A Study to Evaluate Rebif® New Formulation (IFN-beta-1a) in Relapsing Remitting Multiple Sclerosis (IMPROVE)

• Number of Combined Unique (CU) Active MRI Lesions at Week 16 [ Time Frame: 16 Weeks ] [ Designated as safety issue: No ]
• Efficacy - MRI, Neurological Examination, Safety - Incidence, Severity, and Relationship to the Study Drug of Treatment Emergent Adverse Events, Serious Adverse Events, Laboratory Abnormalities, and Binding and Neutralizing Antibodies to IFN-Beta-1a [ Time Frame: Various Timepoints ] [ Designated as safety issue: No ]
  Information on the Primary MRI outcome is posted above. Safety information is included in the adverse events section but is not posted otherwise nor is information on neurological examinations, laboratory abnormalities, or immunological outcomes.

• To Evaluate the Efficacy of RNF by Comparing the Mean Number of Combined Unique (CU) Lesions Per Scan Per Subject Between the Initial 16 Weeks of Placebo Treatment and 24 Weeks of RNF Treatment in the Same Subjects, Originally Randomized to Placebo. [ Time Frame: Various timepoints ] [ Designated as safety issue: No ]
• Difference in Mean Number of CU Active Lesions Per Subject Per Scan in Originally Randomized Placebo Subjects, Over the Following Treatment Periods: Trial Day 1 Through Week 16, and Weeks 17 Through 40 [ Time Frame: 40 Weeks ] [ Designated as safety issue: No ]
  These data are displayed in the outcome above

Objectives:

Primary: To evaluate the efficacy of Rebif® New Formulation (RNF), compared to placebo, in subjects with Relapsing Remitting Multiple Sclerosis and active disease by means of Magnetic Resonance Imaging (MRI) at the end of 16 weeks of treatment Secondary: To evaluate the efficacy of RNF by comparing the mean number of combined unique (CU) lesions per scan per subject between the initial 16 weeks of placebo treatment and 24 weeks of RNF treatment in the same subjects, originally randomized to placebo.

Primary Endpoints: The primary endpoint is the difference between the number of combined unique (CU) active MRI lesions at Week 16 in the RNF group (Group 1) vs. the placebo group (Group 2).

Secondary Endpoints: The secondary endpoint is the difference in the mean number of combined unique (CU) active MRI lesions per scan per subject over the following treatment periods: Study Day 1 - Week 16 vs. Weeks 17 - 40 for the subjects randomized to Group 2.

• Placebo Comparator: 1
  RNF 44 mcg s.c. tiw for 40 weeks
  Intervention: Drug: Rebif® New Formulation (IFN-beta-1a)
• Placebo Comparator: 2
  Matching placebo for 16 weeks, then RNF 44 mcg s.c. tiw for remaining 24 weeks
  Intervention: Drug: Rebif® New Formulation (IFN-beta-1a)

• De Stefano N, Curtin F, Stubinski B, Blevins G, Drulovic J, Issard D, Shotekov P, Gasperini C. Rapid benefits of a new formulation of subcutaneous interferon beta-1a in relapsing-remitting multiple sclerosis. Mult Scler. 2010 Mar 3; [Epub ahead of print]
• De Stefano N, Sormani MP, Stubinski B, Blevins G, Drulovic JS, Issard D, Shotekov P, Gasperini C. Efficacy and safety of subcutaneous interferon β-1a in relapsing-remitting multiple sclerosis: further outcomes from the IMPROVE study. J Neurol Sci. 2012 Jan 15;312(1-2):97-101. Epub 2011 Aug 31.

Inclusion Criteria:

To be eligible for inclusion into this study, the subjects must fulfill all of the following criteria:

• Males and females between 18 and 60 years of age Female subjects must Be neither pregnant nor breast-feeding Be menopausal or surgically sterile or use an effective contraception chemical or mechanical), for the duration of the study
• Have RRMS according to the revised McDonald criteria 2005 (32)(APPENDIX C)
• Have brain and/or spinal MRI with findings typical of MS
• Have disease duration for > 12 months
• Have disease activity characterized by at least one clinical event and one or more Gd-enhancing MRI lesions within the 6 months prior to randomization
• Have score of </=5.5 on the EDSS
• Be willing and able to comply with the protocol for the duration of the study
• Have given written informed consent prior to any study-related procedure not part of the normal medical practice

Exclusion Criteria:

• Have any disease other than MS that could better explain his/her signs and symptoms
• Have complete transverse myelitis or bilateral optic neuritis
• Receive or have used anytime monoclonal antibodies, mitoxantrone, cytotoxic or immunosuppressive therapy (excluding systemic steroids and ACTH), or total lymphoid irradiation
• Have received within 3 months prior to baseline any approved disease- modifying therapy for MS, cytokine or anti-cytokine therapy, intravenous immunoglobulin, plasmapheresis, any investigational drug, or experimental procedure
• Have received within 30 days prior to baseline oral or systemic corticosteroids or ACTH