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| ID | Type | Description | Link |
|---|---|---|---|
| NIAID CRMS ID#: 20681 | Other Identifier | DAIT NIAID |
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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.
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| Name | Class |
|---|---|
| Autoimmunity Centers of Excellence | OTHER |
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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:
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.
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| Label | Type | Description | Intervention Names |
|---|---|---|---|
| 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. |
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| 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. |
|
| Name | Type | Description | Arm Group Labels | Other Names |
|---|---|---|---|---|
| Hydroxychloroquine | Drug | As described. Dosing will be based upon Screening IBW. |
|
| Measure | Description | Time Frame |
|---|---|---|
| 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 |
| Measure | Description | Time Frame |
|---|---|---|
| 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. |
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Inclusion Criteria:
Subjects who meet all of the following criteria are eligible for enrollment into the study:
Exclusion Criteria:
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:
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:
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:
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.
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| Name | Affiliation | Role |
|---|---|---|
| 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 | Study Chair |
| Facility | Status | City | State | ZIP | Country | Contacts |
|---|---|---|---|---|---|---|
| University of Alabama at Birmingham School of Medicine: Division of Clinical Immunology & Rheumatology | Birmingham | Alabama | 35294 | United States |
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| Label | URL |
|---|---|
| National Institute of Allergy and Infectious Diseases (NIAID) | View source |
| Division of Allergy, Immunology, and Transplantation (DAIT) | View source |
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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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After completion of the study.
When posted, the IPD will be available to the public.
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Twenty study sites were activated in the United States, beginning in March 2016. A total of 252 participants were screened from April 2016 to October 2021 at 15 sites. 144 participants were randomized.
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| ID | Title | Description |
|---|---|---|
| FG000 | Hydroxychloroquine | Participants self-administered 1-2 200 mg HCQ pills per day, based on ideal body weight at screening, from the Baseline visit to Week 52. |
| FG001 | Placebo | Participants self-administered 1-2 placebo pills per day, based on ideal body weight at screening, from the Baseline visit to Week 52. |
| Title | Milestones | Reasons Not Completed | |||||
|---|---|---|---|---|---|---|---|
| Overall Study |
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| Type | Includes Protocol | Includes SAP | Includes ICF | Document Label | Document Date | Document Uploaded Date | Document File Name |
|---|---|---|---|---|---|---|---|
| Prot | Yes | No | No | Study Protocol | May 1, 2020 | May 16, 2025 |
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| HCQ Placebo | Drug | As described. Dosing will be based upon Screening IBW. |
|
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| 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. | 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. | 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. | 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. | 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. | 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. | 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. | 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. | 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. | 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. | 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. | 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. | 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. | Non-serious AEs were collected from treatment initiation through month 18. Serious AEs were collected from screening through month 36. |
| 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 |
| COMPLETED |
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| NOT COMPLETED |
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The intent-to-treat population includes all randomized participants.
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| ID | Title | Description |
|---|---|---|
| BG000 | Hydroxychloroquine | Participants self-administered 1-2 200 mg HCQ pills per day, based on ideal body weight at screening, from the Baseline visit to Week 52. |
| BG001 | Placebo | Participants self-administered 1-2 placebo pills per day, based on ideal body weight at screening, from the Baseline visit to Week 52. |
| BG002 | Total | Total of all reporting groups |
| Units | Counts |
|---|---|
| Participants |
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| Title | Description | Population Description | Parameter Type | Dispersion Type | Unit of Measure | Calculate Percentage | Denominator Units Selected | Denominators | Classes | ||||||||||||
|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|
| Age, Categorical | Count of Participants | Participants |
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| Age, Continuous | Mean | Standard Deviation | years |
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| Sex: Female, Male | Count of Participants | Participants |
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| Ethnicity (NIH/OMB) | Count of Participants | Participants |
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| Race (NIH/OMB) | Count of Participants | Participants |
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| Region of Enrollment | Number | participants |
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| Anti-Cyclic Citrullinated Peptide-3 (Anti-CCP3) | 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. A value above 40 units was required to enter the study. | Mean | Standard Deviation | units |
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| Type | Title | Description | Population Description | Reporting Status | Anticipated Posting Date | Parameter Type | Dispersion Type | Unit of Measure | Calculate Percentage | Time Frame | Units Analyzed | Denominator Units Selected | Arm/Group Information | Denominators | Classes | Analyses | ||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||
|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|
| Primary | 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. | The modified-intent-to-treat population includes all randomized participants who received at least one dose of assigned study drug and met entry criteria. | Posted | Count of Participants | Participants | Baseline to Month 36 |
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| Secondary | 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. | The modified-intent-to-treat population includes all randomized participants who received at least one dose of assigned study drug and met entry criteria. | Posted | Count of Participants | Participants | Baseline to Month 12 |
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| Secondary | 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. | The modified-intent-to-treat population includes all randomized participants who received at least one dose of assigned study drug and met entry criteria. | Posted | Count of Participants | Participants | Baseline to Month 12 |
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| Secondary | 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. | The modified-intent-to-treat population includes all randomized participants who received at least one dose of assigned study drug and met entry criteria. | Posted | Mean | 95% Confidence Interval | months | Baseline to Month 36 |
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| Secondary | 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. | The modified-intent-to-treat population includes all randomized participants who received at least one dose of assigned study drug and met entry criteria. | Posted | Count of Participants | Participants | Baseline to Month 36 |
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| Secondary | 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. | Participants in the modified-intent-to-treat population, including all randomized participants who received at least one dose of assigned study drug and met entry criteria, and who have available data at the time point. | Posted | Median | Full Range | joints | At Week 52 and Month 36/End of Study |
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| Secondary | 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. | Participants in the modified-intent-to-treat population, including all randomized participants who received at least one dose of assigned study drug and met entry criteria, and who have available data at the time point. | Posted | Median | Full Range | Joints | At Week 52 and Month 36/End of Study |
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| Secondary | 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. | The modified-intent-to-treat population includes all randomized participants who received at least one dose of assigned study drug and met entry criteria, and who have available data at the time point. | Posted | Median | Full Range | Joints | At Week 52 and Month 36/End of Study |
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| Secondary | 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. | The modified-intent-to-treat population includes all randomized participants who received at least one dose of assigned study drug and met entry criteria, and who have available data at the time point. | Posted | Median | Full Range | Joints | At Week 52 and Month 36/End of Study |
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| Secondary | 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. | The modified-intent-to-treat population includes all randomized participants who received at least one dose of assigned study drug and met entry criteria, and who have available data at the time point. | Posted | Median | Full Range | Joints | At Week 52 and Month 36/End of Study |
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| Secondary | 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. | The modified-intent-to-treat population includes all randomized participants who received at least one dose of assigned study drug and met entry criteria, and who have available data at the time point. | Posted | Median | Full Range | Joints | At Week 52 and Month 36/End of Study |
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| Secondary | 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. | The modified-intent-to-treat population includes all randomized participants who received at least one dose of assigned study drug and met entry criteria, and who have available data at the time point. | Posted | Median | Full Range | units | Baseline, Week 52 (End of Treatment), Month 36/End of Study |
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| Secondary | 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. | The modified-intent-to-treat population includes all randomized participants who received at least one dose of assigned study drug and met entry criteria, and who have available data at the time point. | Posted | Median | Full Range | U/mL | Baseline, Week 52 (End of Treatment), Month 36/End of Study |
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| Secondary | 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. | The modified-intent-to-treat population includes all randomized participants who received at least one dose of assigned study drug and met entry criteria, and who have available data at the time point. | Posted | Median | Full Range | mg/L | Baseline, Week 52 (End of Treatment), Month 36/End of Study |
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| Secondary | 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. | The safety population includes all participants for whom study treatment was initiated. | Posted | Number | Percent of Participants | Non-serious AEs were collected from treatment initiation through month 18. Serious AEs were collected from screening through month 36. |
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Grade 2 or higher treatment-emergent adverse events were collected from the time of administration of the first dose of study drug (HCQ/placebo) until Month 18 or until 30 days after the participant prematurely withdrew (without withdrawing consent) or was withdrawn from the study, whichever occurred first. Serious adverse events were collected from the time of administration of the first dose of study drug until Month 36.
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| ID | Title | Description | Deaths (Affected) | Deaths (At Risk) | Serious Events (Affected) | Serious Events (At Risk) | Other Events (Affected) | Other Events (At Risk) |
|---|---|---|---|---|---|---|---|---|
| EG000 | Hydroxychloroquine | Participants self-administered 1-2 200 mg HCQ pills per day, based on ideal body weight at screening, from the Baseline visit to Week 52. | 1 | 71 | 5 | 71 | 25 | 71 |
| EG001 | Placebo | Participants self-administered 1-2 placebo pills per day, based on ideal body weight at screening, from the Baseline visit to Week 52. | 0 | 73 | 5 | 73 | 31 | 73 |
| Term | Organ System | Source Vocabulary | Assessment Type | Notes | Statistical Information |
|---|---|---|---|---|---|
| Myocardial infarction | Cardiac disorders | 23.0 | Systematic Assessment |
| |
| Goitre | Endocrine disorders | 23.0 | Systematic Assessment |
| |
| Gastrointestinal haemorrhage | Gastrointestinal disorders | 23.0 | Systematic Assessment |
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| Autoimmune hepatitis | Hepatobiliary disorders | 23.0 | Systematic Assessment |
| |
| Osteomyelitis | Infections and infestations | 23.0 | Systematic Assessment |
| |
| Foot fracture | Injury, poisoning and procedural complications | 23.0 | Systematic Assessment |
| |
| Colon cancer | Neoplasms benign, malignant and unspecified (incl cysts and polyps) | 23.0 | Systematic Assessment |
| |
| Desmoid tumour | Neoplasms benign, malignant and unspecified (incl cysts and polyps) | 23.0 | Systematic Assessment |
| |
| Cerebrovascular accident | Nervous system disorders | 23.0 | Systematic Assessment |
| |
| Suicidal ideation | Psychiatric disorders | 23.0 | Systematic Assessment |
| |
| Peripheral ischaemia | Vascular disorders | 23.0 | Systematic Assessment |
|
| Term | Organ System | Source Vocabulary | Assessment Type | Notes | Statistical Information |
|---|---|---|---|---|---|
| Sinusitis | Infections and infestations | 23.0 | Systematic Assessment |
| |
| Upper respiratory tract infection | Infections and infestations | 23.0 | Systematic Assessment |
| |
| Urinary tract infection | Infections and infestations | 23.0 | Systematic Assessment |
| |
| Rheumatoid arthritis | Musculoskeletal and connective tissue disorders | 23.0 | Systematic Assessment |
| |
| Hypertension | Vascular disorders | 23.0 | Systematic Assessment |
|
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.
Not provided
Not provided
| Title | Organization | Phone | Extension | |
|---|---|---|---|---|
| Director, Clinical Research Operations Program | DAIT/NIAID | 301-594-7669 | DAITClinicalTrialsGov@niaid.nih.gov |
| Prot_002.pdf |
| SAP | No | Yes | No | Statistical Analysis Plan | May 8, 2023 | May 16, 2025 | SAP_003.pdf |
| ID | Term |
|---|---|
| D001172 | Arthritis, Rheumatoid |
| ID | Term |
|---|---|
| D001168 | Arthritis |
| D007592 | Joint Diseases |
| D009140 | Musculoskeletal Diseases |
| D012216 | Rheumatic Diseases |
| D003240 | Connective Tissue Diseases |
| D017437 | Skin and Connective Tissue Diseases |
| D001327 | Autoimmune Diseases |
| D007154 | Immune System Diseases |
Not provided
Not provided
| ID | Term |
|---|---|
| D006886 | Hydroxychloroquine |
| ID | Term |
|---|---|
| D002738 | Chloroquine |
| D000634 | Aminoquinolines |
| D011804 | Quinolines |
| D006574 | Heterocyclic Compounds, 2-Ring |
| D000072471 | Heterocyclic Compounds, Fused-Ring |
| D006571 | Heterocyclic Compounds |
Not provided
Not provided
| >=65 years |
|
| Male |
|
| Not Hispanic or Latino |
|
| Unknown or Not Reported |
|
| Asian |
|
| Native Hawaiian or Other Pacific Islander |
|
| Black or African American |
|
| White |
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| More than one race |
|
| Unknown or Not Reported |
|
| Cumulative Probability |
| 0.394 |
| 2-Sided |
| 95 |
| 0.268 |
| 0.519 |
Using Kaplan-Meier product-limit method (and Greenwood's formula for confidence interval), estimated the cumulative probability of development of CL-RA by Month 36 for Placebo. |
| Other |
| Chi-squared | 0.522 | The test statistic is a Wald-type chi-square statistic derived by dividing the difference of the logit-transformed KM survival estimates for each arm by the associated variance derived using the delta-method [Klein, et. al. 2007]. | Risk Difference (RD) | -0.058 | 2-Sided | 95 | -0.336 | 0.220 | Risk difference for HCQ - Placebo | Superiority | The analysis is based on the KM estimated risk of CL- RA at 36 months, where risk = (1-KM estimated probability of "survival"). Survival for this analysis is defined as absence of CL-RA. Estimated risks were derived from a Kaplan-Meier curve using censored time-to-event data to account for attrition under the assumption of non-informative censoring. |
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