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A Study to Evaluate Rebif® New Formulation (IFN-beta-1a) in Relapsing Remitting Multiple Sclerosis (IMPROVE)

This study has been completed.
Sponsor:
Information provided by:
Merck KGaA
ClinicalTrials.gov Identifier:
NCT00441103
First received: February 26, 2007
Last updated: May 27, 2010
Last verified: May 2010
History of Changes
  Purpose

Objectives:

Primary: To evaluate the efficacy of Rebif® New Formulation (RNF), compared to placebo, in subjects with Relapsing Remitting Multiple Sclerosis and active disease by means of Magnetic Resonance Imaging (MRI) at the end of 16 weeks of treatment Secondary: To evaluate the efficacy of RNF by comparing the mean number of combined unique (CU) lesions per scan per subject between the initial 16 weeks of placebo treatment and 24 weeks of RNF treatment in the same subjects, originally randomized to placebo.

Primary Endpoints: The primary endpoint is the difference between the number of combined unique (CU) active MRI lesions at Week 16 in the RNF group (Group 1) vs. the placebo group (Group 2).

Secondary Endpoints: The secondary endpoint is the difference in the mean number of combined unique (CU) active MRI lesions per scan per subject over the following treatment periods: Study Day 1 - Week 16 vs. Weeks 17 - 40 for the subjects randomized to Group 2.


Condition Intervention Phase
Multiple Sclerosis, Relapsing-Remitting
 Drug: Rebif® New Formulation (IFN-beta-1a)
 Phase 3

Study Type: Interventional
Study Design: Allocation: Randomized
Endpoint Classification: Safety/Efficacy Study
Intervention Model: Factorial Assignment
Masking: Double Blind (Subject, Investigator)
Primary Purpose: Treatment
Official Title: A Two-arm, Randomized, Double-blind, Control Group-compared, Multicenter, Phase IIIb Study With Monthly MRI and Biomarker Assessments to Evaluate the Efficacy, Safety, and Tolerability of Rebif® New Formulation (IFN-beta-1a) in Subjects With Relapsing Remitting Multiple Sclerosis

Resource links provided by NLM:

U.S. FDA Resources

Further study details as provided by Merck KGaA:

Primary Outcome Measures:
  • Number of Combined Unique (CU) Active MRI Lesions at Week 16 [ Time Frame: 16 Weeks ] [ Designated as safety issue: No ]
  • Efficacy - MRI, Neurological Examination, Safety - Incidence, Severity, and Relationship to the Study Drug of Treatment Emergent Adverse Events, Serious Adverse Events, Laboratory Abnormalities, and Binding and Neutralizing Antibodies to IFN-Beta-1a [ Time Frame: Various Timepoints ] [ Designated as safety issue: No ]
    Information on the Primary MRI outcome is posted above. Safety information is included in the adverse events section but is not posted otherwise nor is information on neurological examinations, laboratory abnormalities, or immunological outcomes.


Secondary Outcome Measures:
  • To Evaluate the Efficacy of RNF by Comparing the Mean Number of Combined Unique (CU) Lesions Per Scan Per Subject Between the Initial 16 Weeks of Placebo Treatment and 24 Weeks of RNF Treatment in the Same Subjects, Originally Randomized to Placebo. [ Time Frame: Various timepoints ] [ Designated as safety issue: No ]
  • Difference in Mean Number of CU Active Lesions Per Subject Per Scan in Originally Randomized Placebo Subjects, Over the Following Treatment Periods: Trial Day 1 Through Week 16, and Weeks 17 Through 40 [ Time Frame: 40 Weeks ] [ Designated as safety issue: No ]
    These data are displayed in the outcome above


Enrollment: 180
Study Start Date: December 2006
Study Completion Date: February 2009
Primary Completion Date: November 2008 (Final data collection date for primary outcome measure)
Arms Assigned Interventions
Placebo Comparator: 1
RNF 44 mcg s.c. tiw for 40 weeks
 Drug: Rebif® New Formulation (IFN-beta-1a)
Rebif® New Formulation (RNF) 44 mcg s.c. tiw for up to 40 weeks. The dose of study medication will be titrated during the initial four-weeks of treatment. Subjects in Group 2 will be switched to RNF 44 mcg s.c. tiw at the end of the initial 16 weeks of treatment, starting a second titration with the same titration schedule as the initial one, while subjects initially assigned to RNF will after Week 16 continue to receive active treatment at the same dose throughout the whole study period, without any re-titration.
Placebo Comparator: 2
Matching placebo for 16 weeks, then RNF 44 mcg s.c. tiw for remaining 24 weeks
 Drug: Rebif® New Formulation (IFN-beta-1a)
Rebif® New Formulation (RNF) 44 mcg s.c. tiw for up to 40 weeks. The dose of study medication will be titrated during the initial four-weeks of treatment. Subjects in Group 2 will be switched to RNF 44 mcg s.c. tiw at the end of the initial 16 weeks of treatment, starting a second titration with the same titration schedule as the initial one, while subjects initially assigned to RNF will after Week 16 continue to receive active treatment at the same dose throughout the whole study period, without any re-titration.

  Eligibility

Ages Eligible for Study:   18 Years to 60 Years
Genders Eligible for Study:   Both
Accepts Healthy Volunteers:   No
Criteria

Inclusion Criteria:

To be eligible for inclusion into this study, the subjects must fulfill all of the following criteria:

  • Males and females between 18 and 60 years of age Female subjects must Be neither pregnant nor breast-feeding Be menopausal or surgically sterile or use an effective contraception chemical or mechanical), for the duration of the study
  • Have RRMS according to the revised McDonald criteria 2005 (32)(APPENDIX C)
  • Have brain and/or spinal MRI with findings typical of MS
  • Have disease duration for > 12 months
  • Have disease activity characterized by at least one clinical event and one or more Gd-enhancing MRI lesions within the 6 months prior to randomization
  • Have score of </=5.5 on the EDSS
  • Be willing and able to comply with the protocol for the duration of the study
  • Have given written informed consent prior to any study-related procedure not part of the normal medical practice

Exclusion Criteria:

  • Have any disease other than MS that could better explain his/her signs and symptoms
  • Have complete transverse myelitis or bilateral optic neuritis
  • Receive or have used anytime monoclonal antibodies, mitoxantrone, cytotoxic or immunosuppressive therapy (excluding systemic steroids and ACTH), or total lymphoid irradiation
  • Have received within 3 months prior to baseline any approved disease- modifying therapy for MS, cytokine or anti-cytokine therapy, intravenous immunoglobulin, plasmapheresis, any investigational drug, or experimental procedure
  • Have received within 30 days prior to baseline oral or systemic corticosteroids or ACTH
  Contacts and Locations
Please refer to this study by its ClinicalTrials.gov identifier: NCT00441103

Sponsors and Collaborators
Merck KGaA
Investigators
Study Director: Bettina Stubinski, MD Merck Serono SA - Geneva, an affiliate of Merck KGaA Darmstadt, Germany
  More Information

Additional Information:
Full FDA approved prescribing information can be found here  This link exits the ClinicalTrials.gov site

Publications:

Additional publications automatically indexed to this study by ClinicalTrials.gov Identifier (NCT Number):

Responsible Party: Bettina Stubinski, Medical Director, Merck Serono SA - Geneva an affiliate of Merck KGaA Darmstadt, Germany
ClinicalTrials.gov Identifier: NCT00441103     History of Changes
Other Study ID Numbers: 27178, 2006-003037-32
Study First Received: February 26, 2007
Results First Received: May 20, 2010
Last Updated: May 27, 2010
Health Authority: Bulgaria: Bulgarian Drug Agency
Canada: Health Canada
Estonia: The State Agency of Medicine
Germany: Federal Institute for Drugs and Medical Devices
Italy: Ethics Committee
Lithuania: State Medicine Control Agency - Ministry of Health
Romania: National Medicines Agency
Russia: Ministry of Health of the Russian Federation
Serbia and Montenegro: Agency for Drugs and Medicinal Devices
Spain: Ministry of Health and Consumption
Switzerland: Swissmedic

Keywords provided by Merck KGaA:
Subjects with relapsing remitting multiple sclerosis

Additional relevant MeSH terms:
Multiple Sclerosis
Sclerosis
Multiple Sclerosis, Relapsing-Remitting
Demyelinating Autoimmune Diseases, CNS
Autoimmune Diseases of the Nervous System
Nervous System Diseases
Demyelinating Diseases
Autoimmune Diseases
Immune System Diseases
Pathologic Processes
 Interferon-beta
Interferon beta 1a
Antiviral Agents
Anti-Infective Agents
Therapeutic Uses
Pharmacologic Actions
Immunologic Factors
Physiological Effects of Drugs
Antineoplastic Agents
Adjuvants, Immunologic

ClinicalTrials.gov processed this record on June 17, 2013