What side effects are associated with this type of intervention?

Common treatments for Multiple Sclerosis (MS) include interferon beta, glatiramer acetate, and dimethyl fumarate. Interferon beta can cause flu-like symptoms, injection site reactions, and potential liver dysfunction. Glatiramer acetate is associated with injection site reactions and, rarely, hepatotoxicity. Dimethyl fumarate may lead to gastrointestinal issues, flushing, and lymphopenia. While specific side effects of BTK inhibitors like Fenebrutinib are not detailed, they generally include risks of infections and potential liver enzyme elevations. Patients should discuss these potential side effects with their healthcare provider to make informed treatment decisions.

What prior FDA approvals exist?

The FDA has approved several treatments for Multiple Sclerosis (MS), including disease-modifying therapies (DMTs) such as interferon beta-1a, glatiramer acetate, and more recently, oral medications like dimethyl fumarate and fingolimod. These treatments aim to reduce relapse rates and slow disease progression. While Fenebrutinib, a BTK inhibitor, is currently under study, other BTK inhibitors have not yet been widely approved for MS. The focus remains on immunomodulatory and immunosuppressive agents to manage the disease.

What other types of research exist?

Promising, novel alternatives to Fenebrutinib for Multiple Sclerosis patients include: 1) Ocrelizumab, a monoclonal antibody targeting CD20-positive B cells, which has shown efficacy in reducing disability progression in Primary Progressive Multiple Sclerosis (PPMS). 2) Siponimod, a selective sphingosine-1-phosphate receptor modulator, approved for secondary progressive MS. 3) Cladribine, an oral immunosuppressive drug that targets lymphocytes, approved for relapsing forms of MS. 4) Ozanimod, another sphingosine-1-phosphate receptor modulator, approved for relapsing forms of MS. These alternatives offer different mechanisms of action and have demonstrated positive outcomes in clinical trials.

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Bruton's Tyrosine Kinase (BTK) Inhibitor

Fenebrutinib vs Ocrelizumab for Multiple Sclerosis (FENtrepid Trial)

Q: What is the mechanism of action of this treatment?

Multiple Sclerosis (MS) treatments generally aim to modulate or suppress the immune system to reduce inflammation and prevent further damage to the central nervous system. Common treatments include beta interferons, which reduce inflammation and immune response; glatiramer acetate, which mimics myelin protein to divert immune attacks; and monoclonal antibodies like ocrelizumab, which target specific immune cells (B cells) to prevent them from attacking myelin. Fenebrutinib, a BTK inhibitor, works by blocking Bruton's tyrosine kinase, an enzyme crucial for B cell and macrophage activation. This inhibition reduces the immune system's ability to cause inflammation and damage in MS. Understanding these mechanisms is vital for MS patients as it helps in selecting the most appropriate therapy based on their disease activity and individual health profile.

Phase 3

Waitlist Available

Research Sponsored by Hoffmann-La Roche

Eligibility Criteria Checklist

Specific guidelines that determine who can or cannot participate in a clinical trial

Must have

Ability to perform Timed 25-Foot Walk Test (T25FWT) in <150 seconds

Expanded Disability Status Scale (EDSS) score from 3.0 to 6.5 inclusive at screening

Must not have

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)

Presence of cirrhosis (Child-Pugh Class A, B, or C)

Timeline

Screening 3 weeks

Treatment Varies

Follow Up baseline, weeks 12, 24, 36, 48, 60, 72, 84, 96, 108 and 120

Awards & highlights

Pivotal Trial

Summary

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.

Who is the study for?

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.

What is being tested?

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.

What are the potential side effects?

Potential side effects may include allergic reactions related to infusion processes, organ inflammation due to immune response alterations by the drugs being tested, fatigue from treatment regimens, digestive disturbances as common medication-related events and increased risk of infections.

Eligibility Criteria

Inclusion Criteria

You may be eligible if you check “Yes” for the criteria below

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I can walk 25 feet in less than 150 seconds.

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My disability level is moderate to severe but I can still walk.

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I can complete a hand dexterity test in less than 4 minutes.

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My condition is diagnosed as PPMS according to the 2017 criteria.

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I agree to not have sex or use birth control and not donate sperm.

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My disability has worsened in the last year.

Exclusion Criteria

You may be eligible for the trial if you check “No” for criteria below:

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

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I have cirrhosis but can still perform daily activities.

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I haven't taken any immune-altering drugs recently without a break.

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I have a weakened immune system or have had an organ transplant.

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I have had a severe reaction to an infusion or to ocrelizumab.

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I am not on long-term steroids, immunosuppressants, or other drugs that could affect the study.

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I do not have good veins for IV access.

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I have a bleeding disorder, anemia, or a history of serious GI bleeding.

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I have previously been treated with specific immunosuppressive drugs.

Timeline

Screening ~ 3 weeks3 visits

Treatment ~ Varies

Follow Up ~ baseline, weeks 12, 24, 36, 48, 60, 72, 84, 96, 108 and 120

Screening ~ 3 weeks

Treatment ~ Varies

Follow Up ~baseline, weeks 12, 24, 36, 48, 60, 72, 84, 96, 108 and 120

This trial's timeline: 3 weeks for screening, Varies for treatment, and baseline, weeks 12, 24, 36, 48, 60, 72, 84, 96, 108 and 120 for reporting.

Treatment Details

Study Objectives

Study objectives can provide a clearer picture of what you can expect from a treatment.

Secondary study objectives

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

Time to Onset of 12-week Confirmed 4-point Worsening in Symbol Digit Modality Test (SDMT) Score

Awards & Highlights

Pivotal Trial

The final step before approval, pivotal trials feature drugs that have already shown basic safety & efficacy.

Trial Design

2Treatment groups

Experimental Treatment

Active Control

Group I: FenebrutinibExperimental Treatment2 Interventions

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

Group II: OcrelizumabActive Control2 Interventions

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

Treatment

First Studied

Drug Approval Stage

How many patients have taken this drug

Fenebrutinib

2018

Completed Phase 3

~1750

Placebo matched to ocrelizumab

2020

Completed Phase 3

~990

0 / 15Eligibility criteria met

Research Highlights

Information in this section is not a recommendation. We encourage patients to speak with their healthcare team when evaluating any treatment decision.

Mechanism Of Action

Side Effect Profile

Prior Approvals

Other Research

Multiple Sclerosis (MS) treatments generally aim to modulate or suppress the immune system to reduce inflammation and prevent further damage to the central nervous system. Common treatments include beta interferons, which reduce inflammation and immune response; glatiramer acetate, which mimics myelin protein to divert immune attacks; and monoclonal antibodies like ocrelizumab, which target specific immune cells (B cells) to prevent them from attacking myelin. Fenebrutinib, a BTK inhibitor, works by blocking Bruton's tyrosine kinase, an enzyme crucial for B cell and macrophage activation. This inhibition reduces the immune system's ability to cause inflammation and damage in MS. Understanding these mechanisms is vital for MS patients as it helps in selecting the most appropriate therapy based on their disease activity and individual health profile.