Fenebrutinib for Relapsing Multiple Sclerosis

(FENhance Trial)

Recruiting at 261 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

746 Participants Needed

Trial Summary

What is the purpose of this trial?

A study to evaluate the efficacy and safety of fenebrutinib on disability progression and relapse rate in adult participants with RMS. Eligible participants will be randomized 1:1 to either fenebrutinib or teriflunomide. At the end of the DBT phase (after disclosure of the DBT results), the Sponsor will determine whether or not to initiate the open-label extension phase of the study.

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 Fenebrutinib safe for humans?

The research articles focus on the safety of Teriflunomide (Aubagio) for treating multiple sclerosis, showing it is generally well tolerated with no new safety concerns over long-term use. However, they do not provide specific safety data for Fenebrutinib. ^{1 2 3 4 5}

How is the drug Fenebrutinib different from other treatments for relapsing multiple sclerosis?

Fenebrutinib is unique because it is being studied as a potential treatment for relapsing multiple sclerosis, whereas Teriflunomide is already an established oral drug for this condition, known for its anti-inflammatory properties and ability to reduce relapses and disease activity. ^{2 3 4 5 6}

Research Team

Clinical Trials

Principal Investigator

Hoffmann-La Roche

Eligibility Criteria

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

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

Treatment Details

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.

Participant Groups

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

Findings from Research

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]

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]

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]

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]

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]

References

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

Teriflunomide (Aubagio®) for the treatment of multiple sclerosis. [2021]

2. England pubmed.ncbi.nlm.nih.gov

Real-life outcomes of teriflunomide treatment in patients with relapsing multiple sclerosis: TAURUS-MS observational study. [2022]

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

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

4. Switzerland pubmed.ncbi.nlm.nih.gov

Teriflunomide: Pediatric First Approval. [2021]

5. Netherlands 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. [2022]

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

A randomized trial of teriflunomide added to glatiramer acetate in relapsing multiple sclerosis. [2020]