Relapsing-Remitting Multiple Sclerosis MedDRA version: 20.0 Level: SOC Classification code 10029205 Term: Nervous system disorders System Organ Class: 10029205 - Nervous system disorders MedDRA version: 21.1 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: Key inclusion criteria: 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 (from 14 to less than 18 years old in Poland) at the time of informed consent or assent. 3. Must have a body weight of =30 kg (=40 kg in Poland). 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 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. 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. Part 2; - Subjects who have completed week 96 in Part 1 NOTE: Other protocol defined inclusion criteria may apply Are the trial subjects under 18? yes Number of subjects for this age range: 132 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: Key exclusion criteria: 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 to DMF,fumaric acid esters or interferon ß-1a (IFN ß- 1a) 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 ? absolute lymphocyte count 0.2 mg. Note: Documented benign proteinuria is not exclusionary. ? 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 ? cl
Design outcomes
Primary
| Measure | Time frame |
|---|---|
| Main Objective: The main objectives of Part 1 are as follows: • To evaluate the safety, tolerability, and efficacy on the disease course of BG00012 (dimethyl fumarate) in subjects with RRMS, as compared with a disease modifying treatment.. • To assess health outcomes and evolution of disability The primary objective of Part 2 is to evaluate the long-term safety of BG00012 in subjects who completed week 96 in Part 1 of Study 109MS306.;Secondary Objective: Not Applicable;Primary end point(s): The primary endpoint of Part 1 is the proportion of subjects free of new or newly enlarging T2 hyperintense lesions on brain MRI scans at Week 96. The primary endpoint of the Part 2 is the incidence of adverse events, serious adverse events and discontinuations of BG00012 due to an adverse event;Timepoint(s) of evaluation of this end point: Part 1 - Day 1 (baseline visit), weeks 24, 48, 72, 96 Part 2 - up to week 244 | — |
Secondary
| Measure | Time frame |
|---|---|
| Secondary end point(s): English The secondary endpoints of Part 1 are as follows: • Number of new/newly enlarging T2 hyperintense lesions on brain MRI scans at Weeks 24 and 96 • Proportion of participants free of new/newly enlarging T2 hyperintense lesions on brain MRI scans at Weeks 24 and 48 • Proportion of participants free of new MRI activity as measured by brain MRI scans (new MRI activity includes: Gd enhancing MRI lesion on brain MRI scans; new T2 MRI lesions on brain MRI scans and newly enlarging LRI lesions on brain MRI scans) at Weeks 24, 48, and 96 • Time to first relapse up to week 96 • Proportion of participants who do not experience relapse up to Week 96 • Annualized relapse rate at Weeks 48 and 96 • Number of participants that experience adverse events (AEs) and serious adverse events (SAEs), including prospective and follow up of flushing, nausea, abdominal pain, and diarrhea up to week 96 • Participants receiving BG00012 who consent to participate in the PD/PK subset - 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) up to week 4 • Participants receiving BG00012 who consent to participate in the PD/PK subset - PD parameters, derived from PD subset data analysis: changes in the nuclear factor (erythroid derived 2) like 2 activation pathway markers quinone 1 (NQO 1) and heme oxygenase 1 (HO 1)up to week 4 • Fatigue as measured by the Pediatric Quality of Life Inventory (PedsQL) Multidimensional Fatigue Scale scores (Multidimensional Fatigue Scale scores designed as a generic symptomspecific instrument to measure fatigue in patients with acute and chronic health conditions as well as healthy school and community populations.) up to wee | — |
Countries
Belgium, Bulgaria, Canada, Czechia, Czech Republic, Denmark, France, Germany, Hungary, Israel, Italy, Kuwait, Poland, Serbia, Spain, Sweden, Turkey, United Kingdom, United States
Contacts
Public ContactMedical Director
Biogen Idec Research Limited
Outcome results
None listed