Back to resultsEfficacy and Safety of Selective JAK 1 Inhibitor Filgotinib in Active Rheumatoid Arthritis Patients With Inadequate Response to Methotrexate (TRANSFORM)
Primary Purpose
Rheumatoid Arthritis, JAK Inhibitor, IL-6 Inhibitor
Status
Recruiting
Phase
Phase 3
Locations
Japan
Study Type
Interventional
Intervention
filgotinib 200mg/day
subcutaneous tocilizumab 162mg/biweekly
Sponsored by
About this trial
This is an interventional treatment trial for Rheumatoid Arthritis
Eligibility 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
- 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
Exclusion Criteria:
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
- 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
Sites / Locations
- Nagasaki University HospitalRecruiting
Arms of the Study
Arm 1
Arm 2
Arm Type
Experimental
Active Comparator
Arm Label
Filgotinib monotherapy
Tocilizumab monotherapy
Arm Description
The administration of filgotinib 200mg/day switched from MTX ± other csDMARDs throughout the study period.
The administration of subcutaneous tocilizumab 162mg/biweekly switched from MTX ± other csDMARDs throughout the study period.
Outcomes
Primary Outcome Measures
the proportion of patients who achieve an American College of Rheumatology (ACR) 50 response
Secondary Outcome Measures
the proportion of patients who achieve an ACR20 response
the proportion of patients who achieve an ACR50 response
the proportion of patients who achieve an ACR70 response
changes in the clinical disease activity index (CDAI) value
Higher scores mean a more active of RA.
changes in the simplified disease activity index (SDAI) value
Higher scores mean a more active RA.
changes in the Disease Activity Score (DAS)28-ESR value
Higher scores mean a more active RA.
changes in the DAS28-CRP value
Higher scores mean a more active RA.
changes in the serum levels of biomarkers
We analyze the serum levels of multiple biomarkers such as cytokines and chemokines.
changes in the total power Doppler (PD) score
Higher scores mean a more active RA.
changes in the total grayscale (GS) score
Higher scores mean a more active RA.
changes in the combined PD score
Higher scores mean a more active RA.
change in van der Heijde-modified total Sharp score (vdH-mTSS)
Higher scores mean a more joint destruction and deformity.
change in the Health Assessment Questionnaire-Disability Index (HAQ-DI) data
Higher scores mean a more active RA.
change in the EuroQol 5 Dimensions 5-Level (EQ-5D-5L) data
Higher scores mean a worse QOL.
change in the Functional Assessment of Chronic Illness-Fatigue (FACIT-F) data
Higher scores mean a worse fatigue.
changes in the morning stiffness duration
Higher scores mean a more active RA.
changes in the morning stiffness activity
We analyze the visual analog scale of morning stiffness activity. Higher scores mean a more active RA.
Full Information
NCT ID
NCT05090410
First Posted
September 30, 2021
Last Updated
October 23, 2021
Sponsor
Atsushi Kawakami
Collaborators
Gilead Sciences
1. Study Identification
Unique Protocol Identification Number
NCT05090410
Brief Title
Efficacy and Safety of Selective JAK 1 Inhibitor Filgotinib in Active Rheumatoid Arthritis Patients With Inadequate Response to Methotrexate
Acronym
TRANSFORM
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
Study Type
Interventional
2. Study Status
Record Verification Date
October 2021
Overall Recruitment Status
Recruiting
Study Start Date
March 3, 2021 (Actual)
Primary Completion Date
February 28, 2023 (Anticipated)
Study Completion Date
December 31, 2023 (Anticipated)
3. Sponsor/Collaborators
Responsible Party, by Official Title
Sponsor-Investigator
Name of the Sponsor
Atsushi Kawakami
Collaborators
Gilead Sciences
4. Oversight
Studies a U.S. FDA-regulated Drug Product
No
Studies a U.S. FDA-regulated Device Product
No
Product Manufactured in and Exported from the U.S.
No
Data Monitoring Committee
Yes
5. 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.
6. Conditions and Keywords
Primary Disease or Condition Being Studied in the Trial, or the Focus of the Study
Rheumatoid Arthritis, JAK Inhibitor, IL-6 Inhibitor, Musculoskeletal Ultrasound, Biomarker
7. Study Design
Primary Purpose
Treatment
Study Phase
Phase 3
Interventional Study Model
Parallel Assignment
Masking
None (Open Label)
Allocation
Randomized
Enrollment
400 (Anticipated)
8. Arms, Groups, and Interventions
Arm Title
Filgotinib monotherapy
Arm Type
Experimental
Arm Description
The administration of filgotinib 200mg/day switched from MTX ± other csDMARDs throughout the study period.
Arm Title
Tocilizumab monotherapy
Arm Type
Active Comparator
Arm Description
The administration of subcutaneous tocilizumab 162mg/biweekly switched from MTX ± other csDMARDs throughout the study period.
Intervention Type
Drug
Intervention Name(s)
filgotinib 200mg/day
Intervention Description
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
Intervention Name(s)
subcutaneous tocilizumab 162mg/biweekly
Intervention Description
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.
Primary Outcome Measure Information:
Title
the proportion of patients who achieve an American College of Rheumatology (ACR) 50 response
Time Frame
at week 12
Secondary Outcome Measure Information:
Title
the proportion of patients who achieve an ACR20 response
Time Frame
at weeks 2, 4, 8, 12, 24, 36 and 52
Title
the proportion of patients who achieve an ACR50 response
Time Frame
at weeks 2, 4, 8, 24, 36 and 52
Title
the proportion of patients who achieve an ACR70 response
Time Frame
at weeks 2, 4, 8, 12, 24, 36 and 52
Title
changes in the clinical disease activity index (CDAI) value
Description
Higher scores mean a more active of RA.
Time Frame
from baseline to weeks 2, 4, 8, 12, 24, 36, and 52
Title
changes in the simplified disease activity index (SDAI) value
Description
Higher scores mean a more active RA.
Time Frame
from baseline to weeks 2, 4, 8, 12, 24, 36, and 52
Title
changes in the Disease Activity Score (DAS)28-ESR value
Description
Higher scores mean a more active RA.
Time Frame
from baseline to weeks 2, 4, 8, 12, 24, 36, and 52
Title
changes in the DAS28-CRP value
Description
Higher scores mean a more active RA.
Time Frame
from baseline to weeks 2, 4, 8, 12, 24, 36, and 52
Title
changes in the serum levels of biomarkers
Description
We analyze the serum levels of multiple biomarkers such as cytokines and chemokines.
Time Frame
from baseline to weeks 2, 4, 12, 24, 36, and 52
Title
changes in the total power Doppler (PD) score
Description
Higher scores mean a more active RA.
Time Frame
from baseline to weeks 4, 12, 24, 36, and 52
Title
changes in the total grayscale (GS) score
Description
Higher scores mean a more active RA.
Time Frame
from baseline to weeks 4, 12, 24, 36, and 52
Title
changes in the combined PD score
Description
Higher scores mean a more active RA.
Time Frame
from baseline to weeks 4, 12, 24, 36, and 52
Title
change in van der Heijde-modified total Sharp score (vdH-mTSS)
Description
Higher scores mean a more joint destruction and deformity.
Time Frame
from baseline to weeks 24 and 52
Title
change in the Health Assessment Questionnaire-Disability Index (HAQ-DI) data
Description
Higher scores mean a more active RA.
Time Frame
from baseline to weeks 2, 4, 8, 12, 24, 36, and 52
Title
change in the EuroQol 5 Dimensions 5-Level (EQ-5D-5L) data
Description
Higher scores mean a worse QOL.
Time Frame
from baseline to weeks 2, 4, 8, 12, 24, 36, and 52
Title
change in the Functional Assessment of Chronic Illness-Fatigue (FACIT-F) data
Description
Higher scores mean a worse fatigue.
Time Frame
from baseline to weeks 2, 4, 8, 12, 24, 36, and 52
Title
changes in the morning stiffness duration
Description
Higher scores mean a more active RA.
Time Frame
from baseline to weeks 2, 4, 8, 12, 24, 36, and 52
Title
changes in the morning stiffness activity
Description
We analyze the visual analog scale of morning stiffness activity. Higher scores mean a more active RA.
Time Frame
from baseline to weeks 2, 4, 8, 12, 24, 36, and 52
10. Eligibility
Sex
All
Minimum Age & Unit of Time
20 Years
Accepts Healthy Volunteers
No
Eligibility 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
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
Exclusion Criteria:
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
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
Central Contact Person:
First Name & Middle Initial & Last Name or Official Title & Degree
Atsushi Kawakami, MD, PhD
Phone
+81-95-819-7260
Email
atsushik@nagasaki-u.ac.jp
First Name & Middle Initial & Last Name or Official Title & Degree
Toshimasa Shimizu, MD, PhD
Phone
+81-95-819-8527
Email
t.shimizu@nagasaki-u.ac.jp
Overall Study Officials:
First Name & Middle Initial & Last Name & Degree
Atsushi Kawakami, MD, PhD
Organizational Affiliation
Nagasaki University
Official's Role
Principal Investigator
Facility Information:
Facility Name
Nagasaki University Hospital
City
Nagasaki
ZIP/Postal Code
852-8501
Country
Japan
Individual Site Status
Recruiting
Facility Contact:
First Name & Middle Initial & Last Name & Degree
Atsushi Kawakami, MD, PhD
Phone
+81-95-819-7260
Email
atsushik@nagasaki-u.ac.jp
First Name & Middle Initial & Last Name & Degree
Toshimasa Shimizu, MD, PhD
Phone
+81-95-819-8527
Email
t.shimizu@nagasaki-u.ac.jp
First Name & Middle Initial & Last Name & Degree
Atsushi Kawakami, MD, PhD
12. IPD Sharing Statement
Plan to Share IPD
No
Learn more about this trial
Efficacy and Safety of Selective JAK 1 Inhibitor Filgotinib in Active Rheumatoid Arthritis Patients With Inadequate Response to Methotrexate
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