Trial Outcomes & Findings for Will Hydroxychloroquine Impede or Prevent COVID-19 (NCT NCT04341441)

NCT ID: NCT04341441

Last Updated: 2022-06-21

Results Overview

The rate of acquisition of SARS-CoV 2 infections and clinical COVID-19 disease (number of events) in study participants for each randomized hydroxychloroquine treatment arm was compared to the placebo treatment arm. This included both symptomatic and asymptomatic patients.

• Recruitment status: TERMINATED
• Study phase: PHASE3
• Target enrollment: 624 participants
• Primary outcome timeframe: 8 Weeks
• Results posted on: 2022-06-21

Participant Flow

Participant milestones

Measure	Study Drug - Daily Dose 200 mg oral dose daily following day 1 dose of 400 mg orally once. This dose represents approximately half the standard weight-based dosing recommended for management of autoimmune diseases and therefore less likely to produce side effects than standard of care. All treatment groups will receive placebo pills to have the patients take 2 pills a day.	Study Drug - Weekly Dose 6.5 mg/kg per dose (maximum of 400mg per dose) administered orally weekly on the same day of each week. This is based on the recommended dose for prophylaxis of malaria. All treatment groups will receive placebo pills to have the patients take 2 pills a day.	Placebo Placebo oral tablet: Participants randomized to this arm will be provided with daily dosing of oral placebo to have the patients take 2 pills a day. All treatment groups will receive placebo pills to have the patients take 2 pills a day. The randomized placebo arm will receive placebo pills made to resemble the daily dosing of HCQ. Similarly, the once a week treatment arm will receive placebo pills for the days not on HCQ medication.	Non-Randomized Active Comparator (HCQ Cohort) This non-randomized comparator group is comprised of healthcare workers and first responders who are chronically on oral hydroxychloroquine as part of standard of care for autoimmune disease(s).
Overall Study STARTED	197	201	200	26
Overall Study COMPLETED	188	199	191	26
Overall Study NOT COMPLETED	9	2	9	0

Reasons for withdrawal

Withdrawal data not reported

Baseline Characteristics

Will Hydroxychloroquine Impede or Prevent COVID-19

Baseline characteristics by cohort

Measure	Study Drug - Daily Dose n=197 Participants 200 mg oral dose daily following day 1 dose of 400 mg orally once. This dose represents approximately half the standard weight-based dosing recommended for management of autoimmune diseases and therefore less likely to produce side effects than standard of care. All treatment groups will receive placebo pills to have the patients take 2 pills a day.	Study Drug - Weekly Dose n=201 Participants 6.5 mg/kg per dose (maximum of 400mg per dose) administered orally weekly on the same day of each week. This is based on the recommended dose for prophylaxis of malaria. All treatment groups will receive placebo pills to have the patients take 2 pills a day.	Placebo n=200 Participants Placebo oral tablet: Participants randomized to this arm will be provided with daily dosing of oral placebo to have the patients take 2 pills a day. All treatment groups will receive placebo pills to have the patients take 2 pills a day. The randomized placebo arm will receive placebo pills made to resemble the daily dosing of HCQ. Similarly, the once a week treatment arm will receive placebo pills for the days not on HCQ medication.	Non-Randomized Active Comparator n=26 Participants This will be an open enrollment group and will provide information of chronic weight-based daily therapy of HCQ effectiveness as a prophylactic/preventive strategy. This non-randomized comparator group will be enrolled in the study comprising of healthcare workers and first responders who are chronically on oral hydroxychloroquine as part of their standard of care for their autoimmune disease(s).	Total n=624 Participants Total of all reporting groups
Age, Continuous	45.1 years STANDARD_DEVIATION 11.5 • n=93 Participants	45.7 years STANDARD_DEVIATION 11.7 • n=4 Participants	43.7 years STANDARD_DEVIATION 12.7 • n=27 Participants	45.8 years STANDARD_DEVIATION 11.7 • n=483 Participants	44.9 years STANDARD_DEVIATION 12.0 • n=36 Participants
Sex: Female, Male Female	117 Participants n=93 Participants	110 Participants n=4 Participants	120 Participants n=27 Participants	23 Participants n=483 Participants	370 Participants n=36 Participants
Sex: Female, Male Male	80 Participants n=93 Participants	91 Participants n=4 Participants	80 Participants n=27 Participants	3 Participants n=483 Participants	254 Participants n=36 Participants
Race/Ethnicity, Customized Black	11 Participants n=93 Participants	5 Participants n=4 Participants	10 Participants n=27 Participants	6 Participants n=483 Participants	32 Participants n=36 Participants
Race/Ethnicity, Customized White	163 Participants n=93 Participants	179 Participants n=4 Participants	169 Participants n=27 Participants	18 Participants n=483 Participants	529 Participants n=36 Participants
Race/Ethnicity, Customized AS/IN/PI	15 Participants n=93 Participants	10 Participants n=4 Participants	15 Participants n=27 Participants	2 Participants n=483 Participants	42 Participants n=36 Participants
Region of Enrollment United States	197 participants n=93 Participants	201 participants n=4 Participants	200 participants n=27 Participants	26 participants n=483 Participants	624 participants n=36 Participants

PRIMARY outcome

Timeframe: 8 Weeks

The rate of acquisition of SARS-CoV 2 infections and clinical COVID-19 disease (number of events) in study participants for each randomized hydroxychloroquine treatment arm was compared to the placebo treatment arm. This included both symptomatic and asymptomatic patients.

Outcome measures

Measure	Study Drug - Daily Dose n=188 Participants 200 mg oral dose daily following day 1 dose of 400 mg orally once. This dose represents approximately half the standard weight-based dosing recommended for management of autoimmune diseases and therefore less likely to produce side effects than standard of care. All treatment groups will receive placebo pills to have the patients take 2 pills a day.	Study Drug - Weekly Dose n=199 Participants 6.5 mg/kg per dose (maximum of 400mg per dose) administered orally weekly on the same day of each week. This is based on the recommended dose for prophylaxis of malaria. All treatment groups will receive placebo pills to have the patients take 2 pills a day.	Placebo n=191 Participants Placebo oral tablet: Participants randomized to this arm will be provided with daily dosing of oral placebo to have the patients take 2 pills a day. All treatment groups will receive placebo pills to have the patients take 2 pills a day. The randomized placebo arm will receive placebo pills made to resemble the daily dosing of HCQ. Similarly, the once a week treatment arm will receive placebo pills for the days not on HCQ medication.	Non-Randomized Active Comparator n=25 Participants This will be an open enrollment group and will provide information of chronic weight-based daily therapy of HCQ effectiveness as a prophylactic/preventive strategy. This non-randomized comparator group will be enrolled in the study comprising of healthcare workers and first responders who are chronically on oral hydroxychloroquine as part of their standard of care for their autoimmune disease(s).
To Determine if the Use of Hydroxychloroquine as Preventive Therapy Decreases the Rate of Acquisition of SARS-CoV 2 Infections With Clinical COVID-19 Disease in Study Participants for Each Randomized Treatment Arm as Compared to Placebo.	1 Participants	1 Participants	1 Participants	0 Participants

SECONDARY outcome

Timeframe: 8 Weeks

Population: Compare the rates of SARS-CoV 2 symptomatic infections (number of events with both symptoms and positive test for COVID-19) between the randomized hydroxychloroquine treatment arms and the placebo control arm.

Compare the rates of SARS-CoV 2 symptomatic infections (number of events with both symptoms and positive test for COVID-19) between the randomized hydroxychloroquine treatment arms and the placebo control arm to determine the effect of HCQ dose in the prevention of COVID-19 viremia and disease. This analysis only includes only the randomized arms in the study (Study Drug - Daily Dose, Study Drug - Weekly Dose, and Placebo).

Outcome measures

Measure	Study Drug - Daily Dose n=188 Participants 200 mg oral dose daily following day 1 dose of 400 mg orally once. This dose represents approximately half the standard weight-based dosing recommended for management of autoimmune diseases and therefore less likely to produce side effects than standard of care. All treatment groups will receive placebo pills to have the patients take 2 pills a day.	Study Drug - Weekly Dose n=199 Participants 6.5 mg/kg per dose (maximum of 400mg per dose) administered orally weekly on the same day of each week. This is based on the recommended dose for prophylaxis of malaria. All treatment groups will receive placebo pills to have the patients take 2 pills a day.	Placebo n=191 Participants Placebo oral tablet: Participants randomized to this arm will be provided with daily dosing of oral placebo to have the patients take 2 pills a day. All treatment groups will receive placebo pills to have the patients take 2 pills a day. The randomized placebo arm will receive placebo pills made to resemble the daily dosing of HCQ. Similarly, the once a week treatment arm will receive placebo pills for the days not on HCQ medication.	Non-Randomized Active Comparator This will be an open enrollment group and will provide information of chronic weight-based daily therapy of HCQ effectiveness as a prophylactic/preventive strategy. This non-randomized comparator group will be enrolled in the study comprising of healthcare workers and first responders who are chronically on oral hydroxychloroquine as part of their standard of care for their autoimmune disease(s).
Determine the Effect of Hydroxychloroquine Dose in the Prevention of COVID-19 Viremia and Disease.	1 Participants	1 Participants	1 Participants	—

SECONDARY outcome

Timeframe: 8 Weeks

Population: This analysis outcome measure reports the number of occurrences of symptomatic patients with a positive COVID-19 test in all randomized and non-randomized groups in the study.

Compare the rates of SARS-CoV 2 infections (number of events of symptomatic patients with a positive COVID-19 test) in the non-randomized comparator arm to the randomized hydroxychloroquine and placebo arms to assess the impact of chronic weight-based dosing of HCQ for COVID-19 prevention via weekly questionnaire and/or blood samples. This analysis includes all randomized and non-randomized groups in the study.

Outcome measures

Measure	Study Drug - Daily Dose n=188 Participants 200 mg oral dose daily following day 1 dose of 400 mg orally once. This dose represents approximately half the standard weight-based dosing recommended for management of autoimmune diseases and therefore less likely to produce side effects than standard of care. All treatment groups will receive placebo pills to have the patients take 2 pills a day.	Study Drug - Weekly Dose n=199 Participants 6.5 mg/kg per dose (maximum of 400mg per dose) administered orally weekly on the same day of each week. This is based on the recommended dose for prophylaxis of malaria. All treatment groups will receive placebo pills to have the patients take 2 pills a day.	Placebo n=191 Participants Placebo oral tablet: Participants randomized to this arm will be provided with daily dosing of oral placebo to have the patients take 2 pills a day. All treatment groups will receive placebo pills to have the patients take 2 pills a day. The randomized placebo arm will receive placebo pills made to resemble the daily dosing of HCQ. Similarly, the once a week treatment arm will receive placebo pills for the days not on HCQ medication.	Non-Randomized Active Comparator n=25 Participants This will be an open enrollment group and will provide information of chronic weight-based daily therapy of HCQ effectiveness as a prophylactic/preventive strategy. This non-randomized comparator group will be enrolled in the study comprising of healthcare workers and first responders who are chronically on oral hydroxychloroquine as part of their standard of care for their autoimmune disease(s).
Assess the Impact of Chronic Weight-based Dosing of HCQ for COVID-19 Prevention.	1 Participants	1 Participants	1 Participants	0 Participants

SECONDARY outcome

Timeframe: 8 Weeks

Population: This analysis is only for the randomized arms of the study (Study Drug - Daily Dose, Study Drug - Weekly Dose, and Placebo).

Measurement of the rate of SARS-CoV 2 infections as measured by IgM/IgG seroconversion in study participants receiving randomized HCQ versus placebo via blood samples in the randomized arms of the study (Study Drug - Daily Dose, Study Drug - Weekly Dose, and Placebo).

Outcome measures

Measure	Study Drug - Daily Dose n=188 Participants 200 mg oral dose daily following day 1 dose of 400 mg orally once. This dose represents approximately half the standard weight-based dosing recommended for management of autoimmune diseases and therefore less likely to produce side effects than standard of care. All treatment groups will receive placebo pills to have the patients take 2 pills a day.	Study Drug - Weekly Dose n=199 Participants 6.5 mg/kg per dose (maximum of 400mg per dose) administered orally weekly on the same day of each week. This is based on the recommended dose for prophylaxis of malaria. All treatment groups will receive placebo pills to have the patients take 2 pills a day.	Placebo n=191 Participants Placebo oral tablet: Participants randomized to this arm will be provided with daily dosing of oral placebo to have the patients take 2 pills a day. All treatment groups will receive placebo pills to have the patients take 2 pills a day. The randomized placebo arm will receive placebo pills made to resemble the daily dosing of HCQ. Similarly, the once a week treatment arm will receive placebo pills for the days not on HCQ medication.	Non-Randomized Active Comparator This will be an open enrollment group and will provide information of chronic weight-based daily therapy of HCQ effectiveness as a prophylactic/preventive strategy. This non-randomized comparator group will be enrolled in the study comprising of healthcare workers and first responders who are chronically on oral hydroxychloroquine as part of their standard of care for their autoimmune disease(s).
Comparison of the Rate of SARS-CoV 2 Infections as Measured by IgM/IgG Seroconversion in Study Participants Receiving Randomized HCQ Versus Placebo.	1 Participants	1 Participants	2 Participants	—

SECONDARY outcome

Timeframe: 8 Weeks

Population: The analysis reports the number of patient samples that seroconverted to positive serology for IgM and/or IgG by the subject end of study time point in all arms of the study, randomized and non-randomized (Study Drug - Daily Dose, Study Drug - Weekly Dose, Placebo, and Non-Randomized Active Comparator).

Measurement of the seroprevalence of SARS-CoV 2 IgM and/or IgG positive samples in all arms of the study, randomized and non-randomized (Study Drug - Daily Dose, Study Drug - Weekly Dose, Placebo, and Non-Randomized Active Comparator).

Outcome measures

Measure	Study Drug - Daily Dose n=188 Participants 200 mg oral dose daily following day 1 dose of 400 mg orally once. This dose represents approximately half the standard weight-based dosing recommended for management of autoimmune diseases and therefore less likely to produce side effects than standard of care. All treatment groups will receive placebo pills to have the patients take 2 pills a day.	Study Drug - Weekly Dose n=199 Participants 6.5 mg/kg per dose (maximum of 400mg per dose) administered orally weekly on the same day of each week. This is based on the recommended dose for prophylaxis of malaria. All treatment groups will receive placebo pills to have the patients take 2 pills a day.	Placebo n=191 Participants Placebo oral tablet: Participants randomized to this arm will be provided with daily dosing of oral placebo to have the patients take 2 pills a day. All treatment groups will receive placebo pills to have the patients take 2 pills a day. The randomized placebo arm will receive placebo pills made to resemble the daily dosing of HCQ. Similarly, the once a week treatment arm will receive placebo pills for the days not on HCQ medication.	Non-Randomized Active Comparator n=25 Participants This will be an open enrollment group and will provide information of chronic weight-based daily therapy of HCQ effectiveness as a prophylactic/preventive strategy. This non-randomized comparator group will be enrolled in the study comprising of healthcare workers and first responders who are chronically on oral hydroxychloroquine as part of their standard of care for their autoimmune disease(s).
Compare the Seroprevalence of SARS-CoV 2 IgM and/or IgG Positive Samples at Study Entry and Study Conclusion in All Participants Receiving HCQ Compared to Those Receiving Placebo.	1 Participants	1 Participants	2 Participants	0 Participants

SECONDARY outcome

Timeframe: 8 Weeks

Population: All patients were asymptomatic at study entry by observed lack of symptoms and consistent with study eligibility criteria. This analysis planned to evaluate patients who tested positive for COVID-19 at study entry time point, but had yet to develop symptoms when entering the study to assess efficacy of hydroxychloroquine in preventing symptom emergence. Only one participant met the criteria for outcome measure analysis.

Measurement of the emergence of clinical symptoms or COVID-19 diagnosis in participants presenting asymptomatically at study entry but identified as seropositive by serology at entry between the randomized treatment arms and comparator arm and via weekly questionnaire and/or blood samples.

Outcome measures

Measure	Study Drug - Daily Dose n=188 Participants 200 mg oral dose daily following day 1 dose of 400 mg orally once. This dose represents approximately half the standard weight-based dosing recommended for management of autoimmune diseases and therefore less likely to produce side effects than standard of care. All treatment groups will receive placebo pills to have the patients take 2 pills a day.	Study Drug - Weekly Dose n=199 Participants 6.5 mg/kg per dose (maximum of 400mg per dose) administered orally weekly on the same day of each week. This is based on the recommended dose for prophylaxis of malaria. All treatment groups will receive placebo pills to have the patients take 2 pills a day.	Placebo n=191 Participants Placebo oral tablet: Participants randomized to this arm will be provided with daily dosing of oral placebo to have the patients take 2 pills a day. All treatment groups will receive placebo pills to have the patients take 2 pills a day. The randomized placebo arm will receive placebo pills made to resemble the daily dosing of HCQ. Similarly, the once a week treatment arm will receive placebo pills for the days not on HCQ medication.	Non-Randomized Active Comparator n=25 Participants This will be an open enrollment group and will provide information of chronic weight-based daily therapy of HCQ effectiveness as a prophylactic/preventive strategy. This non-randomized comparator group will be enrolled in the study comprising of healthcare workers and first responders who are chronically on oral hydroxychloroquine as part of their standard of care for their autoimmune disease(s).
Comparison of the Emergence of Clinical Symptoms or COVID-19 Diagnosis in Participants Presenting Asymptomatically at Study Entry But Identified as Seropositive by Serology at Entry Between the Randomized Treatment Arms and Comparator Arm.	1 Participants	0 Participants	0 Participants	0 Participants

SECONDARY outcome

Timeframe: 8 Weeks

Review of the level of care needed by participants in each arm developing COVID19 as measured as requiring emergency room visit, hospitalization or able to stay home without hospital care via weekly questionnaire.

Outcome measures

Measure	Study Drug - Daily Dose n=188 Participants 200 mg oral dose daily following day 1 dose of 400 mg orally once. This dose represents approximately half the standard weight-based dosing recommended for management of autoimmune diseases and therefore less likely to produce side effects than standard of care. All treatment groups will receive placebo pills to have the patients take 2 pills a day.	Study Drug - Weekly Dose n=199 Participants 6.5 mg/kg per dose (maximum of 400mg per dose) administered orally weekly on the same day of each week. This is based on the recommended dose for prophylaxis of malaria. All treatment groups will receive placebo pills to have the patients take 2 pills a day.	Placebo n=191 Participants Placebo oral tablet: Participants randomized to this arm will be provided with daily dosing of oral placebo to have the patients take 2 pills a day. All treatment groups will receive placebo pills to have the patients take 2 pills a day. The randomized placebo arm will receive placebo pills made to resemble the daily dosing of HCQ. Similarly, the once a week treatment arm will receive placebo pills for the days not on HCQ medication.	Non-Randomized Active Comparator n=25 Participants This will be an open enrollment group and will provide information of chronic weight-based daily therapy of HCQ effectiveness as a prophylactic/preventive strategy. This non-randomized comparator group will be enrolled in the study comprising of healthcare workers and first responders who are chronically on oral hydroxychloroquine as part of their standard of care for their autoimmune disease(s).
To Examine the Level of Care Needed by Participants in Each Arm Developing COVID19 as Measured as Requiring Emergency Room Visit, Hospitalization or Able to Stay Home Without Hospital Care.	0 Participants	0 Participants	0 Participants	0 Participants

SECONDARY outcome

Timeframe: 8 Weeks

Measurement of the safety and tolerability of HCQ dosing for preventive strategy against COVID-19 as measured by adverse events and serious adverse events reported via weekly questionnaire.

Outcome measures

Measure	Study Drug - Daily Dose n=188 Participants 200 mg oral dose daily following day 1 dose of 400 mg orally once. This dose represents approximately half the standard weight-based dosing recommended for management of autoimmune diseases and therefore less likely to produce side effects than standard of care. All treatment groups will receive placebo pills to have the patients take 2 pills a day.	Study Drug - Weekly Dose n=199 Participants 6.5 mg/kg per dose (maximum of 400mg per dose) administered orally weekly on the same day of each week. This is based on the recommended dose for prophylaxis of malaria. All treatment groups will receive placebo pills to have the patients take 2 pills a day.	Placebo n=191 Participants Placebo oral tablet: Participants randomized to this arm will be provided with daily dosing of oral placebo to have the patients take 2 pills a day. All treatment groups will receive placebo pills to have the patients take 2 pills a day. The randomized placebo arm will receive placebo pills made to resemble the daily dosing of HCQ. Similarly, the once a week treatment arm will receive placebo pills for the days not on HCQ medication.	Non-Randomized Active Comparator n=26 Participants This will be an open enrollment group and will provide information of chronic weight-based daily therapy of HCQ effectiveness as a prophylactic/preventive strategy. This non-randomized comparator group will be enrolled in the study comprising of healthcare workers and first responders who are chronically on oral hydroxychloroquine as part of their standard of care for their autoimmune disease(s).
Determine the Safety and Tolerability of HCQ Dosing for Preventive Strategy Against COVID-19 as Measured by Adverse Events and Serious Adverse Events. Serious adverse events (Level 3 or 4).	0 Number of adverse events.	0 Number of adverse events.	0 Number of adverse events.	0 Number of adverse events.
Determine the Safety and Tolerability of HCQ Dosing for Preventive Strategy Against COVID-19 as Measured by Adverse Events and Serious Adverse Events. Adverse events (only Level 1 and 2) observed in the study.	206 Number of adverse events.	193 Number of adverse events.	188 Number of adverse events.	2 Number of adverse events.

SECONDARY outcome

Timeframe: 8 Weeks

Population: Due to low number of events, this analysis was not performed. No factors were identified.

Examination of other clinical factors contributing to the risk of SARS-CoV 2 infection including demographics, work type and location, positive COVID-19 partners, possible exposures and clinical symptoms via study visits and weekly questionnaire.

Outcome measures

Measure	Study Drug - Daily Dose n=188 Participants 200 mg oral dose daily following day 1 dose of 400 mg orally once. This dose represents approximately half the standard weight-based dosing recommended for management of autoimmune diseases and therefore less likely to produce side effects than standard of care. All treatment groups will receive placebo pills to have the patients take 2 pills a day.	Study Drug - Weekly Dose n=199 Participants 6.5 mg/kg per dose (maximum of 400mg per dose) administered orally weekly on the same day of each week. This is based on the recommended dose for prophylaxis of malaria. All treatment groups will receive placebo pills to have the patients take 2 pills a day.	Placebo n=191 Participants Placebo oral tablet: Participants randomized to this arm will be provided with daily dosing of oral placebo to have the patients take 2 pills a day. All treatment groups will receive placebo pills to have the patients take 2 pills a day. The randomized placebo arm will receive placebo pills made to resemble the daily dosing of HCQ. Similarly, the once a week treatment arm will receive placebo pills for the days not on HCQ medication.	Non-Randomized Active Comparator n=25 Participants This will be an open enrollment group and will provide information of chronic weight-based daily therapy of HCQ effectiveness as a prophylactic/preventive strategy. This non-randomized comparator group will be enrolled in the study comprising of healthcare workers and first responders who are chronically on oral hydroxychloroquine as part of their standard of care for their autoimmune disease(s).
To Examine Other Clinical Factors Contributing to the Risk of SARS-CoV 2 Infection in Healthcare Workers and First Responders.	NA Clinical factors Due to low number of events, this analysis was not performed. No factors were identified.	NA Clinical factors Due to low number of events, this analysis was not performed. No factors were identified.	NA Clinical factors Due to low number of events, this analysis was not performed. No factors were identified.	NA Clinical factors Due to low number of events, this analysis was not performed. No factors were identified.

SECONDARY outcome

Timeframe: 8 Weeks

Population: This analysis was not performed due to low number of events and early termination of the study. Therefore, no data or measures to report.

Examination of the correlation between HCQ drug levels and development of COVID-19 clinical symptoms and/or positive COVID-19 test results via weekly subject questionnaire and/or blood samples.

Outcome measures

Measure	Study Drug - Daily Dose n=188 Participants 200 mg oral dose daily following day 1 dose of 400 mg orally once. This dose represents approximately half the standard weight-based dosing recommended for management of autoimmune diseases and therefore less likely to produce side effects than standard of care. All treatment groups will receive placebo pills to have the patients take 2 pills a day.	Study Drug - Weekly Dose n=199 Participants 6.5 mg/kg per dose (maximum of 400mg per dose) administered orally weekly on the same day of each week. This is based on the recommended dose for prophylaxis of malaria. All treatment groups will receive placebo pills to have the patients take 2 pills a day.	Placebo n=191 Participants Placebo oral tablet: Participants randomized to this arm will be provided with daily dosing of oral placebo to have the patients take 2 pills a day. All treatment groups will receive placebo pills to have the patients take 2 pills a day. The randomized placebo arm will receive placebo pills made to resemble the daily dosing of HCQ. Similarly, the once a week treatment arm will receive placebo pills for the days not on HCQ medication.	Non-Randomized Active Comparator n=25 Participants This will be an open enrollment group and will provide information of chronic weight-based daily therapy of HCQ effectiveness as a prophylactic/preventive strategy. This non-randomized comparator group will be enrolled in the study comprising of healthcare workers and first responders who are chronically on oral hydroxychloroquine as part of their standard of care for their autoimmune disease(s).
Examine the Correlation Between HCQ Drug Levels and Development of COVID-19 Symptoms or Positive COVID-19 Test Results.	NA Correlation coefficient Due to low number of events, this analysis was not performed.	NA Correlation coefficient Due to low number of events, this analysis was not performed. .	NA Correlation coefficient Due to low number of events, this analysis was not performed.	NA Correlation coefficient Due to low number of events, this analysis was not performed.

SECONDARY outcome

Timeframe: 8 weeks

Population: This analysis was not performed due to low number of events and early termination of the study. Therefore, no data or markers to report.

Identification of immunologic, serological and inflammatory markers associated with acquisition and response to COVID-19 in both HCQ and placebo Participants developing laboratory or clinical confirmed disease via study visits, weekly questionnaire, and blood samples.

Outcome measures

Measure	Study Drug - Daily Dose n=188 Participants 200 mg oral dose daily following day 1 dose of 400 mg orally once. This dose represents approximately half the standard weight-based dosing recommended for management of autoimmune diseases and therefore less likely to produce side effects than standard of care. All treatment groups will receive placebo pills to have the patients take 2 pills a day.	Study Drug - Weekly Dose n=199 Participants 6.5 mg/kg per dose (maximum of 400mg per dose) administered orally weekly on the same day of each week. This is based on the recommended dose for prophylaxis of malaria. All treatment groups will receive placebo pills to have the patients take 2 pills a day.	Placebo n=191 Participants Placebo oral tablet: Participants randomized to this arm will be provided with daily dosing of oral placebo to have the patients take 2 pills a day. All treatment groups will receive placebo pills to have the patients take 2 pills a day. The randomized placebo arm will receive placebo pills made to resemble the daily dosing of HCQ. Similarly, the once a week treatment arm will receive placebo pills for the days not on HCQ medication.	Non-Randomized Active Comparator n=25 Participants This will be an open enrollment group and will provide information of chronic weight-based daily therapy of HCQ effectiveness as a prophylactic/preventive strategy. This non-randomized comparator group will be enrolled in the study comprising of healthcare workers and first responders who are chronically on oral hydroxychloroquine as part of their standard of care for their autoimmune disease(s).
Identify Immunologic, Serological and Inflammatory Markers Associated With Acquisition and Response to COVID-19 in Both HCQ and Placebo Participants Developing Laboratory or Clinical Confirmed Disease.	NA Inflammatory markers This analysis was not performed due to low number of events and early termination of the study.	NA Inflammatory markers This analysis was not performed due to low number of events and early termination of the study.	NA Inflammatory markers This analysis was not performed due to low number of events and early termination of the study.	NA Inflammatory markers This analysis was not performed due to low number of events and early termination of the study.

Adverse Events

Study Drug - Daily Dose

Serious events: 0 serious events

Other events: 97 other events

Deaths: 0 deaths

Study Drug - Weekly Dose

Serious events: 0 serious events

Other events: 95 other events

Deaths: 0 deaths

Placebo

Serious events: 0 serious events

Other events: 85 other events

Deaths: 0 deaths

Non-Randomized Active Comparator (HCQ Cohort)

Serious events: 0 serious events

Other events: 2 other events

Deaths: 0 deaths

Serious adverse events

Adverse event data not reported

Other adverse events

Measure	Study Drug - Daily Dose n=188 participants at risk 200 mg oral dose daily following day 1 dose of 400 mg orally once. This dose represents approximately half the standard weight-based dosing recommended for management of autoimmune diseases and therefore less likely to produce side effects than standard of care. All treatment groups will receive placebo pills to have the patients take 2 pills a day.	Study Drug - Weekly Dose n=199 participants at risk 6.5 mg/kg per dose (maximum of 400mg per dose) administered orally weekly on the same day of each week. This is based on the recommended dose for prophylaxis of malaria. All treatment groups will receive placebo pills to have the patients take 2 pills a day.	Placebo n=191 participants at risk Placebo oral tablet: Participants randomized to this arm will be provided with daily dosing of oral placebo to have the patients take 2 pills a day. All treatment groups will receive placebo pills to have the patients take 2 pills a day. The randomized placebo arm will receive placebo pills made to resemble the daily dosing of HCQ. Similarly, the once a week treatment arm will receive placebo pills for the days not on HCQ medication.	Non-Randomized Active Comparator (HCQ Cohort) n=26 participants at risk This non-randomized comparator group is comprised of healthcare workers and first responders who are chronically on oral hydroxychloroquine as part of their standard of care for autoimmune disease(s).
Gastrointestinal disorders All gastrointestinal symptoms reported	19.1% 36/188 • Number of events 54 • 8 weeks.	17.1% 34/199 • Number of events 43 • 8 weeks.	22.0% 42/191 • Number of events 52 • 8 weeks.	0.00% 0/26 • 8 weeks.
Cardiac disorders All cardiac symptoms reported	8.5% 16/188 • Number of events 17 • 8 weeks.	7.5% 15/199 • Number of events 16 • 8 weeks.	5.2% 10/191 • Number of events 10 • 8 weeks.	0.00% 0/26 • 8 weeks.
Ear and labyrinth disorders All ear and labyrinth symptoms reported	4.8% 9/188 • Number of events 10 • 8 weeks.	3.0% 6/199 • Number of events 9 • 8 weeks.	4.2% 8/191 • Number of events 8 • 8 weeks.	0.00% 0/26 • 8 weeks.
Eye disorders All eye symptoms reported	3.2% 6/188 • Number of events 9 • 8 weeks.	0.50% 1/199 • Number of events 1 • 8 weeks.	3.1% 6/191 • Number of events 6 • 8 weeks.	0.00% 0/26 • 8 weeks.
General disorders All general symptoms and administration site symptoms reported	4.3% 8/188 • Number of events 9 • 8 weeks.	6.5% 13/199 • Number of events 15 • 8 weeks.	7.9% 15/191 • Number of events 17 • 8 weeks.	0.00% 0/26 • 8 weeks.
Immune system disorders All immune system symptoms reported	2.1% 4/188 • Number of events 4 • 8 weeks.	2.5% 5/199 • Number of events 6 • 8 weeks.	0.00% 0/191 • 8 weeks.	0.00% 0/26 • 8 weeks.
Infections and infestations All infection and infestation symptoms reported	4.3% 8/188 • Number of events 8 • 8 weeks.	0.50% 1/199 • Number of events 1 • 8 weeks.	1.6% 3/191 • Number of events 3 • 8 weeks.	0.00% 0/26 • 8 weeks.
Injury, poisoning and procedural complications Injury, poisoning and procedural complication symptoms reported	1.6% 3/188 • Number of events 3 • 8 weeks.	0.50% 1/199 • Number of events 2 • 8 weeks.	0.52% 1/191 • Number of events 1 • 8 weeks.	3.8% 1/26 • Number of events 1 • 8 weeks.
Metabolism and nutrition disorders Metabolism and nutrition symptoms reported	0.53% 1/188 • Number of events 1 • 8 weeks.	0.00% 0/199 • 8 weeks.	0.00% 0/191 • 8 weeks.	0.00% 0/26 • 8 weeks.
Musculoskeletal and connective tissue disorders All Musculoskeletal and connective tissue symptoms reported	5.9% 11/188 • Number of events 13 • 8 weeks.	8.0% 16/199 • Number of events 17 • 8 weeks.	7.3% 14/191 • Number of events 16 • 8 weeks.	3.8% 1/26 • Number of events 1 • 8 weeks.
Nervous system disorders All nervous system symptoms reported	21.8% 41/188 • Number of events 43 • 8 weeks.	15.1% 30/199 • Number of events 33 • 8 weeks.	17.8% 34/191 • Number of events 42 • 8 weeks.	0.00% 0/26 • 8 weeks.
Psychiatric disorders All psychiatric symptoms reported	2.7% 5/188 • Number of events 6 • 8 weeks.	5.0% 10/199 • Number of events 13 • 8 weeks.	3.7% 7/191 • Number of events 7 • 8 weeks.	0.00% 0/26 • 8 weeks.
Reproductive system and breast disorders All reproductive system and breast symptoms reported	0.00% 0/188 • 8 weeks.	0.00% 0/199 • 8 weeks.	1.0% 2/191 • Number of events 2 • 8 weeks.	0.00% 0/26 • 8 weeks.
Respiratory, thoracic and mediastinal disorders All respiratory, thoracic and mediastinal symptoms reported	6.9% 13/188 • Number of events 17 • 8 weeks.	11.1% 22/199 • Number of events 27 • 8 weeks.	7.9% 15/191 • Number of events 21 • 8 weeks.	0.00% 0/26 • 8 weeks.
Skin and subcutaneous tissue disorders All skin and subcutaneous tissue symptoms reported	5.9% 11/188 • Number of events 12 • 8 weeks.	3.5% 7/199 • Number of events 10 • 8 weeks.	1.6% 3/191 • Number of events 3 • 8 weeks.	0.00% 0/26 • 8 weeks.

Additional Information

John McKinnon, MD, MSc

Henry Ford Health System

Phone: 313-916-8828

Email: jmckinn3@hfhs.org

Results disclosure agreements

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