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Trial record 1 of 1 for:    ARA08
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Strategy to Prevent the Onset of Clinically-Apparent Rheumatoid Arthritis (StopRA)

The safety and scientific validity of this study is the responsibility of the study sponsor and investigators. Listing a study does not mean it has been evaluated by the U.S. Federal Government. Know the risks and potential benefits of clinical studies and talk to your health care provider before participating. Read our disclaimer for details.
 
ClinicalTrials.gov Identifier: NCT02603146
Recruitment Status : Recruiting
First Posted : November 11, 2015
Last Update Posted : April 1, 2020
Sponsor:
Collaborator:
Autoimmunity Centers of Excellence
Information provided by (Responsible Party):
National Institute of Allergy and Infectious Diseases (NIAID)

Tracking Information
First Submitted Date  ICMJE November 10, 2015
First Posted Date  ICMJE November 11, 2015
Last Update Posted Date April 1, 2020
Actual Study Start Date  ICMJE April 27, 2016
Estimated Primary Completion Date November 2023   (Final data collection date for primary outcome measure)
Current Primary Outcome Measures  ICMJE
 (submitted: November 10, 2015)
Number of Subjects With Clinically-Apparent Rheumatoid Arthritis (RA) By Month 36 [ Time Frame: 36-months post initiation of study treatment ]
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.
Original Primary Outcome Measures  ICMJE Same as current
Change History
Current Secondary Outcome Measures  ICMJE
 (submitted: November 10, 2015)
  • Proportion of Subjects Experiencing Grade 3 or Higher Adverse Events (AEs) [ Time Frame: From treatment initiation (Day 0) through Study Completion (Month 36) ]
    Reference: National Cancer Institute- Common Terminology Criteria for Adverse Events (NCI-CTCAE), Version 4.0, url http://ctep.cancer.gov/reporting/ctc.html.
  • Number of Subjects With Clinically-Apparent RA By Month 12 Post Treatment Initiation [ Time Frame: From treatment initiation (Day 0) to 12-months post treatment initiation ]
    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.
  • Number of Subjects With Clinically-Apparent Inflammatory Arthritis (IA) By Month 36 Post Treatment Initiation [ Time Frame: 36-months post study treatment initiation ]
    Defined as the presence of a swollen joint(s) consistent with RA-like synovitis, in the determination of the examiner, and graded as present (1) or absent (0). these findings.
  • Number of Subjects With Clinically-Apparent RA By Month 36 Post Treatment Initiation [ Time Frame: 36-months post study initiation ]
    Reference: 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.
  • Number of Subjects With Clinically-Apparent Inflammatory Arthritis (IA) By Month 12 Post Treatment Initiation [ Time Frame: 12-months post initiation of study treatment ]
    Defined as the presence of a swollen joint(s) consistent with RA-like synovitis, in the determination of the examiner, and graded as present (1) or absent (0).
  • Change in RA Disease Activity Defined by Joint Pain, Stiffness and Swelling and Overall Fatigue [ Time Frame: Day 0 (Pre-treatment) through Week 52 ]
    Rheumatoid arthritis disease activity will be evaluated over time using multiple indices:
    • Physician assessed tender joint count;
    • Physician assessed swollen joint count;
    • Disease Activity Score Calculator for Rheumatoid Arthritis (DAS28-CRP) score;
    • Clinical Disease Activity Index (CDAI); and
    • Routine Assessment of Patient Index Data 3 (RAPID-3).
    • Physician assessed tender joint count
    • Physician assessed swollen joint count
    • Disease Activity Score Calculator for Rheumatoid Arthritis (DAS28-CRP) score
    • Clinical Disease Activity Index (CDAI)
    • Routine Assessment of Patient Index Data 3 (RAPID-3)
  • Change in RA Disease Activity Defined by Joint Pain, Stiffness and Swelling and Overall Fatigue [ Time Frame: Week 52 (Month 12) through Week 156 (Month 36) ]
    Rheumatoid arthritis disease activity will be evaluated over time using multiple indices:
    • Physician assessed tender joint count;
    • Physician assessed swollen joint count;
    • Disease Activity Score Calculator for Rheumatoid Arthritis (DAS28-CRP) score;
    • Clinical Disease Activity Index (CDAI); and
    • Routine Assessment of Patient Index Data 3 (RAPID-3).
    • Physician assessed tender joint count
    • Physician assessed swollen joint count
    • Disease Activity Score Calculator for Rheumatoid Arthritis (DAS28-CRP) score
    • Clinical Disease Activity Index (CDAI)
    • Routine Assessment of Patient Index Data 3 (RAPID-3).
  • Change in Self- Reported Physical, Mental and Social Health Quality of Life Measures [ Time Frame: Day 0 (Baseline) through Week 52 ]
    Reference: NIH Patient-reported Outcomes Measurement Information System (PROMIS) instrument Profile 29 v2.0).
  • Change in Self- Reported Physical, Mental and Social Health Quality of Life Measures [ Time Frame: Week 52 through Week 156 (Month 36) ]
    Reference: NIH Patient-reported Outcomes Measurement Information System (PROMIS) instrument Profile 29 v2.0).
Original Secondary Outcome Measures  ICMJE Same as current
Current Other Pre-specified Outcome Measures Not Provided
Original Other Pre-specified Outcome Measures Not Provided
 
Descriptive Information
Brief Title  ICMJE Strategy to Prevent the Onset of Clinically-Apparent Rheumatoid Arthritis
Official Title  ICMJE Strategy to Prevent the Onset of Clinically-Apparent Rheumatoid Arthritis
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.
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 Type  ICMJE Interventional
Study Phase  ICMJE Phase 2
Study Design  ICMJE Allocation: Randomized
Intervention Model: Parallel Assignment
Masking: Double (Participant, Investigator)
Primary Purpose: Prevention
Condition  ICMJE
  • Healthy Participants
  • Rheumatoid Arthritis (RA) Prevention
Intervention  ICMJE
  • Drug: Hydroxychloroquine
    As described. Dosing will be based upon Screening IBW.
    Other Names:
    • HCQ
    • Plaquenil
  • Drug: HCQ Placebo
    As described. Dosing will be based upon Screening IBW.
    Other Name: Placebo
Study Arms  ICMJE
  • Experimental: Hydroxychloroquine Group
    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.
    Intervention: Drug: Hydroxychloroquine
  • Placebo Comparator: Placebo Group
    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.
    Intervention: Drug: HCQ Placebo
Publications * Not Provided

*   Includes publications given by the data provider as well as publications identified by ClinicalTrials.gov Identifier (NCT Number) in Medline.
 
Recruitment Information
Recruitment Status  ICMJE Recruiting
Estimated Enrollment  ICMJE
 (submitted: November 10, 2015)
200
Original Estimated Enrollment  ICMJE Same as current
Estimated Study Completion Date  ICMJE November 2023
Estimated Primary Completion Date November 2023   (Final data collection date for primary outcome measure)
Eligibility Criteria  ICMJE

Inclusion Criteria:

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.

Exclusion Criteria:

Subjects who meet any of the following criteria are ineligible to participate in the study:

  • Evidence of significant retinal disease that, in the opinion of the examiner, would make identification of potential future retinal toxicity from hydroxychloroquine difficult to evaluate;
  • 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.

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);
    • INR ≥ 1.25 if not currently taking anticoagulation therapy;
    • 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.
Sex/Gender  ICMJE
Sexes Eligible for Study: All
Ages  ICMJE 18 Years and older   (Adult, Older Adult)
Accepts Healthy Volunteers  ICMJE Yes
Contacts  ICMJE
Listed Location Countries  ICMJE United States
Removed Location Countries  
 
Administrative Information
NCT Number  ICMJE NCT02603146
Other Study ID Numbers  ICMJE DAIT ARA08
NIAID CRMS ID#: 20681 ( Other Identifier: DAIT NIAID )
Has Data Monitoring Committee Yes
U.S. FDA-regulated Product Not Provided
IPD Sharing Statement  ICMJE
Plan to Share IPD: Yes
Plan Description: 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.
Time Frame: After completion of the study.
Access Criteria: When posted, the IPD will be available to the public.
URL: http://www.immport.org/
Responsible Party National Institute of Allergy and Infectious Diseases (NIAID)
Study Sponsor  ICMJE National Institute of Allergy and Infectious Diseases (NIAID)
Collaborators  ICMJE Autoimmunity Centers of Excellence
Investigators  ICMJE
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
PRS Account National Institute of Allergy and Infectious Diseases (NIAID)
Verification Date March 2020

ICMJE     Data element required by the International Committee of Medical Journal Editors and the World Health Organization ICTRP