Clinical trial NCT05090410: Efficacy and Safety of Selective JAK 1 Inhibitor Filgotinib in Active Rheumatoid Arthritis Patients With Inadequate Response to Methotrexate
Official title: Efficacy and Safety of Selective JAK 1 Inhibitor Filgotinib in Active Rheumatoid Arthritis Patients With Inadequate Response to Methotrexate: Comparative Study With Filgotinib and Tocilizumab Examined by Clinical Index as Well as Musculoskeletal Ultrasound Assessment
Study type: INTERVENTIONAL
Overall status: UNKNOWN
Phase: PHASE3
Conditions: Rheumatoid Arthritis
JAK Inhibitor
IL-6 Inhibitor
Musculoskeletal Ultrasound
Biomarker
Lead sponsor: Nagasaki University
Sponsor class: OTHER
Collaborators: name: Gilead Sciences
First posted: 2021-10-22
Enrollment: 400
Sex: ALL
Minimum age (years): 20
Standard ages: ADULT
OLDER_ADULT
Accepts healthy volunteers: no
Allocation: RANDOMIZED
Intervention model: PARALLEL
Primary purpose: TREATMENT

Brief summary: 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.


Eligibility criteria: 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

Primary outcomes:
measure: the proportion of patients who achieve an American College of Rheumatology (ACR) 50 response
timeFrame: at week 12
Secondary outcomes:
measure: the proportion of patients who achieve an ACR20 response
timeFrame: at weeks 2, 4, 8, 12, 24, 36 and 52
measure: the proportion of patients who achieve an ACR50 response
timeFrame: at weeks 2, 4, 8, 24, 36 and 52
measure: the proportion of patients who achieve an ACR70 response
timeFrame: at weeks 2, 4, 8, 12, 24, 36 and 52
measure: changes in the clinical disease activity index (CDAI) value
timeFrame: from baseline to weeks 2, 4, 8, 12, 24, 36, and 52
measure: changes in the simplified disease activity index (SDAI) value
timeFrame: from baseline to weeks 2, 4, 8, 12, 24, 36, and 52
measure: changes in the Disease Activity Score (DAS)28-ESR value
timeFrame: from baseline to weeks 2, 4, 8, 12, 24, 36, and 52
measure: changes in the DAS28-CRP value
timeFrame: from baseline to weeks 2, 4, 8, 12, 24, 36, and 52
measure: changes in the serum levels of biomarkers
timeFrame: from baseline to weeks 2, 4, 12, 24, 36, and 52
measure: changes in the total power Doppler (PD) score
timeFrame: from baseline to weeks 4, 12, 24, 36, and 52
measure: changes in the total grayscale (GS) score
timeFrame: from baseline to weeks 4, 12, 24, 36, and 52
measure: changes in the combined PD score
timeFrame: from baseline to weeks 4, 12, 24, 36, and 52
measure: change in van der Heijde-modified total Sharp score (vdH-mTSS)
timeFrame: from baseline to weeks 24 and 52
measure: change in the Health Assessment Questionnaire-Disability Index (HAQ-DI) data
timeFrame: from baseline to weeks 2, 4, 8, 12, 24, 36, and 52
measure: change in the EuroQol 5 Dimensions 5-Level (EQ-5D-5L) data
timeFrame: from baseline to weeks 2, 4, 8, 12, 24, 36, and 52
measure: change in the Functional Assessment of Chronic Illness-Fatigue (FACIT-F) data
timeFrame: from baseline to weeks 2, 4, 8, 12, 24, 36, and 52
measure: changes in the morning stiffness duration
timeFrame: from baseline to weeks 2, 4, 8, 12, 24, 36, and 52
measure: changes in the morning stiffness activity
timeFrame: from baseline to weeks 2, 4, 8, 12, 24, 36, and 52
Other outcomes:
Locations:
city: Nagasaki
country: Japan
facility: Nagasaki University Hospital
Study officials:
affiliation: Nagasaki University
name: Atsushi Kawakami, MD, PhD
role: PRINCIPAL_INVESTIGATOR
References: