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

NCT05090410 | Unknown Phase 3 DMC

• 1 other identifier: CRB20_026
• Study Type: interventional
• Target: 400
• Locations: 1 country
• Sites: 1

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.

Conditions

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

Outcome Measures

Primary Outcomes (1)

• the proportion of patients who achieve an American College of Rheumatology (ACR) 50 response

  at week 12

Secondary Outcomes (17)

• the proportion of patients who achieve an ACR20 response

  at weeks 2, 4, 8, 12, 24, 36 and 52

• the proportion of patients who achieve an ACR50 response

  at weeks 2, 4, 8, 24, 36 and 52

• 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

• changes in the simplified disease activity index (SDAI) value

  from baseline to weeks 2, 4, 8, 12, 24, 36, and 52

Study Arms (2)

Filgotinib monotherapy

EXPERIMENTAL

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

Drug: filgotinib 200mg/day

Tocilizumab monotherapy

ACTIVE COMPARATOR

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

Drug: subcutaneous tocilizumab 162mg/biweekly

Interventions

filgotinib 200mg/day DRUG

Patients will be randomized in a 1:1 ratio to the administration of filgotinib 200mg/day or subcutaneous tocilizumab 162mg/biweekly switched from MTX ± other csDMARDs throughout the study period.

Filgotinib monotherapy

subcutaneous tocilizumab 162mg/biweekly DRUG

Patients will be randomized in a 1:1 ratio to the administration of filgotinib 200mg/day or subcutaneous tocilizumab 162mg/biweekly switched from MTX ± other csDMARDs throughout the study period.

Tocilizumab monotherapy

Eligibility Criteria

• Age: 20 Years+
• Sex: all
• Healthy Volunteers: No
• Age Groups: Adult (18-64), Older Adult (65+)

You may qualify if:

• Patients must meet all of the following requirements to be considered for entry into the study:
• ≥20 years old
• with the diagnosis of RA based on the ACR/EULAR 2010 RA Classification Criteria
• with at least moderate disease activity defined as a DAS28-ESR ≥3.2 at the eligibility evaluation
• 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)
• ability and willingness to provide written informed consent and comply with the requirements of the study protocol

You may not qualify if:

• concurrent use of a corticosteroid equivalent to \>5 mg/day of prednisolone
• applicable an item for the contraindication of filgotinib or tocilizumab
• a previous use of a JAK inhibitor or IL-6 inhibitor
• treatment with a corticosteroid and csDMARD and change of dose within 4 weeks prior to the providing consent
• 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
• treatment with a TNF inhibitor (ie, etanercept or biosimilar of etanercept) within 4 weeks prior to the providing consent
• use of a prohibited drug or therapy, other than the agents noted above, within 4 weeks prior to the providing consent
• 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)
• current pregnancy, breastfeeding, or noncompliant with a medically approved contraceptive regimen during and 12 months after the study period

Sponsors & Collaborators

• Atsushi Kawakami: lead
• Gilead Sciences: collaborator

Study Sites (1)

Nagasaki University Hospital

Nagasaki, 852-8501, Japan

RECRUITING

Related Publications (1)

• Shimizu T, Kawashiri SY, Morimoto S, Kawazoe Y, Kuroda S, Kawasaki R, Ito Y, Kiya R, Sato S, Yamamoto H, Kawakami A. 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 (TRANSFORM study): study protocol for a randomized, open-label, parallel-group, multicenter, and non-inferiority clinical trial. Trials. 2023 Mar 3;24(1):161. doi: 10.1186/s13063-023-07176-5.

  PMID: 36869356 DERIVED

MeSH Terms

Conditions

Arthritis, Rheumatoid

Interventions

GLPG0634

Condition Hierarchy (Ancestors)

Arthritis; Joint Diseases; Musculoskeletal Diseases; Rheumatic Diseases; Connective Tissue Diseases; Skin and Connective Tissue Diseases; Autoimmune Diseases; Immune System Diseases

Study Officials

• Atsushi Kawakami, MD, PhD

  Nagasaki University

  PRINCIPAL INVESTIGATOR

Central Study Contacts

Atsushi Kawakami, MD, PhD

CONTACT

+81-95-819-7260; atsushik@nagasaki-u.ac.jp

Toshimasa Shimizu, MD, PhD

CONTACT

+81-95-819-8527; t.shimizu@nagasaki-u.ac.jp

Study Design

• Study Type: interventional
• Phase: phase 3
• Allocation: RANDOMIZED
• Masking: NONE
• Purpose: TREATMENT
• Intervention Model: PARALLEL
• Sponsor Type: OTHER
• Responsible Party: SPONSOR INVESTIGATOR
• PI Title: Professor

Study Record Dates

• First Submitted: September 30, 2021
• First Posted: October 22, 2021
• Study Start: March 3, 2021
• Primary Completion: February 28, 2023
• Study Completion: December 31, 2023
• Last Updated: November 1, 2021

Record last verified: 2021-10

Data Sharing

• IPD Sharing: Will not share

Locations

JP (1)