Rheumatoid ArthritisPhase 3TRANSFORMNCT05090410
Efficacy and Safety of Selective JAK 1 Inhibitor Filgotinib in Active Rheumatoid Arthritis Patients With Inadequate Response to Methotrexate
A Phase 3 study testing filgotinib 200mg/day and subcutaneous tocilizumab 162mg/biweekly in people with Rheumatoid Arthritis and JAK Inhibitor, run by Atsushi Kawakami at 1 site in Japan.
Trial 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). Read more about this study
- Who is it for?
- Ages 20 years and older
- Conditions the study is for
- Rheumatoid Arthritis, JAK Inhibitor, IL-6 Inhibitor
- What is being tested?
- filgotinib 200mg/day and subcutaneous tocilizumab 162mg/biweekly
- Type of treatment
- Injection or infusion
- Could I receive a placebo?
- No, everyone receives an active treatment
- How many people
- 400 participants
- Where
- 1 siteJapan
- Study dates
- 3 Mar 2021to 31 Dec 2023
- Phase
- Phase 3
- Are there results?
- None posted in the registry
Key requirements
Who can take part, as listed by the sponsor. Only the study team can confirm whether you are eligible, so take this list to your doctor.
- Ages 20 years and older
- All sexes
- No healthy volunteers
- Adult, Older adult
Who may be able to join
- 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
Who cannot join
- The exclusion criteria are as follows:
- 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
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- 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
- inappropriateness for inclusion in this study as determined by the investigator
Trial locations and contacts
1 site in 1 country.
Japan1 site, 1 recruiting
- Recruiting
Nagasaki University Hospital
Nagasaki, 852-8501
Atsushi Kawakami, MD, PhD, +81-95-819-7260, atsushik@nagasaki-u.ac.jp
Toshimasa Shimizu, MD, PhD, +81-95-819-8527, t.shimizu@nagasaki-u.ac.jp
About this study
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
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
- Being tested
- filgotinib 200mg/day, subcutaneous tocilizumab 162mg/biweekly
- Medical subject headings
- Arthritis, Rheumatoid
What participants receive
What participants receive. In a randomised study each person is assigned to one group by chance.
filgotinib 200mg/dayDrug
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.
subcutaneous tocilizumab 162mg/biweeklyDrug
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.
| Study group | Role | What they receive |
|---|---|---|
| Filgotinib monotherapy | Experimental | The administration of filgotinib 200mg/day switched from MTX ± other csDMARDs throughout the study period. Receives: Drug: filgotinib 200mg/day |
| Tocilizumab monotherapy | Active comparator | The administration of subcutaneous tocilizumab 162mg/biweekly switched from MTX ± other csDMARDs throughout the study period. Receives: Drug: subcutaneous tocilizumab 162mg/biweekly |
What is being measured
The primary outcome is the main question the study is designed to answer.
the proportion of patients who achieve an American College of Rheumatology (ACR) 50 response
Measured: at week 12
Secondary outcomes (17)
the proportion of patients who achieve an ACR20 response
Measured: at weeks 2, 4, 8, 12, 24, 36 and 52
the proportion of patients who achieve an ACR50 response
Measured: at weeks 2, 4, 8, 24, 36 and 52
the proportion of patients who achieve an ACR70 response
Measured: at weeks 2, 4, 8, 12, 24, 36 and 52
changes in the clinical disease activity index (CDAI) value
Higher scores mean a more active of RA.
Measured: from baseline to weeks 2, 4, 8, 12, 24, 36, and 52
changes in the simplified disease activity index (SDAI) value
Higher scores mean a more active RA.
Measured: from baseline to weeks 2, 4, 8, 12, 24, 36, and 52
changes in the Disease Activity Score (DAS)28-ESR value
Higher scores mean a more active RA.
Measured: from baseline to weeks 2, 4, 8, 12, 24, 36, and 52
changes in the DAS28-CRP value
Higher scores mean a more active RA.
Measured: from baseline to weeks 2, 4, 8, 12, 24, 36, and 52
changes in the serum levels of biomarkers
We analyze the serum levels of multiple biomarkers such as cytokines and chemokines.
Measured: from baseline to weeks 2, 4, 12, 24, 36, and 52
changes in the total power Doppler (PD) score
Higher scores mean a more active RA.
Measured: from baseline to weeks 4, 12, 24, 36, and 52
changes in the total grayscale (GS) score
Higher scores mean a more active RA.
Measured: from baseline to weeks 4, 12, 24, 36, and 52
changes in the combined PD score
Higher scores mean a more active RA.
Measured: from baseline to weeks 4, 12, 24, 36, and 52
change in van der Heijde-modified total Sharp score (vdH-mTSS)
Higher scores mean a more joint destruction and deformity.
Measured: from baseline to weeks 24 and 52
change in the Health Assessment Questionnaire-Disability Index (HAQ-DI) data
Higher scores mean a more active RA.
Measured: from baseline to weeks 2, 4, 8, 12, 24, 36, and 52
change in the EuroQol 5 Dimensions 5-Level (EQ-5D-5L) data
Higher scores mean a worse QOL.
Measured: from baseline to weeks 2, 4, 8, 12, 24, 36, and 52
change in the Functional Assessment of Chronic Illness-Fatigue (FACIT-F) data
Higher scores mean a worse fatigue.
Measured: from baseline to weeks 2, 4, 8, 12, 24, 36, and 52
changes in the morning stiffness duration
Higher scores mean a more active RA.
Measured: from baseline to weeks 2, 4, 8, 12, 24, 36, and 52
changes in the morning stiffness activity
We analyze the visual analog scale of morning stiffness activity. Higher scores mean a more active RA.
Measured: from baseline to weeks 2, 4, 8, 12, 24, 36, and 52
Timeline
From the start of the study to its completion; the mark is today. Estimated dates are the sponsor’s plan.
- First posted22 Oct 2021
- Study start3 Mar 2021
- Primary completion28 Feb 2023 (estimated)
- Study completion31 Dec 2023 (estimated)
Resources
- Official record on ClinicalTrials.govThe registry entry this page is built from, with its full change history.
- Publications (2)Papers the sponsor has linked to this study.
- Other trials for Rheumatoid ArthritisStudies of the same condition, open and under way.
- What the trial phases meanHow a treatment moves from first tests in people to approval.
More details
For doctors and researchers: how the study is designed, who runs it, and its registry IDs.
Study design
- Study type
- Interventional
- Phase
- Phase 3
- Primary purpose
- Treatment
- Allocation
- Randomised
- Intervention model
- Parallel groups
- Masking
- None (open label)
- Enrolment
- 400 participants (estimated)
Sponsor and investigators
- Lead sponsor
- Atsushi Kawakami
- Sponsor type
- University, hospital or other
- Collaborators
- Gilead Sciences
- Responsible party
- Sponsor-investigator, Atsushi Kawakami, Nagasaki University
- Investigators
- Atsushi Kawakami, MD, PhD, Principal investigator, Nagasaki University
IDs, dates and publications
- ClinicalTrials.gov ID
- NCT05090410
- Sponsor's protocol ID
- CRB20_026
- Acronym
- TRANSFORM
- Status last verified
- Oct 2021
- First submitted
- 30 Sep 2021
- Last updated
- 1 Nov 2021
- Results posted
- No
- Data monitoring committee
- Yes
- FDA-regulated drug
- No
- FDA-regulated device
- No
- Individual data sharing
- No
Publications
Shimizu T, Kawashiri SY, Koga T, Kiya R, Morita M, Kawasaki R, Kuroda S, Tashiro S, Sato S, Yabe M, Misaki K, Hanai S, Nakagomi D, Ogasawara M, Tamura N, Watanabe R, Kanazawa H, Atsumi T, Ueki Y, Okano T, Suzuki T, Takaoka H, Hamada H, Hidaka T, Furuta S, Hosogaya N, Yamamoto H, Kawakami A. Efficacy and safety of filgotinib versus tocilizumab in active rheumatoid arthritis: A randomized, open-label, multicenter study with clinical and musculoskeletal ultrasound evaluation (TRANSFORM study). Drug Discov Ther. 2026 May 17;20(2):175-189. doi: 10.5582/ddt.2026.01008. Epub 2026 Apr 27.
PubMed 42036316Shimizu 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.
PubMed 36869356
Study at a glance
From the registry record, last updated by the sponsor on 1 Nov 2021. Recruitment status is as the sponsor reported it: confirm with the study team.
- 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
- ClinicalTrials.gov ID
- NCT05090410
- Acronym / sponsor ID
- TRANSFORM / CRB20_026
- Conditions
- Rheumatoid Arthritis, JAK Inhibitor, IL-6 Inhibitor, Musculoskeletal Ultrasound, Biomarker
- Phase
- Phase 3
- Study type
- Interventional
- Recruitment status
- Unknown status
- Enrolment
- 400 participants (estimated)
- Lead sponsor
- Atsushi KawakamiUniversity, hospital or other
- Collaborators
- Gilead Sciences
- Study start
- 3 Mar 2021 (actual)
- Primary completion
- 28 Feb 2023 (estimated)
- Study completion
- 31 Dec 2023 (estimated)
- First posted
- 22 Oct 2021 (actual)
- Results
- Not posted in the source record
Clinical summary
The research question as the sponsor registered it. This describes what the study plans to test, not what it found.
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.
Study design
- Primary purpose
- Treatment
- Allocation
- Randomised
- Intervention model
- Parallel groups
- Masking
- None (open label)
- Number of arms
- 2
| Arm | Type | Receives |
|---|---|---|
| Filgotinib monotherapy | Experimental | Drug: filgotinib 200mg/dayThe administration of filgotinib 200mg/day switched from MTX ± other csDMARDs throughout the study period. |
| Tocilizumab monotherapy | Active comparator | Drug: subcutaneous tocilizumab 162mg/biweeklyThe administration of subcutaneous tocilizumab 162mg/biweekly switched from MTX ± other csDMARDs throughout the study period. |
Who may qualify
- Ages
- 20 years and older
- Sex
- All
- Healthy volunteers
- Not accepted
- Age groups
- Adult, Older adult
Key inclusion criteria (6 listed)
- Patients must meet all of the following requirements to be considered for entry into the study:
Key exclusion criteria (11 listed)
- The exclusion criteria are as follows:
Eligibility is decided by the study team after screening; this overview does not establish that a patient qualifies. Full inclusion and exclusion criteria.
Interventions
| Intervention | Type | Arms |
|---|---|---|
| filgotinib 200mg/dayPatients 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. | Drug | Filgotinib monotherapy |
| subcutaneous tocilizumab 162mg/biweeklyPatients 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. | Drug | Tocilizumab monotherapy |
Primary outcome
the proportion of patients who achieve an American College of Rheumatology (ACR) 50 response
Time frame: at week 12
17 secondary outcomes
the proportion of patients who achieve an ACR20 response
Time frame: at weeks 2, 4, 8, 12, 24, 36 and 52
the proportion of patients who achieve an ACR50 response
Time frame: at weeks 2, 4, 8, 24, 36 and 52
the proportion of patients who achieve an ACR70 response
Time frame: at weeks 2, 4, 8, 12, 24, 36 and 52
changes in the clinical disease activity index (CDAI) value
Time frame: from baseline to weeks 2, 4, 8, 12, 24, 36, and 52
changes in the simplified disease activity index (SDAI) value
Time frame: from baseline to weeks 2, 4, 8, 12, 24, 36, and 52
changes in the Disease Activity Score (DAS)28-ESR value
Time frame: from baseline to weeks 2, 4, 8, 12, 24, 36, and 52
changes in the DAS28-CRP value
Time frame: from baseline to weeks 2, 4, 8, 12, 24, 36, and 52
changes in the serum levels of biomarkers
Time frame: from baseline to weeks 2, 4, 12, 24, 36, and 52
changes in the total power Doppler (PD) score
Time frame: from baseline to weeks 4, 12, 24, 36, and 52
changes in the total grayscale (GS) score
Time frame: from baseline to weeks 4, 12, 24, 36, and 52
changes in the combined PD score
Time frame: from baseline to weeks 4, 12, 24, 36, and 52
change in van der Heijde-modified total Sharp score (vdH-mTSS)
Time frame: from baseline to weeks 24 and 52
change in the Health Assessment Questionnaire-Disability Index (HAQ-DI) data
Time frame: from baseline to weeks 2, 4, 8, 12, 24, 36, and 52
change in the EuroQol 5 Dimensions 5-Level (EQ-5D-5L) data
Time frame: from baseline to weeks 2, 4, 8, 12, 24, 36, and 52
change in the Functional Assessment of Chronic Illness-Fatigue (FACIT-F) data
Time frame: from baseline to weeks 2, 4, 8, 12, 24, 36, and 52
changes in the morning stiffness duration
Time frame: from baseline to weeks 2, 4, 8, 12, 24, 36, and 52
changes in the morning stiffness activity
Time frame: from baseline to weeks 2, 4, 8, 12, 24, 36, and 52
Results and safety
Results are not available in the source record.
Research links
- Official record on ClinicalTrials.govLast updated by the sponsor 1 Nov 2021.
- Derived from this study: PubMed 42036316Shimizu T, Kawashiri SY, Koga T, Kiya R, Morita M, Kawasaki R, Kuroda S, Tashiro S, Sato S, Yabe M, Misaki K, Hanai S, Nakagomi D, Ogasawara M, Tamura N, Watanabe R, Kanazawa H, Atsumi T, Ueki Y, Okano T, Suzuki T, Takaoka H, Hamada H, Hidaka T, Furuta S, Hosogaya N, Yamamoto H, Kawakami A. Efficacy and safety of filgotinib versus tocilizumab in active rheumatoid arthritis: A randomized, open-label, multicenter study with clinical and musculoskeletal ultrasound evaluation (TRANSFORM study). Drug Discov Ther. 2026 May 17;20(2):175-189. doi: 10.5582/ddt.2026.01008. Epub 2026 Apr 27.
- Derived from this study: PubMed 36869356Shimizu 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.
- Individual participant dataSharing planned: No
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Referral and contact
AzTrials does not enrol participants or take referrals. Contact the study team or a site listed below; they decide who can take part. This study is not recruiting at the moment.
Atsushi Kawakami, MD, PhD principal investigator
Nagasaki University
1 site in 1 country: see every site and its status.
Questions about this trial
What is this clinical trial studying?
A Phase 3 study testing filgotinib 200mg/day and subcutaneous tocilizumab 162mg/biweekly in people with Rheumatoid Arthritis and JAK Inhibitor, run by Atsushi Kawakami at 1 site in Japan.
The full registered description is in the About this study section and the official record.
Who may be eligible to take part?
The sponsor lists 6 inclusion and 11 exclusion criteria. Eligibility is decided by the study team after screening, so read the full criteria and contact a listed site.
Is this clinical trial currently recruiting?
The record says: status not confirmed, as of the sponsor's last update on 1 Nov 2021. Status can change between updates, so confirm with the study contact before making plans.
Where is the study taking place?
The record lists 1 site in Japan. Whether a site is taking part right now should be confirmed with that site. See every site.
What are the possible benefits and risks?
They depend on the study and the treatment, and no study can promise a benefit. The study team explains the known risks during informed consent, before anyone joins; the record itself does not list them.
What does this phase mean?
Phase 3 studies compare the treatment with the current standard treatment or a placebo in a large group, to confirm how well it works and watch for side effects.
Not every study follows the same path, and some studies (observational studies, device studies) have no phase.
Are results available for this study?
Results are not available in the source record.
How can a doctor refer a patient or contact the research team?
Contact Atsushi Kawakami, MD, PhD (+81-95-819-7260, atsushik@nagasaki-u.ac.jp), or a site near the patient. AzTrials does not enrol participants or take referrals.
What does the primary outcome measure?
the proportion of patients who achieve an American College of Rheumatology (ACR) 50 response (time frame: at week 12). It is what the study was designed to measure, not a finding.
Where can I read the original study information?
On the ClinicalTrials.gov record for NCT05090410, which also lists 2 linked publications.
Does a listing mean the treatment is approved or proven to work?
No. A listing means the study is registered. It does not show that the treatment is safe, works, or is approved by a regulator.
How often is this information updated?
AzTrials copies changed records from ClinicalTrials.gov every night and reloads the whole registry every week. The sponsor last updated this record on 1 Nov 2021.