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| ID | Type | Description | Link |
|---|---|---|---|
| 2006-003037-32 |
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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.
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| Label | Type | Description | Intervention Names |
|---|---|---|---|
| Rebif® New Formulation (IFN-beta-1a, RNF) | Experimental |
| |
| Placebo/RNF | Placebo Comparator |
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| Name | Type | Description | Arm Group Labels | Other Names |
|---|---|---|---|---|
| Rebif® New Formulation (IFN-beta-1a, RNF) | Drug | RNF will be administered at a dose of 44 mcg subcutaneously three times a week for 40 weeks. |
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| Measure | Description | Time Frame |
|---|---|---|
| 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). | 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). | Baseline up to Week 40 |
| 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. | 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. |
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Inclusion Criteria:
Exclusion Criteria:
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| Name | Affiliation | Role |
|---|---|---|
| Bettina Stubinski, MD | Merck Serono SA - Geneva, an affiliate of Merck KGaA Darmstadt, Germany | Study Director |
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| PubMed Identifier | Type | Citation | Retractions |
|---|---|---|---|
| 20200197 | Result | 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. | |
| 21880336 | Result |
| Label | URL |
|---|---|
| Full FDA approved prescribing information can be found here | View source |
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Participants meeting the eligibility criteria during screening period of up to 14 days were randomly assigned in a 2:1 ratio to receive either Rebif® New Formulation or matching placebo for 16 weeks. There were 33 screening failures: participants who did not meet all eligibility criteria (n=29), withdrawal of consent (n=3), and lost of view (n=1).
Date of first participant first visit: 15 Dec 2006. Date of last participant last visit: 28 Nov 2008. Twenty five trial centers enrolled participants in the following countries: Bulgaria (7), Canada(2), Estonia (2), Germany (1), Italy(2), Lithuania (1), Romania (1), Russian Federation (4), Serbia (2), and Spain (3).
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| ID | Title | Description |
|---|---|---|
| FG000 | Rebif® New Formulation (IFN-beta-1a, RNF) | RNF 44 microgram (mcg) administered subcutaneously three times a week for 40 weeks. |
| FG001 | Placebo/RNF | Matching placebo administered subcutaneously three times a week for 16 weeks, followed by RNF 44 mcg administered subcutaneously three times a week for subsequent 24 weeks. |
| Title | Milestones | Reasons Not Completed | |||||
|---|---|---|---|---|---|---|---|
| Overall Study |
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| Placebo | Drug | Matching placebo will be administered subcutaneously three times a week for 16 weeks. |
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| Rebif® New Formulation (IFN-beta-1a, RNF) | Drug | RNF will be administered at a dose of 44 mcg subcutaneously three times a week from Week 17 to Week 40. |
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| 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). | Up to Week 40 |
| 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. |
| 33329329 | Derived | 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. |
| COMPLETED |
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| NOT COMPLETED |
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Intent to treat (ITT) population included all randomized participants who received at least one dose of study drug.
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| ID | Title | Description |
|---|---|---|
| BG000 | Rebif® New Formulation (IFN-beta-1a, RNF) | RNF 44 mcg administered subcutaneously three times a week for 40 weeks. |
| BG001 | Placebo/RNF | Matching placebo administered subcutaneously three times a week for 16 weeks, followed by RNF 44 mcg administered subcutaneously three times a week for subsequent 24 weeks. |
| BG002 | Total | Total of all reporting groups |
| Units | Counts |
|---|---|
| Participants |
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| Title | Description | Population Description | Parameter Type | Dispersion Type | Unit of Measure | Calculate Percentage | Denominator Units Selected | Denominators | Classes | ||||||||||||
|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|
| Age, Categorical | Count of Participants | Participants |
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| Age, Continuous | Mean | Standard Deviation | years |
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| Sex: Female, Male | Count of Participants | Participants |
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| Region of Enrollment | Number | participants |
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| Type | Title | Description | Population Description | Reporting Status | Anticipated Posting Date | Parameter Type | Dispersion Type | Unit of Measure | Calculate Percentage | Time Frame | Units Analyzed | Denominator Units Selected | Arm/Group Information | Denominators | Classes | Analyses | |||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||
|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|
| Primary | 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). | ITT population included all randomized participants who received at least one dose of study drug. | Posted | Mean | Standard Deviation | lesions | 16 Weeks |
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| Secondary | 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. | ITT population included all randomized participants who received at least one dose of study drug. Here, "N" (number of participants analyzed) signifies those participants who were evaluable for this measure. | Posted | Mean | Standard Deviation | lesions | Day 1 up to Week 16 and Week 17 up to Week 40 |
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| Primary | 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). | Safety population included all randomized participants who received at least one dose of study drug. Here, 'n' signifies those participants who were evaluable for the specified category. | Posted | Number | participants | Baseline up to Week 40 |
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| Secondary | 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). | ITT population included all randomized participants who received at least one dose of study drug. | Posted | Mean | Standard Deviation | lesions | Up to Week 40 |
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Baseline up to Week 40
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| ID | Title | Description | Deaths (Affected) | Deaths (At Risk) | Serious Events (Affected) | Serious Events (At Risk) | Other Events (Affected) | Other Events (At Risk) |
|---|---|---|---|---|---|---|---|---|
| EG000 | Rebif® New Formulation (IFN-beta-1a, RNF) | RNF 44 mcg administered subcutaneously three times a week for 40 weeks. | 4 | 120 | 100 | 120 | ||
| EG001 | Placebo/RNF | Matching placebo administered subcutaneously three times a week for 16 weeks, followed by RNF 44 mcg administered subcutaneously three times a week for subsequent 24 weeks. | 3 | 60 | 39 | 60 |
| Term | Organ System | Source Vocabulary | Assessment Type | Notes | Statistical Information |
|---|---|---|---|---|---|
| Tonsillitis | Infections and infestations | MedDRA (9.1) | Systematic Assessment |
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| Carpal tunnel syndrome | Nervous system disorders | MedDRA (9.1) | Systematic Assessment |
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| Pulmonary tuberculosis | Infections and infestations | MedDRA (9.1) | Systematic Assessment |
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| Pyelonephritis acute | Infections and infestations | MedDRA (9.1) | Systematic Assessment |
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| Road traffic accident | Injury, poisoning and procedural complications | MedDRA (9.1) | Systematic Assessment |
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| Fall | Injury, poisoning and procedural complications | MedDRA (9.1) | Systematic Assessment |
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| Joint dislocation | Injury, poisoning and procedural complications | MedDRA (9.1) | Systematic Assessment |
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| Back pain | Musculoskeletal and connective tissue disorders | MedDRA (9.1) | Systematic Assessment |
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| Term | Organ System | Source Vocabulary | Assessment Type | Notes | Statistical Information |
|---|---|---|---|---|---|
| Influenza like illness | General disorders | MedDRA (9.1) | Systematic Assessment |
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| Injection site erythema | General disorders | MedDRA (9.1) | Systematic Assessment |
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| Injection site pain | General disorders | MedDRA (9.1) | Systematic Assessment |
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| Pyrexia | General disorders | MedDRA (9.1) | Systematic Assessment |
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| Asthenia | General disorders | MedDRA (9.1) | Systematic Assessment |
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| Chills | General disorders | MedDRA (9.1) | Systematic Assessment |
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| Fatigue | General disorders | MedDRA (9.1) | Systematic Assessment |
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| Headache | Nervous system disorders | MedDRA (9.1) | Systematic Assessment |
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| Dizziness | Nervous system disorders | MedDRA (9.1) | Systematic Assessment |
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| Nasopharyngitis | Infections and infestations | MedDRA (9.1) | Systematic Assessment |
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| Upper respiratory tract infection | Infections and infestations | MedDRA (9.1) | Systematic Assessment |
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| Pain in extremity | Musculoskeletal and connective tissue disorders | MedDRA (9.1) | Systematic Assessment |
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| Back pain | Musculoskeletal and connective tissue disorders | MedDRA (9.1) | Systematic Assessment |
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| Myalgia | Musculoskeletal and connective tissue disorders | MedDRA (9.1) | Systematic Assessment |
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| Alanine aminotransferase increased | Investigations | MedDRA (9.1) | Systematic Assessment |
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| Aspartate aminotransferase increased | Investigations | MedDRA (9.1) | Systematic Assessment |
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| Anxiety | Psychiatric disorders | MedDRA (9.1) | Systematic Assessment |
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| Vertigo | Ear and labyrinth disorders | MedDRA (9.1) | Systematic Assessment |
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| Title | Organization | Phone | Extension | |
|---|---|---|---|---|
| Merck KGaA Communication Center | Merck Serono, a division of Merck KGaA | +49-6151-72-5200 | service@merckgroup.com |
| ID | Term |
|---|---|
| D020529 | Multiple Sclerosis, Relapsing-Remitting |
| ID | Term |
|---|---|
| D009103 | Multiple Sclerosis |
| D020278 | Demyelinating Autoimmune Diseases, CNS |
| D020274 | Autoimmune Diseases of the Nervous System |
| D009422 | Nervous System Diseases |
| D003711 | Demyelinating Diseases |
| D001327 | Autoimmune Diseases |
| D007154 | Immune System Diseases |
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| ID | Term |
|---|---|
| C428112 | peginterferon beta-1a |
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| >=65 years |
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| Male |
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| Canada |
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| Estonia |
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| Germany |
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| Italy |
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| Lithuania |
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| Romania |
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| Russian Federation |
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| Serbia |
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| Spain |
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| Units | Counts |
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| Participants |
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