NCT04586023进行中（未招募）3 期
A Phase III Multicenter Randomized, Double-blind, Double-dummy, Parallel-group Study to Evaluate the Efficacy and Safety of Fenebrutinib Compared With Teriflunomide in Adult Patients With Relapsing Multiple Sclerosis
适应症
干预措施
相关药物
试验速览
- 阶段
- 3 期
- 状态
- 进行中（未招募）
- 入组人数
- 751
- 试验地点
- 214
- 主要终点
- Annualized Relapse Rate (ARR)
研究概览
简要总结
A study to evaluate the efficacy and safety of fenebrutinib on disability progression and relapse rate in adult participants with RMS. Eligible participants will be randomized in a 1:1 ratio to receive either fenebrutinib or teriflunomide. At the end of the double-blind treatment (DBT) phase (after disclosure of the DBT results), the Sponsor will determine whether or not to initiate the open-label extension (OLE) phase of the study.
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 (Participant, Investigator)
盲法说明
Sponsor will also be blinded.
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
- •Expanded Disability Status Scale (EDSS) score of 0 - 5.5 at screening
- •A diagnosis of RMS in accordance with the revised 2017 McDonald Criteria
- •Ability to complete the 9-hole Peg Test (9-HPT) for each hand in < 240 seconds
- •Ability to perform the Timed 25-foot Walk Test (T25FWT) in < 150 seconds
- •For female participants of childbearing potential: agreement to remain abstinent (refrain from heterosexual intercourse) or use contraceptive measures, and refrain from donating eggs
- •For male participants: agreement to remain abstinent (refrain from heterosexual intercourse) or use contraceptive measures, and refrain from donating sperm
- •OLE Inclusion Criteria:
- •Completed the DBT phase of the study (remaining on study treatment; no other disease-modifying therapy (DMT) administered) and who, in the opinion of the investigator, may benefit from treatment with fenebrutinib
- •Participants randomized to the teriflunomide treatment arm during the DBT phase must undergo the accelerated teriflunomide elimination procedure (ATEP) prior to the first administration of open-label fenebrutinib
- •For female participants of childbearing potential: agreement to remain abstinent (refrain from heterosexual intercourse) or use contraceptive measures, and refrain from donating eggs
- •For male participants: agreement to remain abstinent (refrain from heterosexual intercourse) or use contraceptive measures, and refrain from donating sperm
排除标准
- •Disease duration of > 10 years from the onset of symptoms and an EDSS score at screening < 2.0
- •Female participants who are pregnant or breastfeeding, or intending to become pregnant
- •Male participants who intend to father a child during the study
- •A diagnosis of primary progressive multiple sclerosis (PPMS) or non-active secondary progressive multiple sclerosis (SPMS)
- •Any known or suspected active infection at screening, including but not limited to a positive screening tests for hepatitis B (HBV) and hepatitis C (HCV), an active or latent or inadequately treated infection with tuberculosis (TB), a confirmed or suspected progressive multifocal leukoencephalopathy (PML)
- •History of cancer including hematologic malignancy and solid tumors within 10 years of screening
- •Known presence of other neurological disorders, that could interfere with the diagnosis of MS or assessments of efficacy or safety during the study and clinically significant cardiovascular, psychiatric, pulmonary, renal, hepatic, endocrine, metabolic or gastrointestinal (GI) disease
- •Rare hereditary problems of galactose intolerance, total lactase deficiency, or glucose-galactose malabsorption
- •Hypoproteinemia
- •Acute liver disease
- •Chronic liver disease unless considered stable for > 6 months
- •Presence of cirrhosis (Child-Pugh Class A, B, or C) or Gilbert's syndrome
- •Participants with significantly impaired bone marrow function or significant anemia, leukopenia, neutropenia or thrombocytopenia
- •Any concomitant disease that may require chronic treatment with systemic corticosteroids or immunosuppressants during the course of the study
- •History of alcohol or other drug abuse within 12 months prior to screening
- •History of or currently active primary or secondary (non-drug-related) immunodeficiency, including known history of human immunodeficiency virus (HIV) infection
- •Inability to complete an MRI scan
- •Adrenocorticotropic hormone or systemic corticosteroid therapy within 4 weeks prior to screening (inhaled and topical corticosteroids are allowed)
- •Receipt of a live-attenuated vaccine within 6 weeks prior to randomization
- •Any previous treatment with immunomodulatory or immunosuppressive medication without an appropriate washout period
- •OLE Exclusion Criteria:
- •Chronic liver disease unless considered stable for > 6 months
- •Acute liver disease
研究组 & 干预措施
Fenebrutinib
Experimental
Participants will receive oral (PO) fenebrutinib, with teriflunomide-matching placebo.
干预措施: Placebo (Drug)
Fenebrutinib
Experimental
Participants will receive oral (PO) fenebrutinib, with teriflunomide-matching placebo.
干预措施: Fenebrutinib (Drug)
Teriflunomide
Active Comparator
Participants will receive PO teriflunomide, with fenebrutinib-matching placebo in a blinded fashion.
干预措施: Teriflunomide (Drug)
Teriflunomide
Active Comparator
Participants will receive PO teriflunomide, with fenebrutinib-matching placebo in a blinded fashion.
干预措施: Placebo (Drug)
结局指标
主要结局
Annualized Relapse Rate (ARR)
时间窗: Minimum of 96 weeks
次要结局
- Time to Onset of Composite 12-week Confirmed Disability Progression (cCDP12)(Minimum of 96 weeks)
- Time to Onset of Composite 24-week Confirmed Disability Progression (cCDP24)(Minimum of 96 weeks)
- Time to Onset of 12-week Confirmed Disability Progression (CDP12)(Minimum of 96 weeks)
- Time to Onset of 24-week Confirmed Disability Progression (CDP24)(Minimum of 96 weeks)
- Plasma Concentrations of Fenebrutinib at Specified Timepoints(Up to 4.5 years)
- Time to Onset of Composite 12-week Confirmed Progression Independent of Relapse Activity (cPIRA12)(Minimum of 96 weeks)
- Number of New T1Gd+ Lesions, as Detected by Brain Magnetic Resonance Imaging (MRI)(Baseline, Weeks 12, 24, 48 and 96)
- Total Number of T1 Gadolinium-enhancing (Gd+) Lesions, New and/or Enlarging T2-weighted Lesions, as Detected by Magnetic Resonance Imaging (MRI)(Minimum of 96 weeks)
- Time to Onset of 12-week Confirmed ≥4-point Worsening in Symbol Digit Modalities Test (SDMT) Score(Minimum of 96 weeks)
- Percent Change From Baseline to Week 48 in the Concentration of Blood Neurofilament Light (NfL) Chain(Baseline, Week 48)
- Time to Onset of Composite 12-week Confirmed Progression Independent of Relapse Activity (cPIRA12)(Up to approximately 232 weeks)
- Number of Participants With Adverse Events (AEs), Serious AEs (SAEs), AEs Leading to Study Treatment Discontinuation, or AEs Leading to Dose Interruptions(Up to approximately 4.5 years)
- Plasma Concentrations of Fenebrutinib at Specified Timepoints(Up to approximately 4.5 years)
- Percentage of Participants With Adverse Events (AEs)(Up to 4.5 years)
- Time to Onset of 12-week Confirmed 4-point Worsening in Symbol Digit Modality Test (SDMT) Score(Minimum of 96 weeks)
- Total Number of T1 Gadolinium-enhancing (Gd+) Lesions, New and/or Enlarging T2-weighted Lesions, as Detected by Magnetic Resonance Imaging (MRI)(Baseline, Weeks 12, 24, 48 and 96)
- Percentage Change in Total Brain Volume From Week 24, as Assessed by MRI(From Week 24 to Week 96)
- Change in Participant-reported Physical Impacts of Multiple Sclerosis (MS), Measured by the Multiple Sclerosis, Impact Scale (29-Item), Version 2 (MSIS-29 v2) Physical Scale(Baseline, Weeks 12, 24, 36, 48, 60, 72, 84 and 96)
- Change From Baseline to Week 48 in the Concentration of Blood Neurofilament Light Chain (NfL)(Up to 48 weeks)
研究者
研究点 (214)
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