Long-term Follow-Up of Patients Who Participated in Study 27025 (REFLEX)
Condition: Multiple Sclerosis; Clinically Isolated Syndrome
MeSH terms: Multiple Sclerosis; Sclerosis
Intervention: RNF; RNF; RNF; Placebo
Intervention description: Single dose of RNF will be administered subcutaneously three times weekly at least 48 hours apart at a starting dose of 8.8 microgram (mcg) for first 2 weeks followed by 22 mcg for next 2 weeks and finally 44 mcg until 60 months.; Single dose of RNF will be administered subcutaneously once weekly at a starting dose of 8.8 mcg for first 2 weeks followed by 22 mcg for next 2 weeks and finally 44 mcg until 60 months.; Participants who were initially randomized in Study 27025 (REFLEX) to the placebo treatment group will be switched to single dose of RNF administered subcutaneously three times weekly at least 48 hours apart at a dose of 8.8 mcg for first 2 weeks followed by 22 mcg for next 2 weeks and finally 44 mcg until 60 months.; Single dose matching placebo will be administered subcutaneously twice weekly. Placebo is supplied as a transparent, sterile solution for injection in pre-filled syringes matching the RNF pre-filled syringes, each containing 0.5 milliliter (mL).
Intervention MeSH terms: Interferon beta-1a
Phase: Phase 3
Study type: Interventional
Primary purpose: Treatment
Allocation: Randomized
Intervention model: Parallel Assignment
Masking: Double (Participant, Investigator)
Enrollment: 402.0
Sex: All
Minimum age: 18 Years
Healthy volunteers: No
Keywords: Interferon 1-beta; Clinical Definite Multiple Sclerosis

Summary:

      REFLEXION is a double blind extension of the study 27025 (NCT00404352) (REFLEX). The purpose
      of the study is to obtain long-term follow-up data in subjects with clinically definite
      multiple sclerosis (MS) and subjects with a first demyelinating event at high risk of
      converting to MS, treated with fetal bovine serum [FBS]-free/human serum albumin [HSA]-free
      formulation of interferon [IFN]-beta-1a (RNF).
    

Eligibility criteria:

        Inclusion Criteria:

          -  Reach scheduled end of study in Study 27025 (REFLEX) (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 (REFLEX). 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 (that is
                  [i.e.] less than 1 percent [%] per year) when used consistently and correctly
                  such as implants, injectables, combined oral contraceptives, some intrauterine
                  devices (IUDs), sexual abstinence or vasectomized 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 greater than 2.5 times upper limit of normal (ULN) at both
             Month 24 and at the previous visit (i.e. Month 21) (subjects with greater than 2.5
             times ULN at Month 24 only are eligible for enrollment and should be managed as per
             label recommendations until normalization of the value)

          -  Subject has total aspartate aminotransferase (AST) or alanine aminotransferase (ALT)
             or alkaline phosphatase (ALP) greater than 2.5 times the ULN values at both Month 24
             and at the previous visit (i.e. Month 21) (subjects with greater than 2.5 times ULN at
             Month 24 only are eligible for enrollment and should be managed as per label
             recommendations until normalization 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-diethylene triamine pentaacetic acid (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