Multiple Sclerosis, Relapsing-RemittingPhase 3IMPROVENCT00441103
A Study to Evaluate Rebif® New Formulation (Interferon-beta-1a) in Relapsing Remitting Multiple Sclerosis
A Phase 3 study testing Rebif® New Formulation (IFN-beta-1a, RNF) in people with Multiple Sclerosis, Relapsing-Remitting, run by Merck KGaA, Darmstadt, Germany.
Trial 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… Read more about this study
- Who is it for?
- Ages 18 to 60 years
- Conditions the study is for
- Multiple Sclerosis, Relapsing-Remitting
- What is being tested?
- Rebif® New Formulation (IFN-beta-1a, RNF)
- Type of treatment
- Injection or infusion
- Could I receive a placebo?
- Yes, some participants may receive a placebo
- How many people
- 180 participants
- Where
- No sites listed yet
- Study dates
- Dec 2006to Feb 2009
- Phase
- Phase 3
- Are there results?
- Yes, posted in the registrySummary in the doctors' view
Key requirements
Who can take part, as listed by the sponsor. Only the study team can confirm whether you are eligible, so take this list to your doctor.
- Ages 18 to 60 years
- All sexes
- No healthy volunteers
- Adult
Who may be able to join
- 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
Show all 9Show fewer
- 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
Who cannot join
- 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
About this study
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
General Note: throughout this record, "Rebif® New Formulation" is used for historical and consistency purposes.
Objectives:
Read more
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.
- Conditions
- Multiple Sclerosis, Relapsing-Remitting
- Being tested
- Rebif® New Formulation (IFN-beta-1a, RNF), Placebo
- Keywords
- Subjects with relapsing remitting multiple sclerosis
- Medical subject headings
- Multiple Sclerosis, Relapsing-Remitting
What participants receive
What participants receive. In a randomised study each person is assigned to one group by chance.
Rebif® New Formulation (IFN-beta-1a, RNF)Drug
Also called IFN-beta-1a
RNF will be administered at a dose of 44 mcg subcutaneously three times a week for 40 weeks.
PlaceboDrug
Matching placebo will be administered subcutaneously three times a week for 16 weeks.
Rebif® New Formulation (IFN-beta-1a, RNF)Drug
Also called IFN-beta-1a
RNF will be administered at a dose of 44 mcg subcutaneously three times a week from Week 17 to Week 40.
| Study group | Role | What they receive |
|---|---|---|
| Rebif® New Formulation (IFN-beta-1a, RNF) | Experimental | Not described Receives: Drug: Rebif® New Formulation (IFN-beta-1a, RNF) |
| Placebo/RNF | Placebo comparator | Not described Receives: Drug: Placebo; Drug: Rebif® New Formulation (IFN-beta-1a, RNF) |
What is being measured
The primary outcome is the main question the study is designed to answer.
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).
Measured: 16 Weeks
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).
Measured: Baseline up to Week 40
Secondary outcomes (2)
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.
Measured: Day 1 up to Week 16 and Week 17 up to Week 40
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).
Measured: Up to Week 40
Timeline
From the start of the study to its completion; the mark is today. Estimated dates are the sponsor’s plan.
- First posted28 Feb 2007 (estimated)
- Study startDec 2006
- Primary completionNov 2008
- Study completionFeb 2009
Resources
- Official record on ClinicalTrials.govThe registry entry this page is built from, with its full change history.
- Posted resultsParticipant flow, outcome measures and adverse events reported by the sponsor.
- Publications (3)Papers the sponsor has linked to this study.
- Other trials for Multiple Sclerosis, Relapsing-RemittingStudies of the same condition, open and under way.
- What the trial phases meanHow a treatment moves from first tests in people to approval.
More details
For doctors and researchers: how the study is designed, who runs it, and its registry IDs.
Study design
- Study type
- Interventional
- Phase
- Phase 3
- Primary purpose
- Treatment
- Allocation
- Randomised
- Intervention model
- Factorial
- Masking
- Double blind
- Who is masked
- Participant, Investigator
- Enrolment
- 180 participants (actual)
Sponsor and investigators
- Lead sponsor
- Merck KGaA, Darmstadt, Germany
- Sponsor type
- Industry (pharma, biotech, devices)
- Responsible party
- Sponsor
- Investigators
- Bettina Stubinski, MD, Study director, Merck Serono SA - Geneva, an affiliate of Merck KGaA Darmstadt, Germany
IDs, dates and publications
- ClinicalTrials.gov ID
- NCT00441103
- Sponsor's protocol ID
- 27178
- Other IDs
- 2006-003037-32
- Acronym
- IMPROVE
- Status last verified
- Jun 2014
- First submitted
- 26 Feb 2007
- Last updated
- 9 Jul 2014
- Results posted
- Yes, on ClinicalTrials.gov
Publications
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.
PubMed 20200197De 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.
PubMed 21880336Giorgio 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.
PubMed 33329329
Study at a glance
From the registry record, last updated by the sponsor on 9 Jul 2014. Recruitment status is as the sponsor reported it: confirm with the study team.
- 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
- ClinicalTrials.gov ID
- NCT00441103
- Acronym / sponsor ID
- IMPROVE / 27178
- Conditions
- Multiple Sclerosis, Relapsing-Remitting
- Keywords
- Subjects with relapsing remitting multiple sclerosis
- Phase
- Phase 3
- Study type
- Interventional
- Recruitment status
- Completed
- Enrolment
- 180 participants (actual)
- Lead sponsor
- Merck KGaA, Darmstadt, GermanyIndustry (pharma, biotech, devices)
- Study start
- Dec 2006
- Primary completion
- Nov 2008 (actual)
- Study completion
- Feb 2009 (actual)
- First posted
- 28 Feb 2007 (estimated)
- Results
- Posted 5 Jul 2010
Clinical summary
The research question as the sponsor registered it. This describes what the study plans to test, not what it found.
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 design
- Primary purpose
- Treatment
- Allocation
- Randomised
- Intervention model
- Factorial
- Masking
- Double blind (participant, investigator)
- Number of arms
- 2
| Arm | Type | Receives |
|---|---|---|
| Rebif® New Formulation (IFN-beta-1a, RNF) | Experimental | Drug: Rebif® New Formulation (IFN-beta-1a, RNF) |
| Placebo/RNF | Placebo comparator | Drug: Placebo, Drug: Rebif® New Formulation (IFN-beta-1a, RNF) |
Who may qualify
- Ages
- 18 to 60 years
- Sex
- All
- Healthy volunteers
- Not accepted
- Age groups
- Adult
Key inclusion criteria (9 listed)
- 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
Key exclusion criteria (6 listed)
- 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
Eligibility is decided by the study team after screening; this overview does not establish that a patient qualifies. Full inclusion and exclusion criteria.
Interventions
| Intervention | Type | Arms |
|---|---|---|
| Rebif® New Formulation (IFN-beta-1a, RNF)Also: IFN-beta-1aRNF will be administered at a dose of 44 mcg subcutaneously three times a week for 40 weeks. | Drug | Rebif® New Formulation (IFN-beta-1a, RNF) |
| PlaceboMatching placebo will be administered subcutaneously three times a week for 16 weeks. | Drug | Placebo/RNF |
| Rebif® New Formulation (IFN-beta-1a, RNF)Also: IFN-beta-1aRNF will be administered at a dose of 44 mcg subcutaneously three times a week from Week 17 to Week 40. | Drug | Placebo/RNF |
Primary outcome
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).
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).
2 secondary outcomes
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
Number of CU Active MRI Lesions
Time frame: Up to Week 40
Results and safety
Loading the posted results from ClinicalTrials.gov…
Research links
- Official record on ClinicalTrials.govLast updated by the sponsor 9 Jul 2014.
- Posted resultsParticipant flow, baseline, all outcome measures and adverse events.
- Results publication: PubMed 20200197De 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 publication: PubMed 21880336De 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.
- Derived from this study: PubMed 33329329Giorgio 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.
- Full FDA approved prescribing information can be found hereLink provided by the sponsor.
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Referral and contact
AzTrials does not enrol participants or take referrals. Contact the study team or a site listed below; they decide who can take part. This study is not recruiting at the moment.
Bettina Stubinski, MD study director
Merck Serono SA - Geneva, an affiliate of Merck KGaA Darmstadt, Germany
Questions about this trial
What is this clinical trial studying?
A Phase 3 study testing Rebif® New Formulation (IFN-beta-1a, RNF) in people with Multiple Sclerosis, Relapsing-Remitting, run by Merck KGaA, Darmstadt, Germany.
The full registered description is in the About this study section and the official record.
Who may be eligible to take part?
The sponsor lists 9 inclusion and 6 exclusion criteria. Eligibility is decided by the study team after screening, so read the full criteria and contact a listed site.
Is this clinical trial currently recruiting?
The record says: finished, as of the sponsor's last update on 9 Jul 2014. Status can change between updates, so confirm with the study contact before making plans.
What are the possible benefits and risks?
They depend on the study and the treatment, and no study can promise a benefit. Some participants in this study may receive a placebo. The study team explains the known risks during informed consent, before anyone joins; the record itself does not list them.
What does this phase mean?
Phase 3 studies compare the treatment with the current standard treatment or a placebo in a large group, to confirm how well it works and watch for side effects.
Not every study follows the same path, and some studies (observational studies, device studies) have no phase.
Are results available for this study?
Yes. Results are posted in the registry (first posted 5 Jul 2010). A summary is in the For doctors view, and the full results are on ClinicalTrials.gov.
How can a doctor refer a patient or contact the research team?
The record lists no contact. The official record names the sponsor, who can be asked directly. AzTrials does not enrol participants or take referrals.
What does the primary outcome measure?
Number of Combined Unique (CU) Active Magnetic Resonance Imaging (MRI) Lesions at Week 16 (time frame: 16 Weeks). The study lists 2 primary outcomes in all. It is what the study was designed to measure, not a finding.
Where can I read the original study information?
On the ClinicalTrials.gov record for NCT00441103, which also lists 3 linked publications.
Does a listing mean the treatment is approved or proven to work?
No. A listing means the study is registered. It does not show that the treatment is safe, works, or is approved by a regulator.
How often is this information updated?
AzTrials copies changed records from ClinicalTrials.gov every night and reloads the whole registry every week. The sponsor last updated this record on 9 Jul 2014.