Multiple Sclerosis, Relapsing-Remitting
Conditions
Keywords
Pediatric, Multiple Sclerosis
Brief summary
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
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.
Interventions
DRUGDimethyl Fumarate
Administered as specified in the treatment arm.
Administered as specified in the treatment arm.
DRUGPlacebo
Administered as specified in the treatment arm.
Sponsors
Biogen
Study design
Allocation
RANDOMIZED
Intervention model
PARALLEL
Primary purpose
TREATMENT
Masking
QUADRUPLE (Subject, Caregiver, Investigator, Outcomes Assessor)
Eligibility
Sex/Gender
ALL
Age
10 Years to 17 Years
Healthy volunteers
No
Inclusion criteria
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/
Design outcomes
Primary
| Measure | Time frame | Description |
|---|---|---|
| Time to First Relapse | Baseline up to Week 96 | 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. |
Secondary
| Measure | Time frame | Description |
|---|---|---|
| Number of Participants With Adverse Events (AEs) and Serious Adverse Events (SAEs) | Baseline up to Week 100 | 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. |
| Number of New or Newly Enlarging T2 Hyperintense Lesions on Brain Magnetic Resonance Imaging (MRI) Scans at Weeks 48 and 96 | 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. |
| Number of Galdolinium (Gd)-Enhancing Lesions at Weeks 48 and 96 | Weeks 48 and 96 | The number of Gd-enhancing lesions was assessed by using MRI scans. |
| Annualized Relapse Rate | Up to Week 96 | 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. |
Countries
Colombia, Estonia, Hungary, Jordan, Malaysia, Mexico, Saudi Arabia, South Korea, Taiwan, Thailand, Tunisia, Turkey (Türkiye), United States
Participant flow
Recruitment details
Participants were enrolled at the investigative sites in Estonia, Tunisia, Turkey, Jordan and Taiwan from 19 March 2019 to 21 July 2022.
Pre-assignment details
A total of 11 participants were enrolled and treated in this study.
Participants by arm
| Arm | Count |
|---|---|
| Dimethyl Fumarate 240 mg Participants received dimethyl fumarate 120 mg capsules BID, orally for 7 days followed by 240 mg capsules, BID, orally for 95 weeks and peginterferon beta-1a matching placebo SC injection Q2W for up to 96 weeks. | 2 |
| Peginterferon Beta-1a 125 µg Participants received peginterferon beta-1a, 63 µg on Day 1, 94 µg at Week 2, 125 µg SC injection Q2W from Week 4 up to 96 weeks and peginterferon beta-1a matching placebo SC injection, Q2W for up to 96 weeks. | 6 |
| Placebo Participants received peginterferon beta-1a matching placebo SC injection Q2W and dimethyl fumarate matching placebo capsules BID, orally for up to 96 weeks. | 3 |
| Total | 11 |
Withdrawals & dropouts
| Period | Reason | FG000 | FG001 | FG002 |
|---|---|---|---|---|
| Overall Study | Study terminated by sponsor | 0 | 2 | 0 |
| Overall Study | Withdrawal by Subject | 0 | 1 | 0 |
| Overall Study | Worsening of multiple sclerosis attack | 0 | 0 | 1 |
Baseline characteristics
| Characteristic | Dimethyl Fumarate 240 mg | Peginterferon Beta-1a 125 µg | Placebo | Total |
|---|---|---|---|---|
| Age, Continuous | 15.5 years STANDARD_DEVIATION 2.12 | 15.7 years STANDARD_DEVIATION 1.51 | 15.7 years STANDARD_DEVIATION 1.15 | 15.6 years STANDARD_DEVIATION 1.36 |
| Ethnicity (NIH/OMB) Hispanic or Latino | 0 Participants | 0 Participants | 0 Participants | 0 Participants |
| Ethnicity (NIH/OMB) Not Hispanic or Latino | 2 Participants | 6 Participants | 3 Participants | 11 Participants |
| Ethnicity (NIH/OMB) Unknown or Not Reported | 0 Participants | 0 Participants | 0 Participants | 0 Participants |
| Race (NIH/OMB) American Indian or Alaska Native | 0 Participants | 0 Participants | 0 Participants | 0 Participants |
| Race (NIH/OMB) Asian | 0 Participants | 1 Participants | 0 Participants | 1 Participants |
| Race (NIH/OMB) Black or African American | 0 Participants | 0 Participants | 0 Participants | 0 Participants |
| Race (NIH/OMB) More than one race | 0 Participants | 0 Participants | 0 Participants | 0 Participants |
| Race (NIH/OMB) Native Hawaiian or Other Pacific Islander | 0 Participants | 0 Participants | 0 Participants | 0 Participants |
| Race (NIH/OMB) Unknown or Not Reported | 0 Participants | 0 Participants | 0 Participants | 0 Participants |
| Race (NIH/OMB) White | 2 Participants | 5 Participants | 3 Participants | 10 Participants |
| Sex: Female, Male Female | 1 Participants | 5 Participants | 2 Participants | 8 Participants |
| Sex: Female, Male Male | 1 Participants | 1 Participants | 1 Participants | 3 Participants |
Adverse events
| Event type | EG000 affected / at risk | EG001 affected / at risk | EG002 affected / at risk |
|---|---|---|---|
| deaths Total, all-cause mortality | 0 / 2 | 0 / 6 | 0 / 3 |
| other Total, other adverse events | 2 / 2 | 6 / 6 | 3 / 3 |
| serious Total, serious adverse events | 1 / 2 | 0 / 6 | 1 / 3 |
Outcome results
Primary
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.
Time frame: Baseline up to Week 96
Population: ITT population included all participants who were randomized and received at least 1 dose of study treatment (BG00012, BIIB017, or placebo).
| Arm | Measure | Value (MEDIAN) |
|---|---|---|
| Dimethyl Fumarate 240 mg | Time to First Relapse | 413 Days |
| Peginterferon Beta-1a 125 µg | Time to First Relapse | NA Days |
| Placebo | Time to First Relapse | 166.5 Days |
Secondary
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.
Time frame: Up to Week 96
Population: ITT population included all participants who were randomized and received at least 1 dose of study treatment (BG00012, BIIB017, or placebo).
| Arm | Measure | Value (NUMBER) |
|---|---|---|
| Dimethyl Fumarate 240 mg | Annualized Relapse Rate | 0.26 relapses per participant year |
| Peginterferon Beta-1a 125 µg | Annualized Relapse Rate | 0.00 relapses per participant year |
| Placebo | Annualized Relapse Rate | 0.46 relapses per participant year |
Secondary
Number of Galdolinium (Gd)-Enhancing Lesions at Weeks 48 and 96
The number of Gd-enhancing lesions was assessed by using MRI scans.
Time frame: Weeks 48 and 96
Population: ITT population included all participants who were randomized and received at least 1 dose of study treatment (BG00012, BIIB017, or placebo). The overall number of participants analyzed signifies number of participants analyzed in this endpoint and the number analyzed signifies number of participants analyzed at a given timepoint.
| Arm | Measure | Group | Value (MEAN) |
|---|---|---|---|
| Dimethyl Fumarate 240 mg | Number of Galdolinium (Gd)-Enhancing Lesions at Weeks 48 and 96 | Week 96 | 0 number of lesions |
| Dimethyl Fumarate 240 mg | Number of Galdolinium (Gd)-Enhancing Lesions at Weeks 48 and 96 | Week 48 | 0 number of lesions |
| Peginterferon Beta-1a 125 µg | Number of Galdolinium (Gd)-Enhancing Lesions at Weeks 48 and 96 | Week 96 | 0.25 number of lesions |
| Peginterferon Beta-1a 125 µg | Number of Galdolinium (Gd)-Enhancing Lesions at Weeks 48 and 96 | Week 48 | 0 number of lesions |
| Placebo | Number of Galdolinium (Gd)-Enhancing Lesions at Weeks 48 and 96 | Week 48 | 1.5 number of lesions |
| Placebo | Number of Galdolinium (Gd)-Enhancing Lesions at Weeks 48 and 96 | Week 96 | 0.5 number of lesions |
Secondary
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.
Time frame: Weeks 48 and 96
Population: ITT population included all participants who were randomized and received at least 1 dose of study treatment (BG00012, BIIB017, or placebo). The overall number of participants analyzed signifies number of participants analyzed in this endpoint and the number analyzed signifies number of participants analyzed at a given timepoint.
| Arm | Measure | Group | Value (MEAN) |
|---|---|---|---|
| Dimethyl Fumarate 240 mg | Number of New or Newly Enlarging T2 Hyperintense Lesions on Brain Magnetic Resonance Imaging (MRI) Scans at Weeks 48 and 96 | Week 48 | 0.5 number of lesions |
| Dimethyl Fumarate 240 mg | Number of New or Newly Enlarging T2 Hyperintense Lesions on Brain Magnetic Resonance Imaging (MRI) Scans at Weeks 48 and 96 | Week 96 | 2.5 number of lesions |
| Peginterferon Beta-1a 125 µg | Number of New or Newly Enlarging T2 Hyperintense Lesions on Brain Magnetic Resonance Imaging (MRI) Scans at Weeks 48 and 96 | Week 48 | 1.0 number of lesions |
| Peginterferon Beta-1a 125 µg | Number of New or Newly Enlarging T2 Hyperintense Lesions on Brain Magnetic Resonance Imaging (MRI) Scans at Weeks 48 and 96 | Week 96 | 1.3 number of lesions |
| Placebo | Number of New or Newly Enlarging T2 Hyperintense Lesions on Brain Magnetic Resonance Imaging (MRI) Scans at Weeks 48 and 96 | Week 48 | 3.3 number of lesions |
| Placebo | Number of New or Newly Enlarging T2 Hyperintense Lesions on Brain Magnetic Resonance Imaging (MRI) Scans at Weeks 48 and 96 | Week 96 | 3.5 number of lesions |
Secondary
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.
Time frame: Baseline up to Week 100
Population: Safety population included all participants who had received at least 1 dose of study treatment.
| Arm | Measure | Group | Value (COUNT_OF_PARTICIPANTS) |
|---|---|---|---|
| Dimethyl Fumarate 240 mg | Number of Participants With Adverse Events (AEs) and Serious Adverse Events (SAEs) | AEs | 2 Participants |
| Dimethyl Fumarate 240 mg | Number of Participants With Adverse Events (AEs) and Serious Adverse Events (SAEs) | SAEs | 1 Participants |
| Peginterferon Beta-1a 125 µg | Number of Participants With Adverse Events (AEs) and Serious Adverse Events (SAEs) | AEs | 6 Participants |
| Peginterferon Beta-1a 125 µg | Number of Participants With Adverse Events (AEs) and Serious Adverse Events (SAEs) | SAEs | 0 Participants |
| Placebo | Number of Participants With Adverse Events (AEs) and Serious Adverse Events (SAEs) | AEs | 3 Participants |
| Placebo | Number of Participants With Adverse Events (AEs) and Serious Adverse Events (SAEs) | SAEs | 1 Participants |