Relapsing-Remitting Multiple Sclerosis

The primary objective of the study is to evaluate the efficacy of BG00012 and BIIB017, both compared with placebo, in pediatric subjects with RRMS.

Tecfidera/Plegridy

Dimethyl fumarate
Peginterferon beta-1a

Hard Capsule
pre-filled syringe
pre-filled pen

120
63 mcg & 94 mcg in 0.5 mL
125 mcg in 0.5 mL

The primary endpoint that relates to this objective is the TTFR
The secondary objectives and endpoints are as follows:
 To evaluate the safety and tolerability of BG00012 and BIIB017
 Occurrence of adverse events (AEs) and serious adverse events (SAEs)
 To assess the effect of BG00012 and BIIB017, both compared with placebo, on
additional clinical and radiological measures of disease activity
 Number of new or newly enlarging T2 hyperintense lesions on brain MRI scans at
Weeks 48 and 96
 Number of Gd-enhancing lesions at Baseline and at Weeks 48 and 96
 Annualized relapse rate at Weeks 48 and 96

1. Ability of a legally authorized representative (LAR; parent or legal guardian) to
understand the purpose and risks of the study and provide signed and dated informed
consent and authorization to use confidential health information in accordance with
national and local subject privacy regulations. Subjects will provide assent in addition to
the LAR’s consent, as appropriate, per local regulations.
2. Aged 10 to 17 years old, inclusive, at the time of informed consent. The minimum age
can be older than 10 years as required by country-specific regulations and/or local ethics
committees.
3. Must have a diagnosis of RRMS as defined by the revised consensus definition for
pediatric MS [Krupp 2013; Polman 2011].
4. Must have an EDSS score between 0.0 and 5.0.
5. Must have a body weight of ≥30 kg; the minimum weight for inclusion in the study may
be greater than 30 kg if required by country-specific regulations and/or local ethics
committees.
6. Must have experienced ≥1 relapse in the 12 months prior to randomization (Day 1), or
must have evidence of asymptomatic disease activity (Gd-positive lesions) seen on MRI
in the 6 months prior to randomization (Day 1), or must have ≥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 (initial) or subsequent
(recurrent) demyelinating event.
7. Sexually active subjects of childbearing potential must practice effective contraception
during the study and be willing and able to continue contraception for 3 months after
their last dose of study treatment. For further details of contraceptive requirements for
this study, please refer to Section 15.5.

Medical history
1. Primary progressive, secondary progressive, or progressive RMS (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 subjects by the lack
of clinically stable periods or clinical improvement.
2. Disorders mimicking MS, such as other demyelinating disorders (e.g., acute disseminated
encephalomyelitis), systemic autoimmune disorders (e.g., Sjögren’s disease and lupus
erythematosus), metabolic disorders (e.g., dystrophies), and infectious disorders.
3. History of severe allergic or anaphylactic reactions or known drug hypersensitivity.
4. Known allergy to any component of DMF, fumaric acid esters, or BIIB017 formulation.
5. 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.
6. History of malignant disease, including solid tumors and hematologic malignancies, with
the exception of basal cell and squamous cell carcinomas of the skin that have been
completely excised and are considered cured.
7. History of seizure disorder or unexplained blackouts or history of a seizure within 3
months prior to randomization (Day 1).
8. History of suicidal ideation within 3 months prior to randomization (Day 1) or an episode
of severe depression within 3 months prior to randomization (Day 1). Severe depression
is defined as an episode of depression that requires hospitalization or is otherwise
regarded as severe by the Investigator.
9. Clinically significant abnormal ECG values as determined by the Investigator.
10. History of human immunodeficiency virus (HIV) infection. Note: HIV testing will be
performed at Screening, only if required by local regulations.
11. Known history or positive test result for hepatitis C antibody, or current hepatitis B
infection (defined as positive for hepatitis B surface antigen [HBsAg] and/or positive for
hepatitis B core antibody [HBcAb]) at Screening. Subjects with immunity to hepatitis B
from either active vaccination (defined as negative HBsAg, positive hepatitis B surface
antibody [HBsAb], and negative HBcAb) or from previous natural infection (defined as
negative HBsAg, positive HBsAb immunoglobulin G, and positive HBcAb) are eligible
to participate in the study (definitions are based on the Centers for Disease Control and
Prevention [CDC] interpretation of the hepatitis B serology panel [CDC 2007]).
12. Abnormal screening blood tests exceeding any of the following limits defined below:
 alanine transaminase (ALT)/serum glutamate pyruvate transaminase (SGPT) >2 
upper limit of normal (ULN), aspartate transaminase (AST)/serum glutamic
oxaloacetic transaminase (SGOT) >2  ULN, gamma glutamyl transferase >2  ULN,
or bilirubin >1.5  ULN
 total WBC count <3700/mm3
 absolute neutrophil count (ANC) of 1500/mm3
 platelet count <150,000/mm3
 absolute lymphocyte count ≤ LLN
 eosinophils >0.7 103
/µL or >0.7 GI/L
 hemoglobin <10 g/dL in female subjects or <11 g/dL in male subjects
 serum creatinine >ULN
 prothrombin time or activated partial thromboplastin time >1.2  ULN
13. Proteinuria (1+ or greater) at Screening confirmed by a second urinalysis approximately 2
weeks later or by a spot protein/creatinine ratio (with morning void) >0.2 mg/mg. Note:
Documented benign proteinuria is not exclusionary.
OR
Either of the following additional abnormal urine tests at Screening confirmed by a second
urinalysis approximately 2 weeks later:
 hematuria, without known etiology
 glycosuria, without known etiology
14. 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.
Treatment history
15. Any previous treatment with Fumaderm®
, BG00012, or BIIB017.
16. History of hypersensitivity or intolerance to acetaminophen (paracetamol), ibuprofen, or
naproxen that would preclude use of at least 1 of these during the study.
17. Treatment with other agents to treat MS symptoms or underlying disease as specified
below:
 Prior treatment with any of the following:
 total lymphoid radiation
 cladribine
 T-cell or T-cell receptor vaccine
 any therapeutic monoclonal antibody (e.g., rituximab, natalizumab, or
alemtuzumab)
 Prior treatment with any of the following within 12 months prior to randomization
(Day 1):
 cyclophosphamide
 mitoxantrone
 Prior treatment with any of the following within 6 months prior to randomization
(Day 1):
 cyclosporine
 fingolimod
 plasma exchange or cytapheresis
 IV immunoglobin
 azathioprine
 mycophenolate mofetil
 methotrexate
 teriflunomide
 laquinimod
 Prior treatment with systemic corticosteroids, including agents that may act through
the corticosteroid pathway (e.g., low-dose naltrexone) within 30 days prior to
randomization (Day 1).
 Prior treatment with GA, IFN, or 4-aminopyridine or related products (except
subjects on a stable dose of controlled-release fampridine for at least 3 months)
within 4 weeks prior to randomization (Day 1).
 Prior treatment that might influence growth, including but not limited to
methylphenidate hydrochloride, thyroid hormone, growth hormone, anabolic steroids,
calcitonin, estrogens, progestins (with the exception of medication used for
contraception), bisphosphonates, anticonvulsants, or phosphate-binding antacids.
18. Treatment with another investigational drug or approved therapy for investigational use
within the 6 months prior to randomization (Day 1).
Miscellaneous
19. Female subjects who are pregnant, breastfeeding, or considering becoming pregnant
while in the study.
20. History of drug or alcohol abuse (as determined by the Investigator) within 2 years prior
to randomization (Day 1).
21. Subjects for whom MRI is contraindicated (e.g., who have pacemakers, other
contraindicated implanted metal devices, or embedded metals such as dental braces,
tattoos, body piercings, etc.), or who are allergic to Gd, or have claustrophobia that
cannot be medically managed.
22. Current enrollment in any other investigational drug study.
23. Previous randomization in this study.
24. Elective surgery performed within 2 weeks prior to randomization (Day 1).
25. Unwillingness or inability to comply with the study requirements.
26. Other unspecified reasons that, in the opinion of the Investigator or Biogen, make the
subject unsuitable for enrollment.