Fenebrutinib for Relapsing Multiple Sclerosis

(FENhance Trial)

Not currently recruiting at 298 trial locations

Overseen By Reference Study ID Number: GN41851 https://forpatients.roche.com/

Age: 18 - 65

Sex: Any

Trial Phase: Phase 3

Sponsor: Hoffmann-La Roche

Must not be taking: Systemic corticosteroids, Immunosuppressants

Disqualifiers: Primary progressive MS, Active infection, Cancer, 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

What You Need to Know Before You Apply

What is the purpose of this trial?

This trial tests two treatments, fenebrutinib and teriflunomide, to determine which better slows disability and reduces relapse rates in people with relapsing multiple sclerosis (RMS). Researchers aim to identify which medication is most effective and safest for managing RMS symptoms. Participants will be randomly assigned to receive either fenebrutinib or teriflunomide, and researchers will closely monitor their progress. Individuals diagnosed with RMS who can perform everyday tasks like walking and handling objects might be suitable for the 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 protocol does not specify if you must stop taking your current medications, but it mentions that any previous treatment with immunomodulatory or immunosuppressive medication requires an appropriate washout period (time without taking certain medications). It's best to discuss your current medications with the study team.

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

A previous study found that patients taking fenebrutinib had low relapse rates and did not develop new brain lesions or experience worsening disability over nearly two years. This suggests that fenebrutinib is generally well-tolerated. Another study examined its safety and found no serious side effects. Fenebrutinib blocks a specific protein involved in immune responses.

Teriflunomide, in contrast, has been used for a long time. Over two years, it significantly reduced the relapse rate. In a study lasting more than eight years, it maintained a good safety record. Serious infections were rare, and no deaths occurred, indicating that teriflunomide is generally safe for people with multiple sclerosis.

Both treatments have undergone safety studies, and findings suggest they are generally well-tolerated by patients. ^{1 2 3 4 5}

Why do researchers think this study treatment might be promising?

Fenebrutinib is unique because it targets a specific enzyme called Bruton’s tyrosine kinase (BTK), which plays a key role in the immune system's signaling pathways. This mechanism is different from most standard treatments for relapsing multiple sclerosis, like interferons or glatiramer acetate, which work by modulating the immune response more broadly. Researchers are excited because BTK inhibitors like fenebrutinib could offer a more targeted approach, potentially reducing inflammation with fewer side effects. Additionally, fenebrutinib is taken orally, which is a convenient alternative to injectable therapies.

What evidence suggests that this trial's treatments could be effective for relapsing multiple sclerosis?

Research has shown that fenebrutinib, one of the treatments in this trial, shows promise for treating relapsing multiple sclerosis (RMS). Patients taking fenebrutinib experienced fewer relapses, and after nearly two years, they did not develop new brain lesions or experience worsening disability. Studies also found that fenebrutinib effectively reduced disease activity in the brain and spinal cord.

Teriflunomide is another treatment option in this trial. It has been shown to lower the risk of relapses and reduce the average number of relapses per year in people with RMS. In one study, after two years of treatment, the average number of relapses per year dropped to 0.17, indicating less frequent relapses. Both treatments are being evaluated in this trial for their effectiveness in managing RMS, with fenebrutinib showing strong early results and teriflunomide having a proven track record. ^{1 2 3 4 6}

Who Is on the Research Team?

Clinical Trials

Principal Investigator

Hoffmann-La Roche

Are You a Good Fit for This Trial?

Adults with Relapsing Multiple Sclerosis (RMS) who meet specific criteria like an EDSS score of 0-5.5, can complete certain physical tests within set times, and agree to use contraception or abstain from sex. Excluded are those with disease duration over 10 years and low disability, pregnant or breastfeeding women, individuals with recent cancer history, active infections including hepatitis B/C and TB, significant blood disorders or immunodeficiency.

Inclusion Criteria

My condition meets the 2017 McDonald Criteria for RMS.

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

I can walk 25 feet in less than 150 seconds.

Exclusion Criteria

I have a rare genetic issue with digesting certain sugars.

Hypoproteinemia.

I have kidney, liver problems, or Gilbert's Syndrome.

Timeline for a Trial Participant

Screening

Participants are screened for eligibility to participate in the trial

2-4 weeks

Double-Blind Treatment

Participants are randomized to receive either fenebrutinib or teriflunomide in a double-blind fashion

96 weeks

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

Follow-up

Participants are monitored for safety and effectiveness after treatment

12 weeks

Open-label Extension (optional)

Participants may opt into continuation of treatment long-term after the double-blind phase

What Are the Treatments Tested in This Trial?

Interventions

• Fenebrutinib
• Placebo
• Teriflunomide

Trial Overview The trial is testing the effectiveness of Fenebrutinib compared to Teriflunomide in managing RMS by looking at disability progression and relapse rate. Participants will be randomly assigned to either drug in a direct comparison study design.

How Is the Trial Designed?

Group I: Fenebrutinib Experimental Treatment 2 Interventions

Participants will receive oral fenebrutinib with teriflunomide-matching placebo.

Group II: Teriflunomide Active Control 2 Interventions

Participants will receive oral teriflunomide with fenebrutinib-matching placebo in a blinded fashion.

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

Teriflunomide (Aubagio®) is an oral medication that works by targeting the mitochondrial enzyme dihydroorotate dehydrogenase, helping to modulate the immune response in patients with relapsing-remitting multiple sclerosis (MS).

On June 18, 2021, teriflunomide was approved for use in pediatric patients aged 10 years and older in the EU, marking a significant milestone in its development for treating MS in younger populations.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Teriflunomide: Pediatric First Approval. Paik, J.[2021]

Teriflunomide (Aubagio®) is an effective once-daily oral treatment for relapsing forms of multiple sclerosis (RMS), approved in multiple regions including Europe and North America.

The review discusses teriflunomide's safety and efficacy based on extensive clinical trials, while also exploring its therapeutic mechanism of action, which is still being researched through various studies.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Teriflunomide (Aubagio®) for the treatment of multiple sclerosis. Bar-Or, A.[2021]

Teriflunomide (Aubagio®) is an effective oral treatment for relapsing multiple sclerosis (MS), showing significant improvements in clinical outcomes and MRI measures compared to placebo and similar efficacy to interferon β-1a, based on extensive randomized controlled trials and real-world evidence.

The drug is generally well tolerated, with long-term treatment (≥ 10 years) showing sustained benefits and no new safety concerns, making it a convenient option for managing relapsing-remitting MS.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Teriflunomide: A Review in Relapsing-Remitting Multiple Sclerosis. Scott, LJ.[2021]

In a real-world study involving 200 patients with relapsing multiple sclerosis, teriflunomide demonstrated stable quality of life over 24 months, with significant reductions in relapse activity compared to the pre-baseline period.

The study indicated high treatment adherence and acceptability of teriflunomide, as reflected in patient-reported outcomes, with no substantial changes in fatigue and a marginal increase in reported disability.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Real-world study of relapsing-remitting multiple sclerosis patients treated with Teriflunomide in Nordic countries: Quality-Of-Life, efficacy, safety and adherence outcomes. Hestvik, ALK., Frederiksen, JL., Nielsen, HH., et al.[2022]

In a Phase II study involving 123 patients with relapsing forms of multiple sclerosis (MS), teriflunomide was found to be well tolerated as an add-on therapy to glatiramer acetate, with low rates of adverse events leading to treatment discontinuation.

Teriflunomide significantly reduced MRI markers of disease activity, showing a 64% relative reduction in T1-Gd lesions at the 7 mg dose compared to placebo, indicating its potential efficacy in managing MS.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

A randomized trial of teriflunomide added to glatiramer acetate in relapsing multiple sclerosis. Freedman, MS., Wolinsky, JS., Truffinet, P., et al.[2020]

In a study of 1128 patients with relapsing-remitting multiple sclerosis, teriflunomide significantly reduced the annualized relapse rate from 0.87 to 0.35 over 24 months, indicating its effectiveness in managing the disease.

Patient satisfaction with teriflunomide was high, with significant improvements in effectiveness, convenience, and overall satisfaction reported after 24 months, while the safety profile was consistent with previous clinical trials, with 35.8% experiencing adverse events.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Real-life outcomes of teriflunomide treatment in patients with relapsing multiple sclerosis: TAURUS-MS observational study. Kallmann, BA., Tiel-Wilck, K., Kullmann, JS., 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. 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 ...

4. 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.

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. clinicaltrials.gov clinicaltrials.gov/study/NCT07161258

Study Details | NCT07161258 | A Pharmacokinetics (PK), ... This open label, single arm study will evaluate the PK and PD effects of fenebrutinib in children and adolescents with RMS aged between 10 and < 18 years. This ...