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

NCT05121298 | Unknown Phase 3 DMC

• 1 other identifier: CRB20-024
• Study Type: interventional
• Target: 155
• Locations: 1 country
• Sites: 1

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.

Conditions

Rheumatoid Arthritis; JAK Inhibitor; Musculoskeletal Ultrasound; Biomarker

Outcome Measures

Primary Outcomes (1)

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

  at week 48

Secondary Outcomes (24)

• achievement of DAS28-CRP <=3.2

  at weeks 12, 24 and 36

• achievement of DAS28-CRP <2.6

  at weeks 12, 24, 36 and 48

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

  at week 48

• achievement of EULAR moderate response

  at week 12

• changes in the DAS28-CRP value

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

Study Arms (1)

Upadacitinib

EXPERIMENTAL

The administration of upadacitinib 15mg/day

Drug: upadacitinib 15mg/day

Interventions

upadacitinib 15mg/day DRUG

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.

Upadacitinib

Eligibility Criteria

• Age: 20 Years+
• Sex: all
• Healthy Volunteers: No
• Age Groups: Adult (18-64), Older Adult (65+)

You may qualify if:

• 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.

Sponsors & Collaborators

• Atsushi Kawakami: lead
• AbbVie: collaborator

Study Sites (1)

Nagasaki University Hospital

Nagasaki, 852-8501, Japan

RECRUITING

Related Publications (1)

• 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.

  PMID: 35029189 DERIVED

MeSH Terms

Conditions

Arthritis, Rheumatoid

Interventions

upadacitinib

Condition Hierarchy (Ancestors)

Arthritis; Joint Diseases; Musculoskeletal Diseases; Rheumatic Diseases; Connective Tissue Diseases; Skin and Connective Tissue Diseases; Autoimmune Diseases; Immune System Diseases

Study Officials

• Atsushi Kawakami, MD, PhD

  Nagasaki University

  PRINCIPAL INVESTIGATOR

Central Study Contacts

Atsushi Kawakami, MD, PhD

CONTACT

+81-95-819-7260; atsushik@nagasaki-u.ac.jp

Toshimasa Shimizu, MD, PhD

CONTACT

+81-95-819-8527; t.shimizu@nagasaki-u.ac.jp

Study Design

• Study Type: interventional
• Phase: phase 3
• Allocation: NON RANDOMIZED
• Masking: NONE
• Purpose: TREATMENT
• Intervention Model: SINGLE GROUP
• Sponsor Type: OTHER
• Responsible Party: SPONSOR INVESTIGATOR
• PI Title: Professor

Study Record Dates

• First Submitted: November 4, 2021
• First Posted: November 16, 2021
• Study Start: January 12, 2021
• Primary Completion: November 30, 2023
• Study Completion: September 30, 2024
• Last Updated: December 8, 2021

Record last verified: 2021-11

Locations

JP (1)