BIIB091 for Relapsing Multiple Sclerosis
(FUSION Trial)
Recruiting in Palo Alto (17 mi)
+80 other locations
Age: 18 - 65
Sex: Any
Travel: May Be Covered
Time Reimbursement: Varies
Trial Phase: Phase 2
Recruiting
Sponsor: Biogen
Must not be taking: Fumarates, BTK inhibitors
Disqualifiers: PPMS, Recent MS relapse, HIV, others
No Placebo Group
Prior Safety Data
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.
12345What 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.
12345What 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.
678910Eligibility 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.
+4 more
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.
+8 more
Trial 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
Participant Groups
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.
6Treatment groups
Experimental Treatment
Active Control
Group I: Part 2: BIIB091 + DRF Standard DoseExperimental Treatment2 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 DoseExperimental Treatment2 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 DRFExperimental Treatment2 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 DRFExperimental Treatment2 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 BIIB091Active Control2 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 BIIB091Active Control2 Interventions
Participants will receive DRF standard dose and matching placebo for BIIB091, orally, for up to 48 weeks.
Find a Clinic Near You
Research Locations NearbySelect from list below to view details:
The University of Texas Health Science Center San AntonioSan Antonio, TX
University of California at Irvine Medical CenterOrange, CA
University of South FloridaTampa, FL
Holy NameTeaneck, NJ
More Trial Locations
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Who Is Running the Clinical Trial?
BiogenLead Sponsor
References
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]Diroximel fumarate (DRF) is a novel oral fumarate approved in the USA for relapsing forms of multiple sclerosis. DRF is converted to monomethyl fumarate, the pharmacologically active metabolite of dimethyl fumarate (DMF). DRF 462 mg and DMF 240 mg produce bioequivalent exposure of monomethyl fumarate and are therefore expected to have similar efficacy/safety profiles; the distinct chemical structure of DRF may contribute to its tolerability profile.
Clinical Significance of Gastrointestinal and Flushing Events in Patients with Multiple Sclerosis Treated with Delayed-Release Dimethyl Fumarate. [2022]In the phase 3 DEFINE and CONFIRM trials, flushing and gastrointestinal (GI) events were associated with delayed-release dimethyl fumarate (DMF; also known as gastroresistant DMF) treatment in people with relapsing-remitting multiple sclerosis (MS). To investigate these events, a post hoc analysis of integrated data from these trials was conducted, focusing on the initial treatment period (months 0-3) with the recommended DMF dosage (240 mg twice daily).
Lymphocyte reconstitution after DMF discontinuation in clinical trial and real-world patients with MS. [2022]Delayed-release dimethyl fumarate (DMF) has demonstrated robust efficacy in treating patients with relapsing-remitting multiple sclerosis. Decreases in absolute lymphocyte count (ALC) are a well-known pharmacodynamic effect of DMF treatment, but lymphocyte recovery dynamics are not well characterized after discontinuation of DMF.
Evaluation of efficacy, safety and tolerability of fingolimod in patients with the relapsing form of multiple sclerosis - 12-month observation. A preliminary report. [2019]Oral fingolimod 0.5 mg daily was approved in the European Union in 2011 for the treatment of relapsing multiple sclerosis in the aggressive form and as a second line treatment in patients with high disease activity despite interferon beta therapy. The aim of this study was the evaluation of efficacy, safety and tolerance of fingolimod in patients with relapsing-remitting multiple sclerosis (RRMS) during a 12-month observation period.
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]Label="Purpose">The efficacy and tolerability of GFF MDI (Bevespi Aerosphere®), a fixed-dose combination of glycopyrronium (GP)/formoterol fumarate dihydrate (FF) 14.4/10 μg (equivalent to glycopyrrolate/formoterol fumarate 18/9.6 μg) delivered by metered dose inhaler (MDI) using innovative co-suspension delivery technology, has been investigated in a Phase III clinical trial program (NCT01854645, NCT01854658, NCT01970878) in patients with COPD. Here, we present findings from a pharmacokinetic (PK) sub-study of NCT01854645 (PINNACLE-1).
Real-World Analysis Affirms the High Persistence and Adherence Observed with Diroximel Fumarate in Patients with Multiple Sclerosis. [2023]Adherence to disease-modifying therapies is key for achieving optimal outcomes in multiple sclerosis (MS). Diroximel fumarate (DRF) is an oral fumarate approved for treatment of relapsing forms of MS. It has the same pharmacologically active metabolite as dimethyl fumarate (DMF) and similar efficacy and safety profiles, but with demonstrated fewer gastrointestinal (GI) related adverse events (AEs). There are limited data characterizing persistence and adherence to DRF in the real world.
Diroximel fumarate in patients with relapsing-remitting multiple sclerosis: Final safety and efficacy results from the phase 3 EVOLVE-MS-1 study. [2023]Diroximel fumarate (DRF) is approved for adults with relapsing-remitting multiple sclerosis (RRMS) in Europe and for relapsing forms of MS in the United States. DRF and dimethyl fumarate (DMF) yield bioequivalent exposure of the active metabolite monomethyl fumarate. Prior studies indicated fewer gastrointestinal (GI)-related adverse events (AEs) with DRF compared with DMF.
Diroximel Fumarate in Relapsing Forms of Multiple Sclerosis: A Profile of Its Use. [2022]Diroximel fumarate (Vumerity®), an orally administered disease-modifying drug (DMD), expands the available treatment options for adults with relapsing forms of multiple sclerosis (MS), including clinically isolated syndrome, relapsing-remitting MS (RRMS), and active secondary progressive MS. It demonstrates bioequivalence to dimethyl fumarate and was developed to provide similar clinical benefits, but with an improved gastrointestinal (GI) tolerability profile. In RRMS patients who are treatment-naïve or were previously treated with interferon-β or glatiramer acetate, diroximel fumarate reduces annualized relapse rates, with most patients experiencing no relapses during treatment, and reduces the formation of new MS-associated brain lesions. Diroximel fumarate has an acceptable tolerability profile that is consistent with that of dimethyl fumarate, albeit with a significantly lower rate of GI adverse events.
Health-Related Quality of Life with Diroximel Fumarate in Patients with Relapsing Forms of Multiple Sclerosis: Findings from Qualitative Research Using Patient Interviews. [2022]Diroximel fumarate (DRF) is an oral fumarate for relapsing multiple sclerosis (MS). Clinical and real-world studies of DRF have demonstrated improved gastrointestinal (GI) tolerability and low (
Matching-Adjusted Indirect Comparisons of Diroximel Fumarate, Ponesimod, and Teriflunomide for Relapsing Multiple Sclerosis. [2023]Diroximel fumarate (DRF), ponesimod (PON), and teriflunomide (TERI) are oral disease-modifying therapies approved for the treatment of relapsing multiple sclerosis. No randomized trials have compared DRF versus PON or TERI.