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) (VOYAGE)

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

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 researchers nor the participants will know which drug or dose the participants will receive in Group B. Participants in Group B will also receive a placebo so they do not know which drug is being given. A placebo looks like a study drug but contains no real medicine.
• All study drugs will be taken by mouth, once or twice a day. Participants who take DRF or DMF will start with a lower dose during the 1st week, then move to a standard dose.
• Treatment in Part 1 will last for 96 weeks. Participants will have up to 11 study visits and 7 phone calls.
• Participants who do not move onto Part 2 will also have a safety follow-up period of 4 to 8 weeks. This will include 1 study visit and 1 phone call.
• The total length of Part 1, including the screening, treatment, and follow-up, will be up to 108 weeks.

Part 2 (Extension Period)

• Participants who complete Part 1 can move on to Part 2 of the study.
• All participants in Part 2 will receive DRF by mouth for 96 weeks.
• Participants will have up to 10 more study visits and 1 telephone call during treatment.
• They will also have a 4-week safety follow-up, including 1 study visit and 1 phone call.
• The total length of Part 2 will be up to 100 weeks.

Study Overview

• Status: Not yet recruiting
• Conditions: Relapsing Forms of Multiple Sclerosis
• Intervention / Treatment: Drug: Diroximel Fumarate; Drug: Placebo matching fingolimod; Drug: Fingolimod; Drug: Placebo matching DRF; Drug: Dimethyl Fumarate; Drug: Placebo matching DMF

Detailed Description

The primary objectives of this study are to evaluate the safety, tolerability of diroximel fumarate (DRF), the noninferiority of the clinical efficacy of monomethyl fumarate (MMF) (pooled DRF and dimethyl fumarate [DMF] treatment) compared to that of fingolimod and long-term safety and tolerability of DRF in participants who completed Week 96 of the Treatment Period. The secondary objectives of this study are to characterize the pharmacokinetic (PK) profile of DRF metabolites (MMF and 2-hydroxyethyl succinimide [HES]), additional safety and tolerability of DRF, noninferiority of the radiological efficacy of MMF (pooled DRF and DMF treatment) compared to that of fingolimod, and to further describe the safety and long-term multiple sclerosis (MS) outcomes of DRF in participants who completed Week 96 of the Treatment Period.

• Study Type: Interventional
• Enrollment (Estimated): 185
• Phase: Phase 3

Contacts and Locations

• Study Contact: Name: US Biogen Clinical Trial Center; Phone Number: 866-633-4636; Email: clinicaltrials@biogen.com
• Study Contact Backup: Name: Global Biogen Clinical Trial Center; Email: clinicaltrials@biogen.com

Participation Criteria

Eligibility Criteria

• Ages Eligible for Study: Child
• Accepts Healthy Volunteers: No

Description

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.

Study Plan

How is the study designed?

Design Details

• Primary Purpose: Treatment
• Allocation: Randomized
• Interventional Model: Parallel Assignment
• Masking: Quadruple

Number of Arms

7

Arms and Interventions

Participant Group / Arm	Intervention / Treatment
Experimental: TP Cohort A; Participants weighing ≤ 40 kilograms (kg) will receive DRF 231 milligrams (mg) orally, once daily (QD) (starting dose) on Days 1 to 7 followed by DRF 231 mg orally, BID (twice daily) (maintenance dose) on Day 8 through Week 96.	Drug: Diroximel Fumarate; Oral capsule; Other Names: BIIB098; Vumerity; ALK8700
Experimental: TP Cohort B: Sub-cohort 1: DRF; Participants weighing >40 kg will receive DRF/placebo matching fingolimod 231 mg orally, BID (starting dose) on Days 1 to 7 followed by DRF 462 mg orally, BID (maintenance dose) on Day 8 through Week 96.	Drug: Diroximel Fumarate; Oral capsule; Other Names: BIIB098; Vumerity; ALK8700; Drug: Placebo matching fingolimod; Oral capsule
Experimental: TP Cohort B: Sub-cohort 1: Fingolimod; Participants weighing >40 kg will receive Fingolimod 0.5 mg orally, QD followed by placebo matching DRF 231 mg (starting dose) orally, BID on Days 1 to 7 followed by placebo matching DRF 462 mg (maintenance dose) orally, BID on Day 8 through Week 96.	Drug: Fingolimod; Oral capsule; Other Names: Gilenya; Drug: Placebo matching DRF; Oral capsule
Experimental: TP Cohort B: Sub-cohort 2: DMF; Participants weighing >40 kg will receive DMF/placebo matching fingolimod 120 mg (starting dose) orally, BID on Days 1 to 7 followed by DMF 240 mg (maintenance dose) orally BID, on Day 8 through Week 96.	Drug: Placebo matching fingolimod; Oral capsule; Drug: Dimethyl Fumarate; Oral capsule; Other Names: BG00012; Tecfidera
Experimental: TP Cohort B: Sub-cohort 2: Fingolimod; Participants weighing >40 kg will receive Fingolimod 0.5 mg oral QD followed by placebo matching DMF 120 mg (starting dose) orally, BID on Days 1 to 7 followed by placebo matching DMF 240 mg (maintenance dose) orally, BID through Week 96.	Drug: Fingolimod; Oral capsule; Other Names: Gilenya; Drug: Placebo matching DMF; Oral capsule
Experimental: Open-label Extension (OLE) Period: Participants from Cohort A; Participants from Cohort A weighing ≤ 40 kg will receive DRF 231 mg orally, BID and participants weighing >40 kg will receive DRF 462 mg orally, BID up to 192 weeks.	Drug: Diroximel Fumarate; Oral capsule; Other Names: BIIB098; Vumerity; ALK8700
Experimental: OLE Period: Participants from Cohort B; Participants from Cohort B will receive DRF 231 mg orally, BID for 7 days, followed by the maintenance dose of DRF 462 mg orally, BID up to 192 weeks.	Drug: Diroximel Fumarate; Oral capsule; Other Names: BIIB098; Vumerity; ALK8700

What is the study measuring?

Primary Outcome Measures

Outcome Measure	Time Frame
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 Outcome Measures

Outcome Measure	Measure Description	Time Frame
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
TP Cohorts A, B and OLE Period: Number of Participants With Change From Baseline in Clinically Relevant Electrocardiogram (ECG) Abnormalities		Cohorts A and B: Baseline up to Week 96, OLE: Baseline (Week 96) up to Week 196
TP Cohorts A, B and OLE Period: Number of Participants with PCS Change from Baseline in Clinical Laboratory Parameters		Cohorts A and B: Baseline up to Week 96, OLE: Baseline (Week 96) up to Week 196
TP Cohorts A, B and OLE Period: Change From Baseline in Height		Cohorts A and B: Baseline up to Week 104, OLE: Baseline (Week 96) up to Week 196
TP Cohorts A, B and OLE Period: Change From Baseline in Weight		Cohorts A and B: Baseline up to Week 104, OLE: Baseline (Week 96) up to Week 196
TP Cohorts A, B and OLE Period: Change From Baseline in Tanner Score	Assessment of Tanner stage will be performed by a healthcare professional experienced with this assessment. Tanner score ranges from Stage 1 (childhood) to Stage 5 (full physical maturity). Information regarding Tanner staging will be collected for all male participants with bone age < 16 years and for female participants who are premenarche and have a bone age of < 16 years and will be stopped once the participant's bone age reaches ≥ 16 years or once the participant is postmenarche.	Cohorts A and B: Baseline up to Week 96, OLE: Baseline (Week 96) up to Week 196
TP Cohorts A, B and OLE Period: Change From Baseline in Bone Age		Cohorts A and B: Baseline up to Week 96, OLE: Baseline (Week 96) up to Week 196
TP Cohorts A, B and OLE Period: Number of Participants with Change From Baseline in Endocrine Tests	Endocrine parameters to be tested will include insulin-like growth factor 1, and insulin-like growth factor binding protein for both females and males; follicle stimulating hormone (FSH), luteinizing hormone (LH), and estradiol (E-2) for females; and testosterone, FSH, and LH for males. All endocrine tests will stop being performed once the participant has reached a bone age of ≥ 16 years or the participant is postmenarche.	Cohorts A and B: Baseline up to Week 96, OLE: Baseline (Week 96) up to Week 196
TP Cohorts A, B and OLE Period: Change From Baseline in Depression Monitored Using the Children's Depression Rating Scale for Participants <18 Years or the Hamilton Rating Scale for Depression (HAMD-17) for Participants ≥18 Years		Cohorts A and B: Baseline up to Week 96, OLE: Baseline (Week 96) up to Week 196
TP Cohorts A, B and OLE Period: Change From Baseline in Depression Monitored Using the Columbia Suicide Severity Rating Scale (C-SSRS)	The C-SSRS is an interview-based rating scale to systematically assess suicidal ideation and suicidal behavior. C-SSRS assesses whether participant experiences any of the following 1. completed suicide, 2. suicide attempt (response of "yes" on "actual attempt"), 3. preparatory acts toward imminent suicidal behavior ("yes" on "aborted attempt", "interrupted attempt", "preparatory acts or behavior"), 4. any suicidal behavior or ideation, suicidal ideation ("yes" on "wish to be dead", "non-specific active suicidal thoughts", "active suicidal ideation with methods without intent to act or some intent to act, without specific plan or with specific plan and intent"), 5. self-injurious behavior, no suicidal intent ("yes" on "has participant engaged in non-suicidal self-injurious behavior").	Cohorts A and B: Baseline up to Week 96, OLE: Baseline (Week 96) up to Week 196
TP Cohort B: Change From Baseline in Annualized Rate of New/Newly Enlarging (N/NE) T2 Hyperintense Lesions Through Week 96		Baseline (Day 1) up to Week 96
TP Cohort B: Time to First Relapse		Baseline (Day 1) up to Week 96
TP Cohort B: Percentage of Participants Free of Relapse up to Week 96		Baseline (Day 1) up to Week 96
TP Cohort B and OLE Period: Change From Baseline in Expanded Disability Status Scale (EDSS) Score	The EDSS is a method of quantifying disability and monitoring changes in the level of disability over time. EDSS score ranges from 0 (normal neurological exam) to 10 (death from MS) with higher scores indicating more disability.	Cohort B: Baseline up to Week 96, OLE: Baseline (Week 96) up to Week 196
TP Cohort B: Change From Baseline in Number of N/NE T2 Hyperintense Lesions on Brain Magnetic Resonance Imaging (MRI) Scans at Weeks 48 and 96		Baseline up to Weeks 48 and 96
TP Cohort B: Number of Gadolinium (Gd)-Enhancing Lesions on Brain MRI Scans at Baseline and at Weeks 48 and 96		At Baseline, Weeks 48 and 96
TP Cohort B: Number of Participants With T1 Hypointense Lesions at Week 96		At Week 96
TP Cohort B: Change From Baseline in Percentage of Participants Free of N/NE T2 Hyperintense Lesions on Brain MRI Scans at Weeks 24, 48, and 96		Baseline up to Weeks 24, 48, and 96
TP Cohort B: Change From Baseline in Percentage of Participants Free of New MRI Activity at Weeks 24, 48, and 96	Free of new MRI activity is defined as free of Gd-enhancing lesions and free of N/NE T2 MRI lesions on brain MRI scans.	Baseline up to Weeks 24, 48, and 96
TP Cohort B: Number of Participants With TEAEs, SAEs and AEs Leading to Treatment Discontinuation		From first dose of study drug up to end of follow-up (up to Week 104)
OLE Period: ARR at Weeks 144 and 192		At Weeks 144 and 192

Collaborators and Investigators

• Sponsor: Biogen
• Investigators: Study Director: Medical Director, Biogen

Study record dates

Study Major Dates

• Study Start (Estimated): November 16, 2026
• Primary Completion (Estimated): July 28, 2034
• Study Completion (Estimated): June 19, 2035

Study Registration Dates

• First Submitted: February 26, 2026
• First Submitted That Met QC Criteria: March 17, 2026
• First Posted (Actual): March 19, 2026

Study Record Updates

• Last Update Posted (Actual): March 19, 2026
• Last Update Submitted That Met QC Criteria: March 17, 2026
• Last Verified: March 1, 2026

More Information

Terms related to this study

• Additional Relevant MeSH Terms: Organic Chemicals; Acids, Acyclic; Carboxylic Acids; Amines; Alcohols; Glycols; Amino Alcohols; Sphingosine; Propylene Glycols; Fumarates; Dicarboxylic Acids; Fingolimod Hydrochloride; Dimethyl Fumarate; diroximel fumarate
• Other Study ID Numbers: 272MS304; 2023-509409-60 (Other Identifier: EU CT Number)

Plan for Individual participant data (IPD)

• Plan to Share Individual Participant Data (IPD)?: YES
• IPD Plan Description: In accordance with Biogen's Clinical Trial Transparency and Data Sharing Policy on https://www.biogentrialtransparency.com/

Drug and device information, study documents

• Studies a U.S. FDA-regulated drug product: Yes
• Studies a U.S. FDA-regulated device product: No
• product manufactured in and exported from the U.S.: Yes