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

October 23, 2021 updated by: Atsushi Kawakami

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.

Study Overview

Status

Status

Indicates the current recruitment status or the expanded access status.
Recruiting

Conditions

Conditions

The disease, disorder, syndrome, illness, or injury that is being studied. On ClinicalTrials.gov, conditions may also include other health-related issues, such as lifespan, quality of life, and health risks.

Intervention / Treatment

Intervention / Treatment

A process or action that is the focus of a clinical study. Interventions include drugs, medical devices, procedures, vaccines, and other products that are either investigational or already available. Interventions can also include noninvasive approaches, such as education or modifying diet and exercise.

Study Type

Study Type

Describes the nature of a clinical study. Study types include interventional studies (also called clinical trials), observational studies (including patient registries), and expanded access.
Interventional

Enrollment (Anticipated)

Enrollment

The number of participants in a clinical study. The "anticipated" enrollment is the target number of participants that the researchers need for the study.
400

Phase

Phase

The stage of a clinical trial studying a drug or biological product, based on definitions developed by the U.S. Food and Drug Administration (FDA). The phase is based on the study's objective, the number of participants, and other characteristics. There are five phases: Early Phase 1 (formerly listed as Phase 0), Phase 1, Phase 2, Phase 3, and Phase 4. Not Applicable is used to describe trials without FDA-defined phases, including trials of devices or behavioral interventions.
  • Phase 3

Contacts and Locations

This section provides the contact details for those conducting the study, and information on where this study is being conducted.

Study Locations

  • Japan
      • Nagasaki, Japan, 852-8501
        • Recruiting
        • Nagasaki University Hospital

Participation Criteria

Researchers look for people who fit a certain description, called eligibility criteria. Some examples of these criteria are a person's general health condition or prior treatments.

Eligibility Criteria

Eligibility Criteria

The key requirements that people who want to participate in a clinical study must meet or the characteristics they must have. Eligibility criteria consist of both inclusion criteria (which are required for a person to participate in the study) and exclusion criteria (which prevent a person from participating). Types of eligibility criteria include whether a study accepts healthy volunteers, has age or age group requirements, or is limited by sex.

Ages Eligible for Study

20 years and older (Adult, Older Adult)

Accepts Healthy Volunteers

No

Genders Eligible for Study

All

Description

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:

  • The exclusion criteria are as follows:

    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

Study Plan

This section provides details of the study plan, including how the study is designed and what the study is measuring.

How is the study designed?

Design Details

  • Primary Purpose: Treatment
  • Allocation: Randomized
  • Interventional Model: Parallel Assignment
  • Masking: None (Open Label)

Arms and Interventions

Participant Group / Arm

Participant Group / Arm

A group or subgroup of participants in a clinical trial that receives a specific intervention/treatment, or no intervention, according to the trial's protocol.
Intervention / Treatment

Intervention / Treatment

A process or action that is the focus of a clinical study. Interventions include drugs, medical devices, procedures, vaccines, and other products that are either investigational or already available. Interventions can also include noninvasive approaches, such as education or modifying diet and exercise.
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.

What is the study measuring?

Primary Outcome Measures

Primary Outcome Measures

In a clinical study's protocol, the planned outcome measure that is the most important for evaluating the effect of an intervention/treatment. Most clinical studies have one primary outcome measure, but some have more than one.
Outcome Measure
Time Frame
the proportion of patients who achieve an American College of Rheumatology (ACR) 50 response
Time Frame: at week 12
at week 12

Secondary Outcome Measures

Secondary Outcome Measures

In a clinical study's protocol, a planned outcome measure that is not as important as the primary outcome measure for evaluating the effect of an intervention but is still of interest. Most clinical studies have more than one secondary outcome measure.
Outcome Measure
Measure Description
Time Frame
the proportion of patients who achieve an ACR20 response
Time Frame: at weeks 2, 4, 8, 12, 24, 36 and 52
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
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
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
Higher scores mean a more active of RA.
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
Higher scores mean a more active RA.
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
Higher scores mean a more active RA.
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
Higher scores mean a more active RA.
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
We analyze the serum levels of multiple biomarkers such as cytokines and chemokines.
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
Higher scores mean a more active RA.
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
Higher scores mean a more active RA.
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
Higher scores mean a more active RA.
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
Higher scores mean a more joint destruction and deformity.
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
Higher scores mean a more active RA.
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
Higher scores mean a worse QOL.
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
Higher scores mean a worse fatigue.
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
Higher scores mean a more active RA.
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
We analyze the visual analog scale of morning stiffness activity. Higher scores mean a more active RA.
from baseline to weeks 2, 4, 8, 12, 24, 36, and 52

Collaborators and Investigators

This is where you will find people and organizations involved with this study.

Sponsor

Sponsor

The organization or person who initiates the study and who has authority and control over the study.
Atsushi Kawakami

Collaborators

Collaborators

An organization other than the sponsor that provides support for a clinical study. This support may include activities related to funding, design, implementation, data analysis, or reporting.
Gilead Sciences

Study record dates

These dates track the progress of study record and summary results submissions to ClinicalTrials.gov. Study records and reported results are reviewed by the National Library of Medicine (NLM) to make sure they meet specific quality control standards before being posted on the public website.

Study Major Dates

Study Start (Actual)

Study Start

The actual date on which the first participant was enrolled in a clinical study. The "anticipated" study start date is the date that the researchers think will be the study start date.
March 3, 2021

Primary Completion (Anticipated)

Primary Completion

The date on which the last participant in a clinical study was examined or received an intervention to collect final data for the primary outcome measure. Whether the clinical study ended according to the protocol or was terminated does not affect this date. For clinical studies with more than one primary outcome measure with different completion dates, this term refers to the date on which data collection is completed for all the primary outcome measures. The "anticipated" primary completion date is the date that the researchers think will be the primary completion date for the study.
February 28, 2023

Study Completion (Anticipated)

Study Completion

The date on which the last participant in a clinical study was examined or received an intervention/treatment to collect final data for the primary outcome measures, secondary outcome measures, and adverse events (that is, the last participant's last visit). The "anticipated" study completion date is the date that the researchers think will be the study completion date.
December 31, 2023

Study Registration Dates

First Submitted

First Submitted

The date on which the study sponsor or investigator first submitted a study record to ClinicalTrials.gov. There is typically a delay of a few days between the first submitted date and the record's availability on ClinicalTrials.gov (the first posted date).
September 30, 2021

First Submitted That Met QC Criteria

First Submitted That Met QC Criteria

The date on which the study sponsor or investigator first submits a study record that is consistent with National Library of Medicine (NLM) quality control (QC) review criteria. The sponsor or investigator may need to revise and submit a study record one or more times before NLM's QC review criteria are met. It is the responsibility of the sponsor or investigator to ensure that the study record is consistent with the NLM QC review criteria.
October 21, 2021

First Posted (Actual)

First Posted

The date on which the study record was first available on ClinicalTrials.gov after National Library of Medicine (NLM) quality control (QC) review has concluded. There is typically a delay of a few days between the date the study sponsor or investigator submitted the study record and the first posted date.
October 22, 2021

Study Record Updates

Last Update Posted (Actual)

Last Update Posted

The most recent date on which changes to a study record were made available on ClinicalTrials.gov. There may be a delay between when the changes were submitted to ClinicalTrials.gov by the study's sponsor or investigator (the last update submitted date) and the last update posted date.
November 1, 2021

Last Update Submitted That Met QC Criteria

Last Update Submitted That Met QC Criteria

The most recent date on which the study sponsor or investigator submitted changes to a study record that are consistent with National Library of Medicine (NLM) quality control (QC) review criteria. It is the responsibility of the sponsor or investigator to ensure that the study record is consistent with the NLM QC review criteria.
October 23, 2021

Last Verified

Last Verified

The most recent date on which the study sponsor or investigator confirmed the information about a clinical study on ClinicalTrials.gov as accurate and current. If a study with a recruitment status of recruiting; not yet recruiting; or active, not recruiting has not been confirmed within the past 2 years, the study's recruitment status is shown as unknown.
October 1, 2021

More Information

Terms related to this study

Additional Relevant MeSH Terms

Other Study ID Numbers

Other Study ID Numbers

Identifiers or ID numbers other than the NCT number that are assigned to a clinical study by the study's sponsor, funders, or others. These numbers may include unique identifiers from other trial registries and National Institutes of Health grant numbers.
  • CRB20_026

Plan for Individual participant data (IPD)

Plan to Share Individual Participant Data (IPD)?

NO

Drug and device information, study documents

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

This information was retrieved directly from the website clinicaltrials.gov without any changes. If you have any requests to change, remove or update your study details, please contact register@clinicaltrials.gov. As soon as a change is implemented on clinicaltrials.gov, this will be updated automatically on our website as well.

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