Efficacy and Safety of Selective JAK 1 Inhibitor Filgotinib in Active Rheumatoid Arthritis Patients With Inadequate Response to Methotrexate (TRANSFORM)

Atsushi Kawakami

Status and phase: Unknown; Phase 3

Conditions: Musculoskeletal Ultrasound; Biomarker; JAK Inhibitor; IL-6 Inhibitor; Rheumatoid Arthritis

Treatments: Drug: filgotinib 200mg/day; Drug: subcutaneous tocilizumab 162mg/biweekly

Study type: Interventional

Funder types: Other; Industry

Identifiers

NCT05090410

CRB20_026

Details and patient eligibility

About

The administration of Janus kinase (JAK) inhibitors as well as biological disease-modifying anti-rheumatic drugs has dramatically improved even the clinical outcomes in rheumatoid arthritis (RA) patients with inadequate response to methotrexate (MTX). The dysregulation of JAK-signal transducer and activator of transcription (STAT) pathways via overproduction of cytokines, such as interleukin-6 (IL-6) is involved in the pathogenesis of RA. Filgotinib is a selective JAK1 inhibitor to be approved for use in RA. Filgotinib is effective in suppressing disease activity and preventing the progression of joint destruction due to inhibition of the JAK-STAT pathway. IL-6 inhibitors such as tocilizumab also inhibit the JAK-STAT pathways due to inhibition of IL-6 signaling. We will evaluate whether the effectiveness and safety of filgotinib monotherapy is non-inferior to those of tocilizumab monotherapy in RA patients with inadequate response to MTX.

Enrollment: 400 estimated patients

Sex: All

Ages: 20+ years old

Volunteers: No Healthy Volunteers

Inclusion criteria

• Patients must meet all of the following requirements to be considered for entry into the study:

  1. ≥20 years old
  2. with the diagnosis of RA based on the ACR/EULAR 2010 RA Classification Criteria
  3. with at least moderate disease activity defined as a DAS28-ESR ≥3.2 at the eligibility evaluation
  4. treated with MTX for ≥8 weeks prior to the providing consent, including 4 weeks or more at the same doses of 8 to 16 mg per week (stable doses of <8 mg per week are allowed only in the presence of intolerance to higher doses)
  5. ability and willingness to provide written informed consent and comply with the requirements of the study protocol

Exclusion criteria

• The exclusion criteria are as follows:

  1. concurrent use of a corticosteroid equivalent to >5 mg/day of prednisolone
  2. applicable an item for the contraindication of filgotinib or tocilizumab
  3. a previous use of a JAK inhibitor or IL-6 inhibitor
  4. treatment with a corticosteroid and csDMARD and change of dose within 4 weeks prior to the providing consent
  5. treatment with a biologic DMARD or a biosimilar DMARD (ie, infliximab, biosimilar of infliximab, adalimumab, biosimilar of adalimumab, golimumab, certolizumab pegol or abatacept) within 8 weeks prior to the providing consent
  6. treatment with a TNF inhibitor (ie, etanercept or biosimilar of etanercept) within 4 weeks prior to the providing consent
  7. use of a prohibited drug or therapy, other than the agents noted above, within 4 weeks prior to the providing consent
  8. a complication causing musculoskeletal disorders other than RA (ie, ankylosing spondyloarthritis, reactive arthritis, psoriatic arthritis, crystal-induced arthritis, systemic lupus erythematosus, systemic scleroderma, inflammatory myopathy, or mixed connective tissue disease)
  9. current pregnancy, breastfeeding, or noncompliant with a medically approved contraceptive regimen during and 12 months after the study period
  10. inappropriateness for inclusion in this study as determined by the investigator

Trial design

Primary purpose: Treatment

Allocation: Randomized

Interventional model: Parallel Assignment

Masking: None (Open label)

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400 participants in 2 patient groups

Filgotinib monotherapy

Experimental group

Description:

The administration of filgotinib 200mg/day switched from MTX ± other csDMARDs throughout the study period.

Treatment:

Drug: filgotinib 200mg/day

Tocilizumab monotherapy

Active Comparator group

Description:

The administration of subcutaneous tocilizumab 162mg/biweekly switched from MTX ± other csDMARDs throughout the study period.

Treatment:

Drug: subcutaneous tocilizumab 162mg/biweekly