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Clinical Trials/NCT00813709
NCT00813709CompletedPhase 3

Double-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)

Merck KGaA, Darmstadt, Germany2 sites in 2 countries402 target enrollmentStarted: December 2008Last updated:
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Conditions
Interventions
Drugs

Trial Snapshot

Phase
Phase 3
Status
Completed
Enrollment
402
Locations
2
Primary Endpoint
Time to Conversion to Clinically Definite Multiple Sclerosis (CDMS) Defined by Either a Second Attack or a Sustained Increase (Greater Than or Equal to 1.5 Points) in the Expanded Disability Status Scale (EDSS) Score up to 36 Months
Study OverviewStudy DesignEligibility CriteriaArms & InterventionsOutcomesInvestigatorsSitesRecords & IdentifiersSimilar Trials

Study Overview

Brief 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).

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 Clinically Definite Multiple Sclerosis (CDMS) conversion up to Month 36 and up to Month 60 since randomization 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 [ARR]) in the long term (up to Month 36 and up to Month 60 since randomization 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 randomization in Study 27025 (REFLEX).

Study Design

Study Type
Interventional
Allocation
Randomized
Intervention Model
Parallel
Primary Purpose
Treatment
Masking
Double (Participant, Investigator)

Eligibility Criteria

Ages
18 Years to — (Adult, Older Adult)
Sex
All
Accepts Healthy Volunteers
No

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

Arms & Interventions

RNF 44 mcg thrice weekly

Active Comparator

Intervention: RNF (Drug)

RNF 44 mcg once weekly and placebo

Active Comparator

Intervention: RNF (Drug)

RNF 44 mcg once weekly and placebo

Active Comparator

Intervention: Placebo (Drug)

Placebo/RNF 44 mcg thrice weekly

Active Comparator

Intervention: RNF (Drug)

Outcomes

Primary Outcomes

Time to Conversion to Clinically Definite Multiple Sclerosis (CDMS) Defined by Either a Second Attack or a Sustained Increase (Greater Than or Equal to 1.5 Points) in the Expanded Disability Status Scale (EDSS) Score up to 36 Months

Time Frame: Baseline (Day 1 of Study 27025) up to 36 Months

CDMS was defined by the occurrence of a second attack or relapse over 36 months in participants who presented with clinically isolated syndrome (CIS) accompanied by an abnormal magnetic resonance imaging (MRI) scan. EDSS assesses disability in 8 functional systems. An overall score ranging from 0 (normal) to 10 (death due to multiple sclerosis \[MS\]) was calculated. Time to conversion to CDMS was represented by Kaplan-Meier estimates of the cumulative percentage (%) of participants with CDMS.

Secondary Outcomes

  • Change From Baseline in Time Constant 1 (T1) Hypointense Lesion Volume and Time Constant 2 (T2) Lesion Volume at Month 36(Baseline (Day 1 of Study 27025), Month 36)
  • Percent Change From Baseline in Brain Volume at Month 36(Baseline (Day 1 of Study 27025), Month 36)
  • Percentage of Participants With Conversion to McDonald Multiple Sclerosis (MS) up to 36 Months(Baseline (Day 1 of Study 27025) up to CDMS conversion and/or up to 36 Months)
  • Time to Confirmed Expanded Disability Status Scale (EDSS) Progression up to 36 Months(Baseline (Day 1 of Study 27025) up to 36 Months)
  • Number of Combined Unique Active (CUA) Lesions, New Time Constant 2 (T2) Lesions, New Gadolinium Enhanced (Gd+) Lesions and New Time Constant 1 (T1) Lesions Per Participant Per Scan at Month 36(Month 36)
  • Change From Baseline in Multiple Sclerosis Functional Composite (MSFC) Score at Month 36(Baseline (Day 1 of Study 27025), Month 36)
  • Number of Combined Unique Active (CUA) Lesions, New Time Constant 2 (T2) Lesions, New Gadolinium Enhanced (Gd+) Lesions and New T1 Lesions Per Participant Per Scan at Month 60(Month 60)
  • Change From Baseline in Time Constant 1 (T1) Hypointense Volume, and Time Constant 2 (T2) Lesion Volume at Month 60(Baseline (Day 1 of Study 27025), Month 60)
  • Time to Conversion to Clinically Definite Multiple Sclerosis (CDMS) Defined by Either a Second Attack or a Sustained Increase (Greater Than or Equal to 1.5 Points) in the Expanded Disability Status Scale (EDSS) Score up to Month 60(Baseline (Day 1 of Study 27025) up to 60 Months)
  • Percentage of Relapse-Free Participants at Month 60(Month 60)
  • Change From Baseline in Paced Auditory Serial Addition Test 3 (PASAT-3) Score at Month 36(Baseline (Day of Study 27025), Month 36)
  • Percentage of Relapse-Free Participants at Month 36(Month 36)
  • Numbers of Participants With Binding Antibodies (BAb) and Neutralizing Antibody (NAb) at Month 36(Month 36)
  • Percent Change From Baseline in Brain Volume at Month 60(Baseline (Day 1 of Study 27025), Month 60)
  • Numbers of Participants With Binding Antibodies (BAb) and Neutralizing Antibody (NAb) at Month 60(Month 60)
  • Change From Baseline in Expanded Disability Status Scale (EDSS) Score at Month 36(Baseline (Day of Study 27025), Month 36)
  • Time to Confirmed Expanded Disability Status Scale (EDSS) Progression up to 60 Months(Baseline (Day 1 of Study 27025) up to 60 Months)
  • Percentage of Participants With Conversion to McDonald Multiple Sclerosis (MS) at Month 60(Month 60)
  • Change From Baseline in Paced Auditory Serial Addition Test 3 (PASAT-3) Score at Month 60(Baseline (Day 1 of Study 27025), Month 60)
  • Change From Baseline in Expanded Disability Status Scale (EDSS) Score at Month 60(Baseline (Day 1 of Study 27025), Month 60)
  • Change From Baseline in Multiple Sclerosis Functional Composite (MSFC) Score at Month 60(Baseline (Day 1 of Study 27025), Month 60)
  • Number of Participants With Adverse Events (AEs), Serious Adverse Events (SAEs) and AEs Leading to Treatment Discontinuation(Month 24 up to Month 60)

Investigators

Sponsor Class
Industry
Responsible Party
Sponsor

Study Sites (2)

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