A Stratification trial to determine key immunological factors predicting Tofacitinib efficacy in Psoriatic Arthritis (PsA). TOFA-PREDICT

Phase 1

• Conditions: psoriatic arthritis; Therapeutic area: Diseases [C] - Musculoskeletal Diseases [C05]

• Registration Number: EUCTR2017-003900-28-NL
• Lead Sponsor: MC Utrecht

Brief Summary

Not available

Detailed Description

Not available

Study Timeline

• Results First Posted: 1900-01-01
• Study Start: 2018-01-25
• Last Update Posted: 4 March 2024

Recruitment & Eligibility

• Status: Authorised-recruitment may be ongoing or finished
• Sex: All
• Target Recruitment: 160

Inclusion Criteria

In order to be eligible to participate in this study, a subject must meet all of the following criteria:
•Age 18-75 years old
•Meets CASPAR criteria for psoriatic arthritis
•Disease duration of at least 8 weeks
•Evidence of active arthritis based upon =2 swollen joints and =2 tender joints
•No evidence of active or latent or inadequately treated infection with Mycobacterium tuberculosis (TB) as defined by all of the following:
oA negative QuantiFERON-TB Gold (QFT-G) In-Tube test performed at or within 3 months prior to a given Screening visit. Subjects with a history of Bacille Calmette Guerin (BCG) vaccination will be tested with the QFT-G test.
oA chest radiograph taken at or within the 3 months prior to screening without changes
osuggestive of active TB infection as determined (and documented) by a qualified radiologist or pulmonologist as per local standard of care.
oNo history of either untreated or inadequately treated latent or active TB infection.
oIf a subject has previously received an adequate course of therapy for either latent (9 months of isoniazid in a locale where rates of primary multi-drug resistant TB infection are <5% or an acceptable alternative regimen) or active (acceptable multi-drug regimen) TB infection, neither a PPD test nor a QuantiFERON- TB Gold In-TubeR™ (QFT Gold test) need be obtained, but a chest radiograph must still be obtained if not done so within the prior 3 months.
•Subjects who are already taking oral corticosteroids (but not injectable) may participate in the study:
oOral corticosteroids: Subjects who are already receiving oral corticosteroids must be on a stable dose of =10 mg/day of prednisone or equivalent for 4 weeks prior to first dose of study drug.
oInjected (eg, intraarticular, intramuscular or intravenous) corticosteroids: Discontinued 4 weeks prior to the first dose of study drug.
•Subjects who are already taking NSAIDs/COX-2 inhibitors may participate in the study provided that that the dose is stable for one week prior to first dose of study drug.
•Subjects are to discontinue active psoriasis treatment prior to being enrolled in the study.
oTopical treatments that could affect psoriasis including: corticosteroids, tars, keratolytics, anthralin, vitamin D analogs, and retinoids must be discontinued for at least 2 weeks prior to the first dose of study drug.
oExceptions: the following topical treatments are allowed: non-medicated emollients for use over the whole body; topical steroids including hydrocortisone and hydrocortisone acetate £1% for the palms, soles, face, and intertriginous areas only; tar and salicylic acid preparations for the scalp only and shampoos free of corticosteroid for the scalp only.
oUVB (narrowband or broadband) phototherapy must be discontinued at least 2 weeks prior to the first dose of study drug. Psoralens + UVA phototherapy (PUVA) must be discontinued for at least 4 weeks prior to the first dose of study drug.

Inclusion criteria for the csDMARD-naïve group (Arm 1):
•No history of csDMARD use or bDMARD therapy use

Inclusion criteria for the csDMARD-IR group (Arm 2):
•Current use of methotrexate, sulfasalazine or leflunomide on the highest tolerated and on a stable dosage for at least 4 weeks prior to randomization. Highest dosage accepted respectively are max =25mg/wk, 20mg/day and 3000mg/day. Subjects on methotrexate should be on an adequate and stable dose of folate supplementation (not less than 5 mg weekly based on folic acid,

Exclusion Criteria

•Currently have pustular psoriasis only
•Participation in other studies involving investigational drug(s) (Phases 1-4) within 4 weeks before the current study begins and/or during study participation. Participation in any observational studies during study participation.
•Pregnant females, breastfeeding females, females of child-bearing potential not using highly effective contraception or not agreeing to continue highly effective contraception for at least one ovulatory cycle after last dose of investigational product or females planning pregnancy.
•Current or recent history of a severe, progressive or uncontrolled renal, hepatic, hematological, gastrointestinal, metabolic, endocrine, pulmonary, cardiovascular, or neurologic disease.
•Blood dyscrasias within 3 months prior to the first dose of study drug including confirmed:
oHemoglobin <10 g/dL; White blood cell count <3.0 x 109/L; Absolute neutrophil count =1.5 x 109/L);
oAbsolute lymphocyte count <1.0x109/L; Platelet count <100 x 109/L.
•Estimated Creatinine Clearance <40 ml/min based on Cockcroft formula.
•Total bilirubin, AST or ALT more than 2.0 times the upper limit of normal at screening visit.
•a known immunodeficiency or a first-degree relative with a hereditary immunodefiency.
•history of any autoimmune rheumatic disease other than PsA (including systemic lupus erythematosis, mixed connective tissue disease, scleroderma, polymyositis) or known diagnosis of fibromyalgia, without approval by sponsor. Prior history of, or current rheumatic inflammatory disease other than PsA
•History of an infected joint prosthesis at any time, with the prosthesis still in situ.
•History of any lymphoproliferative disorder, such as Epstein Barr Virus (EBV) related lymphoproliferative disorder, history of lymphoma, leukemia, or signs and symptoms suggestive of current lymphatic disease.
•History of recurrent (more than one episode) herpes zoster or disseminated (a single episode) herpes zoster or disseminated (a single episode) herpes simplex.
•History of active infection (including localized infection) requiring:
oHospitalization, parenteral antimicrobial therapy, or as otherwise judged clinically significant by the investigator, within the 6 months prior to the first dose of study medication.
oOral antimicrobial therapy within 2 weeks prior to the first dose of study medication.
•Any prior treatment with non-B cell-specific lymphocyte depleting agents/therapies, alkylating agents, or total lymphoid irradiation. Subjects who have received rituximab or other selective B-lymphocyte depleting agents (including experimental agents) are eligible if they have not received such therapy for at least 1 year prior to first dose of study drug and have normal CD19/20+ counts by FACS analysis.
•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 following discontinuation of study medication.
•Any condition possibly affecting oral drug absorption, e.g. gastrectomy, clinically significant diabetic gastroenteropathy, or certain types of bariatric surgery such as gastric bypass.
•History of alcohol or drug abuse unless in full remission for greater than 6 months prior to first dose of study medication.
•A subject with a malignancy may be included only in the following cases:
oadequately treated or excised non-metastatic basal cell o

Study & Design

• Study Type: Interventional clinical trial of medicinal product
• Study Design: Not specified