Multiple Sclerosis, Relapsing-Remitting
Conditions
Keywords
Pediatrics
Brief summary
The primary objective of this study is to evaluate the effect of BG00012 (dimethyl fumarate) on brain magnetic resonance imaging (MRI) lesions in pediatric participants with relapsing-remitting multiple sclerosis (RRMS). The secondary objectives of this study are to characterize the pharmacokinetics of BG00012 in pediatric participants with RRMS and to evaluate the safety and tolerability of BG00012 in pediatric participants with RRMS.
Interventions
DRUGdimethyl fumarate
Sponsors
Biogen
Study design
Allocation
NA
Intervention model
SINGLE_GROUP
Primary purpose
TREATMENT
Masking
NONE
Eligibility
Sex/Gender
ALL
Age
10 Years to 17 Years
Healthy volunteers
No
Inclusion criteria
Key Inclusion Criteria: * Ability of parents or legal guardians to understand the purpose and risks of the study and provide signed and dated informed consent and authorization to use protected health information in accordance with national and local subject privacy regulations. Subjects will provide assent in addition to the parent or legal guardian, as appropriate, as per local regulations. * Must have a body weight of ≥30 kg at Screening and Day 1. * Must have a diagnosis of RRMS according to McDonald criteria for MS (2010) \[Polman 2011\] and International Pediatric Multiple Sclerosis (MS) Study Group criteria for pediatric MS (2013) \[Krupp 2013\]. Key
Exclusion criteria
* Primary progressive, secondary progressive, or progressive relapsing MS (as defined by \[Lublin and Reingold 1996\]). These conditions require the presence of continuous clinical disease worsening over a period of at least 3 months. Subjects with these conditions may also have superimposed relapses but are distinguished from relapsing-remitting subjects by the lack of clinically stable periods or clinical improvement. * Disorders mimicking MS, such as other demyelinating disorders (e.g., acute disseminated encephalomyelitis), systemic autoimmune disorders (e.g., Sjögren disease, lupus erythematosus, and neuromyelitis optica), metabolic disorders (e.g., dystrophies), and infectious disorders. * History of severe allergic or anaphylactic reactions or known drug hypersensitivity to dimethyl fumarate or fumaric acid esters. NOTE: Other protocol-defined inclusion/
Design outcomes
Primary
| Measure | Time frame |
|---|---|
| Change in the Number of New or Newly Enlarging T2 Hyperintense Lesions on Brain Magnetic Resonance Imaging (MRI) Scans From the Baseline Period to On-Treatment Assessment Period | Baseline Period (Week -8 to Day 0), On-Treatment Assessment Period (Week 16 to Week 24) |
Secondary
| Measure | Time frame | Description |
|---|---|---|
| Time to Reach Maximum Observed Plasma Concentration (Tmax) | Day 8 | — |
| Apparent Clearance (CL/F) | Day 8 | — |
| Apparent Volume of Distribution (V/F) | Day 8 | — |
| Maximum Observed Plasma Concentration (Cmax) | Day 8 | — |
| Area Under the Concentration-Time Curve From Time 0 to Infinity (AUC0-inf) | Day 8 | — |
| Number of Participants Who Experienced Treatment-Emergent Adverse Events (AEs) and Serious Adverse Events (SAEs) | Up to Week 28 | AE: any untoward medical occurrence that does not necessarily have a causal relationship with treatment. SAE: any untoward medical occurrence that at any dose: results in death; in the view of the Investigator, places the participant at immediate risk of death (a life-threatening event); requires inpatient hospitalization or prolongation of existing hospitalization; results in persistent or significant disability/incapacity; results in a congenital anomaly/birth defect; any other medically important event that, in the opinion of the Investigator, may jeopardize the participant or may require intervention to prevent one of the other outcomes listed in the definition above. |
| Half-Life Lambda z | Day 8 | — |
Countries
Belgium, Bulgaria, Czechia, Germany, Kuwait, Latvia, Lebanon, Poland, Turkey (Türkiye), United States
Participant flow
Participants by arm
| Arm | Count |
|---|---|
| BG00012 BG00012 taken orally at a dose of 120 mg BID for the first 7 days and at a dose of 240 mg BID thereafter for 24 weeks. | 22 |
| Total | 22 |
Withdrawals & dropouts
| Period | Reason | FG000 |
|---|---|---|
| Overall Study | Adverse Event | 2 |
Baseline characteristics
| Characteristic | BG00012 |
|---|---|
| Age, Continuous | 15.8 years STANDARD_DEVIATION 1.18 |
| Sex: Female, Male Female | 14 Participants |
| Sex: Female, Male Male | 8 Participants |
Adverse events
| Event type | EG000 affected / at risk |
|---|---|
| deaths Total, all-cause mortality | — / — |
| other Total, other adverse events | 19 / 22 |
| serious Total, serious adverse events | 5 / 22 |
Outcome results
Primary
Change in the Number of New or Newly Enlarging T2 Hyperintense Lesions on Brain Magnetic Resonance Imaging (MRI) Scans From the Baseline Period to On-Treatment Assessment Period
Time frame: Baseline Period (Week -8 to Day 0), On-Treatment Assessment Period (Week 16 to Week 24)
Population: Primary Analysis Population: participants having new or newly enlarging T2 lesions during the Baseline period with a post-baseline assessment.
| Arm | Measure | Value (MEAN) | Dispersion |
|---|---|---|---|
| BG00012 | Change in the Number of New or Newly Enlarging T2 Hyperintense Lesions on Brain Magnetic Resonance Imaging (MRI) Scans From the Baseline Period to On-Treatment Assessment Period | -7.9 lesions | Standard Deviation 16.23 |
p-value: 0.009Wilcoxon Signed Rank test
Secondary
Apparent Clearance (CL/F)
Time frame: Day 8
Population: All participants who received at least 1 dose of BG00012 and had at least 1 pharmacokinetic parameter available.
| Arm | Measure | Value (MEAN) | Dispersion |
|---|---|---|---|
| BG00012 | Apparent Clearance (CL/F) | 74.45 L/h | Standard Deviation 30.185 |
Secondary
Apparent Volume of Distribution (V/F)
Time frame: Day 8
Population: All participants who received at least 1 dose of BG00012 and had at least 1 pharmacokinetic parameter available.
| Arm | Measure | Value (MEAN) | Dispersion |
|---|---|---|---|
| BG00012 | Apparent Volume of Distribution (V/F) | 98.19 L | Standard Deviation 91.679 |
Secondary
Area Under the Concentration-Time Curve From Time 0 to Infinity (AUC0-inf)
Time frame: Day 8
Population: All participants who received at least 1 dose of BG00012 and had at least 1 pharmacokinetic parameter available.
| Arm | Measure | Value (MEAN) | Dispersion |
|---|---|---|---|
| BG00012 | Area Under the Concentration-Time Curve From Time 0 to Infinity (AUC0-inf) | 3630.52 h*mcg/mL | Standard Deviation 1153.768 |
Secondary
Half-Life Lambda z
Time frame: Day 8
Population: All participants who received at least 1 dose of BG00012 and had at least 1 pharmacokinetic parameter available.
| Arm | Measure | Value (MEAN) | Dispersion |
|---|---|---|---|
| BG00012 | Half-Life Lambda z | 0.84 hours | Standard Deviation 0.408 |
Secondary
Maximum Observed Plasma Concentration (Cmax)
Time frame: Day 8
Population: All participants who received at least 1 dose of BG00012 and had at least 1 pharmacokinetic parameter available.
| Arm | Measure | Value (MEAN) | Dispersion |
|---|---|---|---|
| BG00012 | Maximum Observed Plasma Concentration (Cmax) | 1998.62 ng/mL | Standard Deviation 1286.467 |
Secondary
Number of Participants Who Experienced Treatment-Emergent Adverse Events (AEs) and Serious Adverse Events (SAEs)
AE: any untoward medical occurrence that does not necessarily have a causal relationship with treatment. SAE: any untoward medical occurrence that at any dose: results in death; in the view of the Investigator, places the participant at immediate risk of death (a life-threatening event); requires inpatient hospitalization or prolongation of existing hospitalization; results in persistent or significant disability/incapacity; results in a congenital anomaly/birth defect; any other medically important event that, in the opinion of the Investigator, may jeopardize the participant or may require intervention to prevent one of the other outcomes listed in the definition above.
Time frame: Up to Week 28
Population: All participants who received at least 1 dose of BG00012.
| Arm | Measure | Group | Value (NUMBER) |
|---|---|---|---|
| BG00012 | Number of Participants Who Experienced Treatment-Emergent Adverse Events (AEs) and Serious Adverse Events (SAEs) | Moderate or severe event | 7 participants |
| BG00012 | Number of Participants Who Experienced Treatment-Emergent Adverse Events (AEs) and Serious Adverse Events (SAEs) | Any event | 20 participants |
| BG00012 | Number of Participants Who Experienced Treatment-Emergent Adverse Events (AEs) and Serious Adverse Events (SAEs) | Severe event | 1 participants |
| BG00012 | Number of Participants Who Experienced Treatment-Emergent Adverse Events (AEs) and Serious Adverse Events (SAEs) | Event related to BG00012 | 16 participants |
| BG00012 | Number of Participants Who Experienced Treatment-Emergent Adverse Events (AEs) and Serious Adverse Events (SAEs) | Serious event | 5 participants |
| BG00012 | Number of Participants Who Experienced Treatment-Emergent Adverse Events (AEs) and Serious Adverse Events (SAEs) | Serious event related to BG00012 | 0 participants |
| BG00012 | Number of Participants Who Experienced Treatment-Emergent Adverse Events (AEs) and Serious Adverse Events (SAEs) | Discontinued treatment due to an event | 2 participants |
| BG00012 | Number of Participants Who Experienced Treatment-Emergent Adverse Events (AEs) and Serious Adverse Events (SAEs) | Withdrew from study due to an event | 2 participants |
Secondary
Time to Reach Maximum Observed Plasma Concentration (Tmax)
Time frame: Day 8
Population: All participants who received at least 1 dose of BG00012 and had at least 1 pharmacokinetic parameter available.
| Arm | Measure | Value (MEAN) | Dispersion |
|---|---|---|---|
| BG00012 | Time to Reach Maximum Observed Plasma Concentration (Tmax) | 4.20 hours | Standard Deviation 1.543 |