Fenebrutinib vs Ocrelizumab for Multiple Sclerosis

(FENtrepid Trial)

Recruiting at 254 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

985 Participants Needed

Trial Summary

What is the purpose of this trial?

This trial is testing a pill (Fenebrutinib) and an intravenous medication (Ocrelizumab) for adults with a type of multiple sclerosis that gets worse over time. The goal is to see if these treatments can slow down the progression of disability by reducing the immune system's harmful effects on the nervous system.

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.

What data supports the effectiveness of the drug Ocrelizumab for treating multiple sclerosis?

Ocrelizumab has been shown to reduce disease progression in patients with relapsing and primary progressive multiple sclerosis, as demonstrated in several studies, including the OPERA I and II trials. It works by targeting B cells, which are involved in the development of multiple sclerosis. ^{1 2 3 4 5}

Is ocrelizumab safe for humans?

Ocrelizumab, used for treating multiple sclerosis, has been generally well tolerated in both clinical trials and real-world settings, with manageable side effects. ^{1 6 7 8 9}

How does the drug Fenebrutinib differ from Ocrelizumab in treating multiple sclerosis?

Fenebrutinib is a novel treatment being compared to Ocrelizumab, which is already approved for both relapsing and progressive forms of multiple sclerosis. Ocrelizumab works by targeting and depleting B cells, a type of immune cell, to reduce relapses and slow disability progression. Fenebrutinib's unique mechanism or benefits in comparison to Ocrelizumab are not detailed in the provided research. ^{3 10 11 12 13}

Research Team

Clinical Trials

Principal Investigator

Hoffmann-La Roche

Eligibility Criteria

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.

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

Pyramidal functional subscore >=2 at screening

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

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

Treatment Details

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.

Participant Groups

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

Findings from Research

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 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 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 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 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]

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 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]

References

1. New Zealand pubmed.ncbi.nlm.nih.gov

Ocrelizumab: First Global Approval. [2022]

2. Germany pubmed.ncbi.nlm.nih.gov

Ocrelizumab efficacy in subgroups of patients with relapsing multiple sclerosis. [2020]

3. United States pubmed.ncbi.nlm.nih.gov

The impact of ocrelizumab on health-related quality of life in individuals with multiple sclerosis. [2022]

4. United States pubmed.ncbi.nlm.nih.gov

Five years of ocrelizumab in relapsing multiple sclerosis: OPERA studies open-label extension. [2021]

5. United States pubmed.ncbi.nlm.nih.gov

An exploratory analysis of the efficacy of ocrelizumab in patients with multiple sclerosis with increased disability. [2022]

6. United States pubmed.ncbi.nlm.nih.gov

Real-world experience of ocrelizumab in multiple sclerosis in a Spanish population. [2021]

7. England pubmed.ncbi.nlm.nih.gov

Ocrelizumab treatment in multiple sclerosis: A Danish population-based cohort study. [2022]

8. Netherlands pubmed.ncbi.nlm.nih.gov

Real world application of ocrelizumab in multiple sclerosis: Single-center experience of 128 patients. [2021]

9. England pubmed.ncbi.nlm.nih.gov

Safety profile of ocrelizumab for the treatment of multiple sclerosis: a systematic review. [2022]

10. United States pubmed.ncbi.nlm.nih.gov

Tolerability and Safety of Switching from Rituximab to Ocrelizumab: Evaluating Factors Associated with Infusion Related Reactions. [2022]

11. Netherlands pubmed.ncbi.nlm.nih.gov

Comparison of the Efficacy and Safety of Anti-CD20 B Cells Depleting Drugs in Multiple Sclerosis. [2022]

12. United States pubmed.ncbi.nlm.nih.gov

Rituximab vs Ocrelizumab in Relapsing-Remitting Multiple Sclerosis. [2023]

13. England pubmed.ncbi.nlm.nih.gov

Efficacy classification of modern therapies in multiple sclerosis. [2021]