Relapsing-Remitting Multiple Sclerosis MedDRA version: 16.1 Level: SOC Classification code 10029205 Term: Nervous system disorders System Organ Class: 10029205 - Nervous system disorders MedDRA version: 16.1 Level: PT Classification code 10063399 Term: Relapsing-remitting multiple sclerosis System Organ Class: 10029205 - Nervous system disorders
Conditions
Sponsors
Biogen Idec Research Limited
Eligibility
Sex/Gender
All
Inclusion criteria
Inclusion criteria: To be eligible to participate in this study, candidates must meet the following eligibility criteria at the time of randomization (Day 1) or at the timepoint specified in the individual eligibility criterion listed: 1. 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 (PHI) in accordance with national and local subject privacy regulations. Subjects will provide assent in addition to the parental or guardian consent, as appropriate, as per local regulations. 2. Males and females aged from 10 to less than 18 years old at the time of informed consent or assent. 3. Must have a body weight of =30 kg. 4. Must have a diagnosis of RRMS (consensus definition for pediatric RRMS [Krupp 2007]). 5. Must be ambulatory with a baseline EDSS score between 0 and 5.5, inclusive. 6. Must have experienced at least 1 relapse within the last 12 months prior to Day 1, with a prior brain MRI demonstrating lesions consistent with MS, or show evidence of Gd enhancing lesions of the brain on an MRI performed within the 6 weeks prior to Day 1. 7. 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. 8. 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. Are the trial subjects under 18? yes Number of subjects for this age range: 142 F.1.2 Adults (18-64 years) no F.1.2.1 Number of subjects for this age range F.1.3 Elderly (>=65 years) no F.1.3.1 Number of subjects for this age range
Exclusion criteria
Exclusion criteria: Candidates will be excluded from study entry if any of the following exclusion criteria exist at the time of randomization (Day 1) or at the timepoint specified in the individual criterion listed: Medical history 1. 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. 2. 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. 3. History of premalignant or malignant disease. Subjects with basal cell carcinoma that has been completely excised prior to screening will remain eligible. 4. History of severe allergic or anaphylactic reactions, or known drug hypersensitivity. 5. 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. 6. 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. 7. History of human immunodeficiency virus. 8. History of drug or alcohol abuse (as defined by the Investigator) within the 2 years prior to Day 1. 9. 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. 10. History or positive test result at Screening for hepatitis C virus antibody or hepatitis B virus (defined as positive for hepatitis B surface antigen [HBsAg] or hepatitis B core antibody [HBcAb]). 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 IgG, and positive HBcAb) are eligible to participate in the study (definitions are based on the Centers for Disease Control and Prevention [CDC]’s interpretation of the hepatitis B serology panel [CDC 2007]; Appendix 4, Section 25]). 11. Any of the following abnormal blood test results at Screening: - ALT, AST, or gamma glutamyl transferase (GGT) =2 × ULN - leukocytes 0.7 × 103/µL or >0.7 GI/L 12. Any of the following abnormal urine tests at Screening confirmed by a second urinalysis approximately 2 weeks later: - proteinuria (1+ or greater) - hematuria, without known etiology - glycosuria, without known etiology Note: If a subject has a positive test at Screening and the etiology is known (e.g., due to menses or urinary tract infection in the case of hematuria or due to recent steroid use or elevated serum glucose in the case of glycosuria), a repeat test is not required. Treatment history 13. Any previous treatment with Fumaderm® or BG00012. 14. Prior treatment with any of the following: - total lymphoid irradiation - cladribine - T-cell or T-cell receptor vaccinati
Design outcomes
Primary
| Measure | Time frame |
|---|---|
| Main Objective: The main objectives of the study are as follows: • To evaluate the safety, tolerability, and effect on the disease course of BG00012 in pediatric subjects with RRMS, as compared with a disease modifying treatment. • To assess PK and PD parameters in a representative subset of pediatric subjects • To assess health outcomes and evolution of disability ;Secondary Objective: Not Applicable;Primary end point(s): The primary endpoint of the study is the proportion of subjects free of new or newly enlarging T2 hyperintense lesions on brain MRI scans at Week 96.;Timepoint(s) of evaluation of this end point: Day 1 (baseline visit), weeks 24, 48, 72, 96 | — |
Secondary
| Measure | Time frame |
|---|---|
| Secondary end point(s): The secondary endpoints of this study are as follows: • Number of new or newly enlarging T2 hyperintense lesions on brain MRI scans at Weeks 24 and 96 • Proportion of subjects free of new or newly enlarging T2 hyperintense lesions on brain MRI scans at Weeks 24 and 48 • Proportion of subjects free of new MRI activity (i.e., free of Gd enhancing and free of new or newly enlarging T2 MRI lesions on brain MRI scans) at Weeks 24, 48, and 96 • Time to first relapse • Proportion of subjects free of relapse up to Week 96 • Annualized relapse rate at Weeks 48 and 96 • Incidence of AEs and serious adverse events (SAEs), including prospective follow up of flushing, nausea, abdominal pain, and diarrhea • Vital signs, electrocardiograms (ECGs), and changes in clinical laboratory data, including liver function, renal function, hematologic, and coagulation parameters • BG00012 PK parameters derived from PK subset data analysis: area under the concentration time curve from time 0 to 10 hours (AUC0 10), maximum observed plasma concentration (Cmax), time to reach maximum observed plasma concentration (Tmax), lag time, elimination half-life (t½), apparent clearance (Cl/F), and apparent volume of distribution (V/F) • PD parameters, derived from PD subset data analysis: changes in the nuclear factor (erythroid derived 2) like 2 activation pathway markers nicotinamide adenine dinucleotide phosphate [NAD(P)H] dehydrogenase, quinone 1 (NQO 1) and heme oxygenase 1 (HO 1) • Fatigue as measured by the PedsQL Multidimensional Fatigue Scale scores • Quality of Life as measured by the PedsQL • Change from baseline to Week 96 in the EDSS score ;Timepoint(s) of evaluation of this end point: The various secondary endpoints will be measured throughout the study as defined by the Schedule of Events. Specifically there are visits at Day 1 (baseline) weeks 4, 8, 12, 24, 36, 48, 60, 72, 84, 96 and a safety follow-up visit at week 100. There is also a safety | — |
Countries
Belgium, Bulgaria, Czech Republic, Denmark, France, Germany, Hungary, Italy, Poland, Serbia, Spain, Sweden, Ukraine, United Kingdom
Contacts
Public ContactClinical Trials - Neurology
Biogen Idec Research Limited
Outcome results
None listed