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

June 6, 2014 updated by: Merck KGaA, Darmstadt, Germany

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

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.

Study Overview

Status

Completed

Conditions

Intervention / Treatment

Study Type

Interventional

Enrollment (Actual)

180

Phase

  • Phase 3

Participation Criteria

Researchers look for people who fit a certain description, called eligibility criteria. Some examples of these criteria are a person's general health condition or prior treatments.

Eligibility Criteria

Ages Eligible for Study

18 years to 60 years (Adult)

Accepts Healthy Volunteers

No

Genders Eligible for Study

All

Description

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

Study Plan

This section provides details of the study plan, including how the study is designed and what the study is measuring.

How is the study designed?

Design Details

  • Primary Purpose: Treatment
  • Allocation: Randomized
  • Interventional Model: Factorial Assignment
  • Masking: Double

Arms and Interventions

Participant Group / Arm
Intervention / Treatment
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 Names:
  • IFN-beta-1a
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 Names:
  • IFN-beta-1a
Placebo Comparator: Placebo/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 Names:
  • IFN-beta-1a
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 Names:
  • IFN-beta-1a
Drug: Placebo
Matching placebo will be administered subcutaneously three times a week for 16 weeks.

What is the study measuring?

Primary Outcome Measures

Outcome Measure
Measure Description
Time Frame
Number of Combined Unique (CU) Active Magnetic Resonance Imaging (MRI) Lesions at Week 16
Time Frame: 16 Weeks
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).
16 Weeks
Number of Participants With Adverse Events (AEs) and Serious Adverse Events (SAEs)
Time Frame: Baseline up to Week 40
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).
Baseline up to Week 40

Secondary Outcome Measures

Outcome Measure
Measure Description
Time Frame
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
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.
Day 1 up to Week 16 and Week 17 up to Week 40
Number of CU Active MRI Lesions
Time Frame: Up to Week 40
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).
Up to Week 40

Collaborators and Investigators

This is where you will find people and organizations involved with this study.

Sponsor

Merck KGaA, Darmstadt, Germany

Investigators

  • Study Director: Bettina Stubinski, MD, Merck Serono SA - Geneva, an affiliate of Merck KGaA Darmstadt, Germany

Publications and helpful links

The person responsible for entering information about the study voluntarily provides these publications. These may be about anything related to the study.

General Publications

Helpful Links

Study record dates

These dates track the progress of study record and summary results submissions to ClinicalTrials.gov. Study records and reported results are reviewed by the National Library of Medicine (NLM) to make sure they meet specific quality control standards before being posted on the public website.

Study Major Dates

Study Start

December 1, 2006

Primary Completion (Actual)

November 1, 2008

Study Completion (Actual)

February 1, 2009

Study Registration Dates

First Submitted

February 26, 2007

First Submitted That Met QC Criteria

February 26, 2007

First Posted (Estimate)

February 28, 2007

Study Record Updates

Last Update Posted (Estimate)

July 9, 2014

Last Update Submitted That Met QC Criteria

June 6, 2014

Last Verified

June 1, 2014

More Information

Terms related to this study

Keywords

Additional Relevant MeSH Terms

Other Study ID Numbers

  • 27178
  • 2006-003037-32

This information was retrieved directly from the website clinicaltrials.gov without any changes. If you have any requests to change, remove or update your study details, please contact register@clinicaltrials.gov. As soon as a change is implemented on clinicaltrials.gov, this will be updated automatically on our website as well.

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