Strategy to Prevent the Onset of Clinically-Apparent Rheumatoid Arthritis

• Register: ClinicalTrials.gov
• Last refreshed on: 25 July 2023
• Main ID: NCT02603146
• Date of registration: 10/11/2015
• Prospective Registration: Yes
• Primary sponsor: National Institute of Allergy and Infectious Diseases (NIAID)
• Public title: Strategy to Prevent the Onset of Clinically-Apparent Rheumatoid Arthritis StopRA
• Scientific title: Strategy to Prevent the Onset of Clinically-Apparent Rheumatoid Arthritis
• Date of first enrolment: April 27, 2016
• Target sample size: 144
• Recruitment status: Completed
• URL: https://clinicaltrials.gov/ct2/show/NCT02603146
• Study type: Interventional
• Study design: Allocation: Randomized. Intervention model: Parallel Assignment. Primary purpose: Prevention. Masking: Double (Participant, Investigator).
• Phase: Phase 2

Countries of recruitment

United States

Contacts

• Name: Michael Holers, MD
• Affiliation: University of Colorado School of Medicine

• Name: Christopher Striebich, MD, PhD
• Affiliation: University of Colorado School of Medicine

• Name: Kevin Deane, MD, PhD
• Affiliation: University of Colorado School of Medicine

Key inclusion & exclusion criteria

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:

-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);

- 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.



Age minimum: 18 Years
Age maximum: N/A
Gender: All

Health Condition(s) or Problem(s) studied

Healthy Participants

Rheumatoid Arthritis (RA) Prevention

Intervention(s)

Drug: HCQ Placebo

Drug: Hydroxychloroquine

Primary Outcome(s)

Number of Participants Who Developed Clinically-Apparent Rheumatoid Arthritis (RA) From Treatment Initiation to Month 36 By Treatment Arm [Time Frame: Up to Month 36]

Secondary Outcome(s)

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 By Treatment Arm [Time Frame: At Week 52 and Month 36/End of Study]

Median Level of Anti-Cyclic Citrullinated Peptide-3 (Anti-CCP3) By Treatment Arm [Time Frame: Baseline, Week 24, Week 52 (End of Treatment), Month 18, Month 24, Month 36/End of Study]

Number of Participant Self-Reported Painful Joints By Treatment Arm [Time Frame: At Week 52 and Month 36/End of Study]

Number of Participants Who Developed Inflammatory Arthritis (IA) From Treatment Initiation to Month 12 by Treatment Arm [Time Frame: Up to Month 12]

Median Level of Immunoglobulin M - Rheumatoid Factor (IgM-RF) By Treatment Arm [Time Frame: Baseline, Week 24, Week 52 (End of Treatment), Month 18, Month 24, Month 36/End of Study]

Median Time to Development of Clinically-Apparent Rheumatoid Arthritis (RA) By Treatment Arm [Time Frame: Up to Month 36]

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]

Number of Participants Who Developed Inflammatory Arthritis (IA) From Treatment Initiation to Month 36 by Treatment Arm [Time Frame: Up to Month 36]

Number of Participant Self-Reported Stiff Joints By Treatment Arm [Time Frame: At Week 52 and Month 36/End of Study]

Median Level of High-Sensitivity C-Reactive Protein (hsCRP) Treatment Arm [Time Frame: Baseline, Week 24, Week 52 (End of Treatment), Month 18, Month 24, 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]

Percent of Participants Experiencing Grade 3 or Higher Adverse Events (AEs) [Time Frame: Treatment Initiation (Day 0) through Month 36]

Number of Participants Who Developed Clinically-Apparent Rheumatoid Arthritis (RA) From Treatment Initiation to Month 12 By Treatment Arm [Time Frame: Up to Month 12]

Secondary ID(s)

DAIT ARA08

NIAID CRMS ID#: 20681

Source(s) of Monetary Support

Please refer to primary and secondary sponsors

Secondary Sponsor(s)

Autoimmunity Centers of Excellence