Fenebrutinib vs Teriflunomide for Multiple Sclerosis

(FENhance 2 Trial)

Recruiting at 162 trial locations

Overseen By Reference Study ID Number: GN42272 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: Cancer, Cardiovascular, Psychiatric, 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: 96 weeks

751 Participants Needed

Trial Summary

What is the purpose of this trial?

This trial is testing fenebrutinib, a medication that may help reduce disability and relapses in adults with relapsing multiple sclerosis (RMS). The study will compare fenebrutinib to another drug, teriflunomide, which is an approved treatment for RMS. Fenebrutinib works by reducing harmful immune system activity that attacks the nervous system.

Will I have to stop taking my current medications?

The trial 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 trial team.

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

Teriflunomide (Aubagio) is shown to be effective in treating relapsing forms of multiple sclerosis (MS) by reducing relapses and disease activity, as evidenced by clinical trials and real-world studies. It has been compared favorably to placebo and is as effective as another MS treatment, interferon beta-1a, in improving clinical outcomes. ^{1 2 3 4 5}

Is teriflunomide safe for humans?

Teriflunomide (Aubagio) is generally well tolerated in patients with relapsing multiple sclerosis, with no new safety concerns identified during long-term treatment of 10 years or more. ^{1 2 3 4 5}

How does the drug Fenebrutinib differ from Teriflunomide for treating multiple sclerosis?

Fenebrutinib is a newer treatment option being compared to Teriflunomide, which is an established oral drug for relapsing multiple sclerosis. Teriflunomide works by inhibiting an enzyme involved in the immune response, helping to reduce inflammation and slow disease progression. ^{1 2 3 4 5}

Research Team

Clinical Trials

Principal Investigator

Hoffmann-La Roche

Eligibility Criteria

Adults with Relapsing Multiple Sclerosis (RMS) who can perform specific physical tests, have an EDSS score of 0-5.5, and meet the revised 2017 McDonald Criteria for RMS diagnosis. Participants must agree to contraception if of childbearing potential and not plan to donate eggs or sperm. Exclusions include those with certain infections, a history of cancer within 10 years, severe allergies or intolerances, immunodeficiencies like HIV, recent vaccinations or steroid treatments, liver issues such as cirrhosis or Gilbert's Syndrome.

Inclusion Criteria

I can walk 25 feet in less than 150 seconds.

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

My disability level allows me to walk without aid or rest for 200 meters.

Exclusion Criteria

I have not received a live vaccine in the last 6 weeks.

My blood tests show I have low blood cell counts.

I have had cancer, including blood or solid tumors, in the last 10 years.

Timeline

Screening

Participants are screened for eligibility to participate in the trial

2-4 weeks

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 if a positive benefit-risk result is observed

Treatment Details

Interventions

• Fenebrutinib
• Placebo
• Teriflunomide

Trial Overview The trial is testing Fenebrutinib against Teriflunomide in adults with RMS to see which is better at slowing disability progression and reducing relapse rate. Participants are randomly assigned to one of the two drugs in equal numbers. The study may extend based on positive initial results.

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

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]

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]

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]

References

1. England pubmed.ncbi.nlm.nih.gov

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

2. 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]

3. Switzerland pubmed.ncbi.nlm.nih.gov

Teriflunomide: Pediatric First Approval. [2021]

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

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

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

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