Study to Evaluate the Efficacy and Safety of Dimethyl Fumarate (Tecfidera) and Peginterferon Beta-1a (Plegridy) for the Treatment of Relapsing-Remitting Multiple Sclerosis in Pediatric Participants

Study Overview
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Brief Summary
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The main objective of the study is to evaluate the efficacy of dimethyl fumarate (Tecfidera) and peginterferon beta-1a (Plegridy), both compared with placebo, in pediatric participants with RRMS. The other objectives of this study are to evaluate the safety and tolerability of dimethyl fumarate and peginterferon beta-1a and to assess the effect of dimethyl fumarate and peginterferon beta-1a, both compared with placebo, on additional clinical and radiological measures of disease activity.

Detailed Description
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Participants will be randomized in a 1:2:2 ratio to receive the double-blind study treatment (Dimethyl Fumarate, Peginterferon Beta-1a, and placebo). Participants experiencing a confirmed relapse or disability progression or high lesion burden on MRI will have the option to discontinue the blinded study treatment and switch to an alternative therapy or open-label BG00012.

Official Title
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A Randomized, Double-Blind, Double-Dummy, Placebo-Controlled, 3-Arm, Parallel Group Study in Pediatric Subjects Aged 10 Through 17 Years to Evaluate the Efficacy and Safety of BG00012 and BIIB017 for the Treatment of Relapsing-Remitting Multiple Sclerosis

Conditions
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Multiple Sclerosis, Relapsing-Remitting

Intervention / Treatment
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* Drug: Dimethyl Fumarate
* Drug: Peginterferon Beta-1a
* Drug: Placebo


Participation Criteria
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Eligibility Criteria
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Key Inclusion Criteria: Must have a diagnosis of RRMS as defined by the revised consensus definition for pediatric MS Must have an EDSS score between 0.0 and 5.0. Must have a body weight of ≥30 kg Must have experienced ≥1 relapse in the 12 months prior to randomization (Day 1), or must have evidence of asymptomatic disease activity seen on MRI in the 6 months prior to randomization, or ≥2 relapses in the 24 months prior to randomization (Day 1). Relapse is defined as the occurrence of a clinical demyelination event regardless of whether the event is a first or subsequent demyelinating event. Key Exclusion Criteria: Participants having primary progressive, secondary progressive, or progressive RMS. Disorders mimicking MS, such as other demyelinating disorders, systemic autoimmune disorders, metabolic disorders, and infectious disorders. History of clinically significant cardiovascular, pulmonary, GI, hepatic, renal, endocrinologic, hematologic, immunologic, metabolic, dermatologic, growth, developmental, psychiatric (including depression), neurologic (other than MS), and/or other major disease and/or laboratory abnormality indicative thereof, that would preclude participation in a clinical study Occurrence of an MS relapse within the 30 days prior to randomization (Day 1) and/or the subject has not stabilized from a previous relapse prior to randomization NOTE: Other protocol defined Inclusion/Exclusion criteria may apply.

Ages Eligible for Study
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Minimum Age: 10 Years
Maximum Age: 17 Years

Sexes Eligible for Study
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All

Accepts Healthy Volunteers
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No

Study Plan
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How is the study designed?
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Design Details

Primary Purpose: Treatment
Allocation: Randomized
Intervention Model: Parallel Assignment
Masking: Quadruple


Arms and Interventions

| Participant Group/Arm | Intervention/Treatment |
| --- | --- |
| Experimental: Dimethyl Fumarate 240 mg<br>Participants will receive dimethyl fumarate 240 milligrams (mg) capsule twice daily (BID) orally and placebo subcutaneous (SC) injection every 2 weeks for up to 96 weeks (2 years). | Drug: Dimethyl Fumarate<br>* Administered as specified in the treatment arm.<br>* Other names: BG00012;|
| Experimental: Peginterferon Beta-1a 125 µg<br>Participants will receive peginterferon beta-1a 125 micrograms (µg) SC injection every 2 weeks and placebo capsule BID orally for up to 96 weeks (2 years). | Drug: Peginterferon Beta-1a<br>* Administered as specified in the treatment arm.<br>* Other names: BIIB017;|
| Placebo Comparator: Placebo<br>Participants will receive placebo SC injection every 2 weeks and placebo capsule BID orally for up to 96 weeks (2 years) | Drug: Placebo<br>* Administered as specified in the treatment arm.<br>|

What is the study measuring?
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Primary Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| Time to First Relapse | A clinical relapse is defined as new or recurrent neurological symptoms, not associated with fever, lasting for at least 24 hours, and followed by a period of 30 days of stability or improvement. Time to relapse is defined as from the first dose of the study drug to the day of relapse. Time to First Relapse is estimated by Kaplan Mayer method. | Baseline up to Week 96 | 

Secondary Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| Number of Participants With Adverse Events (AEs) and Serious Adverse Events (SAEs) | An AE was any untoward medical occurrence in a participant who received study drug without regard to possibility of causal relationship. An SAE is an AE resulting in any of the following outcomes or deemed significant for any other reason: death; Initial or prolonged inpatient hospitalization; life threatening experience (immediate risk of dying); persistent or significant disability/incapacity; congenital anomaly. | Baseline up to Week 100 | 
| Number of New or Newly Enlarging T2 Hyperintense Lesions on Brain Magnetic Resonance Imaging (MRI) Scans at Weeks 48 and 96 | The number of new or newly enlarging T2 hyperintense lesions that developed in each participant assessed on magnetic resonance imaging (MRI) scans. | Weeks 48 and 96 | 
| Number of Galdolinium (Gd)-Enhancing Lesions at Weeks 48 and 96 | The number of Gd-enhancing lesions was assessed by using MRI scans. | Weeks 48 and 96 | 
| Annualized Relapse Rate | A clinical relapse was defined as new or recurrent neurological symptoms, not associated with fever, lasting for at least 24 hours, and followed by a period of 30 days of stability or improvement. The relapse rate for an individual participant was calculated as the number of relapses for that participant divided by the number of participant-years followed. The ARR for each enrolment group was calculated as the total number of relapses experienced in the group divided by the total number of participant-years on the study. An unadjusted relapse rate is reported. | Up to Week 96 | 

 Terms related to the study
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Keywords Provided by Centre Hospitalier Valida
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Pediatric, Multiple Sclerosis