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

Phase 3

• Conditions: Musculoskeletal Ultrasound; Biomarker; Rheumatoid Arthritis; IL-6 Inhibitor; JAK Inhibitor
• Interventions: Drug: filgotinib 200mg/day; Drug: subcutaneous tocilizumab 162mg/biweekly

• Registration Number: NCT05090410
• Lead Sponsor: Atsushi Kawakami

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.

Detailed Description

Not available

Study Timeline

• Study Start: 2021-03-03
• Study First Submitted: 2021-09-30
• Status Verified: 2021-10
• Study First Submitted QC: 2021-10-21
• Study First Posted: 2021-10-22
• Last Update Submitted: 2021-10-23
• Last Update Posted: 2021-11-01
• Primary Completion: 2023-02-28
• Study Completion: 2023-12-31

Recruitment & Eligibility

• Status: UNKNOWN
• Sex: All
• Target Recruitment: 400

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

Study & Design

• Study Type: INTERVENTIONAL
• Study Design: PARALLEL

Arm && Interventions

Group	Intervention	Description
Filgotinib monotherapy	filgotinib 200mg/day	The administration of filgotinib 200mg/day switched from MTX ± other csDMARDs throughout the study period.
Tocilizumab monotherapy	subcutaneous tocilizumab 162mg/biweekly	The administration of subcutaneous tocilizumab 162mg/biweekly switched from MTX ± other csDMARDs throughout the study period.

Primary Outcome Measures

Name	Time	Method
the proportion of patients who achieve an American College of Rheumatology (ACR) 50 response	at week 12

Secondary Outcome Measures

Name	Time	Method
the proportion of patients who achieve an ACR50 response	at weeks 2, 4, 8, 24, 36 and 52
changes in the simplified disease activity index (SDAI) value	from baseline to weeks 2, 4, 8, 12, 24, 36, and 52	Higher scores mean a more active RA.
changes in the serum levels of biomarkers	from baseline to weeks 2, 4, 12, 24, 36, and 52	We analyze the serum levels of multiple biomarkers such as cytokines and chemokines.
the proportion of patients who achieve an ACR20 response	at weeks 2, 4, 8, 12, 24, 36 and 52
changes in the DAS28-CRP value	from baseline to weeks 2, 4, 8, 12, 24, 36, and 52	Higher scores mean a more active RA.
change in van der Heijde-modified total Sharp score (vdH-mTSS)	from baseline to weeks 24 and 52	Higher scores mean a more joint destruction and deformity.
changes in the morning stiffness duration	from baseline to weeks 2, 4, 8, 12, 24, 36, and 52	Higher scores mean a more active RA.
changes in the Disease Activity Score (DAS)28-ESR value	from baseline to weeks 2, 4, 8, 12, 24, 36, and 52	Higher scores mean a more active RA.
the proportion of patients who achieve an ACR70 response	at weeks 2, 4, 8, 12, 24, 36 and 52
changes in the clinical disease activity index (CDAI) value	from baseline to weeks 2, 4, 8, 12, 24, 36, and 52	Higher scores mean a more active of RA.
change in the EuroQol 5 Dimensions 5-Level (EQ-5D-5L) data	from baseline to weeks 2, 4, 8, 12, 24, 36, and 52	Higher scores mean a worse QOL.
change in the Functional Assessment of Chronic Illness-Fatigue (FACIT-F) data	from baseline to weeks 2, 4, 8, 12, 24, 36, and 52	Higher scores mean a worse fatigue.
changes in the combined PD score	from baseline to weeks 4, 12, 24, 36, and 52	Higher scores mean a more active RA.
change in the Health Assessment Questionnaire-Disability Index (HAQ-DI) data	from baseline to weeks 2, 4, 8, 12, 24, 36, and 52	Higher scores mean a more active RA.
changes in the total power Doppler (PD) score	from baseline to weeks 4, 12, 24, 36, and 52	Higher scores mean a more active RA.
changes in the total grayscale (GS) score	from baseline to weeks 4, 12, 24, 36, and 52	Higher scores mean a more active RA.
changes in the morning stiffness activity	from baseline to weeks 2, 4, 8, 12, 24, 36, and 52	We analyze the visual analog scale of morning stiffness activity. Higher scores mean a more active RA.

Trial Locations

Locations (1)

Nagasaki University Hospital; 🇯🇵 Nagasaki, Japan