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

Primary Purpose

Multiple Sclerosis, Relapsing-Remitting

Status

Completed

Phase

Phase 3

Locations

Study Type

Interventional

Intervention

Rebif® New Formulation (IFN-beta-1a, RNF)

Placebo

Rebif® New Formulation (IFN-beta-1a, RNF)

About this trial

This is an interventional treatment trial for Multiple Sclerosis, Relapsing-Remitting focused on measuring Subjects with relapsing remitting multiple sclerosis

Eligibility Criteria

18 Years - 60 Years (Adult)All SexesDoes not accept healthy volunteers

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

Sites / Locations

Arms of the Study

Arm 1

Arm 2

Arm Type

Experimental

Placebo Comparator

Arm Label

Rebif® New Formulation (IFN-beta-1a, RNF)

Placebo/RNF

Arm Description

Outcomes

Primary Outcome Measures

Number of Combined Unique (CU) Active Magnetic Resonance Imaging (MRI) Lesions at Week 16

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)

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.

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

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).

Full Information

NCT ID

NCT00441103

First Posted

February 26, 2007

Last Updated

June 6, 2014

Sponsor

Merck KGaA, Darmstadt, Germany

1. Study Identification

Unique Protocol Identification Number

NCT00441103

Brief Title

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

Acronym

IMPROVE

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

Study Type

Interventional

2. Study Status

Record Verification Date

June 2014

Overall Recruitment Status

Completed

Study Start Date

December 2006 (undefined)

Primary Completion Date

November 2008 (Actual)

Study Completion Date

February 2009 (Actual)

3. Sponsor/Collaborators

Responsible Party, by Official Title

Sponsor

Name of the Sponsor

Merck KGaA, Darmstadt, Germany

4. Oversight

5. Study Description

Brief Summary

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.

6. Conditions and Keywords

Primary Disease or Condition Being Studied in the Trial, or the Focus of the Study

Multiple Sclerosis, Relapsing-Remitting

Keywords

Subjects with relapsing remitting multiple sclerosis

7. Study Design

Primary Purpose

Treatment

Study Phase

Phase 3

Interventional Study Model

Factorial Assignment

Masking

ParticipantInvestigator

Allocation

Randomized

Enrollment

180 (Actual)

8. Arms, Groups, and Interventions

Arm Title

Rebif® New Formulation (IFN-beta-1a, RNF)

Arm Type

Experimental

Arm Title

Placebo/RNF

Arm Type

Placebo Comparator

Intervention Type

Drug

Intervention Name(s)

Rebif® New Formulation (IFN-beta-1a, RNF)

Other Intervention Name(s)

IFN-beta-1a

Intervention Description

RNF will be administered at a dose of 44 mcg subcutaneously three times a week for 40 weeks.

Intervention Type

Drug

Intervention Name(s)

Placebo

Intervention Description

Matching placebo will be administered subcutaneously three times a week for 16 weeks.

Intervention Type

Drug

Intervention Name(s)

Rebif® New Formulation (IFN-beta-1a, RNF)

Other Intervention Name(s)

IFN-beta-1a

Intervention Description

RNF will be administered at a dose of 44 mcg subcutaneously three times a week from Week 17 to Week 40.

Primary Outcome Measure Information:

Title

Number of Combined Unique (CU) Active Magnetic Resonance Imaging (MRI) Lesions at Week 16

Description

Time Frame

16 Weeks

Title

Number of Participants With Adverse Events (AEs) and Serious Adverse Events (SAEs)

Description

Time Frame

Baseline up to Week 40

Secondary Outcome Measure Information:

Title

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.

Description

Time Frame

Day 1 up to Week 16 and Week 17 up to Week 40

Title

Number of CU Active MRI Lesions

Description

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).

Time Frame

Up to Week 40

10. Eligibility

Sex

All

Minimum Age & Unit of Time

18 Years

Maximum Age & Unit of Time

60 Years

Accepts Healthy Volunteers

Eligibility 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

Overall Study Officials:

First Name & Middle Initial & Last Name & Degree

Bettina Stubinski, MD

Organizational Affiliation

Merck Serono SA - Geneva, an affiliate of Merck KGaA Darmstadt, Germany

Official's Role

Study Director

12. IPD Sharing Statement

Citations:

PubMed Identifier

20200197

Citation

De Stefano N, Curtin F, Stubinski B, Blevins G, Drulovic J, Issard D, Shotekov P, Gasperini C; IMPROVE Study Investigators. Rapid benefits of a new formulation of subcutaneous interferon beta-1a in relapsing-remitting multiple sclerosis. Mult Scler. 2010 Jul;16(7):888-92. doi: 10.1177/1352458510362442. Epub 2010 Mar 3.

Results Reference

result

PubMed Identifier

21880336

Citation

De Stefano N, Sormani MP, Stubinski B, Blevins G, Drulovic JS, Issard D, Shotekov P, Gasperini C. Efficacy and safety of subcutaneous interferon beta-1a in relapsing-remitting multiple sclerosis: further outcomes from the IMPROVE study. J Neurol Sci. 2012 Jan 15;312(1-2):97-101. doi: 10.1016/j.jns.2011.08.013. Epub 2011 Aug 31.

Results Reference

result

PubMed Identifier

33329329

Citation

Giorgio A, Battaglini M, Gentile G, Stromillo ML, Gasperini C, Visconti A, Paolillo A, De Stefano N. Mapping the Progressive Treatment-Related Reduction of Active MRI Lesions in Multiple Sclerosis. Front Neurol. 2020 Nov 20;11:585296. doi: 10.3389/fneur.2020.585296. eCollection 2020.

Results Reference

derived

Links:

URL

http://www.mslifelines.com

Description

Full FDA approved prescribing information can be found here

Learn more about this trial

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

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