Ignite Creation Date:
2025-12-25 @ 2:32 AM
Ignite Modification Date:
2026-02-12 @ 5:20 PM
Study NCT ID:
NCT03358134
Status:
COMPLETED
Last Update Posted:
2017-11-30
First Post:
2014-02-12
Is NOT Gene Therapy:
True
Has Adverse Events:
False
Brief Title:
Mechanism of Action of Anti-IL17 Therapy in Peripheral Spondyloarthritis
Sponsor:
Organization:
Raw JSON
{'hasResults': False, 'derivedSection': {'miscInfoModule': {'versionHolder': '2025-12-24'}, 'conditionBrowseModule': {'meshes': [{'id': 'D025242', 'term': 'Spondylarthropathies'}, {'id': 'D015535', 'term': 'Arthritis, Psoriatic'}, {'id': 'D016918', 'term': 'Arthritis, Reactive'}], 'ancestors': [{'id': 'D025241', 'term': 'Spondylarthritis'}, {'id': 'D013166', 'term': 'Spondylitis'}, {'id': 'D013122', 'term': 'Spinal Diseases'}, {'id': 'D001847', 'term': 'Bone Diseases'}, {'id': 'D009140', 'term': 'Musculoskeletal Diseases'}, {'id': 'D001168', 'term': 'Arthritis'}, {'id': 'D007592', 'term': 'Joint Diseases'}, {'id': 'D011565', 'term': 'Psoriasis'}, {'id': 'D017444', 'term': 'Skin Diseases, Papulosquamous'}, {'id': 'D012871', 'term': 'Skin Diseases'}, {'id': 'D017437', 'term': 'Skin and Connective Tissue Diseases'}, {'id': 'D001170', 'term': 'Arthritis, Infectious'}, {'id': 'D007239', 'term': 'Infections'}, {'id': 'D000094025', 'term': 'Post-Infectious Disorders'}, {'id': 'D002908', 'term': 'Chronic Disease'}, {'id': 'D020969', 'term': 'Disease Attributes'}, {'id': 'D010335', 'term': 'Pathologic Processes'}, {'id': 'D013568', 'term': 'Pathological Conditions, Signs and Symptoms'}]}, 'interventionBrowseModule': {'meshes': [{'id': 'C555450', 'term': 'secukinumab'}]}}, 'protocolSection': {'designModule': {'phases': ['PHASE3'], 'studyType': 'INTERVENTIONAL', 'designInfo': {'allocation': 'NA', 'maskingInfo': {'masking': 'NONE'}, 'primaryPurpose': 'BASIC_SCIENCE', 'interventionModel': 'SINGLE_GROUP'}, 'enrollmentInfo': {'type': 'ACTUAL', 'count': 20}}, 'statusModule': {'overallStatus': 'COMPLETED', 'startDateStruct': {'date': '2014-03'}, 'expandedAccessInfo': {'hasExpandedAccess': False}, 'statusVerifiedDate': '2017-11', 'completionDateStruct': {'date': '2017-10', 'type': 'ACTUAL'}, 'lastUpdateSubmitDate': '2017-11-29', 'studyFirstSubmitDate': '2014-02-12', 'studyFirstSubmitQcDate': '2017-11-29', 'lastUpdatePostDateStruct': {'date': '2017-11-30', 'type': 'ACTUAL'}, 'studyFirstPostDateStruct': {'date': '2017-11-30', 'type': 'ACTUAL'}, 'primaryCompletionDateStruct': {'date': '2017-07', 'type': 'ACTUAL'}}, 'outcomesModule': {'primaryOutcomes': [{'measure': 'Biological changes induced by therapy on target tissue (synovium)', 'timeFrame': 'week 0 and week 12', 'description': 'Molecular changes of the synovium as measured by expression of several cytokines/chemokines by quantitative polymerase chain reaction (qPCR) as measured by a change in cytokine expression between baseline and week 12.'}, {'measure': 'Changes of cellular infiltrate in the target tissue (synovium)', 'timeFrame': 'week 0 and week 12', 'description': 'Changes in cell count measured by immunohistochemistry (on a 0-4 semi-quantitative analysis scale)'}], 'secondaryOutcomes': [{'measure': 'Adverse events', 'timeFrame': 'between day0 and 2 yrs of treatment', 'description': 'Number of patients with adverse events as a measure of safety and tolerability'}, {'measure': 'Vessel wall inflammation', 'timeFrame': 'week 0 and week 12', 'description': 'Changes in Fludeoxyglucose (FDG18) PET/CT uptake in the vessel walls of the carotic arteries and aorta as measured by CT values'}]}, 'oversightModule': {'oversightHasDmc': False}, 'conditionsModule': {'keywords': ['Peripheral Spondylarthropathies', 'Psoriatic arthritis', 'Reactive arthritis'], 'conditions': ['Spondylarthropathies']}, 'descriptionModule': {'briefSummary': 'The purpose of this study is to determine the mechanism of action on target tissue level of anti Interleukine-17 (anti-IL-17) an therapy in peripheral spondyloarthritis.\n\nPatients will be treated with anti-IL-17 therapy (secukinumab) for 12 weeks and with a 2 year extension period thereafter.\n\nAt week 0 and 12 peripheral blood, synovial tissue and skin will be analysed with different techniques, including immunohistochemistry, RNA analysis and tissue culture to assess the effect of the therapy on inflammatory pathways.', 'detailedDescription': 'Background of the study:\n\nSpondyloarthritis is the second most frequent form of chronic inflammatory arthritis with a prevalence of 0.5%. It effects mainly young adults and leads to major functional handicap due to inflammation of axial and peripheral joints as well as progressive ankylosis and structural damage.\n\nIn the late nineties Tumor Necrosis Factor (TNF) blockade was introduced as a successful treatment, but: only 50% responds well and tolerates, a-TNF does not halt the structural damage and TNF blockade does not induce long lasting remission as almost all patients relapse within a few weeks after interruption of the treatment. There is thus a high unmet need for alternatives.\n\nThe rationale for anti-IL17 therapy is based on various auto-inflammatory and auto immune models, preliminary efficacy data in psoriasis and Rheumatoid arthritis (RA) and an association of SpA with Interleukin 23 Receptor (IL23R) single nucleotide polymorphism (SNP).\n\nEfficacy data on anti-IL17 shows that it is a highly effective treatment for signs and symptoms in SpA, moreover sub-analysis of the anti-TNF naïve patients shows the same trend.\n\nObjective of the study:\n\nTo assess molecular and cellular effects of the treatment on the synovium.\n\nSecondary:\n\nTo compare which molecular and cellular disease pathways are affected by IL-17 blockade and not by TNF blockade and thereby identify molecular biomarkers which may help to determine which patients may benefit form this treatment in comparison with anti-TNF treatment.\n\nTo assess wether AIN457 silences vessel wall inflammation (by means of 18F-FDG PET(positron emission tomography)/CT of the carotic arteries and aorta.\n\nStudy design:\n\nSingle centre, 12-week open label study in subjects with clinically active peripheral spondylarthritis, with open label extension up to 2 years. Synovial biopsies and 18F-2-fluoro-2-deoxy-D-glucose fluorodeoxyglucose (18F FDG) PET/CT of the aorta and carotid arteries will be obtained from patients before and after 12 weeks of treatment with secukinumab.\n\nStudy population:\n\nPatients with a diagnosis of spondyloarthritis according to the European Spondyloarthropathy Study Group (ESSG) or Assess Spondyloarthritis to international Society (ASAS) criteria with at least one swollen knee or ankle joint.\n\nIntervention :\n\nSecukinumab (AIN457) by subcutaneous injections (weekly for the first 4 weeks and every 4 weeks thereafter).'}, 'eligibilityModule': {'sex': 'ALL', 'stdAges': ['ADULT', 'OLDER_ADULT'], 'maximumAge': '70 Years', 'minimumAge': '18 Years', 'healthyVolunteers': False, 'eligibilityCriteria': 'Inclusion Criteria:\n\n* Male or non-pregnant/non-lactating females age 18-70\n* Diagnosis of SpA according to ESSG criteria and/or ASAS criteria\n* Active disease defined by ≥1 swollen and ≥ 1 tender joint, and at least 1 swollen knee or ankle joint at baseline\n\nExclusion Criteria:\n\n* Evidence for infectious or malignant process (on chest X ray/MRI etc)\n* Patients taking opioid analgetics\n* Previous IL-17 therapy exposure\n* Previous use of cell-depleting therapies, biological immunomodulators (except for TNF blockade , as 25% may have been previously treated with 1 TNF blocking agent)\n* Significant medical problems or diseases'}, 'identificationModule': {'nctId': 'NCT03358134', 'acronym': 'MoA aIL-17', 'briefTitle': 'Mechanism of Action of Anti-IL17 Therapy in Peripheral Spondyloarthritis', 'organization': {'class': 'OTHER', 'fullName': 'Academisch Medisch Centrum - Universiteit van Amsterdam (AMC-UvA)'}, 'officialTitle': 'Mechanism of Action Study of Anti-IL17 Treatment in Spondyloarthritis: Impact on Cellular and Molecular Pathways of Synovial Inflammation and Tissue Remodeling', 'orgStudyIdInfo': {'id': 'AMC__45246_MoA_aIL17'}, 'secondaryIdInfos': [{'id': '2013-002709-79', 'type': 'EUDRACT_NUMBER'}]}, 'armsInterventionsModule': {'armGroups': [{'type': 'EXPERIMENTAL', 'label': 'Secukinumab', 'description': 'All patients will be treated with active treatment. (anti-IL17)', 'interventionNames': ['Drug: Secukinumab']}], 'interventions': [{'name': 'Secukinumab', 'type': 'DRUG', 'otherNames': ['AIN457'], 'description': 'anti IL17 therapy (subcutaneous)', 'armGroupLabels': ['Secukinumab']}]}, 'contactsLocationsModule': {'locations': [{'zip': '1105AZ', 'city': 'Amsterdam', 'state': 'North Holland', 'country': 'Netherlands', 'facility': 'Academic Medical Center Amsterdam', 'geoPoint': {'lat': 52.37403, 'lon': 4.88969}}], 'overallOfficials': [{'name': 'dominique LP Baeten, MD PhD prof.', 'role': 'PRINCIPAL_INVESTIGATOR', 'affiliation': 'AIDS Malignancy Consortium'}]}, 'sponsorCollaboratorsModule': {'leadSponsor': {'name': 'Academisch Medisch Centrum - Universiteit van Amsterdam (AMC-UvA)', 'class': 'OTHER'}, 'collaborators': [{'name': 'Novartis', 'class': 'INDUSTRY'}], 'responsibleParty': {'type': 'PRINCIPAL_INVESTIGATOR', 'investigatorTitle': 'Professor', 'investigatorFullName': 'D.L.P. Baeten', 'investigatorAffiliation': 'Academisch Medisch Centrum - Universiteit van Amsterdam (AMC-UvA)'}}}}