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REbif FLEXible Dosing in Early Multiple Sclerosis (MS)

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

Intervention: RNF (Drug); RNF (Drug); Placebo (Drug)

Phase: Phase 3

Status: Completed

Sponsored by: Merck KGaA

Official(s) and/or principal investigator(s):
Bettina M. Stubinski, MD, Study Director, Affiliation: Merck Serono S.A., Geneva

Summary

The study is a 24 months randomized, double-blind, Placebo-controlled, multi-center clinical trial with an optional 12 months open label extension. The primary objective of the study is to evaluate the effect of fetal bovine serum [FBS]-free/human serum albumin [HSA]-free formulation of Interferon [IFN] beta-1a (RNF) 44 microgram (three times weekly and once weekly) versus placebo on the time to conversion to McDonald multiple sclerosis (MS) criteria (2005) in subjects with a first clinical demyelinating event at high risk of converting to MS. The main secondary objective of study is to evaluate the effect of RNF 44 microgram (three times weekly and once weekly) versus placebo on the "Time to conversion to clinically definite MS (CDMS)" in subjects with a first clinical demyelinating event at high risk of converting to MS. At the end of 24 month double-blind core REFLEX trial, subjects who will not convert to CDMS and decide to receive open-label (OL) treatment will be enrolled into an open-label, 12 month extension period to evaluate the effect of RNF 44 mcg three times weekly treatment on the time to conversion to McDonald MS and time to conversion to CDMS.

Clinical Details

Official title: A Phase III, Randomized, Double-blind, Placebo-controlled, Multicenter Clinical Trial of Rebif New Formulation (44 Microgram [Mcg] Three Times Weekly [Tiw] and 44 Mcg Once Weekly [ow]) in Subjects at High Risk of Converting to Multiple Sclerosis (REFLEX)

Study design: Allocation: Randomized, Endpoint Classification: Safety/Efficacy Study, Intervention Model: Parallel Assignment, Masking: Double Blind (Subject, Caregiver, Investigator, Outcomes Assessor), Primary Purpose: Prevention

Primary outcome:

Time to Conversion to Multiple Sclerosis (MS) According to the McDonald Criteria (2005)

Time to Conversion to Multiple Sclerosis (MS) According to the McDonald Criteria (2005)

Secondary outcome:

Time to Conversion to Clinically Definite Multiple Sclerosis (CDMS) Defined by Either a Second Attack or a 3-Month Sustained Increase (Greater Than or Equal to 1.5 Points) in the Expanded Disability Status Scale (EDSS) Score

Time to Conversion to Clinically Definite Multiple Sclerosis (CDMS) Defined by Either a Second Attack or a 3-Month Sustained Increase (Greater Than or Equal to 1.5 Points) in the Expanded Disability Status Scale (EDSS) Score

Mean Number of Combined Unique Active (CUA) Lesions, New Time Constant 2 (T2) Lesions, Gadolinium Enhanced (Gd+) Lesions and New Time Constant 1 (T1) Hypointense Lesions Per Participant Per Scan

Change From Baseline in Time Constant 2 (T2) Lesion Volume , Time Constant 1 (T1) Hypointense Lesion Volume and Gadolinium Enhanced (Gd+) Lesion Volume at Month 36

Change From Baseline in Expanded Disability Status Score (EDSS) Score at Month 36

Eligibility

Minimum age: 18 Years. Maximum age: 50 Years. Gender(s): Both.

Criteria:

Inclusion Criteria:

- Single, first clinical event suggestive of MS within 60 days prior to study Day 1,

which is the day of randomization (clock starts 24 hours after onset). The event must be a new neurological abnormality present for at least 24 hours, either mono- or polysymptomatic, other than a paresthesia, vegetative or cerebral dysfunction

- At least two clinically silent lesions on the T2-weighted MRI scan, with a size of at

least 3 millimeter (mm), at least one of which is ovoid or periventricular or infratentorial

- EDSS 0 - 5. 0 at least one time point during the screening period before start of

treatment

- 18 and 50 years old, inclusive

- Willing to follow study procedures

- Written informed consent

- 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 vasectomised partner Exclusion Criteria:

- Diagnosis of MS (per McDonald criteria 2005)

- Any other disease that could better explain the subject's signs and symptoms

- Complete transverse myelitis or bilateral optic neuritis

- Subject uses or has used any other approved MS disease-modifying drug (DMD)

- Any investigational drug or undergone an experimental procedure within 12 weeks prior

to study Day 1

- Oral or systemic corticosteroids or adrenocorticotropic hormone (ACTH) within 30 days

prior to study Day 1

- Total bilirubin greater than 2. 5 times upper limit of normal (ULN)

- Subject has total aspartate aminotransferase (AST) or alanine aminotransferase (ALT)

or alkaline phosphatase (ALP) greater than 2. 5 times the ULN

- Inadequate bone marrow reserve, defined as a total white blood cell count less than

3. 0 x 109 per liter (/L), platelet count less than 75 x 109/L, hemoglobin less than 100 gram per liter (g/L)

- Current autoimmune disease

- 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

- History of seizures not adequately controlled by treatment

- Cardiac disease, such as angina, congestive heart failure or arrhythmia

- Known allergy to IFN-beta or the excipient(s) of the study medication

- Any condition that could interfere with the MRI evaluation;

- Known allergy to gadolinium-diethylene triamine pentaacetic acid (DTPA)

- Previously participated in this study

- Participated in any clinical trial within the past 6 months

- Any immunomodulatory or immunosuppressive therapy at any time prior to enrollment,

including, but not limited to, the following products: any IFN, glatiramer acetate (Copolymer I), cyclophosphamide, cyclosporine, methotrexate, linomide, azathioprine, mitoxantrone, teriflunomide, laquinimod, cladribine, total lymphoid irradiation, anti-lymphocyte monoclonal antibody treatment (e. g. natalizumab, alemtuzumab/Campath, anti-cluster of differentiation 4 [CD4]), intravenous, immunoglobulins (Igs), cytokines or anti-cytokine therapy

- Any experimental MS treatment prior to trial entry, including, but not limited to,

any statins (if given to prevent MS) and pentoxyfylline

- History of alcohol or drug abuse

- Intolerance or any contraindication to both paracetamol (acetaminophen) and ibuprofen

- Inability to administer subcutaneous injections either by self or by caregiver

- Moderate to severe renal impairment

Locations and Contacts

Research Site, Mendoza, Argentina

Research Site, Sydney, Australia

Research Site, Graz, Austria

Research Site, Innsbruck, Austria

Research Site, B-Leuven, Belgium

Research Site, Brugge, Belgium

Research Site, Pleven, Bulgaria

Research Site, Rousse, Bulgaria

Research Site, Shumen, Bulgaria

Research Site, Sofia, Bulgaria

Research Site, Varna, Bulgaria

Research Site, Montreal, Quebec, Canada

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, OYS, Finland

Research Site, Vantaa, Finland

Research Site, Paris, France

Research Site, Poissy Cedex, France

Research Site, Hannover, Germany

Research Site, Henningsdorf, Germany

Research Site, Munich, Germany

Research Site, Athens, Greece

Research Site, Ness Ziona, Israel

Research Site, Safed, Israel

Research Site, Tel-Hashomer, Israel

Research Site, Catania, Italy

Research Site, Milano, Italy

Research Site, Padova, Italy

Research Site, Roma, 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, Lisboa, 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, Nizhny Novgorod, Russian Federation

Research Site, Novosibirsk, Russian Federation

Research Site, Saint-Petersburg, Russian Federation

Research Site, Samara, Russian Federation

Research Site, Saratov, Russian Federation

Research Site, Riyadh, Saudi Arabia

Research 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, Sevilla, Spain

Research Site, Istanbul, Turkey

Additional Information

Full FDA approved prescribing information can be found here

Starting date: November 2006
Last updated: December 18, 2013

Page last updated: August 23, 2015

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