Ignite Creation Date:
2025-12-24 @ 7:39 PM
Ignite Modification Date:
2025-12-31 @ 5:43 AM
Study NCT ID:
NCT05115903
Status:
ACTIVE_NOT_RECRUITING
Last Update Posted:
2024-01-17
First Post:
2021-10-28
Is NOT Gene Therapy:
True
Has Adverse Events:
False
Brief Title:
Biologic Tapering Study of TNF Inhibitors in Axial Spondyloarthritis
Sponsor:
Organization:
Raw JSON
{'hasResults': False, 'derivedSection': {'miscInfoModule': {'versionHolder': '2025-12-24'}, 'conditionBrowseModule': {'meshes': [{'id': 'D000089183', 'term': 'Axial Spondyloarthritis'}, {'id': 'D025241', 'term': 'Spondylarthritis'}], 'ancestors': [{'id': 'D025242', 'term': 'Spondylarthropathies'}, {'id': 'D013166', 'term': 'Spondylitis'}, {'id': 'D013122', 'term': 'Spinal Diseases'}, {'id': 'D001847', 'term': 'Bone Diseases'}, {'id': 'D009140', 'term': 'Musculoskeletal Diseases'}, {'id': 'D000844', 'term': 'Ankylosis'}, {'id': 'D007592', 'term': 'Joint Diseases'}, {'id': 'D001168', 'term': 'Arthritis'}]}, 'interventionBrowseModule': {'meshes': [{'id': 'D000068800', 'term': 'Etanercept'}, {'id': 'D000068879', 'term': 'Adalimumab'}, {'id': 'D000068582', 'term': 'Certolizumab Pegol'}, {'id': 'C529000', 'term': 'golimumab'}, {'id': 'D000069285', 'term': 'Infliximab'}], 'ancestors': [{'id': 'D007141', 'term': 'Immunoglobulin Fc Fragments'}, {'id': 'D007128', 'term': 'Immunoglobulin Fragments'}, {'id': 'D010446', 'term': 'Peptide Fragments'}, {'id': 'D010455', 'term': 'Peptides'}, {'id': 'D000602', 'term': 'Amino Acids, Peptides, and Proteins'}, {'id': 'D007127', 'term': 'Immunoglobulin Constant Regions'}, {'id': 'D007136', 'term': 'Immunoglobulins'}, {'id': 'D007162', 'term': 'Immunoproteins'}, {'id': 'D001798', 'term': 'Blood Proteins'}, {'id': 'D011506', 'term': 'Proteins'}, {'id': 'D012712', 'term': 'Serum Globulins'}, {'id': 'D005916', 'term': 'Globulins'}, {'id': 'D018124', 'term': 'Receptors, Tumor Necrosis Factor'}, {'id': 'D018121', 'term': 'Receptors, Cytokine'}, {'id': 'D011971', 'term': 'Receptors, Immunologic'}, {'id': 'D011956', 'term': 'Receptors, Cell Surface'}, {'id': 'D008565', 'term': 'Membrane Proteins'}, {'id': 'D061067', 'term': 'Antibodies, Monoclonal, Humanized'}, {'id': 'D000911', 'term': 'Antibodies, Monoclonal'}, {'id': 'D000906', 'term': 'Antibodies'}, {'id': 'D011092', 'term': 'Polyethylene Glycols'}, {'id': 'D011108', 'term': 'Polymers'}, {'id': 'D046911', 'term': 'Macromolecular Substances'}, {'id': 'D007140', 'term': 'Immunoglobulin Fab Fragments'}]}}, 'protocolSection': {'designModule': {'phases': ['PHASE4'], 'studyType': 'INTERVENTIONAL', 'designInfo': {'allocation': 'RANDOMIZED', 'maskingInfo': {'masking': 'NONE'}, 'primaryPurpose': 'TREATMENT', 'interventionModel': 'PARALLEL'}, 'enrollmentInfo': {'type': 'ACTUAL', 'count': 15}}, 'statusModule': {'overallStatus': 'ACTIVE_NOT_RECRUITING', 'startDateStruct': {'date': '2021-12-01', 'type': 'ACTUAL'}, 'expandedAccessInfo': {'hasExpandedAccess': False}, 'statusVerifiedDate': '2024-01', 'completionDateStruct': {'date': '2024-08-01', 'type': 'ESTIMATED'}, 'lastUpdateSubmitDate': '2024-01-15', 'studyFirstSubmitDate': '2021-10-28', 'studyFirstSubmitQcDate': '2021-11-08', 'lastUpdatePostDateStruct': {'date': '2024-01-17', 'type': 'ACTUAL'}, 'studyFirstPostDateStruct': {'date': '2021-11-10', 'type': 'ACTUAL'}, 'primaryCompletionDateStruct': {'date': '2024-07-01', 'type': 'ESTIMATED'}}, 'outcomesModule': {'primaryOutcomes': [{'measure': 'Proportion of patients able to maintain inactive disease or low disease activity, defined as Ankylosing Spondylitis Disease Activity Score (ASDAS) <1.3 to 2.1 or Bath Ankylosing Spondylitis Disease Activity Score (BASDAI) of <4 on tapered-dose TNFi', 'timeFrame': 'Weeks 12, 24, 36, and 48', 'description': 'The ASDAS and BASDAI are measures of axial spondyloarthritis disease activity for the past week. The ASDAS has 5 components scored from 0 to 10 (none to very severe). The following formula is used to compute for the ASDAS: (0.121 × back pain score) +(0.058 × score for duration of morning stiffness) + (0.11 × patient global assessment score) + (0.073 × peripheral pain/swelling score) + (0.579 × log(CRP+1)). The scores range from 0 (no disease activity) to infinity (being determined by the level of CRP). The disease is considered inactive if the final score is \\<1.3, and low if \\<2.1.\n\nThe BASDAI consists of six items, with each item being scored from 0 ("none") to 10 ("very severe"). The final BASDAI scores ranges from 0 to 10, with lower scores indicating lower disease activity. A BASDAI of \\<4 indicates inactive or low disease.\n\nAs opposed to ASDAS, BASDAI does not include CRP in its formula. Either ASDAS or BASDAI is acceptable in clinical practice.'}], 'secondaryOutcomes': [{'measure': 'Proportion of patients experiencing a disease flare by ASDAS or BASDAI', 'timeFrame': 'Up to Week 48', 'description': 'Flare is defined in this study as either of the following:\n\n1. loss of inactive disease or LDA (ASDAS ≥2.1 or BASDAI ≥4) - see definitions above\n2. minimal clinically important worsening, defined as an increase in ASDAS by ≥0.9 on two consecutive visits'}, {'measure': 'Proportion of patients with functional limitation measured using the Bath Ankylosing Spondylitis Functional Index (BASFI)', 'timeFrame': 'Up to Week 48', 'description': 'The BASFI measures the degree of functional limitation. It is composed of a set of 10 questions relating to activities during the past week. Each item is scored from 0 ("easy") to 10 ("impossible"). The final BASFI is the mean of the 10 scores with the total score ranging from 0 to 10. Lower scores indicate better physical function.'}, {'measure': 'Mean quality of life in the tapered-dose arm vs. the standard-dose arm measured using the Ankylosing Spondylitis Quality of Life (ASQoL) questionnaire', 'timeFrame': 'Up to Week 48', 'description': 'The ASQoL measures health-related quality of life (HRQoL) in subjects with axial spondyloarthritis. The final ASQoL score ranges from 0 to 18, with higher scores indicating worse HRQoL.'}, {'measure': 'Proportion of patients with impaired work productivity and activity measured using the Work Productivity and Activity Impairment Questionnaire for Ankylosing Spondylitis (WPAI:SpA) questionnaire', 'timeFrame': 'Up to Week 48', 'description': 'The WPAI:SpA consists of 6 questions to determine employment status, hours missed from work because of SpA, hours missed from work for other reasons, hours actually worked, the effect of SpA on work productivity while at work, and the effect of SpA on activities outside of work. The 4 scores derived include percentage of absenteeism, percentage of presenteeism (reduced productivity while at work), an overall work impairment combining absenteeism and presenteeism, and percentage of impairment in activities performed outside of work. The computed percentage for each sub-scale ranges from 0 to 100. Higher scores indicate greater impairment and less productivity.'}, {'measure': 'Proportion of patients with radiographic progression, defined as an increase in the modified Stoke Ankylosing Spondylitis Spine Score (mSASSS) by 2 units', 'timeFrame': 'Baseline and Week 48', 'description': 'The mSASSS measures the sum of the lumbar and cervical spine score from 0 (no change) to 72 (progression). The score is derived from grading of the anterior aspect of the vertebral bodies of the lumbar spine (T12 to S1) and the cervical spine (C2 to T1). Grading is as follows: 0 (normal), 1 (erosion, sclerosis, or squaring), 2 (syndesmophyte), 3 (bridging syndesmophyte), or N (vertebral body not evaluable).'}, {'measure': 'Proportion of patients needing concomitant medication', 'timeFrame': 'Up to Week 48', 'description': 'Concomitant medications will include NSAIDs, conventional synthetic DMARDs, and/or targeted synthetic DMARDs used during the study period'}, {'measure': 'Proportion of patients with any related severe adverse event', 'timeFrame': 'Up to Week 48', 'description': 'Severe adverse event, defined as serious infections requiring systemic antibiotic use and/or hospitalization assessed to be at least possibly related to TNFi use or withdrawal'}, {'measure': 'Factors predicting flare', 'timeFrame': 'Up to Week 48', 'description': 'Factors including but not be limited to the following: sex, human leukocyte antigen (HLA)-B27 status, disease duration, duration of remission, ASDAS at the start of taper, and MRI findings at the time of taper'}]}, 'oversightModule': {'isUsExport': False, 'oversightHasDmc': False, 'isFdaRegulatedDrug': False, 'isFdaRegulatedDevice': False}, 'conditionsModule': {'keywords': ['spondyloarthritis', 'TNF inhibitors', 'tapering'], 'conditions': ['Axial Spondyloarthritis']}, 'referencesModule': {'references': [{'pmid': '11955536', 'type': 'BACKGROUND', 'citation': 'Braun J, Brandt J, Listing J, Zink A, Alten R, Golder W, Gromnica-Ihle E, Kellner H, Krause A, Schneider M, Sorensen H, Zeidler H, Thriene W, Sieper J. Treatment of active ankylosing spondylitis with infliximab: a randomised controlled multicentre trial. Lancet. 2002 Apr 6;359(9313):1187-93. doi: 10.1016/s0140-6736(02)08215-6.'}, {'pmid': '16802350', 'type': 'BACKGROUND', 'citation': 'van der Heijde D, Kivitz A, Schiff MH, Sieper J, Dijkmans BA, Braun J, Dougados M, Reveille JD, Wong RL, Kupper H, Davis JC Jr; ATLAS Study Group. Efficacy and safety of adalimumab in patients with ankylosing spondylitis: results of a multicenter, randomized, double-blind, placebo-controlled trial. Arthritis Rheum. 2006 Jul;54(7):2136-46. doi: 10.1002/art.21913.'}, {'pmid': '18975305', 'type': 'BACKGROUND', 'citation': 'Inman RD, Davis JC Jr, Heijde Dv, Diekman L, Sieper J, Kim SI, Mack M, Han J, Visvanathan S, Xu Z, Hsu B, Beutler A, Braun J. Efficacy and safety of golimumab in patients with ankylosing spondylitis: results of a randomized, double-blind, placebo-controlled, phase III trial. Arthritis Rheum. 2008 Nov;58(11):3402-12. doi: 10.1002/art.23969.'}, {'pmid': '26998860', 'type': 'BACKGROUND', 'citation': 'Navarro-Compan V, Plasencia-Rodriguez C, de Miguel E, Balsa A, Martin-Mola E, Seoane-Mato D, Canete JD. Anti-TNF discontinuation and tapering strategies in patients with axial spondyloarthritis: a systematic literature review. Rheumatology (Oxford). 2016 Jul;55(7):1188-94. doi: 10.1093/rheumatology/kew033. Epub 2016 Mar 21.'}, {'pmid': '30621746', 'type': 'BACKGROUND', 'citation': 'Gratacos J, Pontes C, Juanola X, Sanz J, Torres F, Avendano C, Vallano A, Calvo G, de Miguel E, Sanmarti R; REDES-TNF investigators. Non-inferiority of dose reduction versus standard dosing of TNF-inhibitors in axial spondyloarthritis. Arthritis Res Ther. 2019 Jan 8;21(1):11. doi: 10.1186/s13075-018-1772-z.'}, {'pmid': '32536984', 'type': 'BACKGROUND', 'citation': 'Zhang T, Zhu J, He D, Chen X, Wang H, Zhang Y, Xue Q, Liu W, Xiang G, Li Y, Yu Z, Wu H. Disease activity guided stepwise tapering or discontinuation of rhTNFR:Fc, an etanercept biosimilar, in patients with ankylosing spondylitis: a prospective, randomized, open-label, multicentric study. Ther Adv Musculoskelet Dis. 2020 Jun 2;12:1759720X20929441. doi: 10.1177/1759720X20929441. eCollection 2020.'}, {'pmid': '32166872', 'type': 'BACKGROUND', 'citation': 'Lawson DO, Eraso M, Mbuagbaw L, Joanes M, Aves T, Leenus A, Omar A, Inman RD. Tumor Necrosis Factor Inhibitor Dose Reduction for Axial Spondyloarthritis: A Systematic Review and Meta-Analysis of Randomized Controlled Trials. Arthritis Care Res (Hoboken). 2021 Jun;73(6):861-872. doi: 10.1002/acr.24184.'}]}, 'descriptionModule': {'briefSummary': 'Current evidence on tapering of tumor necrosis factor inhibitors (TNFi) in axial spondyloarthritis (axSpA) is still hampered by heterogeneity in tapering regimens, selection and performance biases, and lack of data on optimized treatment dosing strategies especially in real-world clinical settings. This study aims to contribute to the ongoing investigation of disease-activity-guided tapering of TNFi in axSpA in the form of a prospective, randomized controlled trial.', 'detailedDescription': 'This is a 48-week randomized, controlled, open-label, non-inferiority trial of patients with radiographic or non-radiographic axial spondyloarthritis. The study will include 156 patients with inactive disease or low disease activity (LDA) for at least 6 months on a TNFi at the time of randomization.\n\nParticipants will be randomized using a 1:1 ratio to either the tapered-dose arm or the standard-dose arm of TNFi. Progressive tapering of TNFi according to a predefined protocol will be allowed as long as the patient is able to maintain inactive disease or LDA during the study period. We hypothesize that, in patients with 6 months or more of inactive or low-activity axial spondyloarthritis, tapered-dose TNFi are non-inferior to standard-dose TNFi in sustaining the disease state for at least 1 year.'}, 'eligibilityModule': {'sex': 'ALL', 'stdAges': ['ADULT', 'OLDER_ADULT'], 'minimumAge': '18 Years', 'healthyVolunteers': False, 'eligibilityCriteria': 'Inclusion Criteria:\n\n* Adult axSpA patients satisfying the 2009 Assessment of SpondyloArthritis International Society (ASAS) Classification Criteria\n* Currently enrolled in the SPARCC Program with successful completion of standard data collection protocol in the Spondylitis Clinic of UHN-Toronto Western Hospital\n* Have sustained inactive disease or LDA with an ASDAS of \\<2.1 or BASDAI \\<4 for at least 6 months\n* On a stable dose of a TNFi (infliximab, etanercept, adalimumab, certolizumab pegol, or golimumab)\n* Must not be pregnant\n\nExclusion Criteria:\n\n* Adults axSpA patients with active extra-articular manifestations such as inflammatory bowel disease, psoriasis, and/or uveitis\n* Have comorbidities that may preclude clinical assessment (i.e. fibromyalgia or other chronic pain syndromes; chronic inflammatory diseases other than axSpA)\n* Have diagnosed psychiatric or personality disorders\n* Pregnant\n* Not enrolled in the Spondyloarthritis Research Consortium of Canada (SPARCC) Program'}, 'identificationModule': {'nctId': 'NCT05115903', 'acronym': 'BIOTAPE', 'briefTitle': 'Biologic Tapering Study of TNF Inhibitors in Axial Spondyloarthritis', 'organization': {'class': 'OTHER', 'fullName': 'University Health Network, Toronto'}, 'officialTitle': 'A Prospective, Randomized Biologic Tapering Study of TNF Inhibitors in Axial Spondyloarthritis', 'orgStudyIdInfo': {'id': '21-5211'}}, 'armsInterventionsModule': {'armGroups': [{'type': 'EXPERIMENTAL', 'label': 'Tapered doses of TNFi', 'description': 'Tapering of TNFi through standardized increases in the dosing interval between drug administration. The tapering dose intervals for each TNFi are designed to decrease the dose from baseline by 75% for 12 weeks, 50% for 24 weeks, and 25% for 12 weeks', 'interventionNames': ['Drug: Tapered doses of TNFi']}, {'type': 'ACTIVE_COMPARATOR', 'label': 'Standard dose of TNFi', 'description': 'Stable doses of TNFi according to the approved summary of product characteristics for biologic agents used in axial spondyloarthritis', 'interventionNames': ['Drug: Standard dose of TNFi']}], 'interventions': [{'name': 'Tapered doses of TNFi', 'type': 'DRUG', 'otherNames': ['etanercept 50 mg every 10 days (75% of baseline dose), 14 days (50%), 30 days (25%)', 'adalimumab 40 mg every 3 weeks (75%), 4 weeks (50%), 16 weeks (25%)', 'certolizumab pegol 200 mg 3 weeks (75%), 4 weeks (50%), 16 weeks (25%)', 'golimumab 50 mg every 6 weeks (75%), 8 weeks (50%), 16 weeks (25%)', 'infliximab 5 mg/kg every 8 weeks (75%), 12 weeks (50%), 16 weeks (25%)'], 'description': 'To be given subcutaneously via a prefilled syringe/autoinjector (etanercept, adalimumab, certolizumab pegol, golimumab) or intravenously via infusion (infliximab) at increasing dose intervals as specified', 'armGroupLabels': ['Tapered doses of TNFi']}, {'name': 'Standard dose of TNFi', 'type': 'DRUG', 'otherNames': ['etanercept 50 mg every 7 days', 'adalimumab 40 mg every 2 weeks', 'certolizumab pegol 200 mg every 2 weeks', 'golimumab 50 mg every 4 weeks', 'infliximab 5 mg/kg every 6 weeks'], 'description': 'To be given subcutaneously via a prefilled syringe/autoinjector (etanercept, adalimumab, certolizumab pegol, golimumab) or intravenously via infusion (infliximab)', 'armGroupLabels': ['Standard dose of TNFi']}]}, 'contactsLocationsModule': {'locations': [{'zip': 'M5T 2S8', 'city': 'Toronto', 'state': 'Ontario', 'country': 'Canada', 'facility': 'University Health Network - Toronto Western Hospital', 'geoPoint': {'lat': 43.70643, 'lon': -79.39864}}], 'overallOfficials': [{'name': 'Robert D. Inman, MD', 'role': 'PRINCIPAL_INVESTIGATOR', 'affiliation': 'University Health Network - Toronto Western Hospital'}]}, 'ipdSharingStatementModule': {'ipdSharing': 'NO'}, 'sponsorCollaboratorsModule': {'leadSponsor': {'name': 'University Health Network, Toronto', 'class': 'OTHER'}, 'responsibleParty': {'type': 'PRINCIPAL_INVESTIGATOR', 'investigatorTitle': 'Principal Investigator', 'investigatorFullName': 'Robert Inman', 'investigatorAffiliation': 'University Health Network, Toronto'}}}}