A Phase III, Multicenter, Randomized, Parallel Group, Double Blind, Double Dummy, Active Controlled Study of Evobrutinib Compared With an Interferon Beta 1a (Avonex®), in Participants With RMS to Evaluate Efficacy and Safety
试验速览
- 阶段
- 3 期
- 状态
- 终止
- 入组人数
- 1
- 试验地点
- 2
- 主要终点
- Annualized Relapse Rate (ARR)
研究概览
简要总结
The study was to evaluate the efficacy and safety of evobrutinib administered orally twice daily versus Interferon-beta-1a (Avonex®), once a week intramuscularly in participants with Relapsing Multiple Sclerosis (RMS).
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 55 Years（Adult）
- 性别
- All
- 接受健康志愿者
- 否
入选标准
- •Participants diagnosed with RMS (relapsing-remitting multiple sclerosis [RRMS] or secondary progressive multiple sclerosis [SPMS] with relapses) in accordance with 2017 Revised McDonald criteria (Thompson 2018).
- •Participants with one or more documented relapses within the 2 years before Screening with either: a. one relapse which occurred within the last year prior to randomization, OR b. the presence of at least 1 gadolinium-enhancing (Gd+) T1 lesion within 6 months prior to randomization.
- •Participants have EDSS score of 0 to 5.5 at Baseline. Participants with an EDSS score <= 2 at screening are only eligible for participation if their disease duration (time since onset of symptoms) is no more than 10 years.
- •Participants are neurologically stable for >= 30 days prior to both screening and baseline.
- •Female participants must be neither pregnant nor breast-feeding and must lack child-bearing potential, as defined by either: post-menopausal or surgically sterile or use an effective method of contraception for the duration of the study.
- •Participants have given written informed consent prior to any study-related procedure.
- •Other protocol defined inclusion criteria could apply
排除标准
- •Participants diagnosed with Progressive MS, in accordance with the 2017 Revised McDonald criteria as follows: a). Participants with Primary Progressive MS. b). Participants with secondary progressive MS without evidence of relapse.
- •Disease duration more than (>) 10 years in participants with an EDSS =< 2.0 at screening.
- •Immunologic disorder other than MS, or any other condition requiring oral, intravenous (IV) , intramuscular, or intra-articular corticosteroid therapy, with the exception of well-controlled Type 2 diabetes mellitus or well controlled thyroid disease.
- •Other protocol defined exclusion criteria could apply.
研究组 & 干预措施
Evobrutinib + Avonex® matched Placebo
Participants received active evobrutinib twice daily (BID) along with concomitant intramuscular (IM) injection of placebo matched to Avonex® once a week. Treatment period was planned to be of 96 weeks.
干预措施: Evobrutinib (Drug)
Evobrutinib + Avonex® matched Placebo
Participants received active evobrutinib twice daily (BID) along with concomitant intramuscular (IM) injection of placebo matched to Avonex® once a week. Treatment period was planned to be of 96 weeks.
干预措施: Avonex® matched Placebo (Drug)
Avonex® + Evobrutinib matched Placebo
Participants received IM injection of active Avonex® once a week along with concomitant placebo matched to evobrutinib BID. Treatment period was planned to be of 96 weeks.
干预措施: Avonex® (Drug)
Avonex® + Evobrutinib matched Placebo
Participants received IM injection of active Avonex® once a week along with concomitant placebo matched to evobrutinib BID. Treatment period was planned to be of 96 weeks.
干预措施: Evobrutinib matched Placebo (Drug)
结局指标
主要结局
Annualized Relapse Rate (ARR)
时间窗: At Week 96
The annualized relapse rate at 96 weeks was to be calculated based on qualified relapses. A qualifying relapse is the occurrence of new or worsening neurological symptoms attributable to MS. The relapse should be accompanied by an increase of 0.5 points or more on Expanded Disability Status Scale (EDSS), or 2 points increase on one of the Functional System Scores (FSS), or 1 point increase on at least two of the FSS. The increase in FSS scores must be related to the neurological symptoms which were reported as new or worsening.
次要结局
- Time to First Occurrence of 12-Week Confirmed Expanded Disability Status Scale (EDSS) Progression(Baseline up to 96 weeks)
- Change From Baseline in Patient Reported Outcomes Measurement Information System (PROMIS) Fatigue Short Form Score at Week 96(Baseline, Week 96)
- Total Number of Gadolinium-Enhancing (Gd+) Time Constant 1 (T1) Lesions Assessed by Magnetic Resonance Imaging (MRI) Scans at Week 24, 48, and 96(At Week 24, 48 and 96)
- Number of Participants With Clinically Significant Electrocardiogram (ECG) Abnormalities(Baseline up to 254 days)
- Change From Baseline in Patient Reported Outcomes Measurement Information System (PROMIS) Physical Function (PF) Short Form Score at Week 96(Baseline, Week 96)
- Vital Signs: Pulse Rate(At Day 1, Week 2 unscheduled 1, Week 12 and Early Discontinuation ED (up to approximately 36 weeks))
- Absolute Concentrations of Immunoglobulin (Ig) A Level(At Day 1 and Day 92)
- Time to First Occurrence of 24-Week Confirmed Expanded Disability Status Scale (EDSS) Progression(Baseline up to 96 weeks)
- Total Number of New or Enlarging Time Constant 2 (T2) Lesions Assessed by Magnetic Resonance Imaging (MRI) Scans at Week 24, 48, and 96(At Week 24, 48 and 96)
- Number of Participants With Treatment-Emergent Adverse Events (TEAEs), Serious TEAEs and Adverse Events of Special Interest (AESIs)(Baseline up to 254 days)
- Number of Participants With Treatment-Emergent Adverse Events (TEAEs) Based on Severity According to National Cancer Institute-Common Terminology Criteria for Adverse Events Version 4.03 (NCI-CTCAE v4.03)(Baseline up to 254 days)
- Vital Signs: Diastolic Blood Pressure (DBP) and Systolic Blood Pressure (SBP)(At Day 1, Week 2 unscheduled 1, Week 12 and Early Discontinuation (ED) (up to approximately 36 weeks)
- Absolute Concentrations of Immunoglobulin (Ig) G Level(At Day 1 and Day 92)
- Vital Signs: Respiratory Rate(At Day 1, Week 2 unscheduled 1, Week 12 and Early Discontinuation ED (up to approximately 36 weeks))
- Vital Signs: Temperature(At Day 1, Week 2 unscheduled 1, Week 12 and Early Discontinuation (ED) (up to approximately 36 weeks))
- Vital Signs: Weight(At Day 1, Week 2 unscheduled 1, Week 12 and Early Discontinuation (up to approximately 36 weeks))
- Number of Participants With Abnormal Lab Values(Baseline up to 254 days)
- Absolute Concentrations of Immunoglobulin (Ig) M Level(At Day 1 and Day 92)
- Absolute Concentrations of Immunoglobulin (Ig) E Level(At Day 1 and Day 92)
- Change From Baseline in Immunoglobulin (Ig) A Level(At Day 1 and Day 92)
- Change From Baseline in Immunoglobulin (Ig) E Level(At Day 1 and Day 92)
- Change From Baseline in Immunoglobulin (Ig) G Level(At Day 1 and Day 92)
- Change From Baseline in Immunoglobulin (Ig) M Level(At Day 1 and Day 92)