| E.1 Medical condition or disease under investigation |
| E.1.1 | Medical condition(s) being investigated |
| 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. |
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| MedDRA Classification |
| E.1.3 | Condition being studied is a rare disease | No |
| E.2 Objective of the trial |
| E.2.1 | Main objective of the trial |
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.
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| E.2.2 | Secondary objectives of the trial |
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. |
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| E.2.3 | Trial contains a sub-study | Information not present in EudraCT |
| E.3 | Principal 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.
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| E.4 | Principal 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 <3500/mm3
- eosinophils >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.Unwillingness or inability to comply with the requirements of the protocol including the presence of any condition (physical, mental, or social) that is likely to affect the subject’s ability to comply with the protocol.
23.Any other reasons that, in the opinion of the Investigator and/or the Sponsor, the subject is determined to be unsuitable for enrollment in this study.
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| E.5 End points |
| E.5.1 | 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.
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| E.6 and E.7 Scope of the trial |
| E.6 | Scope of the trial |
| E.6.1 | Diagnosis | No |
| E.6.2 | Prophylaxis | No |
| E.6.3 | Therapy | Yes |
| E.6.4 | Safety | Yes |
| E.6.5 | Efficacy | Yes |
| E.6.6 | Pharmacokinetic | No |
| E.6.7 | Pharmacodynamic | No |
| E.6.8 | Bioequivalence | No |
| E.6.9 | Dose response | Yes |
| E.6.10 | Pharmacogenetic | Information not present in EudraCT |
| E.6.11 | Pharmacogenomic | No |
| E.6.12 | Pharmacoeconomic | No |
| E.6.13 | Others | No |
| E.7 | Trial type and phase |
| E.7.1 | Human pharmacology (Phase I) | No |
| E.7.1.1 | First administration to humans | No |
| E.7.1.2 | Bioequivalence study | No |
| E.7.1.3 | Other | Information not present in EudraCT |
| E.7.1.3.1 | Other trial type description | |
| E.7.2 | Therapeutic exploratory (Phase II) | Yes |
| E.7.3 | Therapeutic confirmatory (Phase III) | No |
| E.7.4 | Therapeutic use (Phase IV) | No |
| E.8 Design of the trial |
| E.8.1 | Controlled | Yes |
| E.8.1.1 | Randomised | Yes |
| E.8.1.2 | Open | No |
| E.8.1.3 | Single blind | No |
| E.8.1.4 | Double blind | Yes |
| E.8.1.5 | Parallel group | Yes |
| E.8.1.6 | Cross over | No |
| E.8.1.7 | Other | Yes |
| E.8.1.7.1 | Other trial design description |
| extension phase is "open" |
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| E.8.2 | Comparator of controlled trial |
| E.8.2.1 | Other medicinal product(s) | No |
| E.8.2.2 | Placebo | Yes |
| E.8.2.3 | Other | No |
| E.8.3 |
The trial involves single site in the Member State concerned
| No |
| E.8.4 | The trial involves multiple sites in the Member State concerned | Yes |
| E.8.5 | The trial involves multiple Member States | Yes |
| E.8.6 Trial involving sites outside the EEA |
| E.8.6.1 | Trial being conducted both within and outside the EEA | Yes |
| E.8.6.2 | Trial being conducted completely outside of the EEA | Information not present in EudraCT |
| E.8.6.3 | If E.8.6.1 or E.8.6.2 are Yes, specify the regions in which trial sites are planned |
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| E.8.7 | Trial has a data monitoring committee | Information not present in EudraCT |
| E.8.8 |
Definition of the end of the trial and justification where it is not the last
visit of the last subject undergoing the trial
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| E.8.9 Initial estimate of the duration of the trial |
| E.8.9.1 | In the Member State concerned years | |
| E.8.9.1 | In the Member State concerned months | 18 |
| E.8.9.1 | In the Member State concerned days | |
| E.8.9.2 | In all countries concerned by the trial months | 18 |
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