MS is a chronic disease of the CNS. It's a disease of young adults, primarily women, with disease onset typically occuring between the ages of 20 and 40. Although etiology is uncertain, evidence points to MS being an autoimmune disease directed against protein components of myelin. The majority of patients with MS start out with a clinical course characterised by episodes or attacks (relapses) of neurologic dysfunction, which occurs over many years.
Conditions
Interventions
Product Name: second-generation fumaric acid
Product Code: BG00012
Pharmaceutical Form: Capsule, hard
INN or Proposed INN: dimethyl fumarate
CAS Number: 62008-21
Current Sponsor code: dimethyl fumarat
Sponsors
Biogen Idec Inc.
Biogen Idec Ltd
Eligibility
Sex/Gender
All
Inclusion criteria
Inclusion criteria: 1.Must give written informed consent and authorize the release and use of protected health information (PHI), as required by local law. 2.Must be 18 to 55 years old, inclusive, at the time of informed consent. 3.Must have a confirmed diagnosis of relapsing-remitting MS according to McDonald criteria #1-4 (McDonald et al, 2001; Appendix 2). 4.Must have a baseline EDSS between 0.0 and 5.0, inclusive. 5.Must meet one of the following criteria: - Must have experienced at least one relapse within the 12 months prior to randomization, with a prior cranial MRI demonstrating lesion(s) consistent with MS (it is not necessary to obtain a current scan if a scan performed previously is available from the subject’s history; if a scan is not available from the subject’s history, then the baseline scan may be used). For inclusion purposes, a relapse is defined as neurologic signs and/or symptoms documented by a neurologist in the medical record and of at least 24-hours duration to be determined by the investigator or the treating neurologist. Time since relapse should be measured from the time of relapse onset, OR. - show evidence of Gd-enhancing lesions of the brain on an MRI performed within the 6 weeks prior to randomization (if a scan is not available from the subject's history, then the baseline scan may be used). 6.Male and female subjects must be willing to take appropriate measures to prevent pregnancy while participating in this study. Male subjects and female subjects of child-bearing potential must use adequate contraception as appropriate (either intra-uterine device, oral or depot contraceptive, or barrier plus spermicide) and be willing and able to continue contraception for 30 days after their last dose of investigational drug. The rhythm method is not to be used as the sole method of contraception. Females who have not been stable on oral or depot contraceptives for 3 months prior to the first dose of investigational drug must also agree to use a barrier method throughout the study. Female subjects are exempt from contraceptive use if they are post-menopausal for at least 1 year prior to the start of the study or are surgically sterile (females need to have either no uterus or no ovaries to be considered surgically sterile; males or females who have tubes tied or cut are not considered surgically sterile). All female subjects who are not post-menopausal or surgically sterile must have a negative pregnancy test at screening and at various time points throughout the study to receive investigational drug. Are the trial subjects under 18? no Number of subjects for this age range: F.1.2 Adults (18-64 years) yes 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: Medical History 1.Primary progressive, secondary progressive, or progressive relapsing MS (as defined by Lublin and Reingold, 1996 [Appendix 3]). These conditions require the presence of continuous clinical disease worsening over a period of at least 3 months. Patients with these conditions may also have superimposed relapses, but are distinguished from relapsing-remitting patients by the lack of clinically stable periods or clinical improvement. 2.History of malignancy unless an exception is granted by the Biogen Idec Medical Director. 3.History of severe allergic or anaphylactic reactions or known drug hypersensitivity. 4.History of abnormal laboratory results indicative of any significant cardiac, endocrinologic, hematologic, hepatic, immunologic, metabolic, urologic, pulmonary, gastrointestinal, dermatologic, psychiatric, renal, neurologic (other than MS), and/or other major disease that would preclude administration of BG00012. 5.History of human immunodeficiency virus (HIV). 6.History of drug or alcohol abuse (as defined by the Investigator) within the 2 years prior to randomization. 7.An MS relapse that has occurred within the 50 days prior to randomization AND/OR the subject has not stabilized from a previous relapse prior to randomization. 8.Body weight >100 kg. 9.Positive for hepatitis C antibody and/or positive for hepatitis B surface antigen (HBsAg) at screening. 10.Any of the following abnormal blood tests at screening: - alanine transaminate/serum glutamate-pyruvate transaminase (AST/SGPT), or aspartate transaminase/serum glutamic-oxaloacetic transaminase (AST/SGOT), or gamma-glutamyl-transferase (GGT) >2 times the upper limit of normal (ULN) - leukocytes 10% of the total leukocyte count, and - serum creatinine >ULN. Treatment History 11.Any previous treatment with FUMADERM®, FAG-201 or BG00012. 12.Prior treatment with the any of the following: - total lymphoid irradiation - cladribine - T-cell or T-cell receptor vaccination - any therapeutic monoclonal antibody, with the exception of ANTEGREN® (natalizumab) (see exclusion #14) 13.Prior treatment with any of the following within 1 year prior to randomization: - mitoxantrone - cyclophosphamide 14.Prior treatment with any of the following medications or procedures within the 6 months prior to randomization: - cyclosporine - azathioprine - methotrexate - natalizumab - intravenous immunoglobulin (IVIg) - plasmapheresis or cytapheresis. 15.Prior treatment with any of the following within the 3 months prior to randomization: - subcutaneous or oral glatiramer acetate - interferon-alpha - interferon-beta (subjects who are positive for neutralizing antibodies to interferon beta may receive interferon-beta treatment up to 2 weeks prior to randomization). 16.Treatment with any of the following medications within the 30 days prior to randomization: - IV corticosteroid treatment - oral corticosteroid treatment - 4-aminopyridine or related products. 17.Treatment with another investigational drug or approved therapy for investigational use within the 6 months prior to randomization. Miscellaneous 18.Female subjects considering becoming pregnant while in the study. 19.Female subjects who are currently pregnant or breast-feeding. 20.Previous participation in this study. 21.Current enrollment in any other investigational drug study or participation in any other investigational study within 6 months prior to randomization. 22.Unwill
Design outcomes
Primary
| Measure | Time frame |
|---|---|
| Main Objective: The primary objective of this study is to determine the efficacy of three dose levels of BG00012 on brain lesion activity as measured by MRI in subjects with relapsing-remitting MS when compared to placebo. ;Secondary Objective: Additional study objectives are to determine: - the number of T1 hypointense lesions at Week 24 compared to baseline - the safety and tolerability of BG00012 in subjects with MS - the efficacy of BG00012 in MS on disability progression as measured by EDSS, and - the efficacy of BG00012 in reducing the number of relapses based on annualized relapse rate and proportion of relapse-free subjects.;Primary end point(s): The primary endpoint is the total number of Gd-enhancing lesions over four scans at Weeks 12,16,20 and 24 (calculated as the sum of these four MRI scans). Secondary MRI endpoints include: - the cumulative number of new Gd-enhancing lesions from baseline to Week 24, and - the number of new or newly enlarging T2 hyperintense lesions at Week 24 compared to baseline. | — |
Countries
Hungary, Sweden
Outcome results
None listed