Ignite Creation Date:
2025-12-25 @ 2:36 AM
Ignite Modification Date:
2026-01-24 @ 3:07 AM
Study NCT ID:
NCT02461134
Status:
TERMINATED
Last Update Posted:
2025-02-04
First Post:
2015-04-28
Is Gene Therapy:
True
Has Adverse Events:
True
Brief Title:
Clinical Study to Investigate the Biological Activity, Safety, Tolerability, and Pharmacokinetics of Ponesimod in Subjects With Symptomatic Chronic GVHD
Sponsor:
Organization:
Raw JSON
{'hasResults': True, 'derivedSection': {'miscInfoModule': {'versionHolder': '2025-12-24', 'removedCountries': ['United States']}, 'conditionBrowseModule': {'meshes': [{'id': 'D000092122', 'term': 'Bronchiolitis Obliterans Syndrome'}], 'ancestors': [{'id': 'D000092124', 'term': 'Organizing Pneumonia'}, {'id': 'D001989', 'term': 'Bronchiolitis Obliterans'}, {'id': 'D001988', 'term': 'Bronchiolitis'}, {'id': 'D001991', 'term': 'Bronchitis'}, {'id': 'D001982', 'term': 'Bronchial Diseases'}, {'id': 'D012140', 'term': 'Respiratory Tract Diseases'}, {'id': 'D008173', 'term': 'Lung Diseases, Obstructive'}, {'id': 'D008171', 'term': 'Lung Diseases'}, {'id': 'D006086', 'term': 'Graft vs Host Disease'}, {'id': 'D007154', 'term': 'Immune System Diseases'}]}, 'interventionBrowseModule': {'meshes': [{'id': 'C550169', 'term': 'ponesimod'}]}}, 'resultsSection': {'moreInfoModule': {'pointOfContact': {'email': 'clinical-trials-disclosure@its.jnj.com', 'phone': '+41 61 565 6565', 'title': 'Clinical Trial Disclosure Desk', 'organization': 'Actelion Pharmaceuticals Ltd'}, 'certainAgreement': {'otherDetails': 'Any study-related publication written independently by investigators must be submitted to Actelion for review at least 30 days prior to submission for publication or presentation. Upon review, Actelion may provide comments, and may also request alterations and/or deletions for the sole purpose of protecting its confidential information and/or patent rights.', 'restrictionType': 'OTHER', 'piSponsorEmployee': False, 'restrictiveAgreement': True}, 'limitationsAndCaveats': {'description': 'The study was terminated early due to poor recruitment with 1 subject enrolled. Due to consequent lack of meaningful data, no conclusive analyses could be performed. The statistical analysis plan is obsolete and therefore not applicable.'}}, 'adverseEventsModule': {'timeFrame': 'Study treatment was terminated on Day 81 and the subject was exposed to ponesimod for a total of 81 days (i.e., Day 1 to Day 81). None of the reported adverse events (AEs) were considered by the investigator to be related to the study drug. As there was only 1 patient enrolled in the study, all (S)AEs reported occur with 100% frequency.', 'description': 'All AEs were coded using MedDRA version 19.0. No AEs were reported during the screening period.', 'eventGroups': [{'id': 'EG000', 'title': 'Ponesimod', 'description': 'It was planned that enrolled subjects receive ponesimod in escalating doses of 5, 10 and 20 mg over the course of the treatment period of 24 weeks in total (4 weeks of 5 mg incl. up-titration, 4 weeks of 10 mg incl. up-titration and 16 weeks of 20 mg).', 'otherNumAtRisk': 1, 'deathsNumAtRisk': 1, 'otherNumAffected': 1, 'seriousNumAtRisk': 1, 'deathsNumAffected': 0, 'seriousNumAffected': 1}], 'otherEvents': [{'term': 'Atrial flutter', 'stats': [{'groupId': 'EG000', 'numAtRisk': 1, 'numEvents': 1, 'numAffected': 1}], 'organSystem': 'Cardiac disorders', 'assessmentType': 'SYSTEMATIC_ASSESSMENT', 'sourceVocabulary': 'MedDRA'}, {'term': 'Hypertension', 'stats': [{'groupId': 'EG000', 'numAtRisk': 1, 'numEvents': 1, 'numAffected': 1}], 'organSystem': 'Vascular disorders', 'assessmentType': 'SYSTEMATIC_ASSESSMENT', 'sourceVocabulary': 'MedDRA'}], 'seriousEvents': [{'term': 'Gastritis', 'stats': [{'groupId': 'EG000', 'numAtRisk': 1, 'numEvents': 1, 'numAffected': 1}], 'organSystem': 'Gastrointestinal disorders', 'assessmentType': 'SYSTEMATIC_ASSESSMENT', 'sourceVocabulary': 'MedDRA'}, {'term': 'Virus infection', 'stats': [{'groupId': 'EG000', 'numAtRisk': 1, 'numEvents': 1, 'numAffected': 1}], 'organSystem': 'Infections and infestations', 'assessmentType': 'SYSTEMATIC_ASSESSMENT', 'sourceVocabulary': 'MedDRA'}, {'term': 'Haematemesis, Parainfluenza', 'stats': [{'groupId': 'EG000', 'numAtRisk': 1, 'numEvents': 1, 'numAffected': 1}], 'organSystem': 'Gastrointestinal disorders', 'assessmentType': 'SYSTEMATIC_ASSESSMENT', 'sourceVocabulary': 'MedDRA'}, {'term': 'Hip fracture', 'stats': [{'groupId': 'EG000', 'numAtRisk': 1, 'numEvents': 1, 'numAffected': 1}], 'organSystem': 'Injury, poisoning and procedural complications', 'assessmentType': 'SYSTEMATIC_ASSESSMENT', 'sourceVocabulary': 'MedDRA'}], 'frequencyThreshold': '0'}, 'outcomeMeasuresModule': {'outcomeMeasures': [{'type': 'PRIMARY', 'title': 'Change in Peripheral Absolute Lymphocyte Count From Baseline to Week 4, 8 and 12', 'denoms': [{'units': 'Participants', 'counts': [{'value': '0', 'groupId': 'OG000'}]}], 'groups': [{'id': 'OG000', 'title': 'Ponesimod', 'description': 'It was planned that enrolled subjects receive ponesimod in escalating doses of 5, 10 and 20 mg over the course of the treatment period of 24 weeks in total (4 weeks of 5 mg incl. up-titration, 4 weeks of 10 mg incl. up-titration and 16 weeks of 20 mg).'}], 'timeFrame': 'From baseline to Week 12', 'description': 'The primary pharmacodynamic endpoint assesses intra-subject dose response during the first 12 weeks of treatment.', 'reportingStatus': 'POSTED', 'populationDescription': 'Due to the premature termination of the study and consequent lack of meaningful data, no analyses were performed. The statistical analysis plan issued is obsolete, it was not finalized and was therefore not executed.'}, {'type': 'SECONDARY', 'title': 'Incident Rate of Treatment-emergent Adverse Events (AEs) and Serious Adverse Events (SAEs)', 'denoms': [{'units': 'Participants', 'counts': [{'value': '1', 'groupId': 'OG000'}]}], 'groups': [{'id': 'OG000', 'title': 'Ponesimod', 'description': 'It was planned that enrolled subjects receive ponesimod in escalating doses of 5, 10 and 20 mg over the course of the treatment period of 24 weeks in total (4 weeks of 5 mg incl. up-titration, 4 weeks of 10 mg incl. up-titration and 16 weeks of 20 mg).'}], 'classes': [{'title': 'Participants with AEs', 'categories': [{'measurements': [{'value': '1', 'groupId': 'OG000'}]}]}, {'title': 'Participants with SAEs', 'categories': [{'measurements': [{'value': '1', 'groupId': 'OG000'}]}]}, {'title': 'Participants discontinued prematurely study drug', 'categories': [{'measurements': [{'value': '1', 'groupId': 'OG000'}]}]}], 'paramType': 'COUNT_OF_PARTICIPANTS', 'timeFrame': 'From the first study drug intake up to 30 days after last study drug intake (Week 24)', 'description': 'This outcome measure reports the occurrence of adverse events (AEs), and serious adverse events (SAEs) during the treatment period and the follow-up period, and AEs leading to premature discontinuation of study drug. A treatment-emergent AE is any AE temporally associated with the use of study treatment whether or not considered by the investigator as related to study treatment.', 'unitOfMeasure': 'Participants', 'reportingStatus': 'POSTED', 'populationDescription': 'The premature termination of the study led to a consequent lack of meaningful data. As the statistical analysis plan issued was not finalized and was not executed, no statistical analyses were performed. As there was only 1 patient enrolled in the study, the safety events reported occur with 100% frequency.'}, {'type': 'OTHER_PRE_SPECIFIED', 'title': 'Assessment of a Partial or Complete Overall Response at Week 24', 'denoms': [{'units': 'Participants', 'counts': [{'value': '0', 'groupId': 'OG000'}]}], 'groups': [{'id': 'OG000', 'title': 'Ponesimod', 'description': 'It was planned that enrolled subjects receive ponesimod in escalating doses of 5, 10 and 20 mg over the course of the treatment period of 24 weeks in total (4 weeks of 5 mg incl. up-titration, 4 weeks of 10 mg incl. up-titration and 16 weeks of 20 mg).'}], 'timeFrame': 'At Week 24', 'description': 'The exploratory efficacy endpoint is based on the 2014 NIH Consensus Development Project response criteria. A complete overall response is defined as a resolution of all reversible manifestations due to chronic GVHD in each organ as defined per NIH Consensus Development Project response criteria. A partial overall response is defined as improvement in a measure for at least one organ without progression in measures for any other organ.', 'reportingStatus': 'POSTED', 'populationDescription': 'Due to the premature termination of the study and consequent lack of meaningful data, no analyses were performed. The statistical analysis plan issued is obsolete, it was not finalized and was therefore not executed.'}]}, 'participantFlowModule': {'groups': [{'id': 'FG000', 'title': 'Ponesimod', 'description': 'It was planned that enrolled subjects receive ponesimod in escalating doses of 5, 10 and 20 mg over the course of the treatment period of 24 weeks in total (4 weeks of 5 mg incl. up-titration, 4 weeks of 10 mg incl. up-titration and 16 weeks of 20 mg).'}], 'periods': [{'title': 'Overall Study', 'milestones': [{'type': 'STARTED', 'achievements': [{'groupId': 'FG000', 'numSubjects': '1'}]}, {'type': 'COMPLETED', 'achievements': [{'groupId': 'FG000', 'numSubjects': '0'}]}, {'type': 'NOT COMPLETED', 'achievements': [{'groupId': 'FG000', 'numSubjects': '1'}]}], 'dropWithdraws': [{'type': 'Adverse Event', 'reasons': [{'groupId': 'FG000', 'numSubjects': '1'}]}]}], 'recruitmentDetails': '11 subjects were screened at 5 different sites. 1 subject was finally recruited into the study. The study was prematurely terminated due to poor recruitment.', 'preAssignmentDetails': 'The protocol-defined study population included male and female subjects aged 18 to 70 years with chronic Graft versus Host disease (GVHD). It was planned to recruit 30 subjects.'}, 'baselineCharacteristicsModule': {'denoms': [{'units': 'Participants', 'counts': [{'value': '1', 'groupId': 'BG000'}]}], 'groups': [{'id': 'BG000', 'title': 'Ponesimod', 'description': 'It was planned that enrolled subjects receive ponesimod in escalating doses of 5, 10 and 20 mg over the course of the treatment period of 24 weeks in total (4 weeks of 5 mg incl. up-titration, 4 weeks of 10 mg incl. up-titration and 16 weeks of 20 mg).'}], 'measures': [{'title': 'Age, Categorical', 'classes': [{'denoms': [{'units': 'Participants', 'counts': [{'value': '1', 'groupId': 'BG000'}]}], 'categories': [{'title': '<=18 years', 'measurements': [{'value': '0', 'groupId': 'BG000'}]}, {'title': 'Between 18 and 65 years', 'measurements': [{'value': '1', 'groupId': 'BG000'}]}, {'title': '>=65 years', 'measurements': [{'value': '0', 'groupId': 'BG000'}]}]}], 'paramType': 'COUNT_OF_PARTICIPANTS', 'unitOfMeasure': 'Participants'}, {'title': 'Sex: Female, Male', 'classes': [{'denoms': [{'units': 'Participants', 'counts': [{'value': '1', 'groupId': 'BG000'}]}], 'categories': [{'title': 'Female', 'measurements': [{'value': '1', 'groupId': 'BG000'}]}, {'title': 'Male', 'measurements': [{'value': '0', 'groupId': 'BG000'}]}]}], 'paramType': 'COUNT_OF_PARTICIPANTS', 'unitOfMeasure': 'Participants'}, {'title': 'Race and Ethnicity Not Collected', 'classes': [{'denoms': [{'units': 'Participants', 'counts': [{'value': '0', 'groupId': 'BG000'}]}]}], 'paramType': 'COUNT_OF_PARTICIPANTS', 'unitOfMeasure': 'Participants', 'populationDescription': 'Race and Ethnicity were not collected from any participant.'}]}}, 'documentSection': {'largeDocumentModule': {'largeDocs': [{'date': '2016-07-05', 'size': 6171615, 'label': 'Study Protocol and Statistical Analysis Plan', 'hasIcf': False, 'hasSap': True, 'filename': 'Prot_SAP_000.pdf', 'typeAbbrev': 'Prot_SAP', 'uploadDate': '2018-03-02T04:26', 'hasProtocol': True}]}}, 'protocolSection': {'designModule': {'phases': ['PHASE2'], 'studyType': 'INTERVENTIONAL', 'designInfo': {'allocation': 'NA', 'maskingInfo': {'masking': 'NONE'}, 'primaryPurpose': 'TREATMENT', 'interventionModel': 'SINGLE_GROUP'}, 'enrollmentInfo': {'type': 'ACTUAL', 'count': 1}}, 'statusModule': {'whyStopped': 'Low recruitment', 'overallStatus': 'TERMINATED', 'startDateStruct': {'date': '2016-09-29', 'type': 'ACTUAL'}, 'expandedAccessInfo': {'hasExpandedAccess': False}, 'statusVerifiedDate': '2025-01', 'completionDateStruct': {'date': '2017-03-03', 'type': 'ACTUAL'}, 'lastUpdateSubmitDate': '2025-01-31', 'studyFirstSubmitDate': '2015-04-28', 'resultsFirstSubmitDate': '2018-03-02', 'studyFirstSubmitQcDate': '2015-06-01', 'lastUpdatePostDateStruct': {'date': '2025-02-04', 'type': 'ACTUAL'}, 'resultsFirstSubmitQcDate': '2018-04-09', 'studyFirstPostDateStruct': {'date': '2015-06-03', 'type': 'ESTIMATED'}, 'resultsFirstPostDateStruct': {'date': '2018-05-09', 'type': 'ACTUAL'}, 'primaryCompletionDateStruct': {'date': '2017-03-02', 'type': 'ACTUAL'}}, 'outcomesModule': {'otherOutcomes': [{'measure': 'Assessment of a Partial or Complete Overall Response at Week 24', 'timeFrame': 'At Week 24', 'description': 'The exploratory efficacy endpoint is based on the 2014 NIH Consensus Development Project response criteria. A complete overall response is defined as a resolution of all reversible manifestations due to chronic GVHD in each organ as defined per NIH Consensus Development Project response criteria. A partial overall response is defined as improvement in a measure for at least one organ without progression in measures for any other organ.'}], 'primaryOutcomes': [{'measure': 'Change in Peripheral Absolute Lymphocyte Count From Baseline to Week 4, 8 and 12', 'timeFrame': 'From baseline to Week 12', 'description': 'The primary pharmacodynamic endpoint assesses intra-subject dose response during the first 12 weeks of treatment.'}], 'secondaryOutcomes': [{'measure': 'Incident Rate of Treatment-emergent Adverse Events (AEs) and Serious Adverse Events (SAEs)', 'timeFrame': 'From the first study drug intake up to 30 days after last study drug intake (Week 24)', 'description': 'This outcome measure reports the occurrence of adverse events (AEs), and serious adverse events (SAEs) during the treatment period and the follow-up period, and AEs leading to premature discontinuation of study drug. A treatment-emergent AE is any AE temporally associated with the use of study treatment whether or not considered by the investigator as related to study treatment.'}]}, 'oversightModule': {'oversightHasDmc': False, 'isFdaRegulatedDrug': True, 'isFdaRegulatedDevice': False}, 'conditionsModule': {'keywords': ['GVHD', 'ponesimod'], 'conditions': ['Chronic Graft Versus Host Disease']}, 'descriptionModule': {'briefSummary': "Chronic graft versus host diseasre (GVHD) is a serious reaction that might occur in a person (the host) who has received cells or organs (graft) from another person because the graft attacks the host's cells. Currently there are no approved therapies for chronic GVHD in the USA, and patients with chroninc GVHD are treated with immunosuppressant drugs. T-lymphocytes (a type of white blood cells) are likely to play a role in the development of chronic GVHD. Due to the capacity of ponesimod to block the traffic of T-lymphocytes, ponesimod may be a new therapeutic approach to treat chroninc GVHD.\n\nThe main objective of this study is to assess the effectiveness and safety of several doses of ponesimod in subjects with chronic GVHD who did not respond to standard available treatments."}, 'eligibilityModule': {'sex': 'ALL', 'stdAges': ['ADULT', 'OLDER_ADULT'], 'maximumAge': '70 Years', 'minimumAge': '18 Years', 'healthyVolunteers': False, 'eligibilityCriteria': 'Inclusion Criteria:\n\n* Signed informed consent\n* Symptomatic moderate or severe chronic GVHD patients in need of a change of systemic immunosuppressant (IS) therapy\n* Women of child bearing potential must have a negative pregnancy test and use reliable methods of contraception\n\nExclusion Criteria:\n\n* Clinically significant medical conditions including active or uncontrolled infections, new or recurrent malignancy, serious cardiac, pulmonary, or renal disease, and uncontrolled diabetes.\n* Karnofsky Performance Score \\< 60.\n* Immunosuppressant therapies other than allowed background therapy\n* Anti-arrhythmic and heart rate lowering drugs.\n* Any other circumstances or conditions, which, in the opinion of the investigator, may affect full participation in the study or compliance with the protocol'}, 'identificationModule': {'nctId': 'NCT02461134', 'briefTitle': 'Clinical Study to Investigate the Biological Activity, Safety, Tolerability, and Pharmacokinetics of Ponesimod in Subjects With Symptomatic Chronic GVHD', 'organization': {'class': 'INDUSTRY', 'fullName': 'Actelion'}, 'officialTitle': 'A Phase 2, Open-label, Single-arm, Intra-subject Dose-escalation Study to Investigate the Biological Activity, Safety, Tolerability, and Pharmacokinetics of Ponesimod in Subjects With Symptomatic Moderate or Severe Chronic GVHD Inadequately Responding to First or Second Line Therapy', 'orgStudyIdInfo': {'id': 'AC-058C202'}}, 'armsInterventionsModule': {'armGroups': [{'type': 'EXPERIMENTAL', 'label': 'Ponesimod', 'description': 'Study treatment consists of 3 consecutive periods: 5 mg ponesimod treatment period (including up-titration), 10 mg treatment period (including up-titration) and a 20 mg treatment period.', 'interventionNames': ['Drug: Ponesimod']}], 'interventions': [{'name': 'Ponesimod', 'type': 'DRUG', 'otherNames': ['ACT-128800'], 'description': 'Oral film-coated tablets at the doses of 2, 3, 4, 5, 6, 7, 8, 9, 10, and 20 mg. One tablet of ponesimod at any dose will be taken orally once daily.', 'armGroupLabels': ['Ponesimod']}]}, 'contactsLocationsModule': {'overallOfficials': [{'name': "Daniele D'Ambrosio, MD, PhD", 'role': 'STUDY_CHAIR', 'affiliation': 'Actelion'}]}, 'sponsorCollaboratorsModule': {'leadSponsor': {'name': 'Actelion', 'class': 'INDUSTRY'}, 'responsibleParty': {'type': 'SPONSOR'}}}}