Study Stopped
Enrollment was closed before reaching the target. In the 1st interim analysis after enrollment closure, the follow up \& treatment of active participants were stopped early due to evidence of futility.
Strategy to Prevent the Onset of Clinically-Apparent Rheumatoid Arthritis
StopRA
2 other identifiers
interventional
144
1 country
14
Brief Summary
The purpose of this study is to determine if hydroxychloroquine (HCQ) is safe and effective for the prevention of future onset of rheumatoid arthritis (RA) in individuals who have elevations of an autoantibody, anti-cyclic citrullinated peptide (anti-CCP3). The following recruitment strategies will be employed towards identifying healthy subjects with elevated anti-cyclic citrullinated peptide (anti-CCP3) levels:
- Pre-screening:
- first degree relatives of patients with rheumatoid arthritis (RA);
- subjects at health-fairs; and
- identification of subjects with elevated anti-CCP3 levels in the absence of inflammatory arthritis in rheumatology clinics.
Trial Health
Trial Health Score
Automated assessment based on enrollment pace, timeline, and geographic reach
participants targeted
Target at P75+ for phase_2
Started Apr 2016
Longer than P75 for phase_2
14 active sites
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
First Submitted
Initial submission to the registry
November 10, 2015
CompletedFirst Posted
Study publicly available on registry
November 11, 2015
CompletedStudy Start
First participant enrolled
April 27, 2016
CompletedPrimary Completion
Last participant's last visit for primary outcome
November 1, 2022
CompletedStudy Completion
Last participant's last visit for all outcomes
November 1, 2022
CompletedResults Posted
Study results publicly available
November 21, 2023
CompletedJune 12, 2025
May 1, 2025
6.5 years
November 10, 2015
October 30, 2023
May 27, 2025
Conditions
Keywords
Outcome Measures
Primary Outcomes (1)
Number of Participants Who Developed Clinically-Apparent Rheumatoid Arthritis (CL - RA) From Treatment Initiation to Month 36 By Treatment Arm
Clinically-Apparent RA is defined by the 2010 American College of Rheumatology (ACR)/European League Against Rheumatism (EULAR) Classification Criteria as either: 1.) a score of ≥ 6 defining "definite RA" or 2.) a joint examination consistent with Inflammatory Arthritis (IA) with ≥ 1 erosion confirmed by x-ray imaging of the hands, wrists, and feet.
Baseline to Month 36
Secondary Outcomes (14)
Number of Participants Who Developed Clinically-Apparent Rheumatoid Arthritis (CL-RA) From Treatment Initiation to Month 12 By Treatment Arm
Baseline to Month 12
Number of Participants Who Developed Inflammatory Arthritis (IA) From Treatment Initiation to Month 12.
Baseline to Month 12
Time to Development of Clinically-Apparent Rheumatoid Arthritis (CL - RA) By Treatment Arm
Baseline to Month 36
Number of Participants Who Developed Inflammatory Arthritis (IA) From Treatment Initiation to Month 36
Baseline to Month 36
Number of Participant Self-Reported Painful Joints By Treatment Arm
At Week 52 and Month 36/End of Study
- +9 more secondary outcomes
Study Arms (2)
Hydroxychloroquine Group
EXPERIMENTALSubjects randomized to hydroxychloroquine (HCQ). Subjects will receive 200-400 mg of HCQ (1-2 pills), based upon ideal body weight (IBW), taken daily for 12 months.
Placebo Group
PLACEBO COMPARATORSubjects randomized to placebo HCQ. Subjects will receive 200 - 400 mg of HCQ placebo (1-2 pills), based upon IBW, taken daily for 12 months.
Interventions
As described. Dosing will be based upon Screening IBW.
As described. Dosing will be based upon Screening IBW.
Eligibility Criteria
You may qualify if:
- Subjects who meet all of the following criteria are eligible for enrollment into the study:
- Able and willing to give written informed consent and comply with requirements of the study;
- Age ≥18 years-old at the Screening Visit; and
- Elevation of autoantibody anti-cyclic citrullinated peptide-3 (anti-CCP3) defined by result of anti-CCP3 ≥40 units, at Screening.
You may not qualify if:
- Subjects who meet any of the following criteria are ineligible to participate in the study:
- A medical history of inflammatory arthritis (IA) of any type and/or rheumatic disease and immunologic disease(s) that may be associated with IA . These diseases include but are not limited to:
- rheumatoid arthritis (RA);
- systemic lupus erythematosus (SLE);
- seronegative spondyloarthropathies;
- inflammatory bowel disease;
- Sjögren's syndrome;
- polymyalgia rheumatic; or
- vasculitis.
- A medical history of:
- congestive heart failure or functional status of New York Heart Association (NYHA) Class III or higher at the Screening Visit;
- cardiomyopathy or significant cardiac conduction disorders;
- chronic liver disease;
- psoriasis (due to potential for increased risk for flare of skin disease);
- porphyria;
- +25 more criteria
Contact the study team to confirm eligibility.
Sponsors & Collaborators
Study Sites (14)
University of Alabama at Birmingham School of Medicine: Division of Clinical Immunology & Rheumatology
Birmingham, Alabama, 35294, United States
Cedars Sinai Medical Center: Division of Rheumatology
Los Angeles, California, 90048, United States
UCLA Medical Center: Division of Rheumatology
Los Angeles, California, 90095, United States
University of California San Francisco, San Francisco General Hospital
San Francisco, California, 94110, United States
University of Colorado School of Medicine: Division of Rheumatology
Aurora, Colorado, 80045, United States
Emory Clinic at 1365 Clifton Road: Emory University School of Medicine
Atlanta, Georgia, 30322, United States
Brigham & Women's Hospital: Department of Medicine, Rheumatology, Immunology
Boston, Massachusetts, 02115, United States
University of Massachusetts Memorial Medical Center: Rheumatology
Worcester, Massachusetts, 01605, United States
University of Michigan Health System: Department of Internal Medicine, Division of Rheumatology
Ann Arbor, Michigan, 48109, United States
Mayo Clinic, Division of Rheumatology
Rochester, Minnesota, 55905, United States
University of Nebraska Medical Center: Division of Rheumatology
Omaha, Nebraska, 68198, United States
Northwell Health
Great Neck, New York, 110211, United States
Oklahoma Medical Research Foundation: Arthritis and Clinical Immunology Research Program
Oklahoma City, Oklahoma, 73104, United States
University of Texas Southwestern Medical Center, Division of Rheumatic Diseases
Dallas, Texas, 75390, United States
Related Publications (1)
Deane KD, Striebich CC, Feser ML, O'Dell JR, James JA, Sparks JA, Davis JM, Graf J, McMahon MA, Solow EB, Forbess L, Tiliakos A, Schiopu E, Danila MI, Horowitz DL, Kay J, Strickland CD, Guthridge JM, Arriens C, Grossman JM, Demoruelle MK, Bemis EA, Frazer-Abel A, Fleischer CL, Fox DA, Mikuls TR, Greenleaf M, York K, Walker S, Keyes-Elstein L, Byron M, Fedler J, Goldmuntz EA, Holers VM. A phase 2 trial of hydroxychloroquine in individuals at risk for rheumatoid arthritis. Arthritis Rheumatol. 2025 Aug 29. doi: 10.1002/art.43366. Online ahead of print.
PMID: 40884017DERIVED
Related Links
MeSH Terms
Conditions
Interventions
Condition Hierarchy (Ancestors)
Intervention Hierarchy (Ancestors)
Limitations and Caveats
Enrollment closed at 144 randomized participants before reaching the target of 200 due to slow participant accrual. The decision was supported by a revised power analysis suggesting sufficient power for the study with reduced numbers assuming a clinically-relevant difference in RA rates between arms (50% risk for placebo \& 25% risk for HCQ). In the 1st interim analysis after enrollment closure, the follow up \& treatment of the active participants were stopped early due to evidence of futility.
Results Point of Contact
- Title
- Director, Clinical Research Operations Program
- Organization
- DAIT/NIAID
Study Officials
- STUDY CHAIR
Kevin Deane, MD, PhD
University of Colorado School of Medicine
- STUDY CHAIR
Michael Holers, MD
University of Colorado School of Medicine
- STUDY CHAIR
Christopher Striebich, MD, PhD
University of Colorado School of Medicine
Publication Agreements
- PI is Sponsor Employee
- No
- Restrictive Agreement
- No
Study Design
- Study Type
- interventional
- Phase
- phase 2
- Allocation
- RANDOMIZED
- Masking
- DOUBLE
- Who Masked
- PARTICIPANT, INVESTIGATOR
- Purpose
- PREVENTION
- Intervention Model
- PARALLEL
- Sponsor Type
- NIH
- Responsible Party
- SPONSOR
Study Record Dates
First Submitted
November 10, 2015
First Posted
November 11, 2015
Study Start
April 27, 2016
Primary Completion
November 1, 2022
Study Completion
November 1, 2022
Last Updated
June 12, 2025
Results First Posted
November 21, 2023
Record last verified: 2025-05
Data Sharing
- IPD Sharing
- Will share
- Time Frame
- After completion of the study.
- Access Criteria
- When posted, the IPD will be available to the public.
The plan is to share data in ImmPort, a long-term archive of clinical and mechanistic data from DAIT-funded grants and contracts, upon completion of the trial.