BIIB091 for Relapsing Multiple Sclerosis

(FUSION Trial)

Recruiting at 80 trial locations

Overseen By Lee S. Stein

Age: 18 - 65

Sex: Any

Trial Phase: Phase 2

Sponsor: Biogen

Must not be taking: Fumarates, BTK inhibitors

Disqualifiers: PPMS, Recent MS relapse, HIV, others

No Placebo Group All trial participants will receive the active study treatment (no placebo)

Prior Safety Data This treatment has passed at least one previous human trial

Compensation: Varies

Number of Visits: 40

275 Participants Needed

Trial Summary

What is the purpose of this trial?

In this study, researchers will learn more about a study drug called BIIB091 in participants with MS who may be experiencing relapses. It is a 2-part study. In Part 1, one set of participants will take either BIIB091 or diroximel fumarate (DRF). In Part 2, a different set of participants will take either a combination of BIIB091 and DRF or DRF alone. The goal of the study is to learn more about the safety of BIIB091 and to compare the effects of the study drug when taken alone or together with DRF. The main question researchers are trying to answer are: * How many participants have new or worsening medical problems (adverse events) after taking BIIB091 or DRF? * How many new areas of inflammation occur in the brain after treatment with BIIB091 and DRF? Researchers will use magnetic resonance imaging (MRI) scans to compare images of the brain before and after treatment. They will also explore the effect of BIIB091 and DRF on the heart using electrocardiograms (ECGs). The study will be done as follows: * After screening, participants who joined Part 1 will be randomly assigned to receive either a high or low dose of BIIB091, or the standard dose of DRF. * The results of Part 1 will be used to choose the best dose of BIIB091 to use in Part 2. * Participants who join Part 2 will be randomly assigned to receive either a standard dose of DRF, a combo of BIIB091 and the standard dose of DRF, or a combo of BIIB91 with a low dose of DRF. * Neither the researchers nor the participants will know which drug or dose the participants will receive in either part of the study. * The treatment period will last 48 weeks in each part of the study. Participants will take the drugs by mouth 2 times a day. * Each part will also have a follow-up safety period that lasts up to 2 weeks. * In total, participants in each part will have 20 study visits, or more if they have a relapse. The total study duration for participants will be up to 54 weeks.

Will I have to stop taking my current medications?

The trial information does not specify if you need to stop taking your current medications. It's best to discuss this with the study team or your doctor to get a clear answer based on your specific situation.

What data supports the effectiveness of the drug BIIB091 for treating relapsing multiple sclerosis?

Diroximel fumarate (DRF), a component of the treatment, is known to be effective for relapsing forms of multiple sclerosis, as it is converted to monomethyl fumarate, which has a similar efficacy profile to dimethyl fumarate (DMF), a well-established treatment for this condition. ^{1 2 3 4 5}

What safety information is available for Diroximel Fumarate (BIIB091) in humans?

Diroximel fumarate (DRF) is generally considered safe for humans, with studies showing it has an improved gastrointestinal tolerability compared to dimethyl fumarate (DMF), which can cause flushing and gastrointestinal issues in some patients. ^{1 2 3 4 5}

What makes the drug BIIB091 (Diroximel fumarate) unique for treating relapsing multiple sclerosis?

BIIB091, also known as Diroximel fumarate, is unique because it is an oral medication that offers similar benefits to dimethyl fumarate but with improved gastrointestinal tolerability, meaning it causes fewer stomach-related side effects. ^{6 7 8 9 10}

Research Team

Medical Director

Principal Investigator

Biogen

Eligibility Criteria

This trial is for people with relapsing forms of Multiple Sclerosis (RMS) diagnosed per the 2017 McDonald criteria, who've had symptoms for less than 20 years. Participants should have experienced at least one MS flare-up in the past two years but not within the last month before starting the trial. They must also have an EDSS score between 0 and 5.0, indicating a certain level of disability.

Inclusion Criteria

I have been diagnosed with RMS according to the 2017 criteria.

Must have at least 1 of the following occurring prior to Baseline (Day 1):

I've had 1 relapse and 1 new brain MRI finding in the last year, but no relapses in the last 30 days.

Exclusion Criteria

Known hypersensitivity to any components of the study treatment

History of severe allergic, anaphylactic reactions or hypersensitivity reaction to BIIB091 or DRF, the excipients contained in the formulation, and if appropriate, any diagnostic agents to be administered during the study

I have been diagnosed with primary progressive multiple sclerosis.

Timeline

Screening

Participants are screened for eligibility to participate in the trial

2-4 weeks

Treatment Part 1

Participants receive either a high or low dose of BIIB091, or the standard dose of DRF for 48 weeks

48 weeks

20 visits, or more if relapse occurs

Follow-up Part 1

Participants are monitored for safety and effectiveness after treatment in Part 1

2 weeks

Treatment Part 2

Participants receive either a standard dose of DRF, a combo of BIIB091 and DRF, or a combo of BIIB091 with a low dose of DRF for 48 weeks

48 weeks

20 visits, or more if relapse occurs

Follow-up Part 2

Participants are monitored for safety and effectiveness after treatment in Part 2

2 weeks

Treatment Details

Interventions

• BIIB091
• DRF
• Placebo

Trial Overview The study tests BIIB091 alone or combined with Diroximel Fumarate (DRF) against DRF alone to see how well they control brain inflammation in RMS, as shown by MRI scans. Part one focuses on BIIB091's safety and tolerability; part two compares its effectiveness when added to DRF versus DRF treatment alone.

Participant Groups

Group I: Part 2: BIIB091 + DRF Standard Dose Experimental Treatment 2 Interventions

Participants will receive selected dose of BIIB091 (based on Part 1 data) and DRF standard dose, orally, for up to 48 weeks.

Group II: Part 2: BIIB091 + DRF Low Dose Experimental Treatment 2 Interventions

Participants will receive selected dose of BIIB091 (based on Part 1 data) and DRF low dose, orally, for up to 48 weeks.

Group III: Part 1: BIIB091 Low Dose + Matching Placebo for DRF Experimental Treatment 2 Interventions

Participants will receive BIIB091 low dose and matching placebo for DRF, orally, for up to 48 weeks.

Group IV: Part 1: BIIB091 High Dose + Matching Placebo for DRF Experimental Treatment 2 Interventions

Participants will receive BIIB091 high dose and matching placebo for DRF, orally, for up to 48 weeks.

Group V: Part 1: DRF + Matching Placebo for BIIB091 Active Control 2 Interventions

Participants will receive DRF standard dose and matching placebo for BIIB091, orally, for up to 48 weeks.

Group VI: Part 2: DRF + Matching Placebo for BIIB091 Active Control 2 Interventions

Participants will receive DRF standard dose and matching placebo for BIIB091, orally, for up to 48 weeks.

Who Is Running the Clinical Trial?

Biogen

Lead Sponsor

Trials

655

Recruited

468,000+

Daniel Quirk

Biogen

Chief Medical Officer

MD

Christopher A. Viehbacher

Biogen

Chief Executive Officer since 2022

Graduated from Queen's University, Kingston, Ontario, Canada

Findings from Research

In a 5-week phase III study involving patients with relapsing-remitting multiple sclerosis, diroximel fumarate (DRF) showed a 46% reduction in days with significant gastrointestinal symptoms compared to dimethyl fumarate (DMF), indicating better tolerability.

Patients taking DRF experienced lower rates of gastrointestinal adverse events (34.8% vs 49.0% for DMF) and had fewer discontinuations due to these events (1.6% vs 5.6%), suggesting that DRF may be a safer option for managing gastrointestinal side effects.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Diroximel Fumarate Demonstrates an Improved Gastrointestinal Tolerability Profile Compared with Dimethyl Fumarate in Patients with Relapsing-Remitting Multiple Sclerosis: Results from the Randomized, Double-Blind, Phase III EVOLVE-MS-2 Study. Naismith, RT., Wundes, A., Ziemssen, T., et al.[2021]

In a post hoc analysis of phase 3 trials involving 1538 participants with relapsing-remitting multiple sclerosis, delayed-release dimethyl fumarate (DMF) was associated with a higher incidence of gastrointestinal (GI) events (27% vs. 17% in placebo) and flushing (37% vs. 5% in placebo) during the first three months of treatment.

Most GI and flushing events were mild to moderate in severity, typically resolved during the study, and rarely resulted in discontinuation of DMF treatment, indicating that these side effects are generally manageable.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Clinical Significance of Gastrointestinal and Flushing Events in Patients with Multiple Sclerosis Treated with Delayed-Release Dimethyl Fumarate. Phillips, JT., Selmaj, K., Gold, R., et al.[2022]

Most patients who experienced a decrease in lymphocyte count (lymphopenia) while on delayed-release dimethyl fumarate (DMF) saw their lymphocyte levels return to normal within 2-4 months after stopping the medication, based on data from clinical trials and real-world studies.

The duration of lymphopenia during DMF treatment significantly affects recovery time; patients with prolonged lymphopenia lasting 3 years took 12-18 months to recover, while those with shorter lymphopenia (less than 6 months) recovered in just 2-3 months.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Lymphocyte reconstitution after DMF discontinuation in clinical trial and real-world patients with MS. Chan, A., Rose, J., Alvarez, E., et al.[2022]

In a 12-month study involving 11 patients with relapsing-remitting multiple sclerosis (RRMS), oral fingolimod 0.5 mg daily showed significant efficacy, with no new relapses reported and improvement in disability for seven patients as measured by the EDSS scale.

Fingolimod was found to be safe and well tolerated, as no patients discontinued treatment due to adverse events, indicating its potential as an effective option for patients with high disease activity despite previous therapies.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Evaluation of efficacy, safety and tolerability of fingolimod in patients with the relapsing form of multiple sclerosis - 12-month observation. A preliminary report. Maciejek, Z., Wójcik-Drączkowska, H., Wawrzyniak, S., et al.[2019]

In a Phase III clinical trial involving 2,103 patients with COPD, the pharmacokinetic sub-study showed that the combination inhaler GFF MDI (glycopyrronium/formoterol) had similar plasma concentration profiles to its individual components, indicating effective delivery of both medications.

The study found that there were no significant drug-drug interactions between glycopyrronium and formoterol when administered together in GFF MDI, suggesting that the co-suspension delivery technology is safe and effective for patients.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Pharmacokinetics of glycopyrronium/formoterol fumarate dihydrate delivered via metered dose inhaler using co-suspension delivery technology in patients with moderate-to-very severe COPD. Ferguson, GT., Rodriguez-Roisin, R., Reisner, C., et al.[2018]

In a study of 1143 multiple sclerosis patients treated with diroximel fumarate (DRF), persistence on therapy was high at 82.3% after 16 months, indicating that most patients continued their treatment successfully.

Discontinuation due to gastrointestinal adverse events was low, with only 4.5% of patients stopping DRF, and adherence to therapy was also high, with a mean proportion of days covered of 90.8%.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Real-World Analysis Affirms the High Persistence and Adherence Observed with Diroximel Fumarate in Patients with Multiple Sclerosis. Lager, B., Liseno, J., Božin, I., et al.[2023]

Diroximel fumarate (DRF) was well tolerated in a 96-week study with 1057 patients, showing a low discontinuation rate due to adverse events (AEs), particularly gastrointestinal issues, which were less frequent compared to dimethyl fumarate (DMF).

At the end of the study, DRF significantly reduced the number of gadolinium-enhancing lesions by 72.7% and resulted in a low adjusted annualized relapse rate of 0.13, indicating its efficacy in reducing disease activity in relapsing-remitting multiple sclerosis (RRMS).

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Diroximel fumarate in patients with relapsing-remitting multiple sclerosis: Final safety and efficacy results from the phase 3 EVOLVE-MS-1 study. Singer, BA., Arnold, DL., Drulovic, J., et al.[2023]

Diroximel fumarate (Vumerity®) is an effective oral treatment for adults with relapsing forms of multiple sclerosis, showing similar clinical benefits to dimethyl fumarate but with improved gastrointestinal tolerability.

In treatment-naïve RRMS patients or those previously treated with interferon-β or glatiramer acetate, diroximel fumarate significantly reduces annualized relapse rates and the formation of new brain lesions, with most patients experiencing no relapses during treatment.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Diroximel Fumarate in Relapsing Forms of Multiple Sclerosis: A Profile of Its Use. Paik, J.[2022]

Diroximel fumarate (DRF) shows improved gastrointestinal tolerability and low treatment discontinuation rates (<1%) compared to dimethyl fumarate (DMF), making it a favorable option for patients with relapsing multiple sclerosis (MS).

Patient interviews revealed that key factors influencing the perception of DRF included overall wellness, ease of administration, and minimal side effects, highlighting the importance of patient perspectives in treatment adherence and decision-making.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Health-Related Quality of Life with Diroximel Fumarate in Patients with Relapsing Forms of Multiple Sclerosis: Findings from Qualitative Research Using Patient Interviews. Gudesblatt, M., Roman, C., Singer, BA., et al.[2022]

Diroximel fumarate (DRF) showed a higher proportion of patients free of gadolinium-enhancing (Gd+) T1 lesions compared to ponesimod (PON), indicating better radiological outcomes for DRF, although no significant differences were found in annualized relapse rate (ARR) or confirmed disability progression (CDP) between the two treatments.

When compared to teriflunomide (TERI), DRF demonstrated improved efficacy across all clinical and radiological outcomes, including lower ARR and reduced rates of CDP, suggesting that DRF may be a more effective treatment option for relapsing multiple sclerosis.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Matching-Adjusted Indirect Comparisons of Diroximel Fumarate, Ponesimod, and Teriflunomide for Relapsing Multiple Sclerosis. Jiang, T., Ziemssen, T., Wray, S., et al.[2023]

References

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

Diroximel Fumarate Demonstrates an Improved Gastrointestinal Tolerability Profile Compared with Dimethyl Fumarate in Patients with Relapsing-Remitting Multiple Sclerosis: Results from the Randomized, Double-Blind, Phase III EVOLVE-MS-2 Study. [2021]

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

Clinical Significance of Gastrointestinal and Flushing Events in Patients with Multiple Sclerosis Treated with Delayed-Release Dimethyl Fumarate. [2022]

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

Lymphocyte reconstitution after DMF discontinuation in clinical trial and real-world patients with MS. [2022]

4. Poland pubmed.ncbi.nlm.nih.gov

Evaluation of efficacy, safety and tolerability of fingolimod in patients with the relapsing form of multiple sclerosis - 12-month observation. A preliminary report. [2019]

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

Pharmacokinetics of glycopyrronium/formoterol fumarate dihydrate delivered via metered dose inhaler using co-suspension delivery technology in patients with moderate-to-very severe COPD. [2018]

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

Real-World Analysis Affirms the High Persistence and Adherence Observed with Diroximel Fumarate in Patients with Multiple Sclerosis. [2023]

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

Diroximel fumarate in patients with relapsing-remitting multiple sclerosis: Final safety and efficacy results from the phase 3 EVOLVE-MS-1 study. [2023]

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

Diroximel Fumarate in Relapsing Forms of Multiple Sclerosis: A Profile of Its Use. [2022]

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

Health-Related Quality of Life with Diroximel Fumarate in Patients with Relapsing Forms of Multiple Sclerosis: Findings from Qualitative Research Using Patient Interviews. [2022]

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

Matching-Adjusted Indirect Comparisons of Diroximel Fumarate, Ponesimod, and Teriflunomide for Relapsing Multiple Sclerosis. [2023]