Efficacy and safety of selective JAK 1 inhibitor Filgotinib in active rheumatoid arthritis patients with inadequate response to conventional synthetic disease-modifying antirheumatic drugs: Comparative study with Filgotinib and interleukin 6 inhibitor examined by clinical index as well as musculoskeletal ultrasound assessment(TRANSFORM study): Study protocol for a randomized, open-label, parallel-group, multicenter, and non-inferiority clinical trial

JRCT ID: jRCTs071200107

Registered date:03/03/2021

Basic Information

• Recruitment status: Complete
• Health condition(s) or Problem(s) studied: Rheumatoid arthritis
• Date of first enrollment: 25/05/2021
• Target sample size: 400
• Study type: Interventional
• Intervention(s): Patients with active RA who have had inadequate response after 8-week or longer csDMARDs treatment will be advised to switch to filgotinib or IL-6 inhibitor (tocilizumab or sarilumab) monotherapy. csDMARDs treatment will be interrupted at baseline. Patients meeting eligibility criteria will be randomized (in a ratio of 1:1) to receive filgotinib or IL-6 inhibitor (either tocilizumab or sarilumab) continuously until Week 52. Patients allocated to IL-6 inhibitor will receive either tocilizumab (subcutaneously or intravenously) or sarilumab (subcutaneously) at the discretion of the principal investigator or a subinvestigator. The proportion of patients achieving ACR50 12 weeks after initiation of filgotinib or IL-6 inhibitor (tocilizumab or sarilumab) monotherapy will be the primary endpoint to demonstrate non-inferiority of filgotinib monotherapy to IL-6 inhibitor (tocilizumab or sarilumab) monotherapy.

Outcome(s)

• Primary Outcome: Proportion of subjects who achieve an ACR50 response at week 12

Secondary Outcome

1)Each of the proportions of subjects who achieve an ACR50 response at Week 2, 4, 24, 36, and 52.
2)Each of the proportions of subjects who achieve an ACR 20/70 response at Week 2, 4, 12, 24, 36, and 52.
3)Change from Week0 at 2, 4, 12, 24, 36, and 52 weeks after initiation of first dose for the following tests per case: CDAI/SDAI, DAS28-ESR/CRP, HAQ-DI, EQ-5D-5L, FACIT-F, and morning stiffness duration/activity rating.
4)Changes from Week0 in the following clinical evaluations at Week 4, 12, 24, 36, and 52: MSUS total PD score, MSUS GS score, and MSUS total composite score.
5)Changes from Week0 in the following clinical evaluations at Week 2, 4, 12, 24, 36, and 52: blood concentration of cytokines and chemokines.
6) Changes from Week0 in mTSS at Week 24 and 52.

Key inclusion & exclusion criteria

• Age minimum: >= 18age old
• Age maximum: Not applicable
• Gender: Both

Include criteria

1)Patients aged 18 years or older at the time of providing consent.
2)Patients diagnosed as having RA according to the 2010 RA classification criteria of the American College of Rheumatology/European League Against Rheumatology.
3)Patients with moderate or more disease activity (DAS28-ESR >= 3.2) at the time of the eligibility evaluation.
4) Patients who have been treated with csDMARDs (any or combination of MTX, sodium gold thiolate, auranofin, penicillamine, salazosulfapyridine, lobenzalit, busiramine, actalit, tacrolimus, mizoribine, leflunomide, and iguratimod) for at least 8 weeks at the time of consent and did not have sufficient response after 4-week or longer csDMARDs treatment without modifying the dose.
5)Patients who can personally provide written consent at their own free will after being receiving a thorough explanation of the study and fully understanding their participation in the study.

Exclude criteria

1) Patients receiving more than 5 mg per day of prednisolone equivalent of corticosteroids.
2)Patients with contraindications for filgotinib, tocilizumab and sarilumab treatment.
3)Patients with a history of using filgotinib.
4) Patients treated with corticosteroid but have modified the dose within 4 weeks prior to the time of consent.
5) Patients who have received treatment with TNF inhibitors (ie, infliximab, infliximab BS, adalimumab, adalimumab BS, golimumab, and certolizumab pegol), IL-6 inhibitors (tocilizumab and sarilumab) and abatacept within 8 weeks prior to the time of providing consent.
6)Patients who have received TNF inhibitors (ie. etanercept and etanercept BS) within 4 weeks prior to the time of consent.
7)Patients who have received anti-rheumatic molecular targeted drugs (ie. tofacitinib, baricitinib, peficitinib and upadacitinib) within 4 weeks prior to the time of consent.
8)Patients who have used non-steroidal anti-inflammatory analgesics (suppositories), intra-articular injections, investigational drugs, or medical devices under development within 4 weeks prior to the time of consent.
9) Patients with concurrent musculoskeletal disorders other than RA (i.e. ankylosing spondyloarthritis, reactive arthritis, psoriatic arthritis, crystal-induced arthritis, systemic lupus erythematosus, systemic scleroderma, inflammatory myopathy and mixed connective tissue disease).
10)Women who are breastfeeding, pregnant, or wish to fall pregnant, and those who do not consent to use contraception from the time of the eligibility evaluation until 12 months after the final dose of the investigational drug.
11)Individuals who, for other reasons, are deemed ineligible of study participation by the principal investigator.

Related Information

• Primary Sponsor: Kawakami Atsushi
• Source(s) of Monetary Support: Gilead Sciences, Inc.