Purpose

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 (or placebo) or intravenous (IV) ocrelizumab (or placebo) in a blinded fashion through an interactive voice or web-based response system (IxRS). Approximately 946 participants will be enrolled and will be 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.

Condition

Eligibility

Eligible Ages
Between 18 Years and 65 Years
Eligible Genders
All
Accepts Healthy Volunteers
No

Inclusion Criteria

  • A diagnosis of PPMS in accordance to the revised 2017 McDonald Criteria (Thompson et al. 2018). - Expanded Disability Status Scale (EDSS) score from 3.0 to 6.5 inclusive at screening. - For participants currently receiving proton pump inhibitors (PPIs), H2-receptor antagonists (H2RAs), symptomatic treatment for Multiple Sclerosis (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. - 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). - 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

  • Any known or suspected active infection at screening, including but not limited to a positive screening tests 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. - Known presence of other neurological disorders, clinically significant cardiovascular, psychiatric, pulmonary, renal, hepatic, endocrine, metabolic or gastrointestinal 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 6 or 12 months (as applicable from the local label for ocrelizumab) 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. 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.

Study Design

Phase
Phase 3
Study Type
Interventional
Allocation
Randomized
Intervention Model
Parallel Assignment
Primary Purpose
Treatment
Masking
Double (Participant, Investigator)
Masking Description
Sponsor will also be blinded.

Arm Groups

ArmDescriptionAssigned Intervention
Experimental
fenebrutinib
Participants will receive oral fenebrutinib and intravenous (IV) ocrelizumab-matching placebo.
  • Drug: fenebrutinib
    Participants will receive fenebrutinib.
  • Drug: placebo
    Participants will receive fenebrutinib-matching placebo and ocrelizumab-matching placebo.
Active Comparator
ocrelizumab
Participants will receive intravenous (IV) ocrelizumab and oral fenebrutinib-matching placebo.
  • Drug: ocrelizumab
    Participants will receive ocrelizumab.
  • Drug: placebo
    Participants will receive fenebrutinib-matching placebo and ocrelizumab-matching placebo.

Recruiting Locations

Vanderbilt University Medical Center
Nashville, Tennessee 37232

More Details

Status
Recruiting
Sponsor
Hoffmann-La Roche

Study Contact

Reference Study ID Number: GN41791 http://www.roche.com/about_roche/roche_worldwide.htm
888-662-6728 (U.S. and Canada)
global-roche-genentech-trials@gene.com

Notice

Study information shown on this site is derived from ClinicalTrials.gov (a public registry operated by the National Institutes of Health). The listing of studies provided is not certain to be all studies for which you might be eligible. Furthermore, study eligibility requirements can be difficult to understand and may change over time, so it is wise to speak with your medical care provider and individual research study teams when making decisions related to participation.