A Study to Evaluate the Efficacy and Safety of Fenebrutinib Compared With Ocrelizumab in Adult Participants With Primary Progressive Multiple Sclerosis

Running, not enrolling · Phase 3 · Has a placebo group

Conditions studied: Multiple Sclerosis, Primary Progressive

In brief

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.

Key facts

Study ID

NCT04544449

Run by

Hoffmann-La Roche

People needed

985

Starts

2020-10-26

Expected to finish

2027-07-21

Last updated by the study team

2026-06-23

Who can join

Age: 18 and older, up to 65. Sex: any. Healthy volunteers: not accepted.

You may qualify if…

• 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.

You may not qualify if…

• 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

Where it is running

• Sutter East Bay Medical Foundation — Berkeley, California, United States
• Fullerton Neurology and Headache Center — Fullerton, California, United States
• Palo Alto Medical Foundation Research Center — Sunnyvale, California, United States
• University of Colorado Denver — Aurora, Colorado, United States
• Yale University School Of Medicine — Fairfield, Connecticut, United States
• Georgetown University Medical Center — Washington D.C., District of Columbia, United States
• Neurology Associates PA — Maitland, Florida, United States
• Neurological Services of Orlando — Orlando, Florida, United States
• University of South Florida — Tampa, Florida, United States
• Josephson Wallack Munshower Neurology PC — Indianapolis, Indiana, United States
• University of Kansas Medical Center — Kansas City, Kansas, United States
• Johns Hopkins University School Of Medicine — Baltimore, Maryland, United States
• Dragonfly Research, LLC — Wellesley, Massachusetts, United States
• Wayne State University — Detroit, Michigan, United States
• Minneapolis Clinic of Neurology — Golden Valley, Minnesota, United States
• Washington University — St Louis, Missouri, United States
• Cleveland Clinic Lou Ruvo — Las Vegas, Nevada, United States
• Hackensack U Med Ctr — Hackensack, New Jersey, United States
• Barnabas Health Ambulatory Care Center — Livingston, New Jersey, United States
• Jersey Shore University Medical Centre — Neptune City, New Jersey, United States
• Rutgers New Jersey Medical School — Newark, New Jersey, United States
• Holy Name Hospital — Teaneck, New Jersey, United States
• Dent Neurological Institute — Amherst, New York, United States
• Columbia University Medical Center — New York, New York, United States
• Alabama Neurology Associates — Homewood, Alabama, United States

Full record on ClinicalTrials.gov

Trial information comes from ClinicalTrials.gov and is refreshed daily. TrialsForMe does not provide medical care and does not run the studies it lists.