Phase 3 Efficacy and Safety Study of BG00012 in Pediatric Subjects With Relapsing-remitting Multiple Sclerosis (RRMS)
Information source: Biogen
ClinicalTrials.gov processed this data on August 23, 2015 Link to the current ClinicalTrials.gov record.
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
Summary
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
Clinical Details
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 scansProportion 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
Eligibility
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
Locations and Contacts
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
Additional Information
Starting date: August 2014
Last updated: July 10, 2015
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