Hydroxychloroquine in Outpatient Adults With COVID-19

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

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

Study Overview

• Status: Terminated
• Conditions: Coronavirus Infection
• Intervention / Treatment: Drug: Placebo; Drug: Hydroxychloroquine SAR321068

Detailed Description

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)

• Study Type: Interventional
• Enrollment (Actual): 8
• Phase: Phase 1

Contacts and Locations

Study Locations

• Belgium
  • Bruxelles, Belgium, BE-1200
    • Investigational Site Number 0561001
  • Lodelinsart, Belgium, 6042
    • Investigational Site Number 0561002
• France
  • Bordeaux Cedex, France, 33076
    • Investigational Site Number 2501001
  • Paris, France, 75005
    • Investigational Site Number 2501002
• Netherlands
  • Groningen, Netherlands, 9728 NZ
    • Investigational Site Number 5281001
  • Harderwijk, Netherlands, 3844 DG
    • Investigational Site Number 5281002
• United States
  • Massachusetts
    • Boston, Massachusetts, United States, 02115
      • Investigational Site Number 8400001

Participation Criteria

Eligibility Criteria

• Ages Eligible for Study: 18 years to 80 years (Adult, Older Adult)
• Accepts Healthy Volunteers: No
• Genders Eligible for Study: All

Description

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.

Study Plan

How is the study designed?

Design Details

• Primary Purpose: Treatment
• Allocation: Randomized
• Interventional Model: Parallel Assignment
• Masking: Quadruple

Number of Arms

2

Arms and Interventions

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

What is the study measuring?

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)

Collaborators and Investigators

• Sponsor: Sanofi

Study record dates

Study Major Dates

• Study Start (Actual): April 12, 2020
• Primary Completion (Actual): May 26, 2020
• Study Completion (Actual): May 26, 2020

Study Registration Dates

• First Submitted: April 1, 2020
• First Submitted That Met QC Criteria: April 2, 2020
• First Posted (Actual): April 3, 2020

Study Record Updates

• Last Update Posted (Actual): April 25, 2022
• Last Update Submitted That Met QC Criteria: April 21, 2022
• Last Verified: April 1, 2022

More Information

Terms related to this study

• Additional Relevant MeSH Terms: Coronaviridae Infections; Nidovirales Infections; RNA Virus Infections; Virus Diseases; Infections; Coronavirus Infections; Molecular Mechanisms of Pharmacological Action; Anti-Infective Agents; Enzyme Inhibitors; Antirheumatic Agents; Antiprotozoal Agents; Antiparasitic Agents; Antimalarials; Hydroxychloroquine
• Other Study ID Numbers: EFC16855; 2020-001269-35 (EudraCT Number); U1111-1249-6168 (Other Identifier: UTN)

Plan for Individual participant data (IPD)

• Plan to Share Individual Participant Data (IPD)?: YES
• IPD Plan Description: Qualified researchers may request access to patient level data and related study documents including the clinical study report, study protocol with any amendments, blank case report form, statistical analysis plan, and dataset specifications. Patient level data will be anonymized and study documents will be redacted to protect the privacy of trial participants. Further details on Sanofi's data sharing criteria, eligible studies, and process for requesting access can be found at: https://vivli.org

Drug and device information, study documents

• Studies a U.S. FDA-regulated drug product: Yes
• Studies a U.S. FDA-regulated device product: No