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

NCT ID: NCT05090410

Last Updated: 2021-11-01

Basic Information

• Recruitment Status: UNKNOWN
• Clinical Phase: PHASE3
• Total Enrollment: 400 participants
• Study Classification: INTERVENTIONAL
• Study Start Date: 2021-03-03
• Study Completion Date: 2023-12-31

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

Study Design

• Allocation Method: RANDOMIZED
• Intervention Model: PARALLEL
• Primary Study Purpose: TREATMENT
• Blinding Strategy: NONE

Study Groups

Filgotinib monotherapy

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

Group Type: EXPERIMENTAL

filgotinib 200mg/day

Intervention Type: 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

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

Group Type: ACTIVE_COMPARATOR

subcutaneous tocilizumab 162mg/biweekly

Intervention Type: 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.

Interventions

filgotinib 200mg/day

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.

Intervention Type: DRUG

subcutaneous tocilizumab 162mg/biweekly

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.

Intervention Type: DRUG

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

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

• Minimum Eligible Age: 20 Years
• Eligible Sex: ALL
• Accepts Healthy Volunteers: No

Sponsors

Gilead Sciences

INDUSTRY

Sponsor Role: collaborator

Atsushi Kawakami

OTHER

Sponsor Role: lead

Responsible Party

Atsushi Kawakami

Professor

Responsibility Role: SPONSOR_INVESTIGATOR

Principal Investigators

Atsushi Kawakami, MD, PhD

Role: PRINCIPAL_INVESTIGATOR

Nagasaki University

Locations

Nagasaki University Hospital

Nagasaki, , Japan

Site Status: RECRUITING

Countries

Japan

Central Contacts

Atsushi Kawakami, MD, PhD

Role: CONTACT

Phone: +81-95-819-7260

Email: atsushik@nagasaki-u.ac.jp

Toshimasa Shimizu, MD, PhD

Role: CONTACT

Phone: +81-95-819-8527

Email: t.shimizu@nagasaki-u.ac.jp

Facility Contacts

Atsushi Kawakami, MD, PhD

Role: primary

Toshimasa Shimizu, MD, PhD

Role: backup

References

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.

Reference Type: DERIVED

PMID: 36869356 (View on PubMed)

Other Identifiers

CRB20_026

Identifier Type: -

Identifier Source: org_study_id