Hydroxychloroquine in Outpatient Adults With COVID-19

Study Overview
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Brief Summary
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Primary Objective: To assess the effect of hydroxychloroquine versus placebo on nasopharyngeal SARS-CoV-2 viral load in outpatient adults with COVID-19 Secondary Objectives: To assess the effect of hydroxychloroquine versus placebo on clinical signs and symptoms and progression of disease in outpatient adults with COVID-19 To assess the safety and tolerability of hydroxychloroquine in outpatient adults with COVID-19

Detailed Description
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The duration of the study per participant will be around 18 days (1 or 2 days of screening followed by a 10-day treatment period and a 4 to 6 days follow-up period)

Official Title
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A Phase 1b, Randomized, Double-blinded, Placebo-controlled Study of Hydroxychloroquine in Outpatient Adults With COVID-19

Conditions
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Coronavirus Infection

Intervention / Treatment
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* Drug: Hydroxychloroquine SAR321068
* Drug: Placebo


Participation Criteria
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Eligibility Criteria
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Inclusion criteria : Participants with diagnosis of COVID-19 via an approved or authorized molecular test Presence of symptoms compatible with COVID-19 at the time of screening Time between onset of symptoms and first dose of hydroxychloroquine or placebo is 96 hours or less Female participants must use an acceptable birth control method, as specified by each site and country Exclusion criteria: COVID-19 disease requiring the use of supplemental oxygen Electrocardiogram (ECG) tracing with QTc interval > 450 ms for men, > 470 ms for women (Fridericia algorithm recommended) Bradycardia (< 50 beats/min) History of cardiac disease (eg. congestive heart failure, myocardial infarction) History of Glucose-6-phosphate dehydrogenase (G6PD) deficiency Women who are pregnant or breastfeeding Concurrent antimicrobial therapy Known hypersensitivity to hydroxychloroquine or other 4-aminoquinoline compounds Hydroxychloroquine use within 2 months before enrollment History of severe skin reactions such as Sevens-Johnson syndrome and toxic epidermal necrolysis History of retinopathy History of arrythmia, concurrent use of anti-arrhythmic drugs, or family history of sudden cardiac death History of severe renal disease (treatment with dialysis or phosphate binders) or hepatic impairment The above information is not intended to contain all considerations relevant to a patient's potential participation in a clinical trial.

Ages Eligible for Study
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Minimum Age: 18 Years
Maximum Age: 80 Years

Sexes Eligible for Study
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All

Accepts Healthy Volunteers
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No

Study Plan
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How is the study designed?
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Design Details

Primary Purpose: Treatment
Allocation: Randomized
Intervention Model: Parallel Assignment
Masking: Quadruple


Arms and Interventions

| Participant Group/Arm | Intervention/Treatment |
| --- | --- |
| Experimental: Hydroxychloroquine<br>Hydroxychloroquine, loading dose on day 1 followed by a daily maintenance dose during 9 days | Drug: Hydroxychloroquine SAR321068<br>* Pharmaceutical form:Tablet Route of administration: Oral<br>* Other names: Plaquenil;|
| Placebo Comparator: Placebo<br>Matching placebo | Drug: Placebo<br>* Pharmaceutical form:Tablet Route of administration: Oral<br>|

What is the study measuring?
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Primary Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| Change from baseline to Day 3 in nasopharyngeal SARS-CoV-2 viral load (if quantitative PCR is available) | Viral load assessed by PCR from a nasopharyngeal swab | Baseline to Day 3 | 
| Number of participants by PCR result status (positive or negative) (if quantitative PCR is not available) | Viral load assessed by PCR from a nasopharyngeal swab - 2. Viral load assessed by PCR from a nasopharyngeal swab | Baseline to Day 3 | 

Secondary Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| Change from baseline to Day 5 in nasopharyngeal SARS-CoV-2 viral load | Viral load assessed by PCR from a nasopharyngeal swab | Baseline to Day 5 | 
| Number of participants by PCR result status (positive or negative) | Viral load assessed by PCR from a nasopharyngeal swab | Baseline to end of study (Day14) | 
| Number of participants with COVID-19 symptoms by severity | COVID-19 symptoms (feverishness, sore throat, cough, shortness of breath, myalgias) will be scored by the participant on a 4-point scale ( 0 =none; 1 = mild; 2 = moderate; 3 = severe) | Baseline to end of study (Day14) | 
| Time to resolution of COVID-19 Symptoms | COVID-19 symptoms (feverishness, sore throat, cough, shortness of breath, myalgias) will be scored by the participant on a 4-point scale ( 0 =none; 1 = mild; 2 = moderate; 3 = severe). Resolution of a symptom is defined as when a symptom previously scored ≥ 1 on the scale is scored as 0 | Baseline to end of study (Day14) | 
| Time to resolution of fever | Resolution of fever defined as the first day of 2 consecutive daily temperatures < 37.7 C | Baseline to end of study (Day14) | 
| Percentage of participants with resolution of fever | Resolution of fever defined as the first day of 2 consecutive daily temperatures < 37.7 C | Baseline to end of study (Day14) | 
| Percentage of participants hospitalized |  | Baseline to end of study (Day14) | 
| Number of participants with Adverse Events |  | Baseline to end of study (Day14) |