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.

Plain English Summary

A Study to Evaluate the Efficacy and Safety of Fenebrutinib Compared With Ocrelizumab in Adult Participants With Primary Progressive Multiple Sclerosis is a Phase 3 clinical trial sponsored by Hoffmann-La Roche studying Multiple Sclerosis, Primary Progressive. This study tests if fenebrutinib is as effective and safe as ocrelizumab in slowing disability progression in adults with primary progressive multiple sclerosis (PPMS). It is for adults diagnosed with PPMS who have shown signs of disability worsening in the past year and have a specific level of disability. Participants will receive either daily oral fenebrutinib or an IV infusion of ocrelizumab, with both groups also receiving a placebo, in a blinded manner. The main alternative treatment being compared is ocrelizumab, an established therapy for PPMS. The trial aims to enroll 985 participants.

Official 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.

Who Can Participate

Here is what you need to know about eligibility for this trial. Adults aged 46-65 (in Germany and Italy) with a confirmed diagnosis of PPMS. Individuals who have experienced disability progression in the last 12 months and have an EDSS score between 3.0 and 6.5. Those who can complete specific walking and hand dexterity tests and are neurologically stable. People who are not currently experiencing active infections, have no history of certain cancers, or other severe neurological or medical conditions. This trial is studying Multiple Sclerosis, Primary Progressive, so participants generally need a confirmed diagnosis.

What They're Measuring

The primary outcome measures how long it takes for a patient's disability to worsen by a certain amount, indicating whether the new drug is effective in slowing down the disease's progression. The specific primary outcome measures are: Time to Onset of Composite 12-week Confirmed Disability Progression (cCDP12) (Minimum of 120 weeks). These endpoints are how researchers determine whether the treatment is effective and will form the basis of any future regulatory submissions.

About This Phase

This trial is in Phase 3, the final and most rigorous stage before seeking FDA approval. Phase 3 trials involve 300-3,000+ patients across multiple sites and compare the new treatment directly against the current standard of care. These pivotal trials generate the evidence needed for regulatory review. About 58% of Phase 3 drugs receive FDA approval. Successful Phase 3 results typically lead to a New Drug Application submission.

Why This Trial Matters

This trial is important because it seeks to find a new oral treatment option for primary progressive multiple sclerosis, a form of MS with limited treatment choices that directly addresses disability As a Phase 3 trial, positive results could directly lead to FDA approval, making this treatment available to the broader patient population. This research targets Multiple Sclerosis, Primary Progressive, where improved treatment options are needed.

Investor Insight

This trial represents a significant investment in a new oral therapy for a large patient population with unmet needs in PPMS, potentially offering a competitive alternative to existing infused treatme Phase 3 trials have approximately a 50-60% chance of gaining FDA approval if they reach this stage. The large enrollment target of 985 participants suggests significant investment in this program.

Is This Trial Right for Me?

Ask your doctor if fenebrutinib or ocrelizumab is the right choice for your specific condition and if you meet all the study requirements. Participation involves regular clinic visits for assessments, blood tests, and receiving either daily pills or IV infusions, with a commitment of up to 120 weeks. You will be randomly assigned to one of the two treatment groups, and neither you nor your doctor will know which treatment you are receiving to ensure unbiased results. The trial is being conducted at 20 sites. Always discuss clinical trial participation with your healthcare provider before making any decisions. This information is for educational purposes only and is not medical advice.

AI-generated analysis for educational purposes only. This is not medical advice. Discuss clinical trial participation with your doctor. Data sourced from ClinicalTrials.gov.

Study Design

• Study Type: INTERVENTIONAL
• Allocation: RANDOMIZED
• Model: PARALLEL
• Masking: DOUBLE
• Enrollment: 985 participants

Interventions

• DRUG: Fenebrutinib — Participants will receive fenebrutinib.
• DRUG: Ocrelizumab — Participants will receive ocrelizumab.
• DRUG: Placebo matched to ocrelizumab — Participants will receive ocrelizumab-matching placebo.
• DRUG: Placebo matched to fenebrutinib — Participants will receive fenebrutinib-matching placebo

Primary Outcomes

• Time to Onset of Composite 12-week Confirmed Disability Progression (cCDP12) (Minimum of 120 weeks)

Secondary Outcomes

• 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)

Full Eligibility Criteria

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

Trial Locations

• Alabama Neurology Associates, Homewood, Alabama, United States
• 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
• ...and 10 more locations

Frequently Asked Questions

Related Conditions

• Multiple Sclerosis
• Primary Progressive Multiple Sclerosis
• Neurological Disorders
• Autoimmune Diseases
• Inflammatory Diseases
• Central Nervous System Diseases
• Neurodegenerative Diseases
• Disability Progression
• Immunomodulatory Therapy
• Immunosuppressive Therapy

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