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


Tracking Information

Start Date  ICMJEJanuary 2009
Estimated Primary Completion DateSeptember 2011   (final data collection date for primary outcome measure)
Current Primary Outcome Measures  ICMJE
 (submitted: December 22, 2008)
Time to conversion to CDMS defined by either a second attack or a sustained increase (greater than or equal to 1.5 points) in the EDSS score (as defined in study 27025 (REFLEX)), from randomization in study 27025 (REFLEX) up to Month 36. [ Time Frame: 36 Months from randomization in study 27025 (REFLEX) ] [ Designated as safety issue: No ]
Original Primary Outcome Measures ICMJESame as current
Change HistoryComplete list of historical versions of study NCT00813709 on ClinicalTrials.gov Archive Site
Current Secondary Outcome Measures ICMJE 
 (submitted: November 5, 2009)
Time to conversion to CDMS (only at M36); Time to confirmed EDSS progression (≥1.0 point, confirmed during a visit performed 6 months later); MRI endpoints; Other secondary endpoints (PASAT, relapse-free subjects...); Safety endpoints (SAEs,BAbs&Nabs.) [ Time Frame: 60 months from randomisation in study 27025 (REFLEX) ] [ Designated as safety issue: No ]
Original Secondary Outcome Measures ICMJE 
 (submitted: December 22, 2008)
Time to conversion to CDMS (only at M36); Time to confirmed EDSS progression (≥1.0 point, confirmed during a visit performed 6 months later); MRI endpoints; Other secondary endpoints (PASAT, relapse-free subjects...); Safety endpoints (SAEs,BAbs&Nabs.) [ Time Frame: 36 and 60 months from randomisation in study 27025 (REFLEX) ] [ Designated as safety issue: No ]

Descriptive Information

Brief Title  ICMJELong-term Follow-Up of Patients Who Participated in Study 27025 (REFLEX)
Official Title  ICMJEDouble-blind Extension of the Study 27025 (REFLEX) to Obtain Long-term Follow-up Data in Patients With Clinically Definite MS and Patients With a First Demyelinating Event at High Risk of Converting to MS, Treated With Rebif® New Formulation (REFLEXION)
Brief Summary

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).

Detailed Description

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)).

Study PhasePhase III
Study Type  ICMJEInterventional
Study Design  ICMJETreatment, Randomized, Double Blind (Subject, Investigator), Parallel Assignment, Safety/Efficacy Study
Condition  ICMJE
  • Multiple Sclerosis
  • Clinically Isolated Syndrome
Intervention  ICMJE
  • 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
Study Arms / Comparison Groups
  • 1: Experimental
    Intervention: Drug: RNF
  • 2: Experimental
    Intervention: Drug: RNF
  • 3: Experimental
    Intervention: Drug: RNF
  • 4
    Intervention: Drug: Rebif® New Formulation (RNF)

Recruitment Information

Estimated Enrollment  ICMJE430
Completion Date 
Estimated Primary Completion DateSeptember 2011   (final data collection date for primary outcome measure)
Eligibility Criteria  ICMJE

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.
GenderBoth
Ages18 Years and older
Accepts Healthy VolunteersNo
Contacts  ICMJE
Contact: Central Contact+41 22 414 3000
Location Countries  ICMJEArgentina,   Austria,   Belgium,   Bulgaria,   Canada,   Croatia,   Czech Republic,   Estonia,   Finland,   France,   Germany,   Greece,   Israel,   Italy,   Latvia,   Lebanon,   Morocco,   Poland,   Portugal,   Romania,   Russian Federation,   Saudi Arabia,   Serbia,   Slovakia,   Spain,   Turkey

Administrative Information

NCT ID  ICMJENCT00813709
Responsible PartyBettina Stubinski, MD, Merck Serono S.A. - Geneva
Study ID Numbers  ICMJE28981
Study Sponsor  ICMJEEMD Serono
Collaborators  ICMJE 
Investigators  ICMJE
Study Director:Bettina Stubinski, MDMerck Serono S.A. - Geneva
Information Provided ByEMD Serono