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

NCT ID: NCT00813709

Last Updated: 2017-03-08

Basic Information

• Recruitment Status: COMPLETED
• Clinical Phase: PHASE3
• Total Enrollment: 402 participants
• Study Classification: INTERVENTIONAL
• Study Start Date: 2008-12-31
• Study Completion Date: 2013-09-30

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).

Conditions

Multiple Sclerosis; Clinically Isolated Syndrome

Study Design

• Allocation Method: RANDOMIZED
• Intervention Model: PARALLEL
• Primary Study Purpose: TREATMENT
• Blinding Strategy: DOUBLE

Study Groups

RNF 44 mcg thrice weekly

Group Type: ACTIVE_COMPARATOR

RNF

Intervention Type: 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.

RNF 44 mcg once weekly and placebo

Group Type: ACTIVE_COMPARATOR

RNF

Intervention Type: DRUG

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.

Placebo

Intervention Type: 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).

Placebo/RNF 44 mcg thrice weekly

Group Type: ACTIVE_COMPARATOR

RNF

Intervention Type: DRUG

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.

Interventions

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.

Intervention Type: DRUG

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.

Intervention Type: DRUG

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.

Intervention Type: DRUG

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 Type: DRUG

Other Intervention Names

Rebif®; Rebif®; Rebif®

Eligibility 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

• Minimum Eligible Age: 18 Years
• Eligible Sex: ALL
• Accepts Healthy Volunteers: No

Sponsors

Merck KGaA, Darmstadt, Germany

INDUSTRY

Sponsor Role: lead

Responsible Party

Responsibility Role: SPONSOR

Principal Investigators

Medical Responsible

Role: STUDY_DIRECTOR

Merck Serono S.A., Geneva

Locations

Research Site

Mendoza, , Argentina

Research Site

Graz, , Austria

Research Site

Bruges, , 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 Králové, , Czechia

Research Site

Olomouc, , Czechia

Research Site

Prague, , Czechia

Research Site

Tallinn, , Estonia

Research Site

Tartu, , Estonia

Research Site

Oulu, , Finland

Research Site

Paris, , France

Research Site

Poissy, , France

Research Site

Hanover, , Germany

Research Site

Henningsforf, , Germany

Research Site

Athens, , Greece

Research Site

Safed, , Israel

Research Site

Tel Litwinsky, , Israel

Research Site

Milan, , Italy

Research Site

Padua, , 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

Iași, , Romania

Research Site

Târgu Mureş, , Romania

Research Site

Timișoara, , Romania

Research Site

Moscow, , Russia

Research Site

Novosibirsk, , Russia

Research Site

Saint Petersburg, , Russia

Research Site

Samara, , Russia

Research Site

Saratov, , Russia

Research Site

Veliky Novgorod, , Russia

Research Site

Yekaterinburg, , Russia

Reserch Site

Belgrade, , Serbia

Research Site

Niš, , Serbia

Research Site

Prešov, , Slovakia

Research Site

Barcelona, , Spain

Research Site

Bilbao, , Spain

Research Site

Madrid, , Spain

Research Site

Seville, , Spain

Countries

Argentina; Austria; Belgium; Bulgaria; Canada; Croatia; Czechia; Estonia; Finland; France; Germany; Greece; Israel; Italy; Latvia; Lebanon; Morocco; Poland; Portugal; Romania; Russia; Serbia; Slovakia; Spain

References

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.

Reference Type: DERIVED

PMID: 28039317 (View on PubMed)

Other Identifiers

28981

Identifier Type: -

Identifier Source: org_study_id