NCT04692493

Brief Summary

The 2021 ACR RA treatment guideline, based on widely acknowledged low to moderate quality evidence, recommends switching to a non-tumor necrosis factor (TNFi) biologic (choose among existing medications, currently, rituximab, abatacept, tocilizumab, or sarilumab) or a targeted synthetic DMARD arm (tsDMARD; choose among existing medications, currently, tofacitinib, baricitinib, upadacitinib) in patients with active RA despite the use of a TNFi-biologic. In practice, most patients receive another TNFi-biologic, i.e., a second TNFi-biologic first. This is not based on solid evidence, but on arbitrary algorithms often proposed by health insurance plans, and/or physician experience and habit (TNFis launched 22 yrs ago vs. the first tsDMARD 8 years ago vs. first non-TNF-biologic launched 17 years ago). This study will fill a critical knowledge gap by generating CER data for important PROs between these treatment options, switching to a non-TNFi biologic or a tsDMARD in patients with active RA despite the use of a TNFi-biologic.

Trial Health

80
On Track

Trial Health Score

Automated assessment based on enrollment pace, timeline, and geographic reach

Enrollment
924

participants targeted

Target at P75+ for phase_3 rheumatoid-arthritis

Timeline
33mo left

Started Sep 2021

Longer than P75 for phase_3 rheumatoid-arthritis

Geographic Reach
2 countries

49 active sites

Status
recruiting

Health score is calculated from publicly available data and should be used for screening purposes only.

Trial Relationships

Click on a node to explore related trials.

Study Timeline

Key milestones and dates

Study Progress64%
Sep 2021Dec 2028

First Submitted

Initial submission to the registry

December 15, 2020

Completed
16 days until next milestone

First Posted

Study publicly available on registry

December 31, 2020

Completed
9 months until next milestone

Study Start

First participant enrolled

September 22, 2021

Completed
5.4 years until next milestone

Primary Completion

Last participant's last visit for primary outcome

February 28, 2027

Expected
1.8 years until next milestone

Study Completion

Last participant's last visit for all outcomes

December 31, 2028

Last Updated

July 18, 2025

Status Verified

July 1, 2025

Enrollment Period

5.4 years

First QC Date

December 15, 2020

Last Update Submit

July 15, 2025

Conditions

Outcome Measures

Primary Outcomes (1)

  • Functional Limitation

    Function limitation assessed by Health assessment questionnaire (HAQ); HAQ assesses difficulty in 20 items in 8 categories (dressing, arising, eating, walking, hygiene, reaching, gripping, and outside activity), the total score ranges from 0 (no disability) to 3 (complete disability). Higher score is worse, and indicates poor function.

    Change from baseline to 12 months

Study Arms (2)

targeted synthetic DMARD class

ACTIVE COMPARATOR

Switching to a targeted synthetic DMARD (choice from targeted synthetic DMARDs; currently available are tofacitinib, baricitinib, upadacitinib) in people with active RA despite current treatment

Drug: targeted synthetic DMARD class

non-TNFi-biologic class

ACTIVE COMPARATOR

Switching to a non-TNFi-biologic (choice from non-TNFi-biologics; currently available are rituximab, abatacept, tocilizumab, or sarilumab) in people with active RA despite current treatment,

Drug: non-TNFi-biologic class

Interventions

Switching to a targeted synthetic DMARD (choice from targeted synthetic DMARDs; currently available are tofacitinib, baricitinib, upadacitinib) in people with active RA despite current treatment

targeted synthetic DMARD class

Switching to a non-TNFi-biologic (choice from non-TNFi-biologics; currently available are rituximab, abatacept, tocilizumab, or sarilumab) in people with active RA despite current treatment,

non-TNFi-biologic class

Eligibility Criteria

Age18 Years+
Sexall
Healthy VolunteersNo
Age GroupsAdult (18-64), Older Adult (65+)

You may qualify if:

  • Patients with active, disabling RA (CDAI ≥10 and HAQ ≥0.5) despite the use/experience of a TNFi-biologic OR discontinued the medication(s) due to intolerability or toxicity irrespective of treatment duration prior to the first dose of study drug ;
  • If receiving glucocorticoids (≤10 mg/day of prednisone of equivalent) or NSAIDs, on stable doses for ≥2 weeks prior to randomization; and
  • Insurance plan or patient assistance program allows access to at least 1 drug in each of the two treatment strategies, TNFi-biologic vs. tsDMARD.(TNFi-biologic and tsDMARD) will be obtained through insurance plan or a patient assistance program/plan.
  • Participants will be allowed to continue their conventional synthetic DMARD (csDMARD) therapy if they had been using it for ≥ 3 months and on a stable dose for ≥ 4 weeks prior to the first dose of study drug. The following csDMARDs are allowed: methotrexate (MTX), sulfasalazine, hydroxychloroquine, and leflunomide

You may not qualify if:

  • Prior treatment with more than three biologics, defined as TNFi-biologic or non-TNFi biologic
  • Prior treatment with targeted synthetic DMARD
  • Concomitant use of leflunomide, sulfasalazine, cyclosporine, or azathioprine within 2-months before randomization;
  • History of sensitivity to all 4 non-TNF-biologic or a targeted synthetic DMARD;
  • Glucocorticoid injection (intravenous, intramuscular, or intraarticular) within 1 month of study entry;
  • Live vaccine within 90 days of study entry;
  • Acute or chronic infections with parenteral antibiotics or hospitalization (including tuberculosis, bacterial sepsis; invasive fungal infections (such as histoplasmosis)) within 1 month or oral antibiotics within 2 weeks of study entry;
  • History of HIV or any opportunistic infection;
  • New York Heart Association Class III or IV heart failure;
  • Latent TB for which anti-tubercular treatment has not been started;
  • Untreated Hepatitis B or C infection;
  • History of deep venous thrombosis or pulmonary embolism; or
  • Pregnant or nursing women; or
  • History of herpes zoster or shingles in the previous 12 months and not subsequently vaccinated with herpes zoster vaccine.

Contact the study team to confirm eligibility.

Sponsors & Collaborators

Study Sites (49)

East Alabama Arthritis Center PC

Auburn, Alabama, 36830, United States

RECRUITING

Bendcare, LLC

Birmingham, Alabama, 35244, United States

RECRUITING

University of Alabama at Birmingham

Birmingham, Alabama, 35294, United States

RECRUITING

SunValley Arthritis Center, Ltd

Peoria, Arizona, 85381, United States

RECRUITING

University of Arizona

Tucson, Arizona, 85724, United States

RECRUITING

Pacific Arthritis Care Center

Los Angeles, California, 90045, United States

RECRUITING

University of California, Los Angeles

Los Angeles, California, 90095, United States

RECRUITING

Arthritis Medical Center

Nipomo, California, 93444, United States

RECRUITING

Turlock Arthritis & Osteoporosis Center,

Turlock, California, 95382, United States

RECRUITING

Center for Rheumatology Research

Woodland Hills, California, 91364, United States

RECRUITING

George Munoz MD, PC

Aventura, Florida, 33180, United States

RECRUITING

American Arthritis and Rheumatology Associates LLC

Clearwater, Florida, 33765, United States

RECRUITING

CZ Rheumatology

Coral Springs, Florida, 33065, United States

RECRUITING

American Arthritis and Rheumatology Associates LLC

Fort Lauderdale, Florida, 33309, United States

RECRUITING

Mayo Clinic Jacksonville

Jacksonville, Florida, 32224, United States

RECRUITING

Palm Beach Rheumatology and Wellness

Jupiter, Florida, 33458, United States

RECRUITING

Arthritis & Rheumatology Center of South Florida

Margate, Florida, 33063, United States

RECRUITING

Life Medical Research Group

Miami Gardens, Florida, 33014, United States

RECRUITING

Southwest Florida Rheumatology

Riverview, Florida, 33569, United States

RECRUITING

Southeast Georgia Physician Associates-Rheumatology

Brunswick, Georgia, 31520, United States

RECRUITING

Indiana University Health

Carmel, Indiana, 46280, United States

RECRUITING

Johns Hopkins University

Baltimore, Maryland, 21224, United States

RECRUITING

Tufts University

Boston, Massachusetts, 02111, United States

RECRUITING

University of Massachusetts Chan Medical School

Worcester, Massachusetts, 01655, United States

RECRUITING

American Arthritis and Rheumatology Associates -Mi PLLC

Okemos, Michigan, 48864, United States

RECRUITING

Saint Paul Rheumatology, P.A.

Eagan, Minnesota, 55121, United States

RECRUITING

Mayo Clinic Rochester

Rochester, Minnesota, 55905, United States

RECRUITING

Dr. Jayashree Sinha

Clovis, New Mexico, 88101, United States

RECRUITING

Inspire Santa Fe Medical Group

Santa Fe, New Mexico, 87505, United States

RECRUITING

New York University

New York, New York, 10016, United States

RECRUITING

Hospital for Special Surgery

New York, New York, 10021, United States

RECRUITING

University Hospital Cleveland Medical Ctr

Cleveland, Ohio, 44106, United States

RECRUITING

The MetroHealth System

Cleveland, Ohio, 44109, United States

RECRUITING

Arthritis and Rheumatology of Southwest Ohio

Liberty Township, Ohio, 45069, United States

RECRUITING

Southern Ohio Rheumatology

Wheelersburg, Ohio, 45694, United States

RECRUITING

Oregon Health and Science University

Portland, Oregon, 97239, United States

RECRUITING

Altoona Center for Clinical Research

Duncansville, Pennsylvania, 16635, United States

RECRUITING

Rheumatology and Arthritis Care Center

Exton, Pennsylvania, 19341-2547, United States

RECRUITING

Allegheny Health Network

Pittsburgh, Pennsylvania, 15212, United States

RECRUITING

PA Regional Center for Arthritis and Osteoporosis Research

Wyomissing, Pennsylvania, 19610, United States

RECRUITING

Cumberland Rhematology

Crossville, Tennessee, 38555, United States

RECRUITING

Vanderbilt University

Nashville, Tennessee, 37235, United States

RECRUITING

Heritage Rheumatology and Arthritis Care

Colleyville, Texas, 76034, United States

RECRUITING

Southwest Medical Center

Dallas, Texas, 75235, United States

RECRUITING

Texas Arthritis Center, PA

El Paso, Texas, 77902, United States

RECRUITING

American Arthritis and Rheumatology Associates-Tx PLLC

Harlingen, Texas, 78550, United States

RECRUITING

Baylor University

Houston, Texas, 77030, United States

RECRUITING

Northern Virginia Center for Arthritis-Reston

Reston, Virginia, 20190, United States

RECRUITING

Mount Sinai Hospital (Canada)

Toronto, Ontario, M5T 3L9, Canada

RECRUITING

MeSH Terms

Conditions

Arthritis, Rheumatoid

Condition Hierarchy (Ancestors)

ArthritisJoint DiseasesMusculoskeletal DiseasesRheumatic DiseasesConnective Tissue DiseasesSkin and Connective Tissue DiseasesAutoimmune DiseasesImmune System Diseases

Study Officials

  • Jasvinder Singh, MD

    University of Alabama at Birmingham

    PRINCIPAL INVESTIGATOR

Central Study Contacts

Jasvinder Singh

CONTACT

Jeff Foster, MPH

CONTACT

Study Design

Study Type
interventional
Phase
phase 3
Allocation
RANDOMIZED
Masking
NONE
Purpose
TREATMENT
Intervention Model
PARALLEL
Sponsor Type
OTHER
Responsible Party
PRINCIPAL INVESTIGATOR
PI Title
Professor of Medicine

Study Record Dates

First Submitted

December 15, 2020

First Posted

December 31, 2020

Study Start

September 22, 2021

Primary Completion (Estimated)

February 28, 2027

Study Completion (Estimated)

December 31, 2028

Last Updated

July 18, 2025

Record last verified: 2025-07

Data Sharing

IPD Sharing
Will not share

Locations