Trial Outcomes & Findings for Strategy to Prevent the Onset of Clinically-Apparent Rheumatoid Arthritis (NCT NCT02603146)

NCT ID: NCT02603146

Last Updated: 2025-06-12

Results Overview

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.

• Recruitment status: TERMINATED
• Study phase: PHASE2
• Target enrollment: 144 participants
• Primary outcome timeframe: Baseline to Month 36
• Results posted on: 2025-06-12

Participant Flow

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.

Participant milestones

Measure	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.	Placebo Participants self-administered 1-2 placebo pills per day, based on ideal body weight at screening, from the Baseline visit to Week 52.
Overall Study STARTED	71	73
Overall Study COMPLETED	40	39
Overall Study NOT COMPLETED	31	34

Reasons for withdrawal

Measure	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.	Placebo Participants self-administered 1-2 placebo pills per day, based on ideal body weight at screening, from the Baseline visit to Week 52.
Overall Study Lost to Follow-up	5	6
Overall Study Withdrawal by Subject	8	10
Overall Study Withdrawn by Investigator or NIAID	15	18
Overall Study Participant moved	2	0
Overall Study Participant could not complete the Month 36 visit due to COVID-19	1	0

Baseline Characteristics

Strategy to Prevent the Onset of Clinically-Apparent Rheumatoid Arthritis

Baseline characteristics by cohort

Measure	Hydroxychloroquine n=71 Participants 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.	Placebo n=73 Participants Participants self-administered 1-2 placebo pills per day, based on ideal body weight at screening, from the Baseline visit to Week 52.	Total n=144 Participants Total of all reporting groups
Age, Categorical <=18 years	0 Participants n=5 Participants	0 Participants n=7 Participants	0 Participants n=5 Participants
Age, Categorical Between 18 and 65 years	59 Participants n=5 Participants	61 Participants n=7 Participants	120 Participants n=5 Participants
Age, Categorical >=65 years	12 Participants n=5 Participants	12 Participants n=7 Participants	24 Participants n=5 Participants
Age, Continuous	51.7 years STANDARD_DEVIATION 12.31 • n=5 Participants	49.3 years STANDARD_DEVIATION 14.39 • n=7 Participants	50.5 years STANDARD_DEVIATION 13.41 • n=5 Participants
Sex: Female, Male Female	57 Participants n=5 Participants	58 Participants n=7 Participants	115 Participants n=5 Participants
Sex: Female, Male Male	14 Participants n=5 Participants	15 Participants n=7 Participants	29 Participants n=5 Participants
Ethnicity (NIH/OMB) Hispanic or Latino	15 Participants n=5 Participants	8 Participants n=7 Participants	23 Participants n=5 Participants
Ethnicity (NIH/OMB) Not Hispanic or Latino	55 Participants n=5 Participants	64 Participants n=7 Participants	119 Participants n=5 Participants
Ethnicity (NIH/OMB) Unknown or Not Reported	1 Participants n=5 Participants	1 Participants n=7 Participants	2 Participants n=5 Participants
Race (NIH/OMB) American Indian or Alaska Native	2 Participants n=5 Participants	3 Participants n=7 Participants	5 Participants n=5 Participants
Race (NIH/OMB) Asian	1 Participants n=5 Participants	3 Participants n=7 Participants	4 Participants n=5 Participants
Race (NIH/OMB) Native Hawaiian or Other Pacific Islander	0 Participants n=5 Participants	0 Participants n=7 Participants	0 Participants n=5 Participants
Race (NIH/OMB) Black or African American	8 Participants n=5 Participants	6 Participants n=7 Participants	14 Participants n=5 Participants
Race (NIH/OMB) White	53 Participants n=5 Participants	55 Participants n=7 Participants	108 Participants n=5 Participants
Race (NIH/OMB) More than one race	3 Participants n=5 Participants	4 Participants n=7 Participants	7 Participants n=5 Participants
Race (NIH/OMB) Unknown or Not Reported	4 Participants n=5 Participants	2 Participants n=7 Participants	6 Participants n=5 Participants
Region of Enrollment United States	71 participants n=5 Participants	73 participants n=7 Participants	144 participants n=5 Participants
Anti-Cyclic Citrullinated Peptide-3 (Anti-CCP3)	173.2 units STANDARD_DEVIATION 86.01 • n=5 Participants	147.4 units STANDARD_DEVIATION 86.42 • n=7 Participants	160.1 units STANDARD_DEVIATION 86.89 • n=5 Participants

PRIMARY outcome

Timeframe: Baseline to Month 36

Population: The modified-intent-to-treat population includes all randomized participants who received at least one dose of assigned study drug and met entry criteria.

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.

Outcome measures

Measure	Hydroxychloroquine n=69 Participants 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.	Placebo n=73 Participants Participants self-administered 1-2 placebo pills per day, based on ideal body weight at screening, from the Baseline visit to Week 52.
Number of Participants Who Developed Clinically-Apparent Rheumatoid Arthritis (CL - RA) From Treatment Initiation to Month 36 By Treatment Arm	20 Participants	24 Participants

SECONDARY outcome

Timeframe: Baseline to Month 12

Population: The modified-intent-to-treat population includes all randomized participants who received at least one dose of assigned study drug and met entry criteria.

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.

Outcome measures

Measure	Hydroxychloroquine n=69 Participants 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.	Placebo n=73 Participants Participants self-administered 1-2 placebo pills per day, based on ideal body weight at screening, from the Baseline visit to Week 52.
Number of Participants Who Developed Clinically-Apparent Rheumatoid Arthritis (CL-RA) From Treatment Initiation to Month 12 By Treatment Arm	11 Participants	13 Participants

SECONDARY outcome

Timeframe: Baseline to Month 12

Population: The modified-intent-to-treat population includes all randomized participants who received at least one dose of assigned study drug and met entry criteria.

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.

Outcome measures

Measure	Hydroxychloroquine n=69 Participants 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.	Placebo n=73 Participants Participants self-administered 1-2 placebo pills per day, based on ideal body weight at screening, from the Baseline visit to Week 52.
Number of Participants Who Developed Inflammatory Arthritis (IA) From Treatment Initiation to Month 12.	12 Participants	13 Participants

SECONDARY outcome

Timeframe: Baseline to Month 36

Population: The modified-intent-to-treat population includes all randomized participants who received at least one dose of assigned study drug and met entry criteria.

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.

Outcome measures

Measure	Hydroxychloroquine n=69 Participants 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.	Placebo n=73 Participants Participants self-administered 1-2 placebo pills per day, based on ideal body weight at screening, from the Baseline visit to Week 52.
Time to Development of Clinically-Apparent Rheumatoid Arthritis (CL - RA) By Treatment Arm	29.02 months Interval 25.84 to 32.21	28.49 months Interval 25.4 to 31.58

SECONDARY outcome

Timeframe: Baseline to Month 36

Population: The modified-intent-to-treat population includes all randomized participants who received at least one dose of assigned study drug and met entry criteria.

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.

Outcome measures

Measure	Hydroxychloroquine n=69 Participants 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.	Placebo n=73 Participants Participants self-administered 1-2 placebo pills per day, based on ideal body weight at screening, from the Baseline visit to Week 52.
Number of Participants Who Developed Inflammatory Arthritis (IA) From Treatment Initiation to Month 36	21 Participants	27 Participants

SECONDARY outcome

Timeframe: At Week 52 and Month 36/End of Study

Population: 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.

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.

Outcome measures

Measure	Hydroxychloroquine n=69 Participants 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.	Placebo n=73 Participants Participants self-administered 1-2 placebo pills per day, based on ideal body weight at screening, from the Baseline visit to Week 52.
Number of Participant Self-Reported Painful Joints By Treatment Arm Week 52	1.0 joints Interval 0.0 to 23.0	1.0 joints Interval 0.0 to 38.0
Number of Participant Self-Reported Painful Joints By Treatment Arm Month 36	1.0 joints Interval 0.0 to 13.0	2.0 joints Interval 0.0 to 36.0

SECONDARY outcome

Timeframe: At Week 52 and Month 36/End of Study

Population: 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.

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.

Outcome measures

Measure	Hydroxychloroquine n=69 Participants 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.	Placebo n=73 Participants Participants self-administered 1-2 placebo pills per day, based on ideal body weight at screening, from the Baseline visit to Week 52.
Number of Participant Self-Reported Stiff Joints By Treatment Arm Week 52	1.0 Joints Interval 0.0 to 32.0	1.0 Joints Interval 0.0 to 42.0
Number of Participant Self-Reported Stiff Joints By Treatment Arm Month 36	0.0 Joints Interval 0.0 to 32.0	1.0 Joints Interval 0.0 to 20.0

SECONDARY outcome

Timeframe: At Week 52 and Month 36/End of Study

Population: 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.

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.

Outcome measures

Measure	Hydroxychloroquine n=69 Participants 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.	Placebo n=73 Participants Participants self-administered 1-2 placebo pills per day, based on ideal body weight at screening, from the Baseline visit to Week 52.
Number of Participant Self-Reported Swollen Joints By Treatment Arm Week 52	0.0 Joints Interval 0.0 to 8.0	0.0 Joints Interval 0.0 to 23.0
Number of Participant Self-Reported Swollen Joints By Treatment Arm Month 36	0.0 Joints Interval 0.0 to 3.0	0.0 Joints Interval 0.0 to 24.0

SECONDARY outcome

Timeframe: At Week 52 and Month 36/End of Study

Population: 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.

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.

Outcome measures

Measure	Hydroxychloroquine n=69 Participants 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.	Placebo n=73 Participants Participants self-administered 1-2 placebo pills per day, based on ideal body weight at screening, from the Baseline visit to Week 52.
Number of Participant Self-Reported Painful Joints in the Hands, Wrists and Feet By Treatment Arm Week 52	0.0 Joints Interval 0.0 to 21.0	0.0 Joints Interval 0.0 to 32.0
Number of Participant Self-Reported Painful Joints in the Hands, Wrists and Feet By Treatment Arm Month 36	0.0 Joints Interval 0.0 to 11.0	0.0 Joints Interval 0.0 to 30.0

SECONDARY outcome

Timeframe: At Week 52 and Month 36/End of Study

Population: 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.

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.

Outcome measures

Measure	Hydroxychloroquine n=69 Participants 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.	Placebo n=73 Participants Participants self-administered 1-2 placebo pills per day, based on ideal body weight at screening, from the Baseline visit to Week 52.
Number of Participant Self-Reported Stiff Joints in the Hands, Wrists and Feet By Treatment Arm Week 52 results	0.0 Joints Interval 0.0 to 22.0	0.0 Joints Interval 0.0 to 32.0
Number of Participant Self-Reported Stiff Joints in the Hands, Wrists and Feet By Treatment Arm Month 36 results	0.0 Joints Interval 0.0 to 22.0	12 Joints Interval 0.0 to 20.0

SECONDARY outcome

Timeframe: At Week 52 and Month 36/End of Study

Population: 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.

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.

Outcome measures

Measure	Hydroxychloroquine n=69 Participants 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.	Placebo n=73 Participants Participants self-administered 1-2 placebo pills per day, based on ideal body weight at screening, from the Baseline visit to Week 52.
Number of Participant Self-Reported Swollen Joints in the Hands, Wrists and Feet By Treatment Arm Week 52	0.0 Joints Interval 0.0 to 8.0	0.0 Joints Interval 0.0 to 21.0
Number of Participant Self-Reported Swollen Joints in the Hands, Wrists and Feet By Treatment Arm Month 36	0.0 Joints Interval 0.0 to 3.0	0.0 Joints Interval 0.0 to 22.0

SECONDARY outcome

Timeframe: Baseline, Week 52 (End of Treatment), Month 36/End of Study

Population: 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.

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.

Outcome measures

Measure	Hydroxychloroquine n=69 Participants 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.	Placebo n=73 Participants Participants self-administered 1-2 placebo pills per day, based on ideal body weight at screening, from the Baseline visit to Week 52.
Level of Anti-Cyclic Citrullinated Peptide-3 (Anti-CCP3) By Treatment Arm Baseline	184.20 units Interval 24.3 to 261.7	125.55 units Interval 28.4 to 261.7
Level of Anti-Cyclic Citrullinated Peptide-3 (Anti-CCP3) By Treatment Arm Week 52	105.65 units Interval 19.6 to 261.7	94.4 units Interval 17.9 to 261.7
Level of Anti-Cyclic Citrullinated Peptide-3 (Anti-CCP3) By Treatment Arm Month 36	154.75 units Interval 15.2 to 261.7	85.20 units Interval 9.0 to 261.7

SECONDARY outcome

Timeframe: Baseline, Week 52 (End of Treatment), Month 36/End of Study

Population: 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.

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.

Outcome measures

Measure	Hydroxychloroquine n=69 Participants 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.	Placebo n=73 Participants Participants self-administered 1-2 placebo pills per day, based on ideal body weight at screening, from the Baseline visit to Week 52.
Level of Immunoglobulin M - Rheumatoid Factor (IgM-RF) By Treatment Arm Baseline	13.100 U/mL Interval 0.25 to 104.75	5.350 U/mL Interval 0.14 to 104.75
Level of Immunoglobulin M - Rheumatoid Factor (IgM-RF) By Treatment Arm Week 52	3.600 U/mL Interval 0.25 to 104.75	2.025 U/mL Interval 0.25 to 104.75
Level of Immunoglobulin M - Rheumatoid Factor (IgM-RF) By Treatment Arm Month 36	5.730 U/mL Interval 0.25 to 104.75	0.250 U/mL Interval 0.25 to 104.75

SECONDARY outcome

Timeframe: Baseline, Week 52 (End of Treatment), Month 36/End of Study

Population: 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.

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.

Outcome measures

Measure	Hydroxychloroquine n=69 Participants 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.	Placebo n=73 Participants Participants self-administered 1-2 placebo pills per day, based on ideal body weight at screening, from the Baseline visit to Week 52.
Level of High-Sensitivity C-Reactive Protein (hsCRP) Treatment Arm Baseline	2.030 mg/L Interval 0.21 to 40.4	3.043 mg/L Interval 0.13 to 43.7
Level of High-Sensitivity C-Reactive Protein (hsCRP) Treatment Arm Week 52	2.300 mg/L Interval 0.2 to 56.3	1.430 mg/L Interval 0.21 to 55.7
Level of High-Sensitivity C-Reactive Protein (hsCRP) Treatment Arm Month 36	2.075 mg/L Interval 0.2 to 22.75	1.645 mg/L Interval 0.27 to 29.5

SECONDARY outcome

Timeframe: Non-serious AEs were collected from treatment initiation through month 18. Serious AEs were collected from screening through month 36.

Population: The safety population includes all participants for whom study treatment was initiated.

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.

Outcome measures

Measure	Hydroxychloroquine n=69 Participants 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.	Placebo n=73 Participants Participants self-administered 1-2 placebo pills per day, based on ideal body weight at screening, from the Baseline visit to Week 52.
Percent of Participants Experiencing Grade 3 or Higher Adverse Events (AEs)	14.1 Percent of Participants	12.3 Percent of Participants

Adverse Events

Hydroxychloroquine

Serious events: 5 serious events

Other events: 25 other events

Deaths: 1 deaths

Placebo

Serious events: 5 serious events

Other events: 31 other events

Deaths: 0 deaths

Serious adverse events

Measure	Hydroxychloroquine n=71 participants at risk 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.	Placebo n=73 participants at risk Participants self-administered 1-2 placebo pills per day, based on ideal body weight at screening, from the Baseline visit to Week 52.
Cardiac disorders Myocardial infarction	1.4% 1/71 • Number of events 1 • 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.	1.4% 1/73 • Number of events 1 • 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.
Endocrine disorders Goitre	0.00% 0/71 • 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.	1.4% 1/73 • Number of events 1 • 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.
Gastrointestinal disorders Gastrointestinal haemorrhage	1.4% 1/71 • Number of events 1 • 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.	0.00% 0/73 • 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.
Hepatobiliary disorders Autoimmune hepatitis	1.4% 1/71 • Number of events 1 • 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.	0.00% 0/73 • 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.
Infections and infestations Osteomyelitis	0.00% 0/71 • 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.	1.4% 1/73 • Number of events 1 • 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.
Injury, poisoning and procedural complications Foot fracture	1.4% 1/71 • Number of events 1 • 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.	0.00% 0/73 • 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.
Neoplasms benign, malignant and unspecified (incl cysts and polyps) Colon cancer	1.4% 1/71 • Number of events 1 • 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.	0.00% 0/73 • 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.
Neoplasms benign, malignant and unspecified (incl cysts and polyps) Desmoid tumour	1.4% 1/71 • Number of events 1 • 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.	0.00% 0/73 • 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.
Nervous system disorders Cerebrovascular accident	0.00% 0/71 • 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.	1.4% 1/73 • Number of events 1 • 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.
Psychiatric disorders Suicidal ideation	0.00% 0/71 • 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.	1.4% 1/73 • Number of events 1 • 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.
Vascular disorders Peripheral ischaemia	1.4% 1/71 • Number of events 1 • 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.	0.00% 0/73 • 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.

Other adverse events

Measure	Hydroxychloroquine n=71 participants at risk 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.	Placebo n=73 participants at risk Participants self-administered 1-2 placebo pills per day, based on ideal body weight at screening, from the Baseline visit to Week 52.
Infections and infestations Sinusitis	1.4% 1/71 • Number of events 1 • 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.	6.8% 5/73 • Number of events 6 • 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.
Infections and infestations Upper respiratory tract infection	1.4% 1/71 • Number of events 1 • 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.	5.5% 4/73 • Number of events 5 • 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.
Infections and infestations Urinary tract infection	7.0% 5/71 • Number of events 6 • 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.	2.7% 2/73 • Number of events 2 • 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.
Musculoskeletal and connective tissue disorders Rheumatoid arthritis	22.5% 16/71 • Number of events 16 • 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.	26.0% 19/73 • Number of events 19 • 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.
Vascular disorders Hypertension	9.9% 7/71 • Number of events 7 • 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.	8.2% 6/73 • Number of events 6 • 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.

Additional Information

Director, Clinical Research Operations Program

DAIT/NIAID

Phone: 301-594-7669

Email: DAITClinicalTrialsGov@niaid.nih.gov

Results disclosure agreements

• Principal investigator is a sponsor employee
• Publication restrictions are in place