS-12), the change in manual ability based on the ABILHAND Questionnaire, the impact of natalizumab on participant-reported quality of life using the Multiple Sclerosis Impact Scale-29 Physical (MSIS-29 Physical), the change in whole brain volume between the end of study and Week 24 using magnetic resonance imaging (MRI) and the proportion of participants experiencing progression of disability as measured by individual physical Expanded Disability Status Scale (EDSS) system scores.
Part 2: The primary objective of Part 2 of the study is to evaluate the safety profile of natalizumab in participants with SPMS.
The secondary objectives of Part 2 of the study are to investigate long-term disability (based on clinical or participant-reported assessments) in participants with SPMS receiving natalizumab treatment for approximately 4 years and to assess change in brain volume and T2 lesion volume.
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
- Triple (Participant, Care Provider, Investigator)
入排标准
- 年龄范围
- 18 Years 至 58 Years（Adult）
- 性别
- All
- 接受健康志愿者
- 否
入选标准
- 未提供
排除标准
- 未提供
研究组 & 干预措施
natalizumab
In Part 1 participants were randomized to receive 300 mg of natalizumab intravenously (IV) every 4 weeks for 96 weeks. In Part 2 participants transitioned to receive open-label natalizumab 300 mg IV every 4 weeks for at least 96 weeks.
干预措施: natalizumab (Drug)
Placebo
In Part 1 participants were randomized to receive placebo IV every 4 weeks for 96 weeks. In Part 2 participants transitioned to receive open-label natalizumab 300 mg IV every 4 weeks for at least 96 weeks.
干预措施: natalizumab (Drug)
Placebo
In Part 1 participants were randomized to receive placebo IV every 4 weeks for 96 weeks. In Part 2 participants transitioned to receive open-label natalizumab 300 mg IV every 4 weeks for at least 96 weeks.
干预措施: Placebo (Drug)
结局指标
主要结局
Number of Participants With Treatment-Emergent Adverse Events (AEs) and Serious Adverse Events (SAEs)
时间窗: 218 weeks
AE: any untoward medical occurrence that did not necessarily have a causal relationship with this treatment. SAE: any untoward medical occurrence that at any dose: resulted in death; in the view of the Investigator, placed the participant at immediate risk of death (a life-threatening event); required inpatient hospitalization or prolongation of existing hospitalization; resulted in persistent or significant disability/incapacity; resulted in a congenital anomaly/birth defect. An SAE may have also been any other medically important event in the opinion of the Investigator.
Part 1: Percentage of Participants With Confirmed Progression of Disability in One or More of the Expanded Disability Status Scale (EDSS), Timed 25-Foot Walk (T25FW), or 9-Hole Peg Test (9HPT)
时间窗: Up to 96 weeks (2 years)
Confirmed disability progression, defined as ≥1 of the following criteria (confirmed at a second visit ≥6 months later and at Week 96): * Confirmed progression in EDSS (EDSS score increased from baseline \[BL\] by ≥1 point if BL EDSS ≤5.5 or by ≥0.5 points if BL EDSS ≥6); * Confirmed progression in T25FW (T25FW increased by ≥20% of the BL walk); * Confirmed progression in 9HPT (9HPT increased by ≥20% of the time taken at BL on either hand and confirmed on the same hand). The EDSS measures disability status on a scale ranging from 0 to 10, with higher scores indicating more disability. The T25FW is a quantitative mobility and leg function performance test where the participant is timed while walking for 25 feet. The 9HPT is a quantitative test of upper extremity function that measures the time it takes to place 9 pegs into 9 holes and then remove the pegs. The 95% confidence interval (CI) of the percentage is based on normal approximation.
次要结局
- Part 1: Percentage of Participants With a T25FW Response(Up to 96 weeks)
- Part 1: Change From Baseline in Manual Ability Score Based on the ABILHAND Questionnaire(Baseline and Week 96)
- Part 1: Change From Baseline in the Multiple Sclerosis Impact Scale-29 Physical (MSIS-29 Physical) Score(Baseline and Week 96)
- Part 2: Percentage of Participants With Disability Worsening at 156 Weeks(Week 156)
- Part 2: Percentage Change From Baseline (Part 1) in 9HPT (Dominant Hand)(Baseline (Part 1) and Weeks 156, 204)
- Part 2: Percentage Change From Baseline (Part 1) in 9HPT (Non-Dominant Hand)(Baseline (Part 1) and Weeks 156, 204)
- Part 2: Absolute Change From Baseline (Part 1) in EDSS(Baseline (Part 1) and Weeks 156, 204)
- Part 2: Percentage Change From Baseline (Part 1) in EDSS(Baseline (Part 1) and Weeks 156, 204)
- Part 2: Absolute Change From Baseline (Part 1) in the MSIS-29 Physical Score(Baseline (Part 1) and Weeks 156 and 204)
- Part 2: Percentage Change From Baseline (Part 1) in the MSIS-29 Physical Score(Baseline (Part 1) and Weeks 156, 204)
- Part 1: Percentage Change From Week 24 in Whole Brain Volume at Week 96(Week 24 and Week 96)
- Part 1: Percentage of Participants Defined as Confirmed Progressors on EDSS Functional System Scores(Up to 96 weeks)
- Part 2: Absolute Change From Baseline (Part 1) in 9HPT (Dominant Hand)(Baseline (Part 1) and Weeks 156, 204)
- Part 2: Absolute Change From Baseline (Part 1) in 9HPT (Non-Dominant Hand)(Baseline (Part 1) and Weeks 156, 204)
- Part 2: Absolute Change From Baseline (Part 1) in the 6-Minute Walk Test (6MWT)(Baseline (Part 1) and Weeks 156 and 204)
- Part 1: Change From Baseline in the 12-Item MS Walking Scale (MSWS-12)(Baseline and Week 96)
- Part 2: Percentage Change From Baseline (Part 1) in the 6MWT(Baseline (Part 1) and Weeks 156, 204)
- Part 2: Absolute Change From Baseline (Part 1) in the Symbol Digit Modalities Test (SDMT)(Baseline (Part 1) and every 4 weeks from Week 108 to Week 204)
- Part 2: Percentage Change From Baseline (Part 1) in the SDMT(Baseline (Part 1) and every 4 weeks from Week 108 to Week 204)
- Part 2: Summary of New/Enlarging T2 Lesion Counts(Baseline (Part 1) up to Week 204)
- Part 2: Absolute Change From Baseline (Part 1) in T25FW(Baseline (Part 1) and Weeks 156, 204)
- Part 2: Percentage Change From Baseline (Part 1) in T25FW(Baseline (Part 1) and Weeks 156, 204)
- Part 2: Percentage Change From Baseline (Part 1) in Whole Gray Matter Brain Volume(Baseline (Part 1) and Weeks 156 and 204)
- Part 2: Percentage Change From Baseline (Part 1) in Number of New/Enlarging T2 Lesions(Baseline (Part 1) and Weeks 156 and 204)
- Part 2: Absolute Change From Baseline (Part 2) in the Work Productivity and Activity Impairment - Multiple Sclerosis (WPAI-MS) Questionnaire(Part 2 Baseline (Week 108) and Weeks 156 and 204)
- Part 2: Percentage Change From Baseline (Part 2) in the WPAI-MS Questionnaire(Part 2 Baseline (Week 108) and Weeks 156 and 204)
- Part 2: Percentage Change From Week 24 (Part 1) in Whole Brain Volume(Week 24 (Part 1) and Weeks 156 and 204)