TRANSFORM: Efficacy and Safety of Selective JAK 1 Inhibitor Filgotinib in Active Rheumatoid Arthritis Patients With Inadequate Response to Methotrexate
Study Details
Study Description
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.
| Condition or Disease | Intervention/Treatment | Phase |
|---|---|---|
|
Phase 3 |
Study Design
Arms and Interventions
| Arm | Intervention/Treatment |
|---|---|
| Experimental: Filgotinib monotherapy The administration of filgotinib 200mg/day switched from MTX ± other csDMARDs throughout the study period. |
Drug: 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.
|
| Active Comparator: Tocilizumab monotherapy The administration of subcutaneous tocilizumab 162mg/biweekly switched from MTX ± other csDMARDs throughout the study period. |
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.
|
Outcome Measures
Primary Outcome Measures
- the proportion of patients who achieve an American College of Rheumatology (ACR) 50 response [at week 12]
Secondary Outcome Measures
- 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]
Higher scores mean a more active of RA.
- 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 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.
- 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.
- 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.
- 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 combined PD score [from baseline to weeks 4, 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.
- 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.
- 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 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 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.
Eligibility Criteria
Criteria
Inclusion Criteria:
- 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
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with at least moderate disease activity defined as a DAS28-ESR ≥3.2 at the eligibility evaluation
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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)
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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:
-
concurrent use of a corticosteroid equivalent to >5 mg/day of prednisolone
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applicable an item for the contraindication of filgotinib or tocilizumab
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a previous use of a JAK inhibitor or IL-6 inhibitor
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treatment with a corticosteroid and csDMARD and change of dose within 4 weeks prior to the providing consent
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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
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treatment with a TNF inhibitor (ie, etanercept or biosimilar of etanercept) within 4 weeks prior to the providing consent
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use of a prohibited drug or therapy, other than the agents noted above, within 4 weeks prior to the providing consent
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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)
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current pregnancy, breastfeeding, or noncompliant with a medically approved contraceptive regimen during and 12 months after the study period
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inappropriateness for inclusion in this study as determined by the investigator
Contacts and Locations
Locations
| Site | City | State | Country | Postal Code | |
|---|---|---|---|---|---|
| 1 | Nagasaki University Hospital | Nagasaki | Japan | 852-8501 |
Sponsors and Collaborators
- Atsushi Kawakami
- Gilead Sciences
Investigators
- Principal Investigator: Atsushi Kawakami, MD, PhD, Nagasaki University
Study Documents (Full-Text)
None provided.More Information
Publications
None provided.- CRB20_026