NCT04544449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 Ocrelizumab in Adult Patients With Primary Progressive 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
- 985
- 试验地点
- 371
- 主要终点
- Time to Onset of Composite 12-week Confirmed Disability Progression (cCDP12)
研究概览
简要总结
A study to evaluate the efficacy and safety of fenebrutinib on disability progression in adult participants with Primary Progressive Multiple Sclerosis (PPMS). All eligible participants will be randomized 1:1 to either daily oral fenebrutinib (and placebo) or intravenous (IV) ocrelizumab (and placebo) in a blinded fashion through an interactive voice or web-based response system (IxRS). 985 participants were enrolled and recruited globally. Participants who discontinue study medication early or discontinue from the study will not be replaced. The Open-Label Extension (OLE) phase is contingent on a positive benefit-risk result in the Primary Analysis 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 65 Years（Adult, Older Adult）
- 性别
- All
- 接受健康志愿者
- 否
入选标准
- •For sites in Germany and Italy only, enrollment is restricted to participants aged 46-65 years
- •A diagnosis of PPMS in accordance to the revised 2017 McDonald Criteria (Thompson et al. 2018).
- •Disability progression in the 12 months prior to screening.
- •Expanded Disability Status Scale (EDSS) score from 3.0 to 6.5 inclusive at screening.
- •Pyramidal functional subscore >=2 at screening.
- •For participants currently receiving proton pump inhibitors (PPIs), H2-receptor antagonists (H2RAs), symptomatic treatment for MS (e.g. fampridine, cannabis) and/or physiotherapy: treatment at a stable dose during the screening period prior to the initiation of study treatment and plans to remain at a stable dose for the duration of study treatment.
- •Neurologically stable for at least 30 days prior to randomization and baseline assessments.
- •Ability to complete the 9-Hole Peg Test (9-HPT) for each hand in <240 seconds.
- •Ability to perform 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 Double-Blind Treatment (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.
- •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
- •For participants enrolled in Germany and in Italy only: Presence of gadolinium-enhancing lesions on T1-weighted MRI (T1Gd +) lesion on the screening MRI
- •Any known or suspected active infection (excluding onychomycosis) at screening, including but not limited to a positive screening test for Hepatitis B and C, an active or latent or inadequately treated infection with tuberculosis (TB), a confirmed or suspected progressive multifocal leukoencephalopathy (PML).
- •Participants with a previous history of a serious Infusion-Related Reaction (IRR) (Common Terminology Criteria for Adverse Events [CTCAE] Grade >= 4) and/or any hypersensitivity reaction to ocrelizumab.
- •History of cancer including hematologic malignancy and solid tumors within 10 years of screening. Exceptions: Basal/squamous cell carcinoma of skin cured by excision. In situ carcinoma of the cervix successfully treated by curative therapy >1 year prior to screening.
- •Known presence of other neurological disorders, that could interfere with the diagnosis of MS or assessments of efficacy or safety during the study, clinically significant cardiovascular, psychiatric, pulmonary, renal, hepatic, endocrine, metabolic or gastrointestinal disease.
- •Presence of cirrhosis (Child-Pugh Class A, B, or C)
- •Chronic liver disease unless considered stable for >6 months
- •Acute liver disease
- •Any concomitant disease that may require chronic treatment with systemic corticosteroids, immunosuppressants or specific medication that could impact the primary evaluation of the study.
- •History of alcohol or other drug abuse within 12 months prior to screening.
- •Female participants who are pregnant or breastfeeding or intending to become pregnant during the study or 6 or 12 months (as applicable from the local label for ocrelizumab) after final dose of study drug.
- •Male participants intending to father a child during the study or for 28 days after final dose of study drug.
- •Lack of peripheral venous access.
- •Any previous treatment with immunomodulatory or immunosuppressive medication without an appropriate washout period.
- •Receipt of a live or live-attenuated vaccine within 6 weeks prior to randomization.
- •Immunocompromised state, history of primary or secondary (non-drug related) immunodeficiency, or history of transplantation or antirejection therapy
- •Known bleeding diathesis, anemia, or history of hospitalization or transfusion for gastrointestinal (GI) bleed
- •Any previous treatment with cladribine, mitoxantrone, daclizumab, alemtuzumab, or cyclophosphamide
- •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 fenebrutinib and IV ocrelizumab-matching placebo.
干预措施: Fenebrutinib (Drug)
Fenebrutinib
Experimental
Participants will receive oral fenebrutinib and IV ocrelizumab-matching placebo.
干预措施: Placebo matched to ocrelizumab (Drug)
Ocrelizumab
Active Comparator
Participants will receive IV ocrelizumab and oral fenebrutinib-matching placebo.
干预措施: Placebo matched to fenebrutinib (Drug)
Ocrelizumab
Active Comparator
Participants will receive IV ocrelizumab and oral fenebrutinib-matching placebo.
干预措施: Ocrelizumab (Drug)
结局指标
主要结局
Time to Onset of Composite 12-week Confirmed Disability Progression (cCDP12)
时间窗: Minimum of 120 weeks
Time to Onset of Composite 12-Week Confirmed Disability Progression (cCDP12)
时间窗: Minimum of 120 weeks
次要结局
- Time to Onset of Composite 24-week CDP (cCDP24)(Minimum of 120 weeks)
- Time to Onset of 12-week CDP (CDP12)(Minimum of 120 weeks)
- Time to Onset of 24-week CDP (CDP24)(Minimum of 120 weeks)
- Percentage Change in Total Brain Volume Assessed by Magnetic Resonance Imaging (MRI)(From Week 24 to Week 120)
- Change from Baseline in Participant-Reported Physical Impacts of Multiple Sclerosis (MS) Measured by the Multiple Sclerosis Impact Scale, 29-Item [MSIS-29] Physical Scale(Baseline, Weeks 12, 24, 36, 48, 60, 72, 84, 96, 108 and 120)
- Time to Onset of 12-week Confirmed 4-point Worsening in Symbol Digit Modality Test (SDMT) Score(Minimum of 120 weeks)
- Percentage of Participants with Adverse Events (AEs)(Up to 4.7 years)
- Plasma Concentrations of Fenebrutinib at Specified Timepoints(Up to 4.7 years)
- Percent Change from Screening in Blood Neurofilament Light Chain (NfL) Levels(Up to Week 120)
研究者
研究点 (371)
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