Fenebrutinib vs Ocrelizumab for Multiple Sclerosis

(FENtrepid Trial)

No longer recruiting at 304 trial locations

Overseen By Reference Study ID Number: GN41791 https://forpatients.roche.com/

Age: 18+

Sex: Any

Trial Phase: Phase 3

Sponsor: Hoffmann-La Roche

Must not be taking: Systemic corticosteroids, Immunosuppressants

Disqualifiers: Active infection, Cancer history, Neurological disorders, others

No Placebo Group All trial participants will receive the active study treatment (no placebo)

Pivotal Trial (Near Approval) This treatment is in the last trial phase before FDA approval

Prior Safety Data This treatment has passed at least one previous human trial

Compensation: Varies

Number of Visits: 12

Duration: 120 weeks

What You Need to Know Before You Apply

What is the purpose of this trial?

This trial tests two treatments for Primary Progressive Multiple Sclerosis (PPMS), a condition that gradually worsens over time. Researchers aim to compare the effectiveness of fenebrutinib, a daily pill, with ocrelizumab, an intravenous treatment, in slowing disability progression. Participants will be randomly assigned to receive one of the treatments and a placebo (a substance with no therapeutic effect) to ensure fairness in the study. Individuals with PPMS who have experienced recent disability progression and are neurologically stable might be suitable candidates for this trial. As a Phase 3 trial, this study represents the final step before FDA approval, offering participants a chance to contribute to potentially groundbreaking treatment advancements.

Will I have to stop taking my current medications?

The trial requires that participants stay on a stable dose of certain medications, like proton pump inhibitors, H2-receptor antagonists, and symptomatic treatments for MS, during the study. However, if you are on other medications, especially those that could affect the study's primary evaluation, you might need to stop or adjust them. It's best to discuss your specific medications with the study team.

Is there any evidence suggesting that this trial's treatments are likely to be safe?

Research has shown that fenebrutinib is generally well tolerated by patients. In studies, participants taking fenebrutinib experienced low relapse rates and no new brain lesions after nearly two years. The safety profile of fenebrutinib for multiple sclerosis (MS) aligns with its safety in other conditions like rheumatoid arthritis (RA) and lupus.

For ocrelizumab, studies indicate that the most common side effect is reactions at the injection site, occurring in about 49% of patients. Other possible side effects include infections, such as colds and skin infections.

Both treatments have been tested in people and generally demonstrate a good safety record. However, it is important to be aware of potential side effects and consult a healthcare provider. ^{1 2 3 4 5}

Why are researchers excited about this trial's treatments?

Researchers are excited about fenebrutinib for multiple sclerosis because it offers a fresh approach to treatment. Unlike most current options, which often involve targeting B cells, fenebrutinib works by inhibiting Bruton’s tyrosine kinase (BTK), a protein that plays a crucial role in immune cell signaling. This mechanism might help control immune responses more effectively, potentially offering a new avenue for managing the disease. Additionally, fenebrutinib is taken orally, which could provide a more convenient option compared to some existing treatments that require intravenous administration.

What evidence suggests that this trial's treatments could be effective for Multiple Sclerosis?

Research shows that fenebrutinib, which participants in this trial may receive, may help treat multiple sclerosis. Studies have found it can reduce new brain lesions and control the disease for almost two years. During this period, patients taking fenebrutinib did not develop new brain lesions or experience worsening disability.

Ocrelizumab, another treatment option in this trial, is well-established in treating multiple sclerosis. It has proven to lower disease activity and improve brain function over several years. Many patients experience less disability progression with long-term use. Both treatments hold significant potential to manage symptoms and slow the disease. ^{1 2 4 5 6}

Who Is on the Research Team?

Clinical Trials

Principal Investigator

Hoffmann-La Roche

Are You a Good Fit for This Trial?

Adults with Primary Progressive Multiple Sclerosis (PPMS) who've had disability progression in the past year, can perform certain physical tests within specified times, and are neurologically stable. Women must agree to avoid pregnancy; men must prevent fathering children. Excludes those with severe liver disease, recent drug abuse, certain MS treatments without a washout period, serious reactions to ocrelizumab, immunodeficiency states or other major health issues.

Inclusion Criteria

I can walk 25 feet in less than 150 seconds.

Pyramidal functional subscore >=2 at screening

My neurological condition has been stable for the last 30 days.

Exclusion Criteria

I am a man and plan to try for a child during the study or within 28 days after the last dose.

I do not have any major health issues that could affect the study.

I do not have any active infections, including Hepatitis B or C, TB, or PML.

Timeline for a Trial Participant

Screening

Participants are screened for eligibility to participate in the trial

2-4 weeks

Treatment

Participants receive either daily oral fenebrutinib or intravenous ocrelizumab in a blinded fashion

120 weeks

Visits at Weeks 12, 24, 36, 48, 60, 72, 84, 96, 108, and 120

Follow-up

Participants are monitored for safety and effectiveness after treatment

4 weeks

Open-label extension (optional)

Participants may opt into continuation of treatment long-term if a positive benefit-risk result is observed

What Are the Treatments Tested in This Trial?

Interventions

• Fenebrutinib
• Ocrelizumab
• Placebo
• Placebo matched to fenebrutinib
• Placebo matched to ocrelizumab

Trial Overview The trial is testing fenebrutinib's effect on PPMS disability progression against ocrelizumab. Participants will be randomly assigned to take either oral fenebrutinib plus placebo or IV ocrelizumab plus placebo. The study aims for about 946 global participants and includes an Open-Label Extension phase based on positive initial results.

How Is the Trial Designed?

Group I: Fenebrutinib Experimental Treatment 2 Interventions

Participants will receive oral fenebrutinib and intravenous (IV) ocrelizumab-matching placebo.

Group II: Ocrelizumab Active Control 2 Interventions

Participants will receive intravenous (IV) ocrelizumab and oral fenebrutinib-matching placebo.

Who Is Running the Clinical Trial?

Hoffmann-La Roche

Lead Sponsor

Trials

2,482

Recruited

1,107,000+

Headquarters

Basel, Switzerland

Known For

Precision medicine

Top Products

Avastin, Herceptin, Rituxan, Accu-Chek

Dr. Levi Garraway

Hoffmann-La Roche

Chief Medical Officer since 2019

MD from the University of Basel

Dr. Thomas Schinecker

Hoffmann-La Roche

Chief Executive Officer since 2023

PhD in Molecular Biology from New York University

Published Research Related to This Trial

Ocrelizumab is a humanized anti-CD20 monoclonal antibody specifically designed to deplete B cells, which are implicated in the development of multiple sclerosis (MS).

Approved in March 2017 in the USA for treating both relapsing and primary progressive forms of MS, ocrelizumab represents a significant advancement in MS therapy, with its approval in the EU currently pending.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Ocrelizumab: First Global Approval. Frampton, JE.[2022]

In a review of 78 studies involving 4498 patients, 61.3% of those treated with ocrelizumab experienced adverse events, with the most common being infections (39.2%) and infusion-related reactions (26.2%).

Ocrelizumab was associated with a higher risk of infections compared to beta-interferon, particularly herpes-related and respiratory infections, while the risk of serious adverse events was similar between ocrelizumab and comparator groups.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Safety profile of ocrelizumab for the treatment of multiple sclerosis: a systematic review. Ng, HS., Rosenbult, CL., Tremlett, H.[2022]

In a study of 130 individuals with relapsing and progressive multiple sclerosis, treatment with ocrelizumab led to significant improvements in health-related quality of life (HRQOL) after 12 months, particularly in mental health domains.

The improvements were measured using patient-reported outcome tools, showing enhanced scores in areas like vitality, emotional health, and reduced anxiety, indicating that ocrelizumab not only affects physical symptoms but also positively impacts mental well-being.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

The impact of ocrelizumab on health-related quality of life in individuals with multiple sclerosis. Glanz, BI., Zurawski, J., Casady, EC., et al.[2022]

In a study of 228 multiple sclerosis patients treated with ocrelizumab, 91.2% of those with relapsing forms of MS achieved no evidence of disease activity (NEDA) after one year, indicating strong effectiveness in managing the disease.

The treatment was generally well-tolerated, with the most common side effects being infusion-related reactions and infections, particularly urinary tract infections, suggesting a favorable safety profile in a real-world clinical setting.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Real-world experience of ocrelizumab in multiple sclerosis in a Spanish population. Fernandez-Diaz, E., Perez-Vicente, JA., Villaverde-Gonzalez, R., et al.[2021]

In a post hoc analysis of pivotal trials, ocrelizumab significantly reduced the risk of confirmed disability progression in multiple sclerosis patients with higher baseline disability (Expanded Disability Status Scale scores ≥4.0).

The analysis included patients from the OPERA trials (relapsing MS) and ORATORIO trial (primary progressive MS), showing that ocrelizumab was more effective than interferon β-1a and placebo in slowing disability progression.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

An exploratory analysis of the efficacy of ocrelizumab in patients with multiple sclerosis with increased disability. Wolinsky, JS., Engmann, NJ., Pei, J., et al.[2022]

In a study of 128 multiple sclerosis patients, ocrelizumab was found to be well tolerated, with most side effects being mild and decreasing over time, indicating good short-term safety in a real-world setting.

The treatment also showed efficiency in stabilizing the disease, with no severe side effects reported, suggesting that ocrelizumab is a viable option for managing multiple sclerosis.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Real world application of ocrelizumab in multiple sclerosis: Single-center experience of 128 patients. Prockl, V., Nickel, FT., Utz, KS., et al.[2021]

In a study of 1104 multiple sclerosis patients treated with ocrelizumab over a median follow-up of 1.3 years, 94.5% were free of MRI activity, indicating strong effectiveness in stabilizing the disease.

Ocrelizumab was generally well tolerated, with only 10% of patients reporting side effects, primarily infusion-related reactions and infections, aligning with safety profiles observed in clinical trials.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Ocrelizumab treatment in multiple sclerosis: A Danish population-based cohort study. Pontieri, L., Blinkenberg, M., Bramow, S., et al.[2022]

Citations

1. roche.com roche.com/media/releases/med-cor-2025-05-30

Roche's fenebrutinib maintains near-complete suppression ... Patients on fenebrutinib had low relapse rates with data showing no active brain lesions or disability progression after nearly two years of ...

2. gene.com gene.com/media/press-releases/15064/2025-05-29/genentechs-fenebrutinib-maintains-near-c

Phase III studies for fenebrutinib in relapsing and primary ... Patients on fenebrutinib had low relapse rates with data showing no active brain lesions or disability progression after nearly two years of ...

3. neurology.org neurology.org/doi/10.1212/WNL.0000000000209016

Fenebrutinib Maintains Low Disease Activity in Relapsing ... Fenebrutinib reduced disease activity in relapsing multiple sclerosis (RMS) and demonstrated central nervous system penetrance.

4. pubmed.ncbi.nlm.nih.gov pubmed.ncbi.nlm.nih.gov/40683275/

Safety and efficacy of fenebrutinib in relapsing multiple ... Interpretation: Fenebrutinib was well tolerated and exerted an early, robust, and sustained effect of limiting new focal brain lesions. Further studies are ...

5. thelancet.com thelancet.com/journals/laneur/article/PIIS1474-4422(25)00174-7/abstract

Safety and efficacy of fenebrutinib in relapsing multiple ... Fenebrutinib was well tolerated and exerted an early, robust, and sustained effect of limiting new focal brain lesions. Further studies are needed to better ...

6. neurology.org neurology.org/doi/10.1212/WNL.0000000000205291

The Safety Profile of Fenebrutinib in Patients with Multiple ... Conclusions: The safety and tolerability profile of fenebrutinib in MS remains consistent with that in previously studied AIs (RA, SLE and CSU).