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

This study has been completed.
Sponsor:
Information provided by (Responsible Party):
Merck KGaA
ClinicalTrials.gov Identifier:
NCT00441103
First received: February 26, 2007
Last updated: June 6, 2014
Last verified: June 2014
  Purpose

General Note: throughout this record, "Rebif® New Formulation" is used for historical and consistency purposes.

Objectives:

Primary: To evaluate the efficacy of Rebif® New Formulation (Interferon-beta-1a [IFN-beta-1a], 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 CU active MRI lesions at Week 16 in the RNF group (Group 1) versus the placebo group (Group 2).

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


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


Further study details as provided by Merck KGaA:

Primary Outcome Measures:
  • Number of Combined Unique (CU) Active Magnetic Resonance Imaging (MRI) Lesions at Week 16 [ Time Frame: 16 Weeks ] [ Designated as safety issue: No ]
    CU active lesions were defined as a unique newly active or persistently active lesion on the protocol density/time constant 2 (PD/T2) scan or the gadolinium (Gd-) enhanced time constant 1 (T1) scan (with a method to avoid double counting).

  • Number of Participants With Adverse Events (AEs) and Serious Adverse Events (SAEs) [ Time Frame: Baseline up to Week 40 ] [ Designated as safety issue: Yes ]
    An adverse event (AE) was defined as any new untoward medical occurrences/worsening of pre-existing medical condition without regard to possibility of causal relationship. A serious adverse event (SAE) was an AE that resulted in any of the following outcomes: death; life threatening; persistent/significant disability/incapacity; initial or prolonged inpatient hospitalization; congenital anomaly/birth defect. AEs were categorized based upon the treatment period during which they occurred, that is, double-blind period (up to Week 16) and rater-blind period (Week 17 up to Week 40).


Secondary Outcome Measures:
  • Mean Number of CU Lesions Per Scan Between the Initial 16 Weeks of Placebo Treatment and 24 Weeks of RNF Treatment in the Same Participants, Originally Randomized to Placebo. [ Time Frame: Day 1 up to Week 16 and Week 17 up to Week 40 ] [ Designated as safety issue: No ]
    CU active lesions were defined as a unique newly active or persistently active lesion on the PD/T2 scan or the gadolinium enhanced T1 scan (with a method to avoid double counting). Only "Placebo Followed by RNF" arm was evaluable for this outcome measure.

  • Number of CU Active MRI Lesions [ Time Frame: Up to Week 40 ] [ Designated as safety issue: No ]
    CU active lesions were defined as a unique newly active or persistently active lesion on the PD/T2 scan or the gadolinium enhanced T1 scan (with a method to avoid double counting).


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
Experimental: Rebif® New Formulation (IFN-beta-1a, RNF) Drug: Rebif® New Formulation (IFN-beta-1a, RNF)
RNF will be administered at a dose of 44 mcg subcutaneously three times a week for 40 weeks.
Other Name: IFN-beta-1a
Placebo Comparator: Placebo/RNF Drug: Placebo
Matching placebo will be administered subcutaneously three times a week for 16 weeks.
Drug: Rebif® New Formulation (IFN-beta-1a, RNF)
RNF will be administered at a dose of 44 mcg subcutaneously three times a week from Week 17 to Week 40.
Other Name: IFN-beta-1a

  Eligibility

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

Inclusion Criteria:

  • Males and females between 18 and 60 years of age
  • Female subjects must be neither pregnant nor breast-feeding and must lack child-bearing potential, as defined by either: post-menopausal or surgically sterile or use an effective method of contraception for the duration of the study
  • Have Relapsing Remitting Multiple Sclerosis (RRMS) according to the revised McDonald criteria 2005
  • Have brain and/or spinal MRI with findings typical of Multiple Sclerosis (MS)
  • Have disease duration for more than 12 months
  • Have disease activity characterized by at least one clinical event and one or more Gadolinium-enhancing MRI lesions within the 6 months prior to randomization
  • Have score of <=5.5 on the Expanded Disability Status Scale (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
  • Have received or have used anytime monoclonal antibodies, mitoxantrone, cytotoxic or immunosuppressive therapy (excluding systemic steroids and adrenocorticotrophic hormone [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
  • Other protocol defined exclusion criteria could apply
  Contacts and Locations
Choosing to participate in a study is an important personal decision. Talk with your doctor and family members or friends about deciding to join a study. To learn more about this study, you or your doctor may contact the study research staff using the Contacts provided below. For general information, see Learn About Clinical Studies.

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:
Publications:
Responsible Party: Merck KGaA
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: June 6, 2014
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, Relapsing-Remitting
Multiple Sclerosis
Sclerosis
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 July 24, 2014