Long-term Follow-Up of Patients Who Participated in Study 27025 (REFLEX) (REFLEXION)

REFLEXION is a double-blind (blinding of both investigator and patient) extension of the study 27025 (REFLEX). The purpose of the study is to obtain long-term follow-up data in patients with clinically definite Multiple Scleroris (MS) and patients with a first demyelinating event at high risk of converting to MS, treated with Rebif® New Formulation (RNF).

The objective of the study is to investigate whether RNF treatment initiated after the first clinical event versus delayed treatment results in the prolongation of time to CDMS conversion up to Month 36 and up to Month 60 since randomisation in study 27025 (REFLEX). Furthermore, the study is intended to explore whether RNF treatment initiated after the first clinical event versus delayed treatment delays disability (including development of secondary progressive MS) and reduces disease activity (including the annual relapse rate) in the long term (up to Month 36 and up to Month 60 since randomisation in study 27025 (REFLEX)). The study will also assess the long-term safety profile of RNF (up to Month 36 and up to Month 60 since randomisation in study 27025 (REFLEX)).

• Multiple Sclerosis
• Clinically Isolated Syndrome

• Drug: RNF
  Drug RNF 44 mcg tiw sc
• Drug: RNF
  Drug RNF 44 mcg ow sc
• Drug: RNF
  Drug RNF 44 mcg tiw sc (having originally been randomised to placebo in previous study 27025)
• Drug: Rebif® New Formulation (RNF)
  Drug RNF 44 mcg tiw sc for all patients when they reach CDMS

• Experimental: 1
  Intervention: Drug: RNF
• Experimental: 2
  Intervention: Drug: RNF
• Experimental: 3
  Intervention: Drug: RNF
• 4
  Intervention: Drug: Rebif® New Formulation (RNF)

Inclusion Criteria:

• Reach scheduled End of Study in study 27025 (completion of 24 months participation),
• Medical assessment by the Investigator/treating physician from study 27025 that there is no objection to the subject's participation in this extension trial considering the medical experience from study 27025. Special attention should be given to laboratory abnormalities and clinically significant liver, renal and bone-marrow dysfunction,
• If female, subject must:
• be neither pregnant nor breast-feeding, nor attempting to conceive,
• use a highly effective method of contraception. A highly effective method of contraception is defined as those which result in a low failure rate (i.e. less than 1% per year) when used consistently and correctly such as implants, injectables, combined oral contraceptives, some IUDs, sexual abstinence or vasectomised partner,
• Subject is willing to follow study procedures,
• Subject has given written informed consent.

Exclusion Criteria:

• Subject has any disease other than MS that could better explain the subject's signs and symptoms,
• Subject has a primary progressive course of MS,
• Subject has total bilirubin > 2.5 times upper limit of normal at both Month 24 and at the previous visit (i.e. Month 21) (subjects with > 2.5 times upper limit of normal at Month 24 only are eligible for enrollment and should be managed as per label recommendations until normalisation of the value),
• Subject has total aspartate aminotransferase (AST) or alanine aminotransferase (ALT) or alkaline phosphatase > 2.5 times the upper limit of normal values at both Month 24 and at the previous visit (i.e. Month 21) (subjects with > 2.5 times upper limit of normal at Month 24 only are eligible for enrollment and should be managed as per label recommendations until normalisation of the value),
• Subject suffers from another current autoimmune disease,
• Subject suffers from major medical or psychiatric illness (including history of, or current, severe depressive disorders and/or suicidal ideation) that in the opinion of the investigator creates undue risk to the subject or could affect compliance with the study protocol,
• Subject has a history of seizures not adequately controlled by treatment,
• Subject has cardiac disease, such as angina, congestive heart failure or arrhythmia,
• Subject has a known allergy to IFN-beta or the excipient(s) of the study medication,
• Subject has any condition that could interfere with the MRI evaluation,
• Subject has a known allergy to gadolinium-DTPA,
• Subject has a history of alcohol or drug abuse,
• Subject has previously participated in this study,
• Subject has moderate to severe renal impairment,
• Subject is pregnant or lactating,
• Subject has any medical, psychiatric or other conditions that compromise his/her ability to understand the subject information, to give informed consent, to comply with the study protocol, or to complete the study.