A Phase 3 Study With an Open-Label Extension in Pediatric Participants to Evaluate the Safety, Efficacy, and Pharmacokinetics of Diroximel Fumarate and Dimethyl Fumarate for the Treatment of Relapsing Forms of Multiple Sclerosis

Plain English Summary

A Study to Learn About the Safety of Diroximel Fumarate (DRF) and Dimethyl Fumarate (DMF) and Their Effects on Relapses in Pediatric Participants With Relapsing Forms of Multiple Sclerosis (RMS) is a Phase 3 clinical trial sponsored by Biogen studying Relapsing Forms of Multiple Sclerosis. Tests the safety and effectiveness of Diroximel Fumarate and Dimethyl Fumarate in children with relapsing forms of Multiple Sclerosis. For children aged 2-17 with MS who have had at least one relapse in the last year or have brain lesions. Participation involves taking study drugs for up to 2 years and regular check-ups. Alternative treatments include other MS drugs like fingolimod. The trial aims to enroll 185 participants.

Official Summary

In this study, researchers will learn more about the study drugs diroximel fumarate (DRF) and dimethyl fumarate (DMF) in children with MS who may be experiencing relapses. Participants will be divided into 2 groups based on their weight: * Group A will include children who weigh 40 kilograms (kg) or less. They will receive DRF in both Part 1 and Part 2 of the study. * Group B will include children who weigh more than 40 kg. They will be randomly assigned to receive DRF, DMF, or fingolimod. Fingolimod is a drug already used to treat MS in adults. In Part 2, they will receive DRF. This is a 2-part study. Part 1 treatment will last 96 weeks. Participants who complete Part 1 may move to Part 2. Part 2 is an extension period. Treatment will last another 96 weeks and will help researchers learn about the long-term safety and effects of treatment. The main goal of the study is to learn about the safety of DRF and DMF and compare their effect on relapses and brain lesions with fingolimod. The main questions researchers want to answer are: * How many participants have adverse events and serious adverse events? * How often do participants relapse after treatment with DRF and DMF compared to fingolimod? Researchers will take brain imaging scans to check for any new areas of brain inflammation and compare the brain lesions before and after treatment. Researchers will also measure the amount of drug in the blood to understand how the body processes it. To check safety, they will monitor participants' growth and development, and compare changes in heart tests, vital signs, and lab tests. They will also use rating scales to monitor depression symptoms. The study will be done as follows: Part 1 (Treatment Period) * After screening, participants will join Part 1 and be divided into 2 groups based on their weight. * Participants in Group A will receive DRF. * Participants in Group B will be randomly assigned to receive either DRF, DMF, or fingolimod. * Neither the research

Who Can Participate

Here is what you need to know about eligibility for this trial. Eligible if aged 2-17, diagnosed with pediatric MS, and have had at least one relapse in the last year or brain lesions. Not eligible if have progressive MS, other conditions mimicking MS, or a history of severe allergic reactions. Age range: 2-17 years Health requirements: Diagnosed with pediatric MS, no progressive MS, and no other serious conditions. This trial is studying Relapsing Forms of Multiple Sclerosis, so participants generally need a confirmed diagnosis.

What They're Measuring

The primary outcome measures the safety and relapse rates of the drugs, helping patients understand potential risks and benefits. The specific primary outcome measures are: TP Cohort A and OLE Period: Number of Participants With Treatment Emergent Adverse Events (TEAEs), Serious Adverse Events (SAEs) and AEs Leading to Treatment Discontinuation (Cohort A: From first dose of study drug up to end of follow-up (up to Week 104), OLE: Baseline (Week 96) up to the end of OLE period (up to Week 196)); TP Cohort B: Annualized Relapse Rate (ARR) Through Week 96 (Baseline (Day 1) up to Week 96). These endpoints are how researchers determine whether the treatment is effective and will form the basis of any future regulatory submissions.

About This Phase

This trial is in Phase 3, the final and most rigorous stage before seeking FDA approval. Phase 3 trials involve 300-3,000+ patients across multiple sites and compare the new treatment directly against the current standard of care. These pivotal trials generate the evidence needed for regulatory review. About 58% of Phase 3 drugs receive FDA approval. Successful Phase 3 results typically lead to a New Drug Application submission.

Why This Trial Matters

This trial fills a gap by studying the safety and effectiveness of these drugs in children, a group often underrepresented in MS research. As a Phase 3 trial, positive results could directly lead to FDA approval, making this treatment available to the broader patient population. This research targets Relapsing Forms of Multiple Sclerosis, where improved treatment options are needed.

Investor Insight

Market size is significant, with a growing need for effective treatments in pediatric MS, and a competitive landscape with existing treatments like fingolimod. Phase 3 trials have approximately a 50-60% chance of gaining FDA approval if they reach this stage.

Is This Trial Right for Me?

Ask your doctor about your child's diagnosis and eligibility criteria. Participation involves taking study drugs and regular check-ups, including brain scans and blood tests. The trial is being conducted at multiple sites. Always discuss clinical trial participation with your healthcare provider before making any decisions. This information is for educational purposes only and is not medical advice.

AI-generated analysis for educational purposes only. This is not medical advice. Discuss clinical trial participation with your doctor. Data sourced from ClinicalTrials.gov.

Study Design

• Study Type: INTERVENTIONAL
• Allocation: RANDOMIZED
• Model: PARALLEL
• Masking: QUADRUPLE
• Enrollment: 185 participants

Interventions

• DRUG: Diroximel Fumarate — Oral capsule
• DRUG: Dimethyl Fumarate — Oral capsule
• DRUG: Fingolimod — Oral capsule
• DRUG: Placebo matching DRF — Oral capsule
• DRUG: Placebo matching DMF — Oral capsule

Primary Outcomes

• TP Cohort A and OLE Period: Number of Participants With Treatment Emergent Adverse Events (TEAEs), Serious Adverse Events (SAEs) and AEs Leading to Treatment Discontinuation (Cohort A: From first dose of study drug up to end of follow-up (up to Week 104), OLE: Baseline (Week 96) up to the end of OLE period (up to Week 196))
• TP Cohort B: Annualized Relapse Rate (ARR) Through Week 96 (Baseline (Day 1) up to Week 96)

Secondary Outcomes

• TP Cohorts A and B: Maximum Observed Concentration at Steady State (Cmax,ss) of Monomethyl Fumarate (MMF) (Predose and at multiple timepoints post dose up to Week 96)
• TP Cohorts A and B: Minimum Observed Concentration at Steady State (Cmin,ss) of MMF (Predose and at multiple timepoints post dose up to Week 96)
• TP Cohorts A and B: Cmax,ss of 2-Hydroxyethyl Succinimide (HES) (Predose and at multiple timepoints post dose up to Week 96)
• TP Cohorts A and B: Cmin,ss of HES (Predose and at multiple timepoints post dose up to Week 96)
• TP Cohorts A, B and OLE Period: Number of Participants with Potentially Clinically Serious (PCS) Change from Baseline in Vital Sign Parameters (Cohorts A and B: Baseline up to Week 96, OLE: Baseline (Week 96) up to Week 196)

Full Eligibility Criteria

Key Inclusion Criteria:

Treatment Period:

* Must have a diagnosis of pediatric MS (as defined by the revised consensus definition of pediatric MS).
* Must have an Expanded Disability Status Scale (EDSS) score between 0 and 5.0, inclusive.
* Must have experienced at least 1 of the following conditions:

  1. greater than or equal to 1 relapse in the 12 months prior to the Baseline Visit (Day 1),
  2. greater than or equal to 2 relapses in the 24 months prior to the Baseline Visit (Day 1), or
  3. evidence of gadolinium (Gd)-enhancing lesions of the brain on magnetic resonance imaging (MRI) within 6 months prior to the Baseline Visit (Day 1).
* Participants must be neurologically stable with no evidence of relapse within 30 days prior to the Baseline Visit (Day 1).

Open-Label Extension Period:

\- Participants who completed the study treatment in Cohorts A or B through the Week 96 Visit.

Key Exclusion Criteria

Treatment Period:

* History of progressive MS.
* History of disorders mimicking MS, such as other demyelinating disorders (e.g., acute disseminated encephalomyelitis and neuromyelitis optical spectrum disorder), systemic autoimmune disorders (e.g., Sjögren's disease and lupus erythematosus), metabolic disorders (e.g., dystrophies), and infectious disorders.
* History of severe allergic or anaphylactic reactions or any allergic reactions that in the opinion of the Investigator are likely to be exacerbated by any component of the study treatment.
* History of, or ongoing, malignant disease, including solid tumors, skin malignancies, and hematologic malignancies.
* History of gastrointestinal (GI) surgery (except appendectomy or cholecystectomy that occurred more than 6 months prior to the Screening Visit), inflammatory bowel disease (Crohn's disease, ulcerative colitis), or another clinically significant and active GI condition at the Investigator's discretion.
* Known hypersensitivity to fumaric acid derivatives or any excipients of DRF or DMF.
* Diagnosis of macular edema prior to randomization.

Open-Label Extension Period:

* Any significant changes in medical history occurring after enrollment in the Treatment Period, including laboratory test abnormalities or current clinically significant conditions that, in the opinion of the Investigator, would have excluded the participant's participation in the Treatment Period. The Investigator must reassess the participant's medical fitness for participation and consider any factors that would preclude treatment.
* Participants who discontinued study treatment due to tolerability issues.
* Other unspecified reasons that, in the opinion of the Investigator or the Sponsor, make the participant unsuitable for participation in the OLE Period.

NOTE: Other protocol-defined Inclusion/Exclusion criteria may apply.

Frequently Asked Questions

Related Conditions

• Relapsing Forms of Multiple Sclerosis
• Pediatric Multiple Sclerosis
• Neurology
• Neuroimmunology
• Pediatric Neurology
• Multiple Sclerosis Treatment
• Pediatric Clinical Trials
• Neurological Disorders
• Pediatric Neuroimmunology
• Neurodegenerative Diseases

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