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Trial details imported from ClinicalTrials.gov

For full trial details, please see the original record at https://clinicaltrials.gov/study/NCT00813709




Registration number
NCT00813709
Ethics application status
Date submitted
22/12/2008
Date registered
23/12/2008
Date last updated
8/03/2017

Titles & IDs
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)
Secondary ID [1] 0 0
28981
Universal Trial Number (UTN)
Trial acronym
REFLEXION
Linked study record

Health condition
Health condition(s) or problem(s) studied:
Multiple Sclerosis 0 0
Clinically Isolated Syndrome 0 0
Condition category
Condition code

Intervention/exposure
Study type
Interventional
Description of intervention(s) / exposure
Treatment: Drugs - RNF
Treatment: Drugs - RNF
Treatment: Drugs - RNF
Treatment: Drugs - Placebo

Active comparator: RNF 44 mcg thrice weekly -

Active comparator: RNF 44 mcg once weekly and placebo -

Active comparator: Placebo/RNF 44 mcg thrice weekly -


Treatment: Drugs: RNF
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.

Treatment: Drugs: RNF
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.

Treatment: Drugs: RNF
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.

Treatment: Drugs: Placebo
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 code [1] 0 0
Treatment: Drugs
Comparator / control treatment
Control group

Outcomes
Primary outcome [1] 0 0
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
Timepoint [1] 0 0
Baseline (Day 1 of Study 27025) up to 36 Months
Secondary outcome [1] 0 0
Time to Confirmed Expanded Disability Status Scale (EDSS) Progression up to 36 Months
Timepoint [1] 0 0
Baseline (Day 1 of Study 27025) up to 36 Months
Secondary outcome [2] 0 0
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
Timepoint [2] 0 0
Month 36
Secondary outcome [3] 0 0
Change From Baseline in Time Constant 1 (T1) Hypointense Lesion Volume and Time Constant 2 (T2) Lesion Volume at Month 36
Timepoint [3] 0 0
Baseline (Day 1 of Study 27025), Month 36
Secondary outcome [4] 0 0
Percent Change From Baseline in Brain Volume at Month 36
Timepoint [4] 0 0
Baseline (Day 1 of Study 27025), Month 36
Secondary outcome [5] 0 0
Percentage of Participants With Conversion to McDonald Multiple Sclerosis (MS) up to 36 Months
Timepoint [5] 0 0
Baseline (Day 1 of Study 27025) up to CDMS conversion and/or up to 36 Months
Secondary outcome [6] 0 0
Change From Baseline in Paced Auditory Serial Addition Test 3 (PASAT-3) Score at Month 36
Timepoint [6] 0 0
Baseline (Day of Study 27025), Month 36
Secondary outcome [7] 0 0
Percentage of Relapse-Free Participants at Month 36
Timepoint [7] 0 0
Month 36
Secondary outcome [8] 0 0
Change From Baseline in Expanded Disability Status Scale (EDSS) Score at Month 36
Timepoint [8] 0 0
Baseline (Day of Study 27025), Month 36
Secondary outcome [9] 0 0
Change From Baseline in Multiple Sclerosis Functional Composite (MSFC) Score at Month 36
Timepoint [9] 0 0
Baseline (Day 1 of Study 27025), Month 36
Secondary outcome [10] 0 0
Numbers of Participants With Binding Antibodies (BAb) and Neutralizing Antibody (NAb) at Month 36
Timepoint [10] 0 0
Month 36
Secondary outcome [11] 0 0
Number of Participants With Adverse Events (AEs), Serious Adverse Events (SAEs) and AEs Leading to Treatment Discontinuation
Timepoint [11] 0 0
Month 24 up to Month 36 (DB treatment period for study 28981 (REFLEXION)
Secondary outcome [12] 0 0
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
Timepoint [12] 0 0
Baseline (Day 1 of Study 27025) up to 60 Months
Secondary outcome [13] 0 0
Time to Confirmed Expanded Disability Status Scale (EDSS) Progression up to 60 Months
Timepoint [13] 0 0
Baseline (Day 1 of Study 27025) up to 60 Months
Secondary outcome [14] 0 0
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
Timepoint [14] 0 0
Month 60
Secondary outcome [15] 0 0
Change From Baseline in Time Constant 1 (T1) Hypointense Volume, and Time Constant 2 (T2) Lesion Volume at Month 60
Timepoint [15] 0 0
Baseline (Day 1 of Study 27025), Month 60
Secondary outcome [16] 0 0
Percent Change From Baseline in Brain Volume at Month 60
Timepoint [16] 0 0
Baseline (Day 1 of Study 27025), Month 60
Secondary outcome [17] 0 0
Percentage of Participants With Conversion to McDonald Multiple Sclerosis (MS) at Month 60
Timepoint [17] 0 0
Month 60
Secondary outcome [18] 0 0
Change From Baseline in Paced Auditory Serial Addition Test 3 (PASAT-3) Score at Month 60
Timepoint [18] 0 0
Baseline (Day 1 of Study 27025), Month 60
Secondary outcome [19] 0 0
Percentage of Relapse-Free Participants at Month 60
Timepoint [19] 0 0
Month 60
Secondary outcome [20] 0 0
Change From Baseline in Expanded Disability Status Scale (EDSS) Score at Month 60
Timepoint [20] 0 0
Baseline (Day 1 of Study 27025), Month 60
Secondary outcome [21] 0 0
Change From Baseline in Multiple Sclerosis Functional Composite (MSFC) Score at Month 60
Timepoint [21] 0 0
Baseline (Day 1 of Study 27025), Month 60
Secondary outcome [22] 0 0
Numbers of Participants With Binding Antibodies (BAb) and Neutralizing Antibody (NAb) at Month 60
Timepoint [22] 0 0
Month 60
Secondary outcome [23] 0 0
Number of Participants With Adverse Events (AEs), Serious Adverse Events (SAEs) and AEs Leading to Treatment Discontinuation
Timepoint [23] 0 0
Month 24 up to Month 60

Eligibility
Key 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
Minimum age
18 Years
Maximum age
No limit
Sex
Both males and females
Can healthy volunteers participate?
No
Key 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

Study design
Purpose of the study
Treatment
Allocation to intervention
Randomised controlled trial
Procedure for enrolling a subject and allocating the treatment (allocation concealment procedures)
Methods used to generate the sequence in which subjects will be randomised (sequence generation)
Masking / blinding
Blinded (masking used)
Who is / are masked / blinded?
The people receiving the treatment/s


The people analysing the results/data
Intervention assignment
Parallel
Other design features
Phase
Phase 3
Type of endpoint/s
Statistical methods / analysis

Recruitment
Recruitment status
Completed
Data analysis
Reason for early stopping/withdrawal
Other reasons
Date of first participant enrolment
Anticipated
Actual
1/12/2008
Date of last participant enrolment
Anticipated
Actual
Date of last data collection
Anticipated
Actual
1/09/2013
Sample size
Target
Accrual to date
Final
402
Recruitment in Australia
Recruitment state(s)
Recruitment outside Australia
Country [1] 0 0
Argentina
State/province [1] 0 0
Mendoza
Country [2] 0 0
Austria
State/province [2] 0 0
Graz
Country [3] 0 0
Belgium
State/province [3] 0 0
Brugge
Country [4] 0 0
Belgium
State/province [4] 0 0
Leuven
Country [5] 0 0
Bulgaria
State/province [5] 0 0
Pleven

Funding & Sponsors
Primary sponsor type
Commercial sector/industry
Name
Merck KGaA, Darmstadt, Germany
Address
Country

Ethics approval
Ethics application status

Summary
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).
Trial website
https://clinicaltrials.gov/study/NCT00813709
Trial related presentations / publications
Public notes
This record is viewable in the ANZCTR as it had previously listed Australia and/or New Zealand as a recruitment site, however these sites have since been removed

Contacts
Principal investigator
Name 0 0
Medical Responsible
Address 0 0
Merck Serono S.A., Geneva
Country 0 0
Phone 0 0
Fax 0 0
Email 0 0
Contact person for public queries
Name 0 0
Address 0 0
Country 0 0
Phone 0 0
Fax 0 0
Email 0 0
Contact person for scientific queries



Summary Results

For IPD and results data, please see https://clinicaltrials.gov/study/NCT00813709