Healthy ParticipantsPhase 2StopRANCT02603146
Strategy to Prevent the Onset of Clinically-Apparent Rheumatoid Arthritis
A Phase 2 study testing Hydroxychloroquine in people with Healthy Participants and Rheumatoid Arthritis (RA) Prevention, run by National Institute of Allergy and Infectious Diseases (NIAID) at 14 sites in United States.
Trial 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). Read more about this study
- Who is it for?
- Ages 18 years and olderHealthy volunteers can take part
- Conditions the study is for
- Healthy Participants, Rheumatoid Arthritis (RA) Prevention
- What is being tested?
- Hydroxychloroquine
- Type of treatment
- Pill or oral medicine
- Could I receive a placebo?
- Yes, some participants may receive a placebo
- How many people
- 144 participants
- Where
- 14 sitesUnited States
- Study dates
- 27 Apr 2016to 1 Nov 2022
- Phase
- Phase 2
- Are there results?
- Yes, posted in the registrySummary in the doctors' view
Key requirements
Who can take part, as listed by the sponsor. Only the study team can confirm whether you are eligible, so take this list to your doctor.
- Ages 18 years and older
- All sexes
- Healthy volunteers accepted
- Adult, Older adult
Who may be able to join
- 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.
Who cannot join
- 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;
Show all 41Show fewer
- Sjögren's syndrome;
- polymyalgia rheumatic; or
- vasculitis.
- Note: Crystalline arthropathies are not exclusionary.
- 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;
- and/or serologic evidence during Screening Visit of chronic infections including, but not limited to, human immunodeficiency virus (HIV), hepatitis B (HBV), hepatitis C (HCV);
- ---Exception: hepatitis C antibody positive subjects are eligible with documentation of:
- receipt of HCV treatment AND
- a negative hepatitis C viral load test post-treatment.
- malignancy within the last 5 years, except for treated basal or squamous cell carcinoma, treated cervical dysplasia, or treated in situ cervical cancer Grade I; or
- alcohol or substance abuse within 1 year of treatment randomization.
- Prior or current systemic treatment with disease modifying anti-rheumatic agents, immunomodulatory agents, or glucocorticoids for IA, other rheumatic diseases, or other immunologic diseases;
- Tetracycline class antibiotic use for autoimmune conditions, taken within 12 months prior to Screening;
- Systemic corticosteroid use for non-IA conditions taken 28 days prior to Screening;
- More than 3 local corticosteroid injections, including but not limited to intra-articular, epidural, and intrabursal injections, during the 3 months prior to randomization;
- A history of a chronic condition that, in the opinion of the investigator, is highly likely to require therapy with systemic corticosteroids (oral or intravenous) within the study period, including but not limited to severe asthma and severe crystalline arthropathy;
- Women who are pregnant, breastfeeding or desire to become pregnant and/or breast feed within the duration of the 12-month treatment phase of the study;
- Women of childbearing potential who are not using or who do not agree to use adequate birth control measures (for example, total abstinence, oral contraceptives, intrauterine device, barrier method with spermicide, surgical sterilization, Depo-Provera, or hormonal implants) during the treatment phase of the study;
- An ideal or actual body weight ≤ 24.4 kg (e.g., ≤53 lbs) at Screening Visit;
- Any of the following laboratory abnormalities at the Screening Visit:
- Serum Creatinine Clearance < 50ml/min (as calculated by the Cockcroft-Gault formula: Creatinine clearance (CrCl)= (140-age) X (Weight in kg) X (0.85 if female) / (72 X Creatinine));
- Alanine Aminotransferase (ALT) > 2 times the upper limit of normal (ULN);
- Aspartate Aminotransferase (AST) > 2x the upper limit of normal (ULN);
- Total white blood count (WBC) < 3.0 x 10^9/L;
- Platelet count ≤ 150 x10^9/L;
- Hemoglobin < 11.5g/dL;
- Absolute Neutrophil Count (ANC) < 2.0 x 10^9/L;
- Evidence of significant retinal disease upon eye examination during the screening period that in the opinion of the examiner would make identification of potential future retinal toxicity from HCQ difficult to evaluate:
- -- Retinal exam results may be applied to evaluations of subject eligibility for up to 6 months after the initial retinal exam.
- When, in the opinion of the study physician, the subject is not a good study candidate.
Trial locations and contacts
14 sites in 1 country.
14 sites in 1 country
United States14 sites
University of Michigan Health System: Department of Internal Medicine, Division of Rheumatology
Ann Arbor, Michigan, 48109
Emory Clinic at 1365 Clifton Road: Emory University School of Medicine
Atlanta, Georgia, 30322
University of Colorado School of Medicine: Division of Rheumatology
Aurora, Colorado, 80045
University of Alabama at Birmingham School of Medicine: Division of Clinical Immunology & Rheumatology
Birmingham, Alabama, 35294
Brigham & Women's Hospital: Department of Medicine, Rheumatology, Immunology
Boston, Massachusetts, 02115
University of Texas Southwestern Medical Center, Division of Rheumatic Diseases
Dallas, Texas, 75390
Northwell Health
Great Neck, New York, 110211
Cedars Sinai Medical Center: Division of Rheumatology
Los Angeles, California, 90048
UCLA Medical Center: Division of Rheumatology
Los Angeles, California, 90095
Oklahoma Medical Research Foundation: Arthritis and Clinical Immunology Research Program
Oklahoma City, Oklahoma, 73104
University of Nebraska Medical Center: Division of Rheumatology
Omaha, Nebraska, 68198
Mayo Clinic, Division of Rheumatology
Rochester, Minnesota, 55905
University of California San Francisco, San Francisco General Hospital
San Francisco, California, 94110
University of Massachusetts Memorial Medical Center: Rheumatology
Worcester, Massachusetts, 01605
About this study
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.
Read the detailed description
Rheumatoid arthritis (RA) affects an estimated 1% of the population. RA is a disease where the immune system attacks the joints, leading to joint inflammation and damage that is felt by someone with RA as joint pain, stiffness and swelling.
Recent studies have shown that there are markers in the blood called 'autoantibodies' that precede the onset of joint symptoms of RA. Antibodies are commonly made in the blood to fight infections. Sometimes, these antibodies attack one's own body. These are called autoantibodies.
Certain autoantibodies are specific for certain diseases. The autoantibody known as anti-CCP3 is specific for RA and can predict the development of RA in the future, especially if the level of anti-CCP3 is high. The investigators of this study believe that individuals with elevations of anti-CCP3 ≥2 times the normal value have approximately a 50% chance of developing RA within 3 years.
Hydroxychloroquine (HCQ) is already used successfully and safely in the treatment of malaria, lupus and RA. The objective of this study is to determine whether treatment with HCQ in individuals with elevations of anti-CCP3 without joint inflammation may help prevent the future onset of RA. This will involve a 12-month course of HCQ in the prevention of the development of clinically apparent RA at 36 months in individuals at high-risk for future RA due to high titer elevations of anti-CCP3. This study will recruit for individuals without a history or clinical findings of inflammatory arthritis. Eligible subjects will be randomized in a 1:1 ratio to HCQ versus HCQ placebo.
- Being tested
- Hydroxychloroquine, HCQ Placebo
- Keywords
- RA prevention, hydroxychloroquine (HCQ), anti-CCP3
- Medical subject headings
- Arthritis, Rheumatoid
What participants receive
What participants receive. In a randomised study each person is assigned to one group by chance.
Also called HCQ, Plaquenil
As described. Dosing will be based upon Screening IBW.
HCQ PlaceboDrug
Also called Placebo
As described. Dosing will be based upon Screening IBW.
| Study group | Role | What they receive |
|---|---|---|
| Hydroxychloroquine Group | Experimental | Subjects 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. Receives: Drug: Hydroxychloroquine |
| Placebo Group | Placebo comparator | Subjects randomized to placebo HCQ. Subjects will receive 200 - 400 mg of HCQ placebo (1-2 pills), based upon IBW, taken daily for 12 months. Receives: Drug: HCQ Placebo |
What is being measured
The primary outcome is the main question the study is designed to answer.
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.
Measured: 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
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 IA with ≥ 1 erosion confirmed by x-ray imaging of the hands, wrists, and feet.
Measured: Baseline to Month 12
Number of Participants Who Developed Inflammatory Arthritis (IA) From Treatment Initiation to Month 12.
IA is defined as the development of at least one swollen joint consistent with rheumatoid arthritis-like (RA-like) synovitis. The joint exams conducted by a physician at each clinic visit were used to identify the presence of swollen joints due to IA.
Measured: Baseline to Month 12
Time to Development of Clinically-Apparent Rheumatoid Arthritis (CL - RA) By Treatment Arm
Mean Time from treatment initiation until development of CL-RA. CL- 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 IA with ≥ 1 erosion confirmed by x-ray imaging of the hands, wrists, and feet.
Measured: Baseline to Month 36
Number of Participants Who Developed Inflammatory Arthritis (IA) From Treatment Initiation to Month 36
IA is defined as the development of at least one swollen joint consistent with rheumatoid arthritis-like (RA-like) synovitis. The joint exams conducted by a physician at each clinic visit were used to identify the presence of swollen joints due to IA.
Measured: Baseline to Month 36
Number of Participant Self-Reported Painful Joints By Treatment Arm
The Participant Self-Reported Joint Symptoms assessment was used by participants to indicate which joints were painful on the day of the visit or in the past week. The Participant Self-Reported Joint Symptoms assessment contained a diagram of the body joints which participants used to mark their painful joints.
Measured: At Week 52 and Month 36/End of Study
Number of Participant Self-Reported Stiff Joints By Treatment Arm
The Participant Self-Reported Joint Symptoms assessment was used by participants to indicate which joints were stiff on the day of the visit or in the past week. The Participant Self-Reported Joint Symptoms assessment contained a diagram of the body joints which participants used to mark their stiff joints.
Measured: At Week 52 and Month 36/End of Study
Number of Participant Self-Reported Swollen Joints By Treatment Arm
The Participant Self-Reported Joint Symptoms assessment was used by participants to indicate which joints were swollen on the day of the visit or in the past week. The Participant Self-Reported Joint Symptoms assessment contained a diagram of the body joints which participants used to mark their swollen joints.
Measured: At Week 52 and Month 36/End of Study
Number of Participant Self-Reported Painful Joints in the Hands, Wrists and Feet By Treatment Arm
The Participant Self-Reported Joint Symptoms assessment was used by participants to indicate which joints were painful on the day of the visit or in the past week. The Participant Self-Reported Joint Symptoms assessment contained a diagram of the body joints which participants used to mark their painful joints.
Measured: At Week 52 and Month 36/End of Study
Number of Participant Self-Reported Stiff Joints in the Hands, Wrists and Feet By Treatment Arm
The Participant Self-Reported Joint Symptoms assessment was used by participants to indicate which joints were stiff on the day of the visit or in the past week. The Participant Self-Reported Joint Symptoms assessment contained a diagram of the body joints which participants used to mark their stiff joints.
Measured: At Week 52 and Month 36/End of Study
Number of Participant Self-Reported Swollen Joints in the Hands, Wrists and Feet By Treatment Arm
The Participant Self-Reported Joint Symptoms assessment was used by participants to indicate which joints were swollen on the day of the visit or in the past week. The Participant Self-Reported Joint Symptoms assessment contained a diagram of the body joints which participants used to mark their swollen joints.
Measured: At Week 52 and Month 36/End of Study
Level of Anti-Cyclic Citrullinated Peptide-3 (Anti-CCP3) By Treatment Arm
Anti-CCP3 is a laboratory test for the presence of antibodies to citrullinated protein antigens (ACPAs) in serum. ACPA positivity assists with the classification/diagnosis of Rheumatoid Arthritis (RA) of a patient with Inflammatory Arthritis (IA). In addition, determining autoantibody positivity helps with the prediction of RA disease severity. Anti-CCP3 positivity at any level, and in particular anti-CCP3 levels of ≥2 times the normal cut-off level (or ≥ 40 units) are highly predictive of future RA development.
Measured: Baseline, Week 52 (End of Treatment), Month 36/End of Study
Level of Immunoglobulin M - Rheumatoid Factor (IgM-RF) By Treatment Arm
IgM-RF is a laboratory test for the presence of antibodies to RF in serum. IgM-RF positivity assists with the classification/diagnosis of Rheumatoid Arthritis (RA) of a patient with Inflammatory Arthritis (IA). In addition, determining autoantibody positivity helps with the prediction of RA disease severity. Higher levels of antibodies (e.g. >2-3 times the normal cut-off values) have greater specificity for RA disease.
Measured: Baseline, Week 52 (End of Treatment), Month 36/End of Study
Level of High-Sensitivity C-Reactive Protein (hsCRP) Treatment Arm
HsCRP is used to detect systemic inflammation in the body, assists with the classification/diagnosis of Rheumatoid Arthritis (RA), and elevations of hsCRP in patients with RA have been associated with poor disease outcomes.
Measured: Baseline, Week 52 (End of Treatment), Month 36/End of Study
Percent of Participants Experiencing Grade 3 or Higher Adverse Events (AEs)
Adverse Events (AEs) grading will be defined by the National Cancer Institute (NCI) - Common Terminology Criteria for Adverse Events (CTCAE), version 4.0. The number of AEs will be identified by monitoring participant-reported AEs, vital signs, medical history, physical exams and blood safety tests.
Measured: Non-serious AEs were collected from treatment initiation through month 18. Serious AEs were collected from screening through month 36.
Timeline
From the start of the study to its completion; the mark is today. Estimated dates are the sponsor’s plan.
- First posted11 Nov 2015 (estimated)
- Study start27 Apr 2016
- Primary completion1 Nov 2022
- Study completion1 Nov 2022
Why it 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.
Resources
- Official record on ClinicalTrials.govThe registry entry this page is built from, with its full change history.
- Posted resultsParticipant flow, outcome measures and adverse events reported by the sponsor.
- Publications (1)Papers the sponsor has linked to this study.
- Other trials for Healthy ParticipantsStudies of the same condition, open and under way.
- More trials run by National Institute of Allergy and Infectious Diseases (NIAID)The sponsor's other registered studies.
- What the trial phases meanHow a treatment moves from first tests in people to approval.
More details
For doctors and researchers: how the study is designed, who runs it, and its registry IDs.
Study design
- Study type
- Interventional
- Phase
- Phase 2
- Primary purpose
- Prevention
- Allocation
- Randomised
- Intervention model
- Parallel groups
- Masking
- Double blind
- Who is masked
- Participant, Investigator
- Enrolment
- 144 participants (actual)
Sponsor and investigators
- Sponsor type
- US National Institutes of Health
- Collaborators
- Autoimmunity Centers of Excellence
- Responsible party
- Sponsor
- Investigators
- Kevin Deane, MD, PhD, Study chair, University of Colorado School of MedicineMichael Holers, MD, Study chair, University of Colorado School of MedicineChristopher Striebich, MD, PhD, Study chair, University of Colorado School of Medicine
IDs, dates and publications
- ClinicalTrials.gov ID
- NCT02603146
- Sponsor's protocol ID
- DAIT ARA08
- Other IDs
- NIAID CRMS ID#: 20681
- Acronym
- StopRA
- Status last verified
- May 2025
- First submitted
- 10 Nov 2015
- Last updated
- 12 Jun 2025
- Results posted
- Yes, on ClinicalTrials.gov
- Data monitoring committee
- Yes
- Individual data sharing
- Yes: 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.
Publications
Deane KD, Striebich CC, Feser ML, O'Dell JR, James JA, Sparks JA, Davis JM 3rd, Graf J, McMahon MA, Solow EB, Forbess LJ, Tiliakos A, Schiopu E, Danila MI, Horowitz DL, Kay J, Strickland CD, Guthridge JM, Arriens C, Grossman JM, Kristen Demoruelle M, 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. 2026 Apr;78(4):809-820. doi: 10.1002/art.43366. Epub 2026 Mar 16.
PubMed 40884017
Study at a glance
From the registry record, last updated by the sponsor on 12 Jun 2025. Recruitment status is as the sponsor reported it: confirm with the study team.
- Official title
- Strategy to Prevent the Onset of Clinically-Apparent Rheumatoid Arthritis
- ClinicalTrials.gov ID
- NCT02603146
- Acronym / sponsor ID
- StopRA / DAIT ARA08
- Keywords
- RA prevention, hydroxychloroquine (HCQ), anti-CCP3
- Phase
- Phase 2
- Study type
- Interventional
- Recruitment status
- TerminatedReason 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.
- Enrolment
- 144 participants (actual)
- Lead sponsor
- National Institute of Allergy and Infectious Diseases (NIAID)US National Institutes of Health
- Collaborators
- Autoimmunity Centers of Excellence
- Study start
- 27 Apr 2016 (actual)
- Primary completion
- 1 Nov 2022 (actual)
- Study completion
- 1 Nov 2022 (actual)
- First posted
- 11 Nov 2015 (estimated)
- Results
- Posted 21 Nov 2023
Clinical summary
The research question as the sponsor registered it. This describes what the study plans to test, not what it found.
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.
Detailed description
Rheumatoid arthritis (RA) affects an estimated 1% of the population. RA is a disease where the immune system attacks the joints, leading to joint inflammation and damage that is felt by someone with RA as joint pain, stiffness and swelling.
Recent studies have shown that there are markers in the blood called 'autoantibodies' that precede the onset of joint symptoms of RA. Antibodies are commonly made in the blood to fight infections. Sometimes, these antibodies attack one's own body. These are called autoantibodies.
Certain autoantibodies are specific for certain diseases. The autoantibody known as anti-CCP3 is specific for RA and can predict the development of RA in the future, especially if the level of anti-CCP3 is high. The investigators of this study believe that individuals with elevations of anti-CCP3 ≥2 times the normal value have approximately a 50% chance of developing RA within 3 years.
Hydroxychloroquine (HCQ) is already used successfully and safely in the treatment of malaria, lupus and RA. The objective of this study is to determine whether treatment with HCQ in individuals with elevations of anti-CCP3 without joint inflammation may help prevent the future onset of RA. This will involve a 12-month course of HCQ in the prevention of the development of clinically apparent RA at 36 months in individuals at high-risk for future RA due to high titer elevations of anti-CCP3. This study will recruit for individuals without a history or clinical findings of inflammatory arthritis. Eligible subjects will be randomized in a 1:1 ratio to HCQ versus HCQ placebo.
Study design
- Primary purpose
- Prevention
- Allocation
- Randomised
- Intervention model
- Parallel groups
- Masking
- Double blind (participant, investigator)
- Number of arms
- 2
| Arm | Type | Receives |
|---|---|---|
| Hydroxychloroquine Group | Experimental | Drug: HydroxychloroquineSubjects 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 comparator | Drug: HCQ PlaceboSubjects randomized to placebo HCQ. Subjects will receive 200 - 400 mg of HCQ placebo (1-2 pills), based upon IBW, taken daily for 12 months. |
Who may qualify
- Ages
- 18 years and older
- Sex
- All
- Healthy volunteers
- Accepted
- Age groups
- Adult, Older adult
Key inclusion criteria (4 listed)
- 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.
Key exclusion criteria (41 listed)
- 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;
Eligibility is decided by the study team after screening; this overview does not establish that a patient qualifies. Full inclusion and exclusion criteria.
Interventions
| Intervention | Type | Arms |
|---|---|---|
| HydroxychloroquineAlso: HCQ, PlaquenilAs described. Dosing will be based upon Screening IBW. | Drug | Hydroxychloroquine Group |
| HCQ PlaceboAlso: PlaceboAs described. Dosing will be based upon Screening IBW. | Drug | Placebo Group |
Primary outcome
Number of Participants Who Developed Clinically-Apparent Rheumatoid Arthritis (CL - RA) From Treatment Initiation to Month 36 By Treatment Arm
Time frame: Baseline to Month 36
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.
14 secondary outcomes
Number of Participants Who Developed Clinically-Apparent Rheumatoid Arthritis (CL-RA) From Treatment Initiation to Month 12 By Treatment Arm
Time frame: Baseline to Month 12
Number of Participants Who Developed Inflammatory Arthritis (IA) From Treatment Initiation to Month 12.
Time frame: Baseline to Month 12
Time to Development of Clinically-Apparent Rheumatoid Arthritis (CL - RA) By Treatment Arm
Time frame: Baseline to Month 36
Number of Participants Who Developed Inflammatory Arthritis (IA) From Treatment Initiation to Month 36
Time frame: Baseline to Month 36
Number of Participant Self-Reported Painful Joints By Treatment Arm
Time frame: At Week 52 and Month 36/End of Study
Number of Participant Self-Reported Stiff Joints By Treatment Arm
Time frame: At Week 52 and Month 36/End of Study
Number of Participant Self-Reported Swollen Joints By Treatment Arm
Time frame: At Week 52 and Month 36/End of Study
Number of Participant Self-Reported Painful Joints in the Hands, Wrists and Feet By Treatment Arm
Time frame: At Week 52 and Month 36/End of Study
Number of Participant Self-Reported Stiff Joints in the Hands, Wrists and Feet By Treatment Arm
Time frame: At Week 52 and Month 36/End of Study
Number of Participant Self-Reported Swollen Joints in the Hands, Wrists and Feet By Treatment Arm
Time frame: At Week 52 and Month 36/End of Study
Level of Anti-Cyclic Citrullinated Peptide-3 (Anti-CCP3) By Treatment Arm
Time frame: Baseline, Week 52 (End of Treatment), Month 36/End of Study
Level of Immunoglobulin M - Rheumatoid Factor (IgM-RF) By Treatment Arm
Time frame: Baseline, Week 52 (End of Treatment), Month 36/End of Study
Level of High-Sensitivity C-Reactive Protein (hsCRP) Treatment Arm
Time frame: Baseline, Week 52 (End of Treatment), Month 36/End of Study
Percent of Participants Experiencing Grade 3 or Higher Adverse Events (AEs)
Time frame: Non-serious AEs were collected from treatment initiation through month 18. Serious AEs were collected from screening through month 36.
Results and safety
Loading the posted results from ClinicalTrials.gov…
Research links
- Official record on ClinicalTrials.govLast updated by the sponsor 12 Jun 2025.
- Posted resultsParticipant flow, baseline, all outcome measures and adverse events.
- Derived from this study: PubMed 40884017Deane KD, Striebich CC, Feser ML, O'Dell JR, James JA, Sparks JA, Davis JM 3rd, Graf J, McMahon MA, Solow EB, Forbess LJ, Tiliakos A, Schiopu E, Danila MI, Horowitz DL, Kay J, Strickland CD, Guthridge JM, Arriens C, Grossman JM, Kristen Demoruelle M, 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. 2026 Apr;78(4):809-820. doi: 10.1002/art.43366. Epub 2026 Mar 16.
- National Institute of Allergy and Infectious Diseases (NIAID)Link provided by the sponsor.
- Division of Allergy, Immunology, and Transplantation (DAIT)Link provided by the sponsor.
- Individual participant dataSharing planned: Yes. 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.
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Referral and contact
AzTrials does not enrol participants or take referrals. Contact the study team or a site listed below; they decide who can take part. This study is not recruiting at the moment.
Kevin Deane, MD, PhD study chair
University of Colorado School of Medicine
Michael Holers, MD study chair
University of Colorado School of Medicine
Christopher Striebich, MD, PhD study chair
University of Colorado School of Medicine
14 sites in 1 country: see every site and its status.
Questions about this trial
What is this clinical trial studying?
A Phase 2 study testing Hydroxychloroquine in people with Healthy Participants and Rheumatoid Arthritis (RA) Prevention, run by National Institute of Allergy and Infectious Diseases (NIAID) at 14 sites in United States.
The full registered description is in the About this study section and the official record.
Who may be eligible to take part?
The sponsor lists 4 inclusion and 41 exclusion criteria. Eligibility is decided by the study team after screening, so read the full criteria and contact a listed site.
Is this clinical trial currently recruiting?
The record says: stopped early, as of the sponsor's last update on 12 Jun 2025. Status can change between updates, so confirm with the study contact before making plans.
Where is the study taking place?
The record lists 14 sites in United States. Whether a site is taking part right now should be confirmed with that site. See every site.
What are the possible benefits and risks?
They depend on the study and the treatment, and no study can promise a benefit. Some participants in this study may receive a placebo. The study team explains the known risks during informed consent, before anyone joins; the record itself does not list them.
What does this phase mean?
Phase 2 studies give the treatment to a larger group to see whether it has the intended effect and to keep checking safety.
Not every study follows the same path, and some studies (observational studies, device studies) have no phase.
Are results available for this study?
Yes. Results are posted in the registry (first posted 21 Nov 2023). A summary is in the For doctors view, and the full results are on ClinicalTrials.gov.
How can a doctor refer a patient or contact the research team?
The record lists no contact. The official record names the sponsor, who can be asked directly. AzTrials does not enrol participants or take referrals.
What does the primary outcome measure?
Number of Participants Who Developed Clinically-Apparent Rheumatoid Arthritis (CL - RA) From Treatment Initiation to Month 36 By Treatment Arm (time frame: Baseline to Month 36). It is what the study was designed to measure, not a finding.
Where can I read the original study information?
On the ClinicalTrials.gov record for NCT02603146, which also lists 1 linked publication.
Does a listing mean the treatment is approved or proven to work?
No. A listing means the study is registered. It does not show that the treatment is safe, works, or is approved by a regulator.
How often is this information updated?
AzTrials copies changed records from ClinicalTrials.gov every night and reloads the whole registry every week. The sponsor last updated this record on 12 Jun 2025; AzTrials last refreshed its copy on 26 Oct 2026.