NCT02975349终止2 期
A Randomized, Double-Blind, Placebo-Controlled Phase II Study of M2951 With a Parallel, Open-Label, Active Control Group (Tecfidera), in Patients With Relapsing Multiple Sclerosis to Evaluate Efficacy, Safety, Tolerability, Pharmacokinetics, and Biological Activity.
适应症
干预措施
相关药物
试验速览
- 阶段
- 2 期
- 状态
- 终止
- 入组人数
- 267
- 试验地点
- 3
- 主要终点
- Total Number of Gadolinium-Enhancing T1 Lesions
研究概览
简要总结
The aim of this protocol is to find out about the safety and effectiveness of M2951 in participants with relapsing multiple sclerosis. Participants were placed into 1 of 3 groups to receive M2951, placebo or tecfidera for 24 weeks. After 24 weeks, the participants on placebo were given M2951.
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
- Double (Investigator, Outcomes Assessor)
入排标准
- 年龄范围
- 18 Years 至 65 Years（Adult, Older Adult）
- 性别
- All
- 接受健康志愿者
- 否
入选标准
- •Participants with a diagnosis of relapsing multiple sclerosis (may include participants with Secondary Progressive Multiple Sclerosis (SPMS) with superimposed relapses provided they meet the other criteria) in accordance with revised McDonald criteria for MS and Lublin and Reingold
- •Male or female aged 18 to 65 years
- •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-positive (Gd+) T1 lesion within 6 months prior to randomization would make the patient eligible.
- •Expanded Disability Status Scale score of 0 to 6 at Baseline
- •Women of childbearing potential must use a supplementary barrier method together with a highly effective method of contraception (according to International Council for Harmonisation [ICH] guidance M3[R2]) for 4 weeks prior to randomization, throughout the trial, and for 90 days after the last dose of IMP.
- •Signed and dated informed consent (participant must be able to understand the informed consent) indicating that the participant has been informed of all the pertinent aspects of the trial prior to enrolment and will comply with the requirements of the protocol.
排除标准
- •Progressive MS
- •Disease duration > 15 years in participants with EDSS of 2 or less
- •Use of the following, as determined in the protocol ; rituximab, ocrelizumab, mitoxantrone, or lymphocyte-depleting therapies, lymphocyte trafficking blockers (eg, natalizumab, fingolimod), intravenous (IV) immunoglobulins (Ig), plasmapheresis, immunosuppressive treatments, B-interferons or glatiramer acetate, Systemic glucocorticoids, teriflunomide
- •Exposure to Tecfidera within 6 months prior to randomization
- •Any allergy, contraindication, or inability to tolerate Tecfidera
- •Treatment with dalfampridine (fampridine, Ampyra) unless on a stable dose for ≥ 30 days prior to randomization
- •Inability to comply with MRI scanning
- •Immunologic disorder other than MS, with the exception of secondary well-controlled diabetes or thyroid disorder, or any other condition requiring oral, IV, intramuscular, or intra-articular corticosteroid therapy
- •Vaccination with live or live-attenuated virus vaccine within 1 month prior to Screening
- •Severe drug allergy or history of anaphylaxis, or allergy to the IMP or any of its incipients
- •Active, clinically significant viral, bacterial, or fungal infection, or any major episode of infection requiring hospitalization or treatment with parenteral anti-infectives within 4 weeks of Screening, or completion of oral anti-infectives within 2 weeks before or during Screening, or a history of recurrent infections (ie, 3 or more of the same type of infection in a 12-month rolling period). Vaginal candidiasis, onychomycosis, and genital or oral herpes simplex virus considered by the Investigator to be sufficiently controlled would not be exclusionary.
- •History of or positive testing for human immunodeficiency virus (HIV), hepatitis C (HCV) antibody and/or polymerase chain reaction, hepatitis B surface antigen (HBsAg) (+) and/or hepatitis B core total, and/or immunoglobulin M (IgM) antibody (+) at Screening.
- •The participant: • Has a history of or current diagnosis of active tuberculosis (TB) or • Is currently undergoing treatment for latent TB infection (LTBI) or • Has an untreated LTBI or • Has a positive QuantiFERON®-TB test at Screening.
- •Indeterminate QuantiFERON®
- •Participants with current household contacts with active TB will also be excluded
- •History of splenectomy or any major surgery within 2 months prior to Screening
- •History of myocardial infarction or cerebrovascular event as per the protocol
- •History of attempted suicide within 6 months prior to Screening or a positive response to items 4 or 5 of Columbia-Suicide Severity Rating Scale (C-SSRS)
- •An episode of major depression within the last 6 months prior to Screening
- •On anticoagulation, fish oil supplements, or antiplatelet therapy other than daily aspirin for cardioprotection and treatment of Tecfidera induced flushing
- •History of cancer, except adequately treated basal cell or squamous cell carcinoma of the skin
- •Breastfeeding/lactating or pregnant women
- •Participation in any investigational drug trial within 1 month or 5 half-lives of the investigational drug, whichever is longest, prior to Screening
- •Participants currently receiving (or unable to stop using prior to receiving the first dose of IMP) medications or herbal supplements known to be potent inhibitors of cytochrome P450 3A (CYP3A)
- •History of or current alcohol or substance abuse
- •Clinically significant abnormality on electrocardiogram or screening chest X-ray
- •Clinically significant laboratory abnormality
研究组 & 干预措施
Placebo then Evobrutinib 25 mg QD (Period 2)
Experimental
Participants who received placebo matched to Evobrutinib tablet orally for 24 weeks in active treatment period 1 received Evobrutinib 25 milligram (mg) orally, once daily (QD) in blinded extension (BE) period from week 25 to week 48.
干预措施: Evobrutinib (Drug)
Evobrutinib 25 mg QD (Period 1, 2 and 3)
Experimental
Participants received Evobrutinib 25 mg orally, QD up to Week 48 in active treatment period 1 and BE period received Evobrutinib 25 mg QD orally from Week 48 of BE period (OLE period Day 1) to Week 336 in OLE period.
干预措施: Evobrutinib (Drug)
Evobrutinib 75 mg QD (Period 1, 2 and 3)
Experimental
Participants received Evobrutinib 75 mg orally, QD up to Week 48 in active treatment period 1 and BE period received Evobrutinib 75 mg QD orally from Week 48 of BE period (OLE period Day 1) to Week 336 in OLE period.
干预措施: Evobrutinib (Drug)
Evobrutinib 75 mg BID (Period 1, 2 and 3)
Experimental
Participants received Evobrutinib 75 mg orally, twice daily (BID) up to Week 48 in active treatment period 1 and BE period received Evobrutinib 75 mg BID orally from Week 48 of BE period (OLE period Day 1) to Week 336 in OLE period.
干预措施: Evobrutinib (Drug)
Tecfidera (Period 1, 2 and 3)
Active Comparator
Participants received Tecfidera 120 mg twice daily (BID) for first 7 days followed by 240 mg orally, BID up to Week 48 in active treatment period 1 and BE period received Tecfidera 120 mg BID orally from Week 48 of BE period (OLE period Day 1) to Week 336 in OLE period.
干预措施: Tecfidera (Drug)
Placebo
Placebo Comparator
Participants received placebo matched to Evobrutinib tablet orally for 24 weeks in active treatment period 1.
干预措施: Placebo (Drug)
Placebo + Evobrutinib 25 mg QD (Period 3)
Experimental
Participants who received placebo matched to Evobrutinib tablet orally for 24 weeks in active treatment period 1 received Evobrutinib 25 mg orally, QD from Week 48 of BE period (OLE period Day 1) to Week 336 in OLE period.
干预措施: Evobrutinib (Drug)
结局指标
主要结局
Total Number of Gadolinium-Enhancing T1 Lesions
时间窗: Week 12 to Week 24
Analysis of T1-Gadolinium enhancing lesions was done using magnetic resonance imaging (MRI) scans. As per planned analysis, Tecfidera treatment group was not included in inferential analysis.
次要结局
- Annualized Relapse Rate (ARR)(Week 0 to Week 48)
- Qualified Relapse-free Status(Week 25 to Week 48)
- Change From Week 24 in Expanded Disability Status Scale (EDSS) at Week 48(Week 24, Week 48)
- Total Number of New or Enlarging T2 Lesions at Week 48 Relative to Week 24(Week 24 to Week 48)
- Change From Week 24 in Volume of Gadolinium-positive (Gd+) T1 Lesions at Week 48(Week 24, Week 48)
- Change From Week 24 in Volume of T2 Lesions at Week 48(Week 24, Week 48)
- OLE Period: Total Number of Gadolinium-Enhancing T1 Lesions(OLE Baseline (BE period Week 48), OLE Weeks 96, 144, 192, 240, 288 and 336)
- Annualized Relapse Rate (ARR) at Week 24(Week 24)
- Qualified Relapse-Free Status at Week 24(Week 24)
- Change From Baseline in Expanded Disability Status Scale (EDSS) at Week 24(Baseline, Week 24)
- OLE Period: Annualized Relapse Rate (ARR)(OLE Baseline (BE period Week 48), OLE Weeks 96, 144, 192, 240, 288 and 336)
- OLE Period: Percentage of Participants With Qualified Relapse-Free Status(OLE Baseline (BE period Week 48) up to OLE Week 336)
- OLE Period: Change From Baseline in Expanded Disability Status Scale (EDSS) at Week 96, 144, 192, 240, 288 and 336(OLE Baseline (BE period Week 48), OLE Weeks 96, 144, 192, 240, 288 and 336)
- Number of Participants With Treatment-emergent Adverse Events (TEAEs), Serious TEAEs and TEAEs Leading to Death(Baseline up to Safety Follow-up (Week 52))
- Number of Participants With Clinically Significant Changes From Baseline in Vital Signs and Electrocardiograms (ECGs)(Baseline up to Safety Follow-up (Week 52))
- Number of Participants With Grade 3 or Higher Hematology, Biochemistry and Urinalysis Values(Baseline up to Safety Follow-up (Week 52))
- Absolute Concentrations of Immunoglobulin (Ig) Levels (Active Treatment Period)(Baseline (Day 1), Weeks 4, 16, and 24)
- Absolute Concentrations of Immunoglobulin (Ig) Levels (Blinded Extension Period)(Week 48)
- Change From Baseline in Immunoglobulin (Ig) Levels (Active Treatment Period)(Baseline (Day 1), Weeks 4, 16, and 24)
- Change From Baseline in Immunoglobulin (Ig) Levels (Blinded Extension Period)(Baseline (Week 25), Week 48)
- Absolute Concentration of B Cells (Active Treatment Period)(Baseline (Day 1), Weeks 4, and 24)
- Absolute Concentration of B Cells (Blinded Extension Period)(Weeks 48 and 52)
- Change From Baseline in Absolute B Cells (Active Treatment Period)(Baseline (Day 1), Weeks 4 and 24)
- Change From Baseline in Absolute B Cells (Blinded Extension Period)(Baseline (Week 25), Weeks 48 and 52)
- Total Number of New Gadolinium-positive (Gd+) T1 Lesions(Week 12 to 24)
- Mean Per-scan Number of Gadolinium-positive (Gd+) T1 Lesions(Week 12 to Week 24)
- Total Number of New or Enlarging T2 Lesions(Week 12 to Week 24)
- Change From Baseline in Volume of T2 Lesions at Week 24(Baseline, Week 24)
- Change From Baseline in Volume of Gadolinium-positive (Gd+) T1 Lesions at Week 24(Baseline, Week 24)
- Number of Gadolinium-positive (Gd+) T1 Lesions at Week 48(Week 48)
- Number of New Gadolinium-positive (Gd+) T1 Lesions at Week 48(Week 48)
- OLE Period: Number of Participants With Treatment-emergent Adverse Events (TEAEs)(OLE Baseline (BE period Week 48) up to OLE Week 336)
- OLE Period: Number of Participants With Clinically Significant Changes From Baseline in Vital Signs(OLE Baseline (BE period Week 48) up to OLE Week 336)
- OLE Period: Number of Participants With Clinically Significant Changes From Baseline in Laboratory Parameters(OLE Baseline (BE period Week 48) up to OLE Week 336)
- OLE Period: Number of Participants With Clinically Significant Changes From Baseline in Electrocardiograms (ECGs)(OLE Baseline (BE period Week 48) up to OLE Week 336)
- OLE Period: Absolute Concentrations of Immunoglobulin (Ig) Levels(OLE Baseline (BE period Week 48), OLE Weeks 96, 144, 192, 240 and 288)
- OLE Period: Change From Baseline in Immunoglobulin (Ig) Levels(OLE Baseline (BE period Week 48), OLE Weeks 96, 144, 192, 240 and 288)
研究者
研究点 (3)
Loading locations...
相似试验
已完成
2 期
Phase IIb Study of Evobrutinib in Subjects With Rheumatoid ArthritisRheumatoid ArthritisNCT03233230EMD Serono Research & Development Institute, Inc.390
已完成
2 期
A Study to Evaluate the Efficacy and Safety of Therapeutic Hepatitis B VaccineHepatitis B, ChronicNCT04289987CHA Vaccine Institute Co., Ltd.134
已完成
2 期
A Study to Test the Safety and Efficacy of MK0249 in Patients With ADHD (0249-018)(COMPLETED)Attention-Deficit/Hyperactivity Disorder (ADHD)NCT00475735Merck Sharp & Dohme LLC72
终止
2 期
Assessment of the Safety, Tolerability and Efficacy of MEDI8968 in Subjects With Moderate to Severe Hidradenitis SuppurativaHidradenitis SuppurativaNCT01838499AstraZeneca224
已完成
3 期
A Study to Investigate Mepolizumab in the Treatment of Eosinophilic Granulomatosis With PolyangiitisChurg-Strauss SyndromeNCT02020889GlaxoSmithKline136