Long-term Follow-Up of Patients Who Participated in Study 27025 (REFLEX)
Information source: Merck KGaA
ClinicalTrials.gov processed this data on August 23, 2015 Link to the current ClinicalTrials.gov record.
Condition(s) targeted: Multiple Sclerosis; Clinically Isolated Syndrome
Intervention: RNF (Drug); RNF (Drug); RNF (Drug); Placebo (Drug)
Phase: Phase 3
Status: Completed
Sponsored by: Merck KGaA Official(s) and/or principal investigator(s): Medical Responsible, Study Director, Affiliation: Merck Serono S.A., Geneva
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).
Clinical Details
Official title: 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)
Study design: Allocation: Randomized, Endpoint Classification: Safety/Efficacy Study, Intervention Model: Parallel Assignment, Masking: Double Blind (Subject, Investigator), Primary Purpose: Treatment
Primary outcome: 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
Secondary outcome: Time to Confirmed Expanded Disability Status Scale (EDSS) Progression up to 36 MonthsNumber 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 Change From Baseline in Time Constant 1 (T1) Hypointense Lesion Volume and Time Constant 2 (T2) Lesion Volume at Month 36 Percent Change From Baseline in Brain Volume at Month 36 Percentage of Participants With Conversion to McDonald Multiple Sclerosis (MS) up to 36 Months Change From Baseline in Paced Auditory Serial Addition Test 3 (PASAT-3) Score at Month 36 Percentage of Relapse-Free Participants at Month 36 Change From Baseline in Expanded Disability Status Scale (EDSS) Score at Month 36 Change From Baseline in Multiple Sclerosis Functional Composite (MSFC) Score at Month 36 Numbers of Participants With Binding Antibodies (BAb) and Neutralizing Antibody (NAb) at Month 36 Number of Participants With Adverse Events (AEs), Serious Adverse Events (SAEs) and AEs Leading to Treatment Discontinuation 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 Time to Confirmed Expanded Disability Status Scale (EDSS) Progression up to 60 Months 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 Change From Baseline in Time Constant 1 (T1) Hypointense Volume, and Time Constant 2 (T2) Lesion Volume at Month 60 Percent Change From Baseline in Brain Volume at Month 60 Percentage of Participants With Conversion to McDonald Multiple Sclerosis (MS) at Month 60 Change From Baseline in Paced Auditory Serial Addition Test 3 (PASAT-3) Score at Month 60 Percentage of Relapse-Free Participants at Month 60 Change From Baseline in Expanded Disability Status Scale (EDSS) Score at Month 60 Change From Baseline in Multiple Sclerosis Functional Composite (MSFC) Score at Month 60 Numbers of Participants With Binding Antibodies (BAb) and Neutralizing Antibody (NAb) at Month 60 Number of Participants With Adverse Events (AEs), Serious Adverse Events (SAEs) and AEs Leading to Treatment Discontinuation
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).
Eligibility
Minimum age: 18 Years.
Maximum age: N/A.
Gender(s): Both.
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
Locations and Contacts
Research Site, Mendoza, Argentina
Research Site, Graz, Austria
Research Site, Brugge, Belgium
Research Site, Leuven, Belgium
Research Site, Pleven, Bulgaria
Research Site, Rousse, Bulgaria
Research Site, Shumen, Bulgaria
Research Site, Sofia, Bulgaria
Research Site, Varna, Bulgaria
Research Site, Ontario, Canada
Research Site, Victoria British Columbia, Canada
Research Site, Karlovac, Croatia
Research Site, Osijek, Croatia
Research Site, Rijeka, Croatia
Research Site, Split, Croatia
Research Site, Zagreb, Croatia
Research Site, Hradec Kralove, Czech Republic
Research Site, Olomouc, Czech Republic
Research Site, Prague, Czech Republic
Research Site, Tallinn, Estonia
Research Site, Tartu, Estonia
Research Site, Oulu, Finland
Research Site, Paris, France
Research Site, Poissy Cedex, France
Research Site, Hannover, Germany
Research Site, Henningsforf, Germany
Research Site, Athens, Greece
Research Site, Safed, Israel
Research Site, Tel-Hashomer, Israel
Research Site, Milano, Italy
Research Site, Padova, Italy
Research Site, Riga, Latvia
Research Site, Beirut, Lebanon
Research Site, Rabat, Morocco
Research Site, Bialystok, Poland
Research Site, Lodz, Poland
Research Site, Warsaw, Poland
Research Site, Wroclaw, Poland
Research Site, Lisbon, Portugal
Research Site, Bucharest, Romania
Research Site, Iasi, Romania
Research Site, Targu-Mures, Romania
Research Site, Timisoara, Romania
Research Site, Ekaterinburg, Russian Federation
Research Site, Moscow, Russian Federation
Research Site, Novgorod, Russian Federation
Research Site, Novosibirsk, Russian Federation
Research Site, Saint-Petersburg, Russian Federation
Research Site, Samara, Russian Federation
Research Site, Saratov, Russian Federation
Reserch Site, Belgrade, Serbia
Research Site, Nis, Serbia
Research Site, Presov, Slovakia
Research Site, Barcelona, Spain
Research Site, Bilbao, Spain
Research Site, Madrid, Spain
Research Site, Seville, Spain
Additional Information
Starting date: December 2008
Last updated: July 23, 2015
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