Phase 3 Efficacy and Safety Study of BG00012 in Pediatric Subjects With Relapsing-remitting Multiple Sclerosis (RRMS)

Condition(s) targeted: Relapsing-Remitting Multiple Sclerosis

Intervention: dimethyl fumarate (Drug); Interferon β-1a (Drug)

Phase: Phase 3

Status: Recruiting

Sponsored by: Biogen

Official(s) and/or principal investigator(s):
Medical Director, Study Director, Affiliation: Biogen

Overall contact:
Biogen, Email: clinicaltrials@biogen.com

The main objectives of the study are as follows: To evaluate the safety, tolerability, and effect on the disease course of BG00012 (dimethyl fumarate) in pediatric participants with RRMS, as compared with a disease-modifying treatment; To assess pharmacokinetic (PK) and pharmacodynamic (PD) parameters in a representative subset of pediatric participants; and To assess health outcomes and evolution of disability

Official title: Open-Label, Randomized, Multicenter, Multiple-Dose, Active-Controlled, Parallel-Group, Efficacy and Safety Study of BG00012 in Children From 10 to Less Than 18 Years of Age With Relapsing-Remitting Multiple Sclerosis

Study design: Allocation: Randomized, Endpoint Classification: Safety/Efficacy Study, Intervention Model: Parallel Assignment, Masking: Open Label, Primary Purpose: Treatment

Primary outcome: Proportion of participants free of new/newly enlarging T2 hyperintense lesions on brain MRI scans

Secondary outcome:

The number of new/newly enlarging T2 hyperintense lesions on brain MRI scans

Proportion of participants free of new/newly enlarging T2 hyperintense lesions on brain MRI scans

Proportion of participants free of new MRI activity as measured by brain MRI scans

Time to first relapse

Proportion of participants who do not experience relapse

Annualized relapse rate

Number of participants that experience Adverse Events (AEs) and serious adverse events (SAEs)

Area under the concentration-time curve from time 0 to 10 hours (AUC0-10) of BG00012

Maximum observed plasma concentration (Cmax) of BG00012

Time to reach maximum observed plasma concentration (Tmax) of BG00012

Lag time of BG00012

Elimination half-life (t½) of BG00012

Apparent clearance (Cl/F) of BG00012

Apparent volume of distribution (V/F) of BG00012

Changes in the nuclear factor (erythroid derived 2) like 2 activation pathway markers nicotinamide adenine dinucleotide phosphate [NAD(P)H] dehydrogenase

Changes in the nuclear factor (erythroid derived 2) like 2 activation pathway markers Quinone 1 (NQO-1)

Changes in the nuclear factor (erythroid derived 2) like 2 activation pathway markers Heme oxygenase 1 (HO-1)

Fatigue as measured by the Pediatric Quality of Life Inventory (PedsQL) Multidimensional Fatigue Scale scores

Quality of Life as measured by the PedsQL

Change from baseline to Week 96 in the Expanded Disability Status Scale (EDSS) score

Vital signs, electrocardiograms (ECGs) and changes in clinical laboratory data, including monitoring of liver function, renal function, hematologic, and coagulation parameters

Minimum age: 10 Years. Maximum age: 17 Years. Gender(s): Both.

Criteria:

Key Inclusion Criteria:

- Must have a body weight of ≥30 kg.

- Must have a diagnosis of RRMS (consensus definition for pediatric RRMS [Krupp 2007]).

- Must be ambulatory with a baseline EDSS score between 0 and 5. 5, inclusive.

- Must have experienced at least 1 relapse within the last 12 months prior to Day 1 or

at least 2 relapses within the last 24 months prior to Day 1, with a prior brain MRI demonstrating lesions consistent with MS, or evidence of Gd-enhancing lesions of the brain on an MRI performed within the 6 weeks prior to Day 1.

- Must be neurologically stable, with no evidence of relapse within 50 days prior to

Day 1 and no evidence of corticosteroid treatment within 30 days prior to Day 1.

- Subjects of childbearing potential who are sexually active must be willing to

practice effective contraception during the study and be willing and able to continue contraception for at least 30 days after their final dose of study treatment. 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), metabolic disorders (e. g., dystrophies), and infectious disorders.

- History of premalignant or malignant disease. Subjects with basal cell carcinoma that

has been completely excised prior to screening will remain eligible.

- History of severe allergic or anaphylactic reactions, or known drug hypersensitivity

to DMF or fumaric acid esters.

- History of abnormal laboratory results indicative of any significant endocrinologic,

hematologic, hepatic, immunologic, metabolic, urologic, renal, and/or any other major disease that would preclude participation in a clinical study.

- History of clinically significant cardiovascular, pulmonary, GI, dermatologic,

growth, developmental, psychiatric (including depression), neurologic (other than MS), and/or other major disease that would preclude participation in a clinical study.

- .History of human immunodeficiency virus.

- An MS relapse that has occurred within 50 days prior to Day 1 AND/OR the subject has

not stabilized from a previous relapse prior to Day 1.

- Other unspecified reasons that, in the opinion of the Investigator or Biogen Idec,

make the subject unsuitable for enrollment.

- For the PD/PK subset of subjects: subjects unable to swallow the BG00012 capsule

whole. Key Treatment history

- Any previous treatment with Fumaderm (fumaric acid esters) or BG00012.

- Prior treatment with any of the following: total lymphoid irradiation, cladribine,

T-cell or T-cell receptor vaccination, any therapeutic monoclonal antibody, with the exception of rituximab or natalizumab.

- Prior treatment with any of the following medications within the 12 months prior to

Day 1: mitoxantrone, cyclophosphamide, rituximab.

- Prior treatment with any of the following medications or procedures within 6 months

prior to Day 1: fingolimod; teriflunomide; natalizumab; cyclosporine; azathioprine; methotrexate; mycophenolate mofetil; laquinimod; intravenous (IV) immunoglobulin; plasmapheresis or cytapheresis

- Prior treatment with any of the following within 3 months prior to Day 1: glatiramer

acetate; interferon-alpha; interferon-β (subjects who are positive for neutralizing antibodies to interferon-β may receive interferon-β treatment up to 2 weeks prior to Day 1)

- Treatment with any of the following medications within 30 days prior to Day 1:

steroids (IV or oral corticosteroid treatment, including agents that may not act through the corticosteroid pathway [e. g.low dose naltrexone]), 4-aminopyridine or related products (except subjects on a stable dose of controlled-release fampridine for 3 months) NOTE: Other protocol-defined inclusion/exclusion criteria may apply

Biogen, Email: clinicaltrials@biogen.com

Research Site, Brussels 1020, Belgium; Recruiting

Research Site, Gent 9000, Belgium; Recruiting

Research Site, La Louvière 7100, Belgium; Recruiting

Research Site, Brno 60 200, Czech Republic; Recruiting

Research Site, Hradec Kralove 500 05, Czech Republic; Recruiting

Research Site, Jihlava 58633, Czech Republic; Recruiting

Research Site, Ostrava - Poruba 708 52, Czech Republic; Not yet recruiting

Research Site, København Ø 2100, Denmark; Recruiting

Research Site, Odense 5000, Denmark; Recruiting

Research Site, Århus C 8000, Denmark; Recruiting

Research Site, Lille Cedex 59037, France; Not yet recruiting

Research Site, Budapest 1083, Hungary; Recruiting

Research Site, Budapest 1086, Hungary; Recruiting

Research Site, Como 22100, Italy; Recruiting

Research Site, Genova 16132, Italy; Recruiting

Research Site, Milano 20132, Italy; Recruiting

Research Site, Roma 00133, Italy; Not yet recruiting

Research Site, Bialystok 15-274, Poland; Not yet recruiting

Research Site, Gdansk 80-952, Poland; Not yet recruiting

Research Site, Poznan 60-355, Poland; Not yet recruiting

Research Site, Belgrade 11000, Serbia; Recruiting

Research Site, Belgrade 11070, Serbia; Recruiting

Research Site, Göteborg 41345, Sweden; Recruiting

Research Site, Stockholm 17176, Sweden; Recruiting

Research Site, Strasbourg, Bas Rhin 67098, France; Recruiting

Research Site, Dijon Cedex, Cote dÝOr 21033, France; Recruiting

Research Site, London, Greater London SE1 7EH, United Kingdom; Recruiting

Research Site, London, Greater London WC1N 3JH, United Kingdom; Recruiting

Research Site, Rennes cedex 09, Ille et Vilaine 35033, France; Recruiting

Research Site, Bron Cedex, Rhone 69677, France; Recruiting

Research Site, Amiens Cedex 1, Somme 80054, France; Recruiting

Research Site, Gallarate, Varese 21013, Italy; Recruiting

Research Site, Birmingham, West Midlands B4 6NH, United Kingdom; Recruiting

Starting date: August 2014
Last updated: July 10, 2015