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

• Register: EUCTR
• Last refreshed on: 16 December 2013
• Main ID: EUCTR2008-004954-34-PL
• Date of registration: 05/06/2009
• Prospective Registration: Yes
• Primary sponsor: Merck Serono S.A. - Geneva, an affiliate of Merck KGaA, Darmstadt, Germany
• Public title: Long-term Follow-Up of Patients Who Participated in Study 27025 (REFLEX)
• Scientific 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) - REFLEXION
• Date of first enrolment: 09/09/2009
• Target sample size: 492
• Recruitment status: Not Recruiting
• URL: https://www.clinicaltrialsregister.eu/ctr-search/search?query=eudract_number:2008-004954-34
• Study type: Interventional clinical trial of medicinal product
• Study design: Controlled: yes Randomised: yes Open: no Single blind: no Double blind: yes Parallel group: yes Cross over: no Other: no Other trial design description: Not applicable If controlled, specify comparator, Other Medicinial Product: no Placebo: no Other: yes Other specify the comparator: The control group is the “delayed treatment” group - subjects randomized to placebo in study 27025 Number of treatment arms in the trial: 2

Countries of recruitment

Argentina, Austria, Belgium, Bulgaria, Canada, Croatia, Czech Republic, Estonia, Finland, France, Germany, Greece, Israel, Italy, Latvia, Lebanon, Morocco, Poland, Portugal, Romania, Russian Federation, Serbia, Slovakia, Spain, Turkey

Contacts

• Name: Communication Center Merck KGaA
• Affiliation: Merck KGaA

• Name: Communication Center Merck KGaA
• Affiliation: Merck KGaA

Key inclusion & exclusion criteria

Inclusion criteria:
All of the following criteria must be met for inclusion of a subject into the trial:
· 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.
Are the trial subjects under 18? no
Number of subjects for this age range: 0
F.1.2 Adults (18-64 years) yes
F.1.2.1 Number of subjects for this age range 492
F.1.3 Elderly (>=65 years) no
F.1.3.1 Number of subjects for this age range 0

Exclusion criteria:
Subjects are to be excluded from enrolment into the trial if they fulfill any of the following 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.


Age minimum:
Age maximum:
Gender:
Female: yes
Male: yes

Health Condition(s) or Problem(s) studied

Subjects of high risk of converting to Multiple Sclerosis or subjects already converted to Multiple Sclerosis.
MedDRA version: 14.0 Level: PT Classification code 10028245 Term: Multiple sclerosis System Organ Class: 10029205 - Nervous system disorders

Therapeutic area: Diseases [C] - Nervous System Diseases [C10]

Intervention(s)

Trade Name: Rebif


Pharmaceutical Form: Solution for injection
INN or Proposed INN: Interferon-beta 1a
Concentration unit: µg microgram(s)
Concentration type: equal
Concentration number: 44-
Pharmaceutical form of the placebo: Solution for injection
Route of administration of the placebo: Subcutaneous use

Primary Outcome(s)

Timepoint(s) of evaluation of this end point: Up to 36 months.

Secondary Objective: · 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 60 since randomisation in study 27025.
· To investigate 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).
· To assess the long-term safety profile of RNF (up to Month 36 and up to Month 60 since randomisation in study 27025).

Primary end point(s): The primary endpoint is the time to conversion to CDMS, defined by either a second attack or a sustained increase (=1.5 points) in the EDSS score (as defined in study 27025), from randomisation in study 27025 up to Month 36.

Main Objective: Primary objective: 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 since randomisation in study 27025.

Secondary Outcome(s)

Secondary end point(s): Secondary endpoints up to Month 36 from randomisation in study 27025:
.Time to confirmed EDSS progression (=1.0 point, confirmed during a visit performed 6
months later) from randomisation in study 27025 up to Month 36.
.MRI endpoints including, but not limited to:
.Mean number of combined unique active MRI lesions per subject per scan.
.Mean number of new T2 lesions per subject per scan.
.Mean number of new T1 lesions per subject per scan.
.T2 lesion load.
.T1 lesion load.
.Mean number of new Gd-enhancing lesions per subject per scan.
.Brain volume.
.Other secondary endpoints including:
.Percentage of subjects with conversion to McDonald MS.
.Cognition by means of PASAT.
.Proportion of relapse-free subjects.
.EDSS changes from baseline over time.
.Changes from baseline in MSFC (composite score, timed-25-footwalk, 9-hole-pegtest
and 3’’PASAT) over time.
Secondary endpoints up to Month 60 from randomisation in study 27025:
Time to conversion to CDMS from randomisation in study 27025 up to Month 60.
.Time to confirmed EDSS progression from randomisation in study 27025 up to Month
60.
.All other secondary endpoints described above for up to Month 36 (MRI endpoints and
other).
Safety endpoints evaluated up to Month 36 and up to Month 60 from randomisation in
study 27025 include:
.Incidence, severity and relationship to the trial drug of AEs,
.SAEs,
.AEs leading to permanent treatment discontinuation,
.Clinically significant changes in laboratory tests (according to laboratory reference
ranges),
.Use of concomitant medications,
.Development of BAbs and NAbs to IFN-beta-1a, and
.Vital signs.

Timepoint(s) of evaluation of this end point: Up to 36 months or up to 60 months

Secondary ID(s)

28981

2008-004954-34-CZ

NCT00813709

Source(s) of Monetary Support

Merck Serono S.A. - Geneva