NCT04338061终止3 期
A Phase III, Multicenter, Randomized, Parallel Group, Double Blind, Double Dummy, Active Controlled Study of Evobrutinib Compared With Teriflunomide, in Participants With Relapsing Multiple Sclerosis to Evaluate Efficacy and Safety (evolutionRMS 2)
Merck Healthcare KGaA, Darmstadt, Germany, an affiliate of Merck KGaA, Darmstadt, Germany278 个研究点 分布在 4 个国家目标入组 1,166 人开始时间: 2020年7月2日最近更新:
适应症
干预措施
相关药物
试验速览
- 阶段
- 3 期
- 状态
- 终止
- 发起方
- 入组人数
- 1,166
- 试验地点
- 278
- 主要终点
- Double Blind Treatment Period (DBTP) and Double Blind Extension (DBE) Period: Annualized Relapse Rate (ARR)
研究概览
简要总结
The study is to evaluate the efficacy and safety of evobrutinib administered orally twice daily versus Teriflunomide (Aubagio®), administered orally once daily in participants with Relapsing Multiple Sclerosis (RMS). Participants who complete the double-blind treatment period (DBTP) and double-blind extension period (DBEP) prior to approval of a separate long-term follow-up study in their country will get an option for evobrutinib treatment continuation through a 96-week open-label extension (OLE) period.
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 are 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 Expanded Disability Status Scale (EDSS) score of 0 to 5.5 at Screening and Baseline (Day 1). Participants with an EDSS score less than or equal to [<=] 2 at Screening and Baseline (Day 1) 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 (Day 1)
- •Female participants must be neither pregnant nor breast-feeding or 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 and at least 2 years after study intervention due to the long elimination period for teriflunomide of 2 years, unless the participant undergoes an accelerated elimination procedure
- •Male participants must refrain from donating sperm and/or abstain from intercourse with women of child-bearing potential or use an effective method of contraception for the duration of the study and at least 2 years after study intervention due to the long elimination period for teriflunomide of 2 years, unless the participant undergoes an accelerated elimination procedure
- •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 and Baseline (Day 1)
- •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
Teriflunomide
Active Comparator
干预措施: Teriflunomide (Drug)
Evobrutinib
Experimental
干预措施: Evobrutinib (Drug)
结局指标
主要结局
Double Blind Treatment Period (DBTP) and Double Blind Extension (DBE) Period: Annualized Relapse Rate (ARR)
时间窗: Baseline up to 170 weeks
The qualifying relapse is the occurrence of new or worsening neurological symptoms attributable to Multiple Sclerosis (MS) (for more than \[\>\] 24 hours, no fever, infection, injury, adverse events (AEs), and preceded by a stable or improving neurological state for more than or equal to \[\>=\] 30 days).
次要结局
- DBTP and DBE Period: Percentage of Participants Without 12-Week Confirmed Disability Progression (CDP) as Measured by Expanded Disability Status Scale (EDSS)(Week 96 and Week 156 (combined DBTP and DBE periods))
- DBTP and DBE Period: Percentage of Participants Without 24-Week Confirmed Disability Progression (CDP) as Measured by Expanded Disability Status Scale (EDSS)(Week 96 and Week 156 (combined DBTP and DBE periods))
- DBTP and DBE Period: Percentage of Participants With 24-Week Confirmed Disability Improvement (CDI) as Measured by Expanded Disability Status Scale (EDSS)(Week 96 and Week 156 (combined DBTP and DBE periods))
- DBTP and DBE Period: Change From Baseline in Patient Reported Outcomes Measurement Information System (PROMIS) Physical Function (PF) Score at Week 48, Week 96, Week 120, Week 144 and Week 156(Baseline, Week 48, Week 96, Week 120, Week 144 and Week 156 (Combined DBTP and DBE periods))
- DBTP and DBE Periods: Change From Baseline in Electrocardiograms (ECGs): QT Interval - Fridericia's Correction Formula, PR Interval and QRS Duration(Baseline up to 170 weeks)
- DBTP and DBE Period: Change From Baseline in Patient Reported Outcomes Measurement Information System (PROMIS) Fatigue Score at Week 48, Week 96, Week 120, Week 144 and Week 156(Baseline, Week 48, Week 96, Week 120, Week 144 and Week 156 ((combined DBTP and DBE periods))
- DBTP and DBE Period: Total Number of T1 Gadolinium-positive (Gd+) Lesions(Baseline up to 170 weeks)
- DBTP and DBE Period: New or Enlarging T2 Lesions Rate(Baseline up to 170 weeks)
- DBTP Period: Neurofilament Light Chain (NfL) Concentration at Week 12(Week 12)
- DBTP and DBE Periods: Change From Baseline in Biochemistry Parameters: Bilirubin and Creatinine(Baseline up to 170 weeks)
- DBTP and DBE Periods: Number of Participants With Treatment-Emergent Adverse Events (TEAEs) and Adverse Events of Special Interest (AESIs)(Baseline up to 170 weeks)
- DBTP and DBE Periods: Number of Participants With Treatment-Emergent Adverse Events (TEAEs) by Severity(Baseline up to 170 weeks)
- DBTP and DBE Periods: Change From Baseline in Vital Signs: Diastolic Blood Pressure and Systolic Blood Pressure(Baseline up to 170 weeks)
- DBTP and DBE Periods: Change From Baseline in Vital Signs: Pulse Rate(Baseline up to 170 weeks)
- DBTP and DBE Periods: Change From Baseline in Vital Signs: Respiratory Rate(Baseline up to 170 weeks)
- DBTP and DBE Periods: Change From Baseline in Vital Signs: Weight(Baseline up to 170 weeks)
- DBTP and DBE Periods: Change From Baseline in Vital Signs: Temperature(Baseline up to 170 weeks)
- DBTP and DBE Periods: Change From Baseline in Electrocardiograms (ECGs): Heart Rate(Baseline up to 170 weeks)
- DBTP and DBE Periods: Change From Baseline in Hematology Parameter: Hemoglobin and Erythrocytes Mean Corpuscular Hemoglobin (HGB) Concentration(Baseline up to 170 weeks)
- DBTP and DBE Periods: Change From Baseline in Hematology Parameter: Platelets, Leukocytes, Neutrophils, Eosinophils, Basophils, Monocytes, Lymphocytes and Reticulocytes(Baseline up to 170 weeks)
- DBTP and DBE Periods: Change From Baseline in Hematology Parameters: Hematocrit(Baseline up to 170 weeks)
- DBTP and DBE Periods: Change From Baseline in Hematology Parameter: Erythrocytes Mean Corpuscular Hemoglobin(Baseline up to 170 weeks)
- DBTP and DBE Periods: Change From Baseline in Hematology Parameter: Erythrocytes Mean Corpuscular Volume(Baseline up to 170 weeks)
- DBTP and DBE Periods: Change From Baseline in Biochemistry Parameters: Aspartate Aminotransferase, Alanine Aminotransferase, Alkaline Phosphatase, Amylase, Lipase, Gamma Glutamyl Transferase and Lactate Dehydrogenase(Baseline up to 170 weeks)
- DBTP and DBE Periods: Change From Baseline in Biochemistry Parameters: Sodium, Potassium, Calcium, Magnesium, Glucose, Chloride, Urea Nitrogen, Phosphate, Bicarbonate and Corrected Calcium(Baseline up to 170 weeks)
- DBTP and DBE Periods: Change From Baseline in Biochemistry Parameters: Total Protein and Albumin(Baseline up to 170 weeks)
- DBTP and DBE Periods: Change From Baseline in Biochemistry Parameters: Glomerular Filtration Rate(Baseline up to 170 weeks)
- DBTP and DBE Periods: Change From Baseline in Urinalyses Parameter: Potential of Hydrogen (pH) of Urine(Baseline up to 170 weeks)
- DBTP and DBE Periods: Change From Baseline in Urinalyses Parameter: Specific Gravity of Urine(Baseline up to 170 weeks)
- DBTP and DBE Periods: Absolute Concentrations of Immunoglobulin (Ig) Levels(At Week 170)
- DBTP and DBE Periods: Change From Baseline in Immunoglobulin (Ig) Levels(Baseline up to 170 weeks)
研究者
研究点 (278)
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