Ignite Creation Date:
2025-12-24 @ 7:11 PM
Ignite Modification Date:
2025-12-27 @ 2:37 PM
Study NCT ID:
NCT00441103
Status:
COMPLETED
Last Update Posted:
2014-07-09
First Post:
2007-02-26
Is NOT Gene Therapy:
True
Has Adverse Events:
True
Brief Title:
A Study to Evaluate Rebif® New Formulation (Interferon-beta-1a) in Relapsing Remitting Multiple Sclerosis
Sponsor:
Organization:
Raw JSON
{'hasResults': True, 'derivedSection': {'miscInfoModule': {'versionHolder': '2025-12-24', 'removedCountries': ['Canada', 'Germany', 'Italy', 'Russia', 'Spain', 'Switzerland']}, 'conditionBrowseModule': {'meshes': [{'id': 'D020529', 'term': 'Multiple Sclerosis, Relapsing-Remitting'}], 'ancestors': [{'id': 'D009103', 'term': 'Multiple Sclerosis'}, {'id': 'D020278', 'term': 'Demyelinating Autoimmune Diseases, CNS'}, {'id': 'D020274', 'term': 'Autoimmune Diseases of the Nervous System'}, {'id': 'D009422', 'term': 'Nervous System Diseases'}, {'id': 'D003711', 'term': 'Demyelinating Diseases'}, {'id': 'D001327', 'term': 'Autoimmune Diseases'}, {'id': 'D007154', 'term': 'Immune System Diseases'}]}, 'interventionBrowseModule': {'meshes': [{'id': 'C428112', 'term': 'peginterferon beta-1a'}]}}, 'resultsSection': {'moreInfoModule': {'pointOfContact': {'email': 'service@merckgroup.com', 'phone': '+49-6151-72-5200', 'title': 'Merck KGaA Communication Center', 'organization': 'Merck Serono, a division of Merck KGaA'}, 'certainAgreement': {'restrictionType': 'OTHER', 'piSponsorEmployee': False, 'restrictiveAgreement': True}}, 'adverseEventsModule': {'timeFrame': 'Baseline up to Week 40', 'eventGroups': [{'id': 'EG000', 'title': 'Rebif® New Formulation (IFN-beta-1a, RNF)', 'description': 'RNF 44 mcg administered subcutaneously three times a week for 40 weeks.', 'otherNumAtRisk': 120, 'otherNumAffected': 100, 'seriousNumAtRisk': 120, 'seriousNumAffected': 4}, {'id': 'EG001', 'title': 'Placebo/RNF', 'description': '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.', 'otherNumAtRisk': 60, 'otherNumAffected': 39, 'seriousNumAtRisk': 60, 'seriousNumAffected': 3}], 'otherEvents': [{'term': 'Influenza like illness', 'stats': [{'groupId': 'EG000', 'numAtRisk': 120, 'numEvents': 110, 'numAffected': 60}, {'groupId': 'EG001', 'numAtRisk': 60, 'numEvents': 10, 'numAffected': 10}], 'organSystem': 'General disorders', 'assessmentType': 'SYSTEMATIC_ASSESSMENT', 'sourceVocabulary': 'MedDRA (9.1)'}, {'term': 'Injection site erythema', 'stats': [{'groupId': 'EG000', 'numAtRisk': 120, 'numEvents': 60, 'numAffected': 39}, {'groupId': 'EG001', 'numAtRisk': 60, 'numEvents': 6, 'numAffected': 4}], 'organSystem': 'General disorders', 'assessmentType': 'SYSTEMATIC_ASSESSMENT', 'sourceVocabulary': 'MedDRA (9.1)'}, {'term': 'Injection site pain', 'stats': [{'groupId': 'EG000', 'numAtRisk': 120, 'numEvents': 13, 'numAffected': 12}, {'groupId': 'EG001', 'numAtRisk': 60, 'numEvents': 1, 'numAffected': 1}], 'organSystem': 'General disorders', 'assessmentType': 'SYSTEMATIC_ASSESSMENT', 'sourceVocabulary': 'MedDRA (9.1)'}, {'term': 'Pyrexia', 'stats': [{'groupId': 'EG000', 'numAtRisk': 120, 'numEvents': 14, 'numAffected': 9}, {'groupId': 'EG001', 'numAtRisk': 60, 'numEvents': 5, 'numAffected': 3}], 'organSystem': 'General disorders', 'assessmentType': 'SYSTEMATIC_ASSESSMENT', 'sourceVocabulary': 'MedDRA (9.1)'}, {'term': 'Asthenia', 'stats': [{'groupId': 'EG000', 'numAtRisk': 120, 'numEvents': 11, 'numAffected': 8}, {'groupId': 'EG001', 'numAtRisk': 60, 'numEvents': 8, 'numAffected': 3}], 'organSystem': 'General disorders', 'assessmentType': 'SYSTEMATIC_ASSESSMENT', 'sourceVocabulary': 'MedDRA (9.1)'}, {'term': 'Chills', 'stats': [{'groupId': 'EG000', 'numAtRisk': 120, 'numEvents': 11, 'numAffected': 8}, {'groupId': 'EG001', 'numAtRisk': 60, 'numEvents': 3, 'numAffected': 1}], 'organSystem': 'General disorders', 'assessmentType': 'SYSTEMATIC_ASSESSMENT', 'sourceVocabulary': 'MedDRA (9.1)'}, {'term': 'Fatigue', 'stats': [{'groupId': 'EG000', 'numAtRisk': 120, 'numEvents': 8, 'numAffected': 7}, {'groupId': 'EG001', 'numAtRisk': 60, 'numEvents': 0, 'numAffected': 0}], 'organSystem': 'General disorders', 'assessmentType': 'SYSTEMATIC_ASSESSMENT', 'sourceVocabulary': 'MedDRA (9.1)'}, {'term': 'Headache', 'stats': [{'groupId': 'EG000', 'numAtRisk': 120, 'numEvents': 66, 'numAffected': 37}, {'groupId': 'EG001', 'numAtRisk': 60, 'numEvents': 17, 'numAffected': 10}], 'organSystem': 'Nervous system disorders', 'assessmentType': 'SYSTEMATIC_ASSESSMENT', 'sourceVocabulary': 'MedDRA (9.1)'}, {'term': 'Dizziness', 'stats': [{'groupId': 'EG000', 'numAtRisk': 120, 'numEvents': 3, 'numAffected': 3}, {'groupId': 'EG001', 'numAtRisk': 60, 'numEvents': 4, 'numAffected': 4}], 'organSystem': 'Nervous system disorders', 'assessmentType': 'SYSTEMATIC_ASSESSMENT', 'sourceVocabulary': 'MedDRA (9.1)'}, {'term': 'Nasopharyngitis', 'stats': [{'groupId': 'EG000', 'numAtRisk': 120, 'numEvents': 7, 'numAffected': 7}, {'groupId': 'EG001', 'numAtRisk': 60, 'numEvents': 3, 'numAffected': 2}], 'organSystem': 'Infections and infestations', 'assessmentType': 'SYSTEMATIC_ASSESSMENT', 'sourceVocabulary': 'MedDRA (9.1)'}, {'term': 'Upper respiratory tract infection', 'stats': [{'groupId': 'EG000', 'numAtRisk': 120, 'numEvents': 5, 'numAffected': 4}, {'groupId': 'EG001', 'numAtRisk': 60, 'numEvents': 4, 'numAffected': 4}], 'organSystem': 'Infections and infestations', 'assessmentType': 'SYSTEMATIC_ASSESSMENT', 'sourceVocabulary': 'MedDRA (9.1)'}, {'term': 'Pain in extremity', 'stats': [{'groupId': 'EG000', 'numAtRisk': 120, 'numEvents': 7, 'numAffected': 6}, {'groupId': 'EG001', 'numAtRisk': 60, 'numEvents': 2, 'numAffected': 2}], 'organSystem': 'Musculoskeletal and connective tissue disorders', 'assessmentType': 'SYSTEMATIC_ASSESSMENT', 'sourceVocabulary': 'MedDRA (9.1)'}, {'term': 'Back pain', 'stats': [{'groupId': 'EG000', 'numAtRisk': 120, 'numEvents': 7, 'numAffected': 6}, {'groupId': 'EG001', 'numAtRisk': 60, 'numEvents': 1, 'numAffected': 1}], 'organSystem': 'Musculoskeletal and connective tissue disorders', 'assessmentType': 'SYSTEMATIC_ASSESSMENT', 'sourceVocabulary': 'MedDRA (9.1)'}, {'term': 'Myalgia', 'stats': [{'groupId': 'EG000', 'numAtRisk': 120, 'numEvents': 7, 'numAffected': 6}, {'groupId': 'EG001', 'numAtRisk': 60, 'numEvents': 0, 'numAffected': 0}], 'organSystem': 'Musculoskeletal and connective tissue disorders', 'assessmentType': 'SYSTEMATIC_ASSESSMENT', 'sourceVocabulary': 'MedDRA (9.1)'}, {'term': 'Alanine aminotransferase increased', 'stats': [{'groupId': 'EG000', 'numAtRisk': 120, 'numEvents': 7, 'numAffected': 7}, {'groupId': 'EG001', 'numAtRisk': 60, 'numEvents': 0, 'numAffected': 0}], 'organSystem': 'Investigations', 'assessmentType': 'SYSTEMATIC_ASSESSMENT', 'sourceVocabulary': 'MedDRA (9.1)'}, {'term': 'Aspartate aminotransferase increased', 'stats': [{'groupId': 'EG000', 'numAtRisk': 120, 'numEvents': 6, 'numAffected': 6}, {'groupId': 'EG001', 'numAtRisk': 60, 'numEvents': 0, 'numAffected': 0}], 'organSystem': 'Investigations', 'assessmentType': 'SYSTEMATIC_ASSESSMENT', 'sourceVocabulary': 'MedDRA (9.1)'}, {'term': 'Anxiety', 'stats': [{'groupId': 'EG000', 'numAtRisk': 120, 'numEvents': 2, 'numAffected': 2}, {'groupId': 'EG001', 'numAtRisk': 60, 'numEvents': 4, 'numAffected': 3}], 'organSystem': 'Psychiatric disorders', 'assessmentType': 'SYSTEMATIC_ASSESSMENT', 'sourceVocabulary': 'MedDRA (9.1)'}, {'term': 'Vertigo', 'stats': [{'groupId': 'EG000', 'numAtRisk': 120, 'numEvents': 1, 'numAffected': 1}, {'groupId': 'EG001', 'numAtRisk': 60, 'numEvents': 4, 'numAffected': 3}], 'organSystem': 'Ear and labyrinth disorders', 'assessmentType': 'SYSTEMATIC_ASSESSMENT', 'sourceVocabulary': 'MedDRA (9.1)'}], 'seriousEvents': [{'term': 'Tonsillitis', 'stats': [{'groupId': 'EG000', 'numAtRisk': 120, 'numEvents': 1, 'numAffected': 1}, {'groupId': 'EG001', 'numAtRisk': 60, 'numEvents': 0, 'numAffected': 0}], 'organSystem': 'Infections and infestations', 'assessmentType': 'SYSTEMATIC_ASSESSMENT', 'sourceVocabulary': 'MedDRA (9.1)'}, {'term': 'Carpal tunnel syndrome', 'stats': [{'groupId': 'EG000', 'numAtRisk': 120, 'numEvents': 0, 'numAffected': 0}, {'groupId': 'EG001', 'numAtRisk': 60, 'numEvents': 1, 'numAffected': 1}], 'organSystem': 'Nervous system disorders', 'assessmentType': 'SYSTEMATIC_ASSESSMENT', 'sourceVocabulary': 'MedDRA (9.1)'}, {'term': 'Pulmonary tuberculosis', 'stats': [{'groupId': 'EG000', 'numAtRisk': 120, 'numEvents': 1, 'numAffected': 1}, {'groupId': 'EG001', 'numAtRisk': 60, 'numEvents': 0, 'numAffected': 0}], 'organSystem': 'Infections and infestations', 'assessmentType': 'SYSTEMATIC_ASSESSMENT', 'sourceVocabulary': 'MedDRA (9.1)'}, {'term': 'Pyelonephritis acute', 'stats': [{'groupId': 'EG000', 'numAtRisk': 120, 'numEvents': 1, 'numAffected': 1}, {'groupId': 'EG001', 'numAtRisk': 60, 'numEvents': 0, 'numAffected': 0}], 'organSystem': 'Infections and infestations', 'assessmentType': 'SYSTEMATIC_ASSESSMENT', 'sourceVocabulary': 'MedDRA (9.1)'}, {'term': 'Road traffic accident', 'stats': [{'groupId': 'EG000', 'numAtRisk': 120, 'numEvents': 1, 'numAffected': 1}, {'groupId': 'EG001', 'numAtRisk': 60, 'numEvents': 0, 'numAffected': 0}], 'organSystem': 'Injury, poisoning and procedural complications', 'assessmentType': 'SYSTEMATIC_ASSESSMENT', 'sourceVocabulary': 'MedDRA (9.1)'}, {'term': 'Fall', 'stats': [{'groupId': 'EG000', 'numAtRisk': 120, 'numEvents': 0, 'numAffected': 0}, {'groupId': 'EG001', 'numAtRisk': 60, 'numEvents': 1, 'numAffected': 1}], 'organSystem': 'Injury, poisoning and procedural complications', 'assessmentType': 'SYSTEMATIC_ASSESSMENT', 'sourceVocabulary': 'MedDRA (9.1)'}, {'term': 'Joint dislocation', 'stats': [{'groupId': 'EG000', 'numAtRisk': 120, 'numEvents': 0, 'numAffected': 0}, {'groupId': 'EG001', 'numAtRisk': 60, 'numEvents': 1, 'numAffected': 1}], 'organSystem': 'Injury, poisoning and procedural complications', 'assessmentType': 'SYSTEMATIC_ASSESSMENT', 'sourceVocabulary': 'MedDRA (9.1)'}, {'term': 'Back pain', 'stats': [{'groupId': 'EG000', 'numAtRisk': 120, 'numEvents': 0, 'numAffected': 0}, {'groupId': 'EG001', 'numAtRisk': 60, 'numEvents': 1, 'numAffected': 1}], 'organSystem': 'Musculoskeletal and connective tissue disorders', 'assessmentType': 'SYSTEMATIC_ASSESSMENT', 'sourceVocabulary': 'MedDRA (9.1)'}], 'frequencyThreshold': '5'}, 'outcomeMeasuresModule': {'outcomeMeasures': [{'type': 'PRIMARY', 'title': 'Number of Combined Unique (CU) Active Magnetic Resonance Imaging (MRI) Lesions at Week 16', 'denoms': [{'units': 'Participants', 'counts': [{'value': '120', 'groupId': 'OG000'}, {'value': '60', 'groupId': 'OG001'}]}], 'groups': [{'id': 'OG000', 'title': 'Rebif® New Formulation (IFN-beta-1a, RNF)', 'description': 'RNF 44 mcg administered subcutaneously three times a week for 40 weeks.'}, {'id': 'OG001', 'title': 'Placebo/RNF', 'description': '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.'}], 'classes': [{'categories': [{'measurements': [{'value': '0.9', 'spread': '1.4', 'groupId': 'OG000'}, {'value': '3.0', 'spread': '4.1', 'groupId': 'OG001'}]}]}], 'analyses': [{'pValue': '<0.001', 'groupIds': ['OG000', 'OG001'], 'pValueComment': 'Non-parametric analysis of variance (ANOVA) with effects for treatment and the absence/presence of Gd-enhancing lesions at baseline as factors', 'statisticalMethod': 'ANOVA', 'nonInferiorityType': 'SUPERIORITY_OR_OTHER', 'testedNonInferiority': False}], 'paramType': 'MEAN', 'timeFrame': '16 Weeks', 'description': '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).', 'unitOfMeasure': 'lesions', 'dispersionType': 'Standard Deviation', 'reportingStatus': 'POSTED', 'populationDescription': 'ITT population included all randomized participants who received at least one dose of study drug.'}, {'type': 'SECONDARY', '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.', 'denoms': [{'units': 'Participants', 'counts': [{'value': '57', 'groupId': 'OG000'}]}], 'groups': [{'id': 'OG000', 'title': 'Placebo/RNF', 'description': '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.'}], 'classes': [{'title': 'Day 1 up to Week 16', 'categories': [{'measurements': [{'value': '2.31', 'spread': '2.63', 'groupId': 'OG000'}]}]}, {'title': 'Week 17 up to Week 40', 'categories': [{'measurements': [{'value': '0.65', 'spread': '0.95', 'groupId': 'OG000'}]}]}], 'analyses': [{'pValue': '<0.001', 'groupIds': ['OG000'], 'paramType': 'Mean Difference (Final Values)', 'paramValue': '-1.67', 'dispersionType': 'STANDARD_DEVIATION', 'dispersionValue': '2.33', 'groupDescription': "Mean difference was calculated by subtracting 'Day 1 up to Week 16' from 'Week 17 up to Week 40' and analyzed using Wilcoxon signed-rank test.", 'statisticalMethod': 'Wilcoxon signed-rank test', 'nonInferiorityType': 'SUPERIORITY_OR_OTHER', 'testedNonInferiority': False}], 'paramType': 'MEAN', 'timeFrame': 'Day 1 up to Week 16 and Week 17 up to Week 40', '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). Only "Placebo Followed by RNF" arm was evaluable for this outcome measure.', 'unitOfMeasure': 'lesions', 'dispersionType': 'Standard Deviation', 'reportingStatus': 'POSTED', 'populationDescription': '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.'}, {'type': 'PRIMARY', 'title': 'Number of Participants With Adverse Events (AEs) and Serious Adverse Events (SAEs)', 'denoms': [{'units': 'Participants', 'counts': [{'value': '120', 'groupId': 'OG000'}, {'value': '60', 'groupId': 'OG001'}]}], 'groups': [{'id': 'OG000', 'title': 'Rebif® New Formulation (IFN-beta-1a, RNF)', 'description': 'RNF 44 mcg administered subcutaneously three times a week for 40 weeks.'}, {'id': 'OG001', 'title': 'Placebo/RNF', 'description': '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.'}], 'classes': [{'title': 'AEs during double-blind period (n = 120, 60)', 'categories': [{'measurements': [{'value': '100', 'groupId': 'OG000'}, {'value': '39', 'groupId': 'OG001'}]}]}, {'title': 'AEs during rater-blind period (n = 112, 57)', 'categories': [{'measurements': [{'value': '72', 'groupId': 'OG000'}, {'value': '43', 'groupId': 'OG001'}]}]}, {'title': 'SAEs during overall period (n = 120, 60)', 'categories': [{'measurements': [{'value': '4', 'groupId': 'OG000'}, {'value': '3', 'groupId': 'OG001'}]}]}], 'paramType': 'NUMBER', 'timeFrame': 'Baseline up to Week 40', 'description': '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).', 'unitOfMeasure': 'participants', 'reportingStatus': 'POSTED', 'populationDescription': "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."}, {'type': 'SECONDARY', 'title': 'Number of CU Active MRI Lesions', 'denoms': [{'units': 'Participants', 'counts': [{'value': '120', 'groupId': 'OG000'}, {'value': '60', 'groupId': 'OG001'}]}], 'groups': [{'id': 'OG000', 'title': 'Rebif® New Formulation (IFN-beta-1a, RNF)', 'description': 'RNF 44 mcg administered subcutaneously three times a week for 40 weeks.'}, {'id': 'OG001', 'title': 'Placebo/RNF', 'description': '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.'}], 'classes': [{'categories': [{'measurements': [{'value': '0.62', 'spread': '1.29', 'groupId': 'OG000'}, {'value': '1.27', 'spread': '1.33', 'groupId': 'OG001'}]}]}], 'paramType': 'MEAN', 'timeFrame': 'Up to Week 40', '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).', 'unitOfMeasure': 'lesions', 'dispersionType': 'Standard Deviation', 'reportingStatus': 'POSTED', 'populationDescription': 'ITT population included all randomized participants who received at least one dose of study drug.'}]}, 'participantFlowModule': {'groups': [{'id': 'FG000', 'title': 'Rebif® New Formulation (IFN-beta-1a, RNF)', 'description': 'RNF 44 microgram (mcg) administered subcutaneously three times a week for 40 weeks.'}, {'id': 'FG001', 'title': 'Placebo/RNF', 'description': '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.'}], 'periods': [{'title': 'Overall Study', 'milestones': [{'type': 'STARTED', 'achievements': [{'comment': 'Intent to treat (ITT) population: all participants who received at least one dose of study drug.', 'groupId': 'FG000', 'numSubjects': '120'}, {'comment': 'Intent to treat (ITT) population: all participants who received at least one dose of study drug.', 'groupId': 'FG001', 'numSubjects': '60'}]}, {'type': 'COMPLETED', 'achievements': [{'groupId': 'FG000', 'numSubjects': '109'}, {'groupId': 'FG001', 'numSubjects': '56'}]}, {'type': 'NOT COMPLETED', 'achievements': [{'groupId': 'FG000', 'numSubjects': '11'}, {'groupId': 'FG001', 'numSubjects': '4'}]}], 'dropWithdraws': [{'type': 'Adverse Event', 'reasons': [{'groupId': 'FG000', 'numSubjects': '2'}, {'groupId': 'FG001', 'numSubjects': '1'}]}, {'type': 'Death', 'reasons': [{'groupId': 'FG000', 'numSubjects': '1'}, {'groupId': 'FG001', 'numSubjects': '0'}]}, {'type': 'Disease Progression', 'reasons': [{'groupId': 'FG000', 'numSubjects': '2'}, {'groupId': 'FG001', 'numSubjects': '0'}]}, {'type': 'Lost to Follow-up', 'reasons': [{'groupId': 'FG000', 'numSubjects': '1'}, {'groupId': 'FG001', 'numSubjects': '0'}]}, {'type': 'Protocol Violation', 'reasons': [{'groupId': 'FG000', 'numSubjects': '1'}, {'groupId': 'FG001', 'numSubjects': '0'}]}, {'type': 'Participant unable to use Rebiject II', 'reasons': [{'groupId': 'FG000', 'numSubjects': '1'}, {'groupId': 'FG001', 'numSubjects': '0'}]}, {'type': 'Participant refused MRI', 'reasons': [{'groupId': 'FG000', 'numSubjects': '1'}, {'groupId': 'FG001', 'numSubjects': '0'}]}, {'type': 'Inclusion criteria absent', 'reasons': [{'groupId': 'FG000', 'numSubjects': '1'}, {'groupId': 'FG001', 'numSubjects': '0'}]}, {'type': 'Non-compliant', 'reasons': [{'groupId': 'FG000', 'numSubjects': '0'}, {'groupId': 'FG001', 'numSubjects': '1'}]}, {'type': 'Participant decided to withdraw', 'reasons': [{'groupId': 'FG000', 'numSubjects': '1'}, {'groupId': 'FG001', 'numSubjects': '0'}]}, {'type': "Participant's reason", 'reasons': [{'groupId': 'FG000', 'numSubjects': '0'}, {'groupId': 'FG001', 'numSubjects': '1'}]}, {'type': 'Participant decided to stop', 'reasons': [{'groupId': 'FG000', 'numSubjects': '0'}, {'groupId': 'FG001', 'numSubjects': '1'}]}]}], 'recruitmentDetails': '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).', 'preAssignmentDetails': '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).'}, 'baselineCharacteristicsModule': {'denoms': [{'units': 'Participants', 'counts': [{'value': '120', 'groupId': 'BG000'}, {'value': '60', 'groupId': 'BG001'}, {'value': '180', 'groupId': 'BG002'}]}], 'groups': [{'id': 'BG000', 'title': 'Rebif® New Formulation (IFN-beta-1a, RNF)', 'description': 'RNF 44 mcg administered subcutaneously three times a week for 40 weeks.'}, {'id': 'BG001', 'title': 'Placebo/RNF', 'description': '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.'}, {'id': 'BG002', 'title': 'Total', 'description': 'Total of all reporting groups'}], 'measures': [{'title': 'Age, Categorical', 'classes': [{'categories': [{'title': '<=18 years', 'measurements': [{'value': '0', 'groupId': 'BG000'}, {'value': '0', 'groupId': 'BG001'}, {'value': '0', 'groupId': 'BG002'}]}, {'title': 'Between 18 and 65 years', 'measurements': [{'value': '120', 'groupId': 'BG000'}, {'value': '60', 'groupId': 'BG001'}, {'value': '180', 'groupId': 'BG002'}]}, {'title': '>=65 years', 'measurements': [{'value': '0', 'groupId': 'BG000'}, {'value': '0', 'groupId': 'BG001'}, {'value': '0', 'groupId': 'BG002'}]}]}], 'paramType': 'COUNT_OF_PARTICIPANTS', 'unitOfMeasure': 'Participants'}, {'title': 'Age, Continuous', 'classes': [{'categories': [{'measurements': [{'value': '34.0', 'spread': '7.8', 'groupId': 'BG000'}, {'value': '35.2', 'spread': '10.5', 'groupId': 'BG001'}, {'value': '34.4', 'spread': '8.8', 'groupId': 'BG002'}]}]}], 'paramType': 'MEAN', 'unitOfMeasure': 'years', 'dispersionType': 'STANDARD_DEVIATION'}, {'title': 'Sex: Female, Male', 'classes': [{'categories': [{'title': 'Female', 'measurements': [{'value': '88', 'groupId': 'BG000'}, {'value': '42', 'groupId': 'BG001'}, {'value': '130', 'groupId': 'BG002'}]}, {'title': 'Male', 'measurements': [{'value': '32', 'groupId': 'BG000'}, {'value': '18', 'groupId': 'BG001'}, {'value': '50', 'groupId': 'BG002'}]}]}], 'paramType': 'COUNT_OF_PARTICIPANTS', 'unitOfMeasure': 'Participants'}, {'title': 'Region of Enrollment', 'classes': [{'title': 'Bulgaria', 'categories': [{'measurements': [{'value': '40', 'groupId': 'BG000'}, {'value': '12', 'groupId': 'BG001'}, {'value': '52', 'groupId': 'BG002'}]}]}, {'title': 'Canada', 'categories': [{'measurements': [{'value': '3', 'groupId': 'BG000'}, {'value': '3', 'groupId': 'BG001'}, {'value': '6', 'groupId': 'BG002'}]}]}, {'title': 'Estonia', 'categories': [{'measurements': [{'value': '8', 'groupId': 'BG000'}, {'value': '5', 'groupId': 'BG001'}, {'value': '13', 'groupId': 'BG002'}]}]}, {'title': 'Germany', 'categories': [{'measurements': [{'value': '1', 'groupId': 'BG000'}, {'value': '0', 'groupId': 'BG001'}, {'value': '1', 'groupId': 'BG002'}]}]}, {'title': 'Italy', 'categories': [{'measurements': [{'value': '7', 'groupId': 'BG000'}, {'value': '4', 'groupId': 'BG001'}, {'value': '11', 'groupId': 'BG002'}]}]}, {'title': 'Lithuania', 'categories': [{'measurements': [{'value': '5', 'groupId': 'BG000'}, {'value': '3', 'groupId': 'BG001'}, {'value': '8', 'groupId': 'BG002'}]}]}, {'title': 'Romania', 'categories': [{'measurements': [{'value': '11', 'groupId': 'BG000'}, {'value': '8', 'groupId': 'BG001'}, {'value': '19', 'groupId': 'BG002'}]}]}, {'title': 'Russian Federation', 'categories': [{'measurements': [{'value': '20', 'groupId': 'BG000'}, {'value': '12', 'groupId': 'BG001'}, {'value': '32', 'groupId': 'BG002'}]}]}, {'title': 'Serbia', 'categories': [{'measurements': [{'value': '20', 'groupId': 'BG000'}, {'value': '9', 'groupId': 'BG001'}, {'value': '29', 'groupId': 'BG002'}]}]}, {'title': 'Spain', 'categories': [{'measurements': [{'value': '5', 'groupId': 'BG000'}, {'value': '4', 'groupId': 'BG001'}, {'value': '9', 'groupId': 'BG002'}]}]}], 'paramType': 'NUMBER', 'unitOfMeasure': 'participants'}], 'populationDescription': 'Intent to treat (ITT) population included all randomized participants who received at least one dose of study drug.'}}, 'protocolSection': {'designModule': {'phases': ['PHASE3'], 'studyType': 'INTERVENTIONAL', 'designInfo': {'allocation': 'RANDOMIZED', 'maskingInfo': {'masking': 'DOUBLE', 'whoMasked': ['PARTICIPANT', 'INVESTIGATOR']}, 'primaryPurpose': 'TREATMENT', 'interventionModel': 'FACTORIAL'}, 'enrollmentInfo': {'type': 'ACTUAL', 'count': 180}}, 'statusModule': {'overallStatus': 'COMPLETED', 'startDateStruct': {'date': '2006-12'}, 'expandedAccessInfo': {'hasExpandedAccess': False}, 'statusVerifiedDate': '2014-06', 'completionDateStruct': {'date': '2009-02', 'type': 'ACTUAL'}, 'lastUpdateSubmitDate': '2014-06-06', 'studyFirstSubmitDate': '2007-02-26', 'resultsFirstSubmitDate': '2010-05-20', 'studyFirstSubmitQcDate': '2007-02-26', 'lastUpdatePostDateStruct': {'date': '2014-07-09', 'type': 'ESTIMATED'}, 'resultsFirstSubmitQcDate': '2010-05-27', 'studyFirstPostDateStruct': {'date': '2007-02-28', 'type': 'ESTIMATED'}, 'resultsFirstPostDateStruct': {'date': '2010-07-05', 'type': 'ESTIMATED'}, 'primaryCompletionDateStruct': {'date': '2008-11', 'type': 'ACTUAL'}}, 'outcomesModule': {'primaryOutcomes': [{'measure': 'Number of Combined Unique (CU) Active Magnetic Resonance Imaging (MRI) Lesions at Week 16', 'timeFrame': '16 Weeks', 'description': '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).'}, {'measure': 'Number of Participants With Adverse Events (AEs) and Serious Adverse Events (SAEs)', 'timeFrame': 'Baseline up to Week 40', 'description': '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).'}], 'secondaryOutcomes': [{'measure': '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.', 'timeFrame': 'Day 1 up to Week 16 and Week 17 up to Week 40', '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). Only "Placebo Followed by RNF" arm was evaluable for this outcome measure.'}, {'measure': 'Number of CU Active MRI Lesions', 'timeFrame': 'Up to Week 40', '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).'}]}, 'conditionsModule': {'keywords': ['Subjects with relapsing remitting multiple sclerosis'], 'conditions': ['Multiple Sclerosis, Relapsing-Remitting']}, 'referencesModule': {'references': [{'pmid': '20200197', 'type': 'RESULT', '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.'}, {'pmid': '21880336', 'type': 'RESULT', '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.'}, {'pmid': '33329329', 'type': 'DERIVED', '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.'}], 'seeAlsoLinks': [{'url': 'http://www.mslifelines.com', 'label': 'Full FDA approved prescribing information can be found here'}]}, 'descriptionModule': {'briefSummary': 'General Note: throughout this record, "Rebif® New Formulation" is used for historical and consistency purposes.\n\nObjectives:\n\nPrimary: 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.\n\nPrimary 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).\n\nSecondary 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.'}, 'eligibilityModule': {'sex': 'ALL', 'stdAges': ['ADULT'], 'maximumAge': '60 Years', 'minimumAge': '18 Years', 'healthyVolunteers': False, 'eligibilityCriteria': 'Inclusion Criteria:\n\n* Males and females between 18 and 60 years of age\n* 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\n* Have Relapsing Remitting Multiple Sclerosis (RRMS) according to the revised McDonald criteria 2005\n* Have brain and/or spinal MRI with findings typical of Multiple Sclerosis (MS)\n* Have disease duration for more than 12 months\n* 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\n* Have score of \\<=5.5 on the Expanded Disability Status Scale (EDSS)\n* Be willing and able to comply with the protocol for the duration of the study\n* Have given written informed consent prior to any study-related procedure not part of the normal medical practice\n\nExclusion Criteria:\n\n* Have any disease other than MS that could better explain his/her signs and symptoms\n* Have complete transverse myelitis or bilateral optic neuritis\n* Have received or have used anytime monoclonal antibodies, mitoxantrone, cytotoxic or immunosuppressive therapy (excluding systemic steroids and adrenocorticotrophic hormone \\[ACTH\\]), or total lymphoid irradiation\n* 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\n* Have received within 30 days prior to baseline oral or systemic corticosteroids or ACTH\n* Other protocol defined exclusion criteria could apply'}, 'identificationModule': {'nctId': 'NCT00441103', 'acronym': 'IMPROVE', 'briefTitle': 'A Study to Evaluate Rebif® New Formulation (Interferon-beta-1a) in Relapsing Remitting Multiple Sclerosis', 'organization': {'class': 'INDUSTRY', 'fullName': 'Merck KGaA, Darmstadt, Germany'}, 'officialTitle': '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', 'orgStudyIdInfo': {'id': '27178'}, 'secondaryIdInfos': [{'id': '2006-003037-32'}]}, 'armsInterventionsModule': {'armGroups': [{'type': 'EXPERIMENTAL', 'label': 'Rebif® New Formulation (IFN-beta-1a, RNF)', 'interventionNames': ['Drug: Rebif® New Formulation (IFN-beta-1a, RNF)']}, {'type': 'PLACEBO_COMPARATOR', 'label': 'Placebo/RNF', 'interventionNames': ['Drug: Placebo', 'Drug: Rebif® New Formulation (IFN-beta-1a, RNF)']}], 'interventions': [{'name': 'Rebif® New Formulation (IFN-beta-1a, RNF)', 'type': 'DRUG', 'otherNames': ['IFN-beta-1a'], 'description': 'RNF will be administered at a dose of 44 mcg subcutaneously three times a week for 40 weeks.', 'armGroupLabels': ['Rebif® New Formulation (IFN-beta-1a, RNF)']}, {'name': 'Placebo', 'type': 'DRUG', 'description': 'Matching placebo will be administered subcutaneously three times a week for 16 weeks.', 'armGroupLabels': ['Placebo/RNF']}, {'name': 'Rebif® New Formulation (IFN-beta-1a, RNF)', 'type': 'DRUG', 'otherNames': ['IFN-beta-1a'], 'description': 'RNF will be administered at a dose of 44 mcg subcutaneously three times a week from Week 17 to Week 40.', 'armGroupLabels': ['Placebo/RNF']}]}, 'contactsLocationsModule': {'overallOfficials': [{'name': 'Bettina Stubinski, MD', 'role': 'STUDY_DIRECTOR', 'affiliation': 'Merck Serono SA - Geneva, an affiliate of Merck KGaA Darmstadt, Germany'}]}, 'sponsorCollaboratorsModule': {'leadSponsor': {'name': 'Merck KGaA, Darmstadt, Germany', 'class': 'INDUSTRY'}, 'responsibleParty': {'type': 'SPONSOR'}}}}