Tofacitinib in early active axial spondyloarthritis: a prospective, randomized, double-blind, placebo-controlled multicentre study - FASTLANE
- Conditions
- Axial spondyloarthritisMedDRA version: 21.1Level: PTClassification code: 10071400Term: Axial spondyloarthritis Class: 100000004859Therapeutic area: Diseases [C] - Musculoskeletal Diseases [C05]Therapeutic area: Diseases [C] - Immune System Diseases [C20]
- Registration Number
- CTIS2023-505050-18-00
- Lead Sponsor
- Charite Universitaetsmedizin Berlin KöR
- Brief Summary
Not available
- Detailed Description
Not available
Recruitment & Eligibility
- Status
- Recruiting
- Sex
- All
- Target Recruitment
- 104
Subject =18 and = 45 years of age at the screening visit., Subjects who are regularly taking NSAIDs or analgesics as part of their SpA therapy are required to be on a stable dose/dose regimen for at least 2 weeks prior to the baseline visit., Subjects taking oral corticosteroids must be on an average daily dose of =10mg/day prednisone or equivalent for at least 2 weeks prior to the baseline visit., Subjects taking Methotrexate (=25 mg /week), Sulfasalazine (up to 3g/day) or Mesalazine (= 4.5g/day) are allowed to continue their medication if started at least 12 weeks prior to baseline, with a stable dose for at least 4 weeks before randomization. Subjects on methotrexate should be on an adequate and stable dose of folate supplementation by local standards (not less than 5 mg weekly, unless such doses would violate the local label guidelines or standard of care) for at least 4 weeks prior to the first dose of investigational product. Subject must not have had previous serious toxicity while on methotrexate and not be expected to require evaluation for possible methotrexate toxicity (eg, require a liver biopsy for methotrexate toxicity) during the study., The subject is able and willing to give written informed consent and comply with the requirements of the study protocol. Only patients who give written informed consent will be included in the trial., Clinical diagnosis of axSpA by their treating rheumatologist., Fulfilment of the ASAS classification criteria for axSpA: a) Back pain for at least 3 months; b) Onset before 45 years of age; c) Sacroiliitis on imaging (x-rays or MRI) with = 1 SpA feature OR HLA-B27 positive with = 2 SpA features; i. Sacroiliitis on imaging defined as by x-rays as definite radiographic sacroiliitis grad II bilaterally or grade 3-4 unilaterally; according to the mNY criteria 1984; or as by MRI as active (acute) inflammation of SIJ on MRI, highly suggestive of sacroiliitis associated with SpA.”; ii. SpA features are considered: inflammatory back pain; extra-spinal manifestations (arthritis, enthesitis (heel), anterior acute uveitis, psoriasis, inflammatory bowel disease); good response to NSAIDs; family history of SpA; HLA-B27 positivity; elevated CRP or ESR., Symptom (back pain) duration for = 2 years, according to the recently defined early axial SpA” by ASAS., Active disease activity as defined by: a) BASDAI =4 and Back pain score (BASDAI Question 2) of =4 (on a 0-10 NRS) at screening and baseline.; AND b) Objective signs of inflammation at screening, evident by: i. MRI with SIJ inflammation (assessed by two central readers); AND/OR ii. Elevated serum CRP levels (>5mg/l), History of an inadequate response to at least one NSAID, other than naproxen. An inadequate response to a previous NSAID is defined as a lack of sufficient clinical response to the maximum recommended or tolerated daily dose for a minimum of 2 weeks based on a clinical judgment or based on a related adverse event PLUS the presence of active disease. This will be documented on the relevant case report form (CRF). Concerning patients who have received naproxen prior to screening visit: those who have had an inadequate response as per description above will be excluded. Only patients who have had naproxen but do not fulfill the abovementioned definition for inadequate responder will be considered for inclusion (e.g. patients with well-tolerated naproxen at doses below the maximum recommended dose)., If female: either unable to bear children (p
Current or previous treatment with any biologic or targeted synthetic disease modifying antirheumatic drug (bDMARD or tsDMARD, respectively) including but not limited to TNF inhibitors, IL-17 inhibitors, IL-23 inhibitors, JAK inhibitors, and TYK inhibitors, PDE4 inhibitors, thalidomide (including previous use) and other prohibited concomitant medications., Current malignancy or history of malignancies except adequately treated or excised basal cell or squamous cell carcinoma or cervical carcinoma in situ., A subject with any condition possibly affecting oral drug absorption, e.g. gastrectomy, clinically significant diabetic gastroenteropathy, or certain types of bariatric surgery such as gastric bypass. Procedures such as gastric banding, that simply divides the stomach into separate chambers, are NOT exclusionary., Any significant acute or chronic infection (at the discretion of the investigator)., Significant trauma or surgery procedure within 4 weeks prior to baseline or any pre-planned elective surgery during the study period., Evidence of other severe uncontrolled gastrointestinal, hepatic (serum albumin <25 mg/l or Child-Pugh-Score >10), renal, pulmonary, cardiovascular, nervous or endocrine disorders., Patients with a history of a severe psychiatric illness, which might interfere with the patient’s ability to understand the requirements of the study and assessment and may interfere with the interpretation of study results., Any subject who has been vaccinated with live or attenuated vaccines within the 6 weeks prior to the first dose of study medication or is to be vaccinated with these vaccines at any time during treatment or within 6 weeks after the last dose of study drug., Any of the following lab abnormalities detected at screening: a. Hemoglobin <10g/dl; b. Absolute neutrophil count <1.0 x 109/L (<1000/mm3); c. Absolute lymphocyte count <1.0 x 109/L (<750/mm3); d. Platelet count <100 x 109/L (<100,000/mm3); e. Aspartate aminotransferase (AST) or alanine aminotransferase (ALT)) >1.5times upper limit of normal; f. Creatinine-Clearance < 40 ml/min. One re-testing of a laboratory-acceptable specimen (e.g., appropriately labeled, within stability parameters, not hemolyzed, appropriate type (tube and reagent) and volume) is allowed of any above parameters if the abnormal lab(s) was an uncharacteristic result(s). Documentation in the source of the typical results to allow a repeat lab is required. Re-test must be completed within the screening period., Patients who are defined as vulnerable patients according to Art. 10 REGULATION (EU) No 536/2014: patients who are institutionalized due to regulatory or juridical order; patients who are an employee of the investigator or study site, with direct involvement in the proposed study or other studies under the direction of that investigator or study site; family members of the employees or the investigator., Any other conditions making the patient unsuitable in the opinion of the investigator for the participation in the current study or treatment with tofacitinib and/or naproxen., Female subjects who are breastfeeding, pregnant, or plan to become pregnant during the study or within 4 weeks following the last dose of study drug., Patients with contraindications for the MRI including but not limited to: claustrophobia, seizure disorders, presence of an implanted electronic device (e.g., heart pacemaker, insulin pump, etc.) or metal implants not known to be MRI safe and metal foreign bodi
Study & Design
- Study Type
- Interventional clinical trial of medicinal product
- Study Design
- Not specified
- Primary Outcome Measures
Name Time Method
- Secondary Outcome Measures
Name Time Method