Efficacy and Safety of the Biosimilar Natalizumab PB006 in Comparison to Tysabri® in Patients With Relapsing-Remitting Multiple Sclerosis (RRMS)
试验速览
- 阶段
- 3 期
- 状态
- 已完成
- 入组人数
- 265
- 试验地点
- 73
- 主要终点
- Cumulative Number of New Active Lesions Over 24 Weeks
研究概览
简要总结
This is a multi-center, randomized, parallel arm, double-blind study with a total duration of subjects' participation of 48 weeks. Approximately 260 participants with relapsing-remitting multiple sclerosis will be randomized to receive 12 doses of either PB006 or EU-licensed Natalizumab.
详细描述
This is a Phase 3 multicenter, double-blind, active-controlled, randomized, parallel-group study to assess the equivalence in efficacy and similarity in safety of biosimilar PB006 compared to Tysabri in patients with RRMS.
All eligible patients will be randomly assigned to one of two treatment groups in a 1:1 ratio, to receive a total of twelve intravenous (IV) infusion of either PB006 or Tysabri at a dose of 300 mg at each intravenous (IV) infusion administered with every single one intravenous (IV) infusion administered every 4 weeks of either PB006 or Tysabri at a dose of 300 mg starting at visit 1 (week 0) through visit 12 (week 44), for a total of 12 infusions. The End-of-Study Visit (visit 13, week 48) will be performed 4 weeks after the last infusion
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
- Quadruple (Participant, Care Provider, Investigator, Outcomes Assessor)
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
- •Male and female patients (age ≥18 to 60 years), with relapsing-remitting multiple sclerosis (RRMS) defined by the 2010 revised McDonald criteria
- •At least 1 documented relapse within the previous year and either ≥1 GdE T1-weighted brain lesions or ≥9 T2-weighted brain lesions at Screening
- •Kurtzke Expanded Disability Status Scale (EDSS) score from 0 to 5 (inclusive) at Screening
排除标准
- •Manifestation of multiple sclerosis (MS) other than relapsing-remitting multiple sclerosis (RRMS)
- •Relapse within the 30 days prior Screening and until administration of the first dose of study drug
- •Prior treatment with natalizumab, alemtuzumab, ocrelizumab, daclizumab, rituximab, cladribine, or other B- and T-cell targeting therapies
- •Prior total lymphoid irradiation or bone marrow or organ transplantation
- •Patients with John Cunningham Virus (JCV) index >1.5 at Screening
- •Past or current Progressive Multi-focal leukoencephalopathy (PML) diagnosis
- •Severe renal function impairment as defined by serum creatinine values >120 micromol per litre
结局指标
主要结局
Cumulative Number of New Active Lesions Over 24 Weeks
时间窗: Scans performed at week 0 (baseline), week 8, 16, 20 and 24.
Cumulative number of new active lesions over 24 weeks, calculated as the sum of all new gadolinium-enhancing (GdE) T1-weighted and new/enlarging T2-weighted lesion. Assessment was performed using Magnetic Resonance Imaging (MRI). Identification of GdE T1-weighted and T2-weighted lesions was done by a trained and certified radiology reviewer according to standard procedures at the MRI central reading center.
次要结局
- Cumulative Number of New Active Lesions Over 48 Weeks(Scans performed at week 0 (baseline), week 8, 16, 20, 24 and 48.)
- Cumulative Number of New GdE T1-weighted Lesions Over 24 Weeks(Scans performed at week 0 (baseline), week 8, 16, 20 and 24.)
- Cumulative Number of New GdE T1-weighted Lesions Over 48 Weeks(Scans performed at week 0 (baseline), week 8, 16, 20, 24 and 48.)
- Number of Patients Without New GdE T1-weighted Lesions Over 48 Weeks(Scans performed at week 0 (baseline), week 8, 16, 20, 24 and 48.)
- Annualized Relapse Rate After 48 Weeks(Up to 48 weeks.)
- Percentage of Subjects With Neutralizing Antibodies After 48 Weeks(Up to 48 weeks.)
- Number of Patients Without New GdE T1-weighted Lesions Over 24 Weeks(Scans performed at week 0 (baseline), week 8, 16, 20 and 24.)
- Cumulative Number of New/Enlarging T2-weighted Lesions Over 48 Weeks(Scans performed at week 0 (baseline), week 8, 16, 20, 24 and 48.)
- Number of Persistent Lesions After 48 Weeks(Scans performed at week 0 (baseline), week 8, 16, 20, 24 and 48.)
- Annualized Relapse Rate After 24 Weeks(Up to 24 weeks.)
- Number of Patients Without New/Enlarging T2-weighted Lesions Over 48 Weeks(Scans performed at week 0 (baseline), week 8, 16, 20, 24 and 48.)
- Cumulative Number of New/Enlarging T2-weighted Lesions Over 24 Weeks(Scans performed at week 0 (baseline), week 8, 16, 20 and 24.)
- Percentage of Subjects With Neutralizing Antibodies After 24 Weeks(Up to 24 weeks.)
- Number of Subjects With Any Treatment-Emergent Adverse Event (TEAE) or Any Treatment-Emergent Serious Adverse Event (SAE) After 24 Weeks(Up to week 24)
- Natalizumab Trough Concentration (Ctrough) Over Time, Week 16(Week 16)
- Number of Patients With Abnormal Clinical Laboratory Tests at Week 24(At week 24.)
- Change From Baseline in Blood Pressure at Week 48(At baseline and end of study (week 48).)
- Number of Persistent Lesions After 24 Weeks(Scans performed at week 0 (baseline), week 8, 16, 20 and 24.)
- Percentage of Subjects With Anti-drug (Natalizumab) Antibodies (ADA) and Persistent Antibodies After 48 Weeks(Up to 48 weeks.)
- Number of Subjects With Any Treatment-Emergent Adverse Event (TEAE) or Any Treatment-Emergent Serious Adverse Event (SAE) After 48 Weeks(Up to 48 weeks.)
- Change From Baseline in Blood Pressure at Week 24(At baseline and week 24.)
- Change From Baseline in Heart Rate at Week 48(At baseline and end of study (week 48).)
- Change From Baseline in Expanded Disability Status Scale (EDSS) After 24 Weeks(Baseline and week 24.)
- Change From Baseline in Expanded Disability Status Scale (EDSS) After 48 Weeks(FAS: Baseline (week 0) and week 48. SSW: Baseline (week 24) and week 48.)
- Percentage of Subjects With Anti-drug (Natalizumab) Antibodies (ADA) and Persistent Antibodies After 24 Weeks(Up to 24 weeks.)
- Natalizumab Trough Concentration (Ctrough) Over Time, Week 8(Week 8)
- Natalizumab Trough Concentration (Ctrough) Over Time, Week 24(Week 24)
- Natalizumab Trough Concentration (Ctrough) Over Time, Week 32(Week 32)
- Natalizumab Trough Concentration (Ctrough) Over Time, Week 48(Week 48)
- Number of Patients Without New/Enlarging T2-weighted Lesions Over 24 Weeks(Week 0 (baseline), week 8, 16, 20 and 24.)
- Number of Patients With Abnormal Findings in Physical Examination at Week 24(Week 24.)
- Number of Patients With Abnormal Findings in Physical Examination at Week 48(End of study (week 48).)
- Number of Patients With Abnormal Clinical Laboratory Tests at Week 48(At week 48.)
- Change From Baseline in Heart Rate at Week 24(At baseline and week 24.)