BIIB091 for Relapsing Multiple Sclerosis

(FUSION Trial)

Recruiting at 92 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

What You Need to Know Before You Apply

What is the purpose of this trial?

This trial tests a new drug, BIIB091, for individuals with relapsing multiple sclerosis (MS), a condition where the immune system attacks the brain and spinal cord. The study aims to determine if BIIB091 is safe and effective, both alone and in combination with another drug, DRF (Diroximel fumarate). Researchers will examine how these treatments impact brain inflammation and any new or worsening health issues. Individuals with relapsing forms of MS, such as those who have experienced two or more flare-ups in the past two years, might be suitable candidates for this study. As a Phase 2 trial, this research focuses on assessing the treatment's effectiveness in an initial, smaller group, offering participants a chance to contribute to significant advancements in MS treatment.

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.

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

Research has shown that DRF (diroximel fumarate) is generally safe for people with relapsing multiple sclerosis (MS). It reduces the number of relapses and is gentler on the stomach compared to its predecessor, dimethyl fumarate. Most people continue the treatment, with only a few experiencing side effects that lead to discontinuation.

BIIB091 is a newer treatment under study. Early reports suggest it targets specific cells involved in MS. Detailed safety information is limited due to its early testing stage. However, its progression to a later trial phase indicates some confidence in its safety, with more details expected as the trial progresses.

Overall, while DRF has a proven track record, BIIB091 remains under investigation. Participants in the trial will help researchers learn more about the safety of BIIB091, both alone and in combination with DRF. ^{1 2 3 4 5}

Why are researchers excited about this trial's treatments?

BIIB091 is unique because it represents a new approach to treating relapsing multiple sclerosis (MS) by targeting specific proteins involved in the inflammatory process. Unlike traditional treatments, which often focus on broad immune suppression, BIIB091 is designed to selectively modulate the immune response, potentially reducing side effects and improving patient outcomes. Researchers are excited about BIIB091 because it may offer a more targeted therapy with the promise of better efficacy and safety compared to current options like interferons and glatiramer acetate. Additionally, BIIB091 is administered orally, which can be more convenient for patients compared to injectable treatments.

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

Research has shown that Diroximel Fumarate (DRF), one of the treatments in this trial, can reduce relapses in people with relapsing forms of multiple sclerosis. Studies indicate that DRF lowers disease activity, visible in MRI scans, and is safer than its predecessor, Dimethyl Fumarate. BIIB091, another treatment option in this trial, is a new therapy under investigation for relapsing multiple sclerosis. It targets specific parts of the immune system, potentially reducing inflammation and slowing the disease. Early results suggest BIIB091 could be promising, but further research is needed to confirm its effectiveness. ^{1 6 7 8 9}

Who Is on the Research Team?

Medical Director

Principal Investigator

Biogen

Are You a Good Fit for This Trial?

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 for a Trial Participant

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

What Are the Treatments Tested in This Trial?

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.

How Is the Trial Designed?

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

Published Research Related to This Trial

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]

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 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]

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]

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 (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]

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]

Citations

1. clinicaltrials.gov clinicaltrials.gov/study/NCT05798520

NCT05798520 | A Study to Learn About the Safety of ... 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.

2. pmc.ncbi.nlm.nih.gov pmc.ncbi.nlm.nih.gov/articles/PMC12052076/

Update on novel multiple sclerosis treatments - PubMed Central A phase 3 trial (NCT01433497) demonstrated clinical efficacy in slowing disease progression in primary progressive and clinically inactive ...

3. clinicaltrials.eu clinicaltrials.eu/inn/biib091/

BIIB091: A Promising New Drug for Multiple Sclerosis ... BIIB091 shows promise as a potential new treatment option for people with relapsing forms of multiple sclerosis. If the ongoing clinical trials demonstrate that ...

4. neurologylive.com neurologylive.com/view/phase-2-fusion-trial-btk-inhibitor-biib091-diana-gallagher

The Phase 2 FUSION Trial of BTK Inhibitor BIIB091: Diana ... A new phase 2, 2-part study assessing the efficacy and safety of BIIB091, an investigational Bruton's tyrosine kinase inhibitor.

5. sutterhealth.org sutterhealth.org/research/clinical-trials/relapsing-multiple-sclerosis257ms201-1078067744

Relapsing Multiple Sclerosis/257MS201 - Clinical Trials In this study, researchers will learn more about a study drug called BIIB091 in participants with MS who may be experiencing relapses.

6. biogentriallink.com biogentriallink.com/en-us/home/find-a-clinical-trial/clinical-trials-study-details.html?nctId=NCT05798520

Clinical Trials - Study Details A study to learn about the safety of BIIB091 and its effect on brain inflammation when taken alone or with Diroximel Fumarate (DRF) in adults with relapsing ...

7. pmc.ncbi.nlm.nih.gov pmc.ncbi.nlm.nih.gov/articles/PMC11025433/

A review of Bruton's tyrosine kinase inhibitors in multiple ... This narrative review investigates the potential of BTK inhibitors as an MS DMT, the improved selectivity of second-generation inhibitors, comparative safety ...

8. clinicalresearch.com clinicalresearch.com/en/find-trials/Study/NCT05798520

NCT05798520 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.

9. clinicaltrials.eu clinicaltrials.eu/trial/study-on-the-safety-and-efficacy-of-biib091-and-diroximel-fumarate-for-patients-with-relapsing-multiple-sclerosis/

Study on the Safety and Efficacy of BIIB091 and Diroximel ... This study investigates the safety and effectiveness of BIIB091, both alone and in combination with Diroximel Fumarate (Vumerity), ...