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

NCT00813709 | Completed Phase 3 Results

• 1 other identifier: 28981
• Study Type: interventional
• Target: 402
• Locations: 23 countries
• Sites: 55

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).

Conditions

Multiple Sclerosis; Clinically Isolated Syndrome

Keywords

Interferon 1-beta; Clinical Definite Multiple Sclerosis

Outcome Measures

Primary Outcomes (1)

• 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

  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.

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

Secondary Outcomes (23)

• 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 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

Study Arms (3)

RNF 44 mcg thrice weekly

ACTIVE COMPARATOR

Drug: RNF

RNF 44 mcg once weekly and placebo

ACTIVE COMPARATOR

Drug: RNF; Drug: Placebo

Placebo/RNF 44 mcg thrice weekly

ACTIVE COMPARATOR

Drug: RNF

Interventions

RNF DRUG

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.

Also known as: Rebif®

RNF 44 mcg thrice weekly

Placebo DRUG

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).

RNF 44 mcg once weekly and placebo

Eligibility Criteria

• Age: 18 Years+
• Sex: all
• Healthy Volunteers: No
• Age Groups: Adult (18-64), Older Adult (65+)

You may qualify if:

• 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

You may not qualify if:

• 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

Sponsors & Collaborators

• Merck KGaA, Darmstadt, Germany: lead

Study Sites (57)

Research Site

Mendoza, Argentina

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Graz, Austria

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Bruges, Belgium

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Leuven, Belgium

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Pleven, Bulgaria

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Rousse, Bulgaria

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Shumen, Bulgaria

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Sofia, Bulgaria

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Varna, Bulgaria

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Ontario, Canada

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Victoria British Columbia, Canada

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Karlovac, Croatia

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Osijek, Croatia

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Rijeka, Croatia

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Split, Croatia

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Zagreb, Croatia

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Hradec Králové, Czechia

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Olomouc, Czechia

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Prague, Czechia

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Tallinn, Estonia

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Tartu, Estonia

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Oulu, Finland

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Paris, France

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Poissy, France

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Hanover, Germany

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Henningsforf, Germany

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Athens, Greece

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Safed, Israel

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Tel Litwinsky, Israel

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Milan, Italy

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Padua, Italy

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Riga, Latvia

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Beirut, Lebanon

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Rabat, Morocco

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Bialystok, Poland

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Lodz, Poland

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Warsaw, Poland

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Wroclaw, Poland

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Lisbon, Portugal

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Bucharest, Romania

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Iași, Romania

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Târgu Mureş, Romania

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Timișoara, Romania

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Moscow, Russia

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Novosibirsk, Russia

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Saint Petersburg, Russia

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Samara, Russia

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Saratov, Russia

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Veliky Novgorod, Russia

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Yekaterinburg, Russia

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Belgrade, Serbia

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Niš, Serbia

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Prešov, Slovakia

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Barcelona, Spain

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Bilbao, Spain

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Madrid, Spain

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Seville, Spain

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Related Publications (1)

• Comi G, De Stefano N, Freedman MS, Barkhof F, Uitdehaag BM, de Vos M, Marhardt K, Chen L, Issard D, Kappos L. Subcutaneous interferon beta-1a in the treatment of clinically isolated syndromes: 3-year and 5-year results of the phase III dosing frequency-blind multicentre REFLEXION study. J Neurol Neurosurg Psychiatry. 2017 Apr;88(4):285-294. doi: 10.1136/jnnp-2016-314843. Epub 2016 Dec 30.

  PMID: 28039317 DERIVED

MeSH Terms

Conditions

Multiple Sclerosis

Interventions

Interferon beta-1a

Condition Hierarchy (Ancestors)

Demyelinating Autoimmune Diseases, CNS; Autoimmune Diseases of the Nervous System; Nervous System Diseases; Demyelinating Diseases; Autoimmune Diseases; Immune System Diseases

Intervention Hierarchy (Ancestors)

Interferon-beta; Interferon Type I; Interferons; Cytokines; Intercellular Signaling Peptides and Proteins; Peptides; Amino Acids, Peptides, and Proteins; Proteins; Biological Factors

Results Point of Contact

• Title: Merck KGaA Communication Center
• Organization: Merck Serono, a division of Merck KGaA

service@merckgroup.com

+49-6151-72-5200

Study Officials

• Medical Responsible

  Merck Serono S.A., Geneva

  STUDY DIRECTOR

Publication Agreements

• PI is Sponsor Employee: No
• Restriction Type: OTHER
• Restrictive Agreement: Yes

Study Design

• Study Type: interventional
• Phase: phase 3
• Allocation: RANDOMIZED
• Masking: DOUBLE
• Who Masked: PARTICIPANT, INVESTIGATOR
• Purpose: TREATMENT
• Intervention Model: PARALLEL
• Sponsor Type: INDUSTRY
• Responsible Party: SPONSOR

Study Record Dates

• First Submitted: December 22, 2008
• First Posted: December 23, 2008
• Study Start: December 1, 2008
• Primary Completion: August 1, 2011
• Study Completion: September 1, 2013
• Last Updated: March 8, 2017
• Results First Posted: October 28, 2013

Record last verified: 2017-01

Locations

FI (1); PL (4); CA (2); BU (5); FR (2); CR (5); BE (2); AR (1); LA (1); MO (1); SE (2); RO (4); DE (2); LE (1); IT (2); RU (7); SL (1); CZ (3); ES (4); GR (1); AU (1); IL (2); PT (1)