A Study to Evaluate the Efficacy and Safety of Fenebrutinib Compared With Ocrelizumab in Adult Participants With Primary Progressive Multiple Sclerosis
Fenebrutinib: Participants will receive fenebrutinib.
Ocrelizumab: Participants will receive ocrelizumab.
Placebo matched to ocrelizumab: Participants will receive ocrelizumab-matching placebo.
Placebo matched to fenebrutinib: Participants will receive fenebrutinib-matching placebo
Study summary
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.
Eligibility
Sex
ALL
Min age
18 Years
Max age
65 Years
Healthy volunteers
No
Inclusion Criteria:
* 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.
Exclusion Criteria:
* 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
* Cirrhosis (Child-pugh Class A, B or C)
* Gilbert's syndrome
Primary outcome measure(s)
Time to Onset of Composite 12-Week Confirmed Disability Progression (cCDP12) — Minimum of 120 weeks
Trial sites (190)
Facility
City
Region
Status
Alabama Neurology Associates
Homewood
Alabama
Sutter East Bay Medical Foundation
Berkeley
California
Fullerton Neurology and Headache Center
Fullerton
California
Palo Alto Medical Foundation Research Center
Sunnyvale
California
University of Colorado Denver
Aurora
Colorado
Yale University School Of Medicine
Fairfield
Connecticut
Georgetown University Medical Center
Washington D.C.
District of Columbia
Neurology Associates PA
Maitland
Florida
Neurological Services of Orlando
Orlando
Florida
University of South Florida
Tampa
Florida
Josephson Wallack Munshower Neurology PC
Indianapolis
Indiana
University of Kansas Medical Center
Kansas City
Kansas
Johns Hopkins University School Of Medicine
Baltimore
Maryland
Dragonfly Research, LLC
Wellesley
Massachusetts
Wayne State University
Detroit
Michigan
Minneapolis Clinic of Neurology
Golden Valley
Minnesota
Washington University
St Louis
Missouri
Cleveland Clinic Lou Ruvo
Las Vegas
Nevada
Hackensack U Med Ctr
Hackensack
New Jersey
Barnabas Health Ambulatory Care Center
Livingston
New Jersey
Jersey Shore University Medical Centre
Neptune City
New Jersey
Rutgers New Jersey Medical School
Newark
New Jersey
Holy Name Hospital
Teaneck
New Jersey
Dent Neurological Institute
Amherst
New York
Columbia University Medical Center
New York
New York
University of Rochester
Rochester
New York
Stony Brook University Medical Center
Stony Brook
New York
SUNY Upstate Medical University
Syracuse
New York
Atrium Health Neurosciences Institute ? Charlotte
Charlotte
North Carolina
Raleigh Neurology Associates
Raleigh
North Carolina
Miami Valley Hospital South
Centerville
Ohio
UC Health, LLC.
Cincinnati
Ohio
OhioHealth Riverside Methodist Hospital
Columbus
Ohio
Providence Brain and Spine Institute
Portland
Oregon
Neurology Clinic PC
Cordova
Tennessee
Hope Neurology
Knoxville
Tennessee
Vanderbilt University Medical Center
Nashville
Tennessee
Uni of Texas Health Science Center At Houston
Houston
Texas
Texas Institute for Neurological Disorders
Sherman
Texas
Evergreen MS Center
Kirkland
Washington
+ 150 more sites — see the full list on the official registry below.
This page summarises publicly available registry data for informational purposes — not medical advice. Eligibility is determined by each study team; patients should discuss participation with their clinician.
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