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Discontinuation of Methotrexate in Rheumatoid Arthritis Patients Achieving Clinical Remission by Treatment With Upadacitinib Plus Methotrexate (DOPPLER)

Primary Purpose

Rheumatoid Arthritis, JAK Inhibitor, Musculoskeletal Ultrasound

Status

Recruiting

Phase

Phase 3

Locations

Japan

Study Type

Interventional

Intervention

upadacitinib 15mg/day

About this trial

This is an interventional treatment trial for Rheumatoid Arthritis

Eligibility Criteria

20 Years - undefined (Adult, Older Adult)All SexesDoes not accept healthy volunteers

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 American College of Rheumatology (ACR) /EULAR 2010 RA Classification Criteria
3. with at least moderate DAS28-CRP >3.2 at the eligibility evaluation
4. with at least one PD score positive joint of 22 joints examined MSUS at the eligibility evaluation
5. treated with MTX for ≥8 weeks prior to the providing consent, including 4 weeks or more at the same doses of 6 to 16 mg per week
6. 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 >7.5 mg/day of prednisolone (2) applicable an item for the contraindication of upadacitinib (3) a previous use of a JAK inhibitor (4) treatment with a corticosteroid and change of dose within 4 weeks prior to the providing consent (5) treatment with a csDMARD except MTX within 2 weeks prior to the providing consent; (6) treatment with a biologic DMARD or a biosimilar DMARD (ie, infliximab, biosimilar of infliximab, adalimumab, golimumab, certolizumab pegol, tocilizumab, sarilumab or abatacept) within 8 weeks prior to the providing consent (7) treatment with a TNF inhibitor (ie, etanercept or biosimilar of etanercept) within 4 weeks prior to the providing consent (8) use of a prohibited drug or therapy, other than the agents noted above, within 4 weeks prior to the providing consent (9) 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) (10) current pregnancy, breastfeeding, or noncompliant with a medically approved contraceptive regimen during and 12 months after the study period (11) inappropriateness for inclusion in this study as determined by the investigator

Sites / Locations

Nagasaki University HospitalRecruiting

Arms of the Study

Arm 1

Arm Type

Experimental

Arm Label

Upadacitinib

Arm Description

The administration of upadacitinib 15mg/day

Outcomes

Primary Outcome Measures

maintenance of DAS28-CRP <=3.2 from week 24 to 48 in patients who achieve the DAS28-CRP <2.6 at week 24.

Secondary Outcome Measures

achievement of DAS28-CRP <=3.2

achievement of DAS28-CRP <2.6

clinical relapse (DAS28-CRP >3.2) at week 48 in patients who achieve the DAS28-CRP <2.6 at week 24

achievement of EULAR moderate response

changes in the DAS28-CRP value

Higher scores mean a more active RA.

changes in the DAS28-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 DAS28-ESR value

Higher scores mean a more active RA.

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 of RA.

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 of RA.

achievement of CDAI <=2.8

achievement of SDAI <=3.3

changes in the serum levels of biomarkers

We analyze the serum levels of multiple biomarkers such as cytokines and chemokines.

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

The minimum: 0, max: 66. Higher scores mean a more active RA.

changes in the total grayscale (GS) score

The minimum: 0, max: 66. Higher scores mean a more active RA.

changes in the combined PD score

The minimum: 0, max: 66. Higher scores mean a more active RA.

changes in the total PD score

The minimum: 0, max: 66. Higher scores mean a more active RA.

changes in the total GS score

The minimum: 0, max: 66. Higher scores mean a more active RA.

changes in the combined PD score

The minimum: 0, max: 66. Higher scores mean a more active RA.

change in van der Heijde-modified total Sharp score (vdH-mTSS)

The minimum: 0, max: 3. Higher scores mean a more joint destruction and deformity.

change in vdH-mTSS

Higher scores mean a more joint destruction and deformity.

Full Information

NCT ID

NCT05121298

First Posted

November 4, 2021

Last Updated

November 24, 2021

Sponsor

Atsushi Kawakami

Collaborators

AbbVie GK.

1. Study Identification

Unique Protocol Identification Number

NCT05121298

Brief Title

Discontinuation of Methotrexate in Rheumatoid Arthritis Patients Achieving Clinical Remission by Treatment With Upadacitinib Plus Methotrexate

Acronym

DOPPLER

Official Title

Discontinuation of Methotrexate in Rheumatoid Arthritis Patients Achieving Clinical Remission by Treatment With Upadacitinib Plus Methotrexate: an Interventional, Multicenter, Prospective, Open-label, Single-arm Clinical Trial With Clinical, Ultrasound and Biomarker Assessments

Study Type

Interventional

2. Study Status

Record Verification Date

November 2021

Overall Recruitment Status

Recruiting

Study Start Date

January 12, 2021 (Actual)

Primary Completion Date

November 30, 2023 (Anticipated)

Study Completion Date

September 30, 2024 (Anticipated)

3. Sponsor/Collaborators

Responsible Party, by Official Title

Sponsor-Investigator

Name of the Sponsor

Atsushi Kawakami

Collaborators

AbbVie GK.

4. Oversight

Studies a U.S. FDA-regulated Drug Product

Studies a U.S. FDA-regulated Device Product

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). Upadacitinib is a selective JAK1 inhibitor to be approved for use in RA. Nearly half of patients added JAK inhibitors including upadacitinib can achieve clinical remission in RA patients with inadequate response to MTX. As the next step, it is the great issue whether disease activity can be maintained in good condition even if MTX is discontinued after achieving clinical remission in patients treated with the combination of JAK inhibitors and MTX. Thus, it is desirable to investigate the maintenance of clinical non-relapse after discontinuation of MTX in RA patients with clinical remission during treatment with upadacitinib plus MTX. In this study, we will evaluate the proportion of patients who maintained nonclinical relapse after discontinuation of MTX in patients with RA who achieved clinical remission after treatment with upadacitinib plus MTX. We will also use musculoskeletal ultrasound (MSUS) assessments to determine whether discontinuation of MTX can be maintained nonclinical relapse in RA patients achieving clinical remission.

6. Conditions and Keywords

Primary Disease or Condition Being Studied in the Trial, or the Focus of the Study

Rheumatoid Arthritis, JAK Inhibitor, Musculoskeletal Ultrasound, Biomarker

7. Study Design

Primary Purpose

Treatment

Study Phase

Phase 3

Interventional Study Model

Single Group Assignment

Masking

None (Open Label)

Allocation

Non-Randomized

Enrollment

155 (Anticipated)

8. Arms, Groups, and Interventions

Arm Title

Upadacitinib

Arm Type

Experimental

Arm Description

The administration of upadacitinib 15mg/day

Intervention Type

Drug

Intervention Name(s)

upadacitinib 15mg/day

Intervention Description

Patients will receive upadacitinib 15mg/day and continue to receive same doses of MTX until 24 weeks. If patients achieve a European League Against Rheumatism (EULAR) moderate response or a Disease Activity Score 28 (DAS28-CRP) ≤3.2 at 12 weeks, and a DAS28-CRP of <2.6 at 24 weeks, they will discontinue MTX, and continue upadacitinib until 48 weeks.

Primary Outcome Measure Information:

Title

maintenance of DAS28-CRP <=3.2 from week 24 to 48 in patients who achieve the DAS28-CRP <2.6 at week 24.

Time Frame

at week 48

Secondary Outcome Measure Information:

Title

achievement of DAS28-CRP <=3.2

Time Frame

at weeks 12, 24 and 36

Title

achievement of DAS28-CRP <2.6

Time Frame

at weeks 12, 24, 36 and 48

Title

clinical relapse (DAS28-CRP >3.2) at week 48 in patients who achieve the DAS28-CRP <2.6 at week 24

Time Frame

at week 48

Title

achievement of EULAR moderate response

Time Frame

at week 12

Title

changes in the DAS28-CRP value

Description

Higher scores mean a more active RA.

Time Frame

from baseline to weeks 12, 24, 36, and 48

Title

changes in the DAS28-ESR value

Description

Higher scores mean a more active RA.

Time Frame

from baseline to weeks 12, 24, 36, and 48

Title

changes in the DAS28-CRP value

Description

Higher scores mean a more active RA.

Time Frame

from week 24 to weeks 36 and 48

Title

changes in the DAS28-ESR value

Description

Higher scores mean a more active RA.

Time Frame

from week 24 to weeks 36 and 48

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 12, 24, 36, and 48

Title

changes in the simplified disease activity index (SDAI) value

Description

Higher scores mean a more active of RA.

Time Frame

from baseline to weeks 12, 24, 36, and 48

Title

changes in the clinical disease activity index (CDAI) value

Description

Higher scores mean a more active of RA.

Time Frame

from week 24 to weeks 36 and 48

Title

changes in the simplified disease activity index (SDAI) value

Description

Higher scores mean a more active of RA.

Time Frame

from week 24 to weeks 36 and 48

Title

achievement of CDAI <=2.8

Time Frame

at weeks 12, 24, 36 and 48

Title

achievement of SDAI <=3.3

Time Frame

at weeks 12, 24, 36 and 48

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 12, 24, 36, and 48

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 week 24 to weeks 36 and 48

Title

changes in the total power Doppler (PD) score

Description

The minimum: 0, max: 66. Higher scores mean a more active RA.

Time Frame

from baseline to weeks 12, 24, 36, and 48

Title

changes in the total grayscale (GS) score

Description

The minimum: 0, max: 66. Higher scores mean a more active RA.

Time Frame

from baseline to weeks 12, 24, 36, and 48

Title

changes in the combined PD score

Description

The minimum: 0, max: 66. Higher scores mean a more active RA.

Time Frame

from baseline to weeks 12, 24, 36, and 48

Title

changes in the total PD score

Description

The minimum: 0, max: 66. Higher scores mean a more active RA.

Time Frame

from week 24 to weeks 36 and 48

Title

changes in the total GS score

Description

The minimum: 0, max: 66. Higher scores mean a more active RA.

Time Frame

from week 24 to weeks 36 and 48

Title

changes in the combined PD score

Description

The minimum: 0, max: 66. Higher scores mean a more active RA.

Time Frame

from week 24 to weeks 36 and 48

Title

change in van der Heijde-modified total Sharp score (vdH-mTSS)

Description

The minimum: 0, max: 3. Higher scores mean a more joint destruction and deformity.

Time Frame

from baseline to weeks 12, 24, 36 and 48

Title

change in vdH-mTSS

Description

Higher scores mean a more joint destruction and deformity.

Time Frame

from week 24 to weeks 36 and 48

10. Eligibility

Sex

All

Minimum Age & Unit of Time

20 Years

Accepts Healthy Volunteers

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 American College of Rheumatology (ACR) /EULAR 2010 RA Classification Criteria with at least moderate DAS28-CRP >3.2 at the eligibility evaluation with at least one PD score positive joint of 22 joints examined MSUS 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 6 to 16 mg per week 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 >7.5 mg/day of prednisolone (2) applicable an item for the contraindication of upadacitinib (3) a previous use of a JAK inhibitor (4) treatment with a corticosteroid and change of dose within 4 weeks prior to the providing consent (5) treatment with a csDMARD except MTX within 2 weeks prior to the providing consent; (6) treatment with a biologic DMARD or a biosimilar DMARD (ie, infliximab, biosimilar of infliximab, adalimumab, golimumab, certolizumab pegol, tocilizumab, sarilumab or abatacept) within 8 weeks prior to the providing consent (7) treatment with a TNF inhibitor (ie, etanercept or biosimilar of etanercept) within 4 weeks prior to the providing consent (8) use of a prohibited drug or therapy, other than the agents noted above, within 4 weeks prior to the providing consent (9) 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) (10) current pregnancy, breastfeeding, or noncompliant with a medically approved contraceptive regimen during and 12 months after the study period (11) 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

atsushik@nagasaki-u.ac.jp

First Name & Middle Initial & Last Name or Official Title & Degree

Toshimasa Shimizu, MD, PhD

Phone

+81-95-819-8527

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

atsushik@nagasaki-u.ac.jp

First Name & Middle Initial & Last Name & Degree

Toshimasa Shimizu, MD, PhD

Phone

+81-95-819-8527

t.shimizu@nagasaki-u.ac.jp

First Name & Middle Initial & Last Name & Degree

Atsushi Kawakami, MD, PhD

12. IPD Sharing Statement

Citations:

PubMed Identifier

35029189

Citation

Shimizu T, Kawashiri SY, Sato S, Kawazoe Y, Kuroda S, Kawasaki R, Ito Y, Morimoto S, Yamamoto H, Kawakami A. Discontinuation of methotrexate in rheumatoid arthritis patients achieving clinical remission by treatment with upadacitinib plus methotrexate (DOPPLER study): A study protocol for an interventional, multicenter, open-label and single-arm clinical trial with clinical, ultrasound and biomarker assessments. Medicine (Baltimore). 2022 Jan 14;101(2):e28463. doi: 10.1097/MD.0000000000028463.

Results Reference

derived

Learn more about this trial

Discontinuation of Methotrexate in Rheumatoid Arthritis Patients Achieving Clinical Remission by Treatment With Upadacitinib Plus Methotrexate

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