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The DEFINE Study

A Randomized, Multicenter, Double-Blind, Placebo-Controlled, Dose-Comparison Study to Determine the Efficacy and Safety of BG00012 in Subjects with Relapsing-Remitting Multiple Sclerosis.  109MS301

Protocol Version 4.0, dated 22 May 2007


Length of study:  2 years


Inclusion Criteria

Unless otherwise specified, to be eligible to participate in this study, candidates must meet the following eligibility criteria at the time of the randomization:

1. Must give written informed consent and any authorizations required by local law (e.g.,Protected Health Information [PHI]).

2. Aged 18 to 55 years old, inclusive, at the time of informed consent.

3. Must have a confirmed diagnosis of RRMS according to McDonald criteria #1-4

4. Must have a baseline EDSS between 0.0 and 5.0, inclusive.

5. Must have experienced at least 1 relapse within the 12 months prior to randomization, with a prior brain MRI demonstrating lesion(s) consistent with MS, or show evidence of Gd-enhancing lesion(s) of the brain on an MRI performed within the six weeks prior to randomization.

6. Male subjects and female subjects of child-bearing potential (including female subjects who are not post-menopausal for at least 1 year) must be willing to practice effective contraception (as defined by the Investigator) during the study and be willing and able to continue contraception for 30 days after their last dose of study treatment.


Exclusion Criteria

Unless otherwise specified, candidates will be excluded from study entry if any of the following exclusion criteria exist at randomization:

Medical History

1. Primary progressive, secondary progressive or progressive relapsing MS. 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. Unable to perform the Timed 25-Foot Walk, Nine-Hole Peg Test (9HPT) with both upper extremities, and PASAT 3.

3. Unable to perform visual function tests.

4. History of malignancy, unless an exception is granted by the Biogen Idec Medical Director. (Subjects with basal cell carcinoma that has been completely excised prior to study entry remain eligible.)

5. History of severe allergic or anaphylactic reactions or known drug hypersensitivity.

6. History of abnormal laboratory results indicative of any significant endocrinologic, hematologic, hepatic, immunologic, metabolic, urologic, renal, and/or other major disease that would preclude participation in a clinical trial.

7. History of clinically significant cardiovascular, pulmonary, gastrointestinal, dermatologic, psychiatric, neurologic (other than MS), and/or other major disease that would preclude participation in a clinical trial.

8. History of human immunodeficiency virus (HIV).

9. History of drug or alcohol abuse (as defined by the Investigator) within the 2 years prior to randomization.

10. 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.

11. Positive for hepatitis C antibody and/or positive for hepatitis B surface antigen (HBsAg) at screening.

12. Any of the following abnormal blood tests at screening:

• Alanine transaminase/serum glutamate-pyruvate transaminase (ALT/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 >0.7 × 10³/μL or >0.7 GI/L.

13. Any of the following abnormal urine tests at screening confirmed by a second urinalysis 2 weeks later:

• Proteinuria (1+ or greater)

• Hematuria, without known etiology (e.g., urinary tract infection, menses)

• Glycosuria, without known etiology (e.g., recent steroid use, elevated serum glucose).

Treatment History

14. Any previous treatment with FUMADERM® or BG00012 (FAG-201).

15. 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 TYSABRI® (natalizumab)

16. Prior treatment with any of the following within 1 year prior to randomization:

• Mitoxantrone

• Cyclophosphamide.

17. Prior treatment with any of the following medications or procedures within the 6 months prior to randomization:

• Cyclosporine

• Azathioprine

• Methotrexate

• Natalizumab (TYSABRI®)

• Intravenous immunoglobulin

• Plasmapheresis or cytapheresis.

18. Prior treatment with any of the following within the 3 months prior to randomization:

• Subcutaneous or oral glatiramer acetate

• Interferon-alpha

• Interferon-beta.

19. Treatment with any of the following medications within the 50 days prior to randomization:

• Intravenous (IV) corticosteroid treatment

• Oral corticosteroid treatment

• 4-aminopyridine or related products.

20. Treatment with another investigational drug or approved therapy for investigational use within the 6 months prior to randomization.


21. Female subjects considering becoming pregnant while in the study.

22. Female subjects who are currently pregnant or breast-feeding.

23. Current enrollment in any other investigational drug study or participation in any other investigational study within 6 months prior to randomization.

24. 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.

25. 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.