Hydroxychloroquine in Outpatient Adults With COVID-19

• ClinicalTrials.gov Identifier: NCT04333654
• Recruitment Status: Terminated
• First Posted: April 3, 2020
• Last Update Posted: April 25, 2022
• Sponsor: Sanofi
• Information provided by (Responsible Party): Sanofi

Study Description

Brief Summary:

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

Condition or disease	Intervention/treatment	Phase
Coronavirus Infection	Drug: Hydroxychloroquine SAR321068; Drug: Placebo	Phase 1

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 Design

• Study Type: Interventional (Clinical Trial)
• Actual Enrollment: 8 participants
• Allocation: Randomized
• Intervention Model: Parallel Assignment
• Masking: Quadruple (Participant, Care Provider, Investigator, Outcomes Assessor)
• Primary Purpose: Treatment
• Official Title: A Phase 1b, Randomized, Double-blinded, Placebo-controlled Study of Hydroxychloroquine in Outpatient Adults With COVID-19
• Actual Study Start Date: April 12, 2020
• Actual Primary Completion Date: May 26, 2020
• Actual Study Completion Date: May 26, 2020

Arms and Interventions

Arm	Intervention/treatment
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 Name: Plaquenil
Placebo Comparator: Placebo; Matching placebo	Drug: Placebo; Pharmaceutical form:Tablet Route of administration: Oral

Outcome Measures

Primary Outcome Measures :

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

Secondary Outcome Measures :

1. Change from baseline to Day 5 in nasopharyngeal SARS-CoV-2 viral load [ Time Frame: Baseline to Day 5 ]
   Viral load assessed by PCR from a nasopharyngeal swab
2. Number of participants by PCR result status (positive or negative) [ Time Frame: Baseline to end of study (Day14) ]
   Viral load assessed by PCR from a nasopharyngeal swab
3. Number of participants with COVID-19 symptoms by severity [ Time Frame: Baseline to end of study (Day14) ]
   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)
4. Time to resolution of COVID-19 Symptoms [ Time Frame: Baseline to end of study (Day14) ]
   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
5. Time to resolution of fever [ Time Frame: Baseline to end of study (Day14) ]
   Resolution of fever defined as the first day of 2 consecutive daily temperatures < 37.7 C
6. Percentage of participants with resolution of fever [ Time Frame: Baseline to end of study (Day14) ]
   Resolution of fever defined as the first day of 2 consecutive daily temperatures < 37.7 C
7. Percentage of participants hospitalized [ Time Frame: Baseline to end of study (Day14) ]
8. Number of participants with Adverse Events [ Time Frame: Baseline to end of study (Day14) ]

Eligibility Criteria

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

Criteria

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.

Contacts and Locations

Locations

United States, Massachusetts

Investigational Site Number 8400001

Boston, Massachusetts, United States, 02115

Belgium

Investigational Site Number 0561001

Bruxelles, Belgium, BE-1200

Investigational Site Number 0561002

Lodelinsart, Belgium, 6042

France

Investigational Site Number 2501001

Bordeaux Cedex, France, 33076

Investigational Site Number 2501002

Paris, France, 75005

Netherlands

Investigational Site Number 5281001

Groningen, Netherlands, 9728 NZ

Investigational Site Number 5281002

Harderwijk, Netherlands, 3844 DG

Sponsors and Collaborators

Sanofi

Investigators

• Study Director: Clinical Sciences & Operations; Sanofi

More Information

• Responsible Party: Sanofi
• ClinicalTrials.gov Identifier: NCT04333654
• Other Study ID Numbers: EFC16855; 2020-001269-35 ( EudraCT Number ); U1111-1249-6168 ( Other Identifier: UTN )
• First Posted: April 3, 2020
• Last Update Posted: April 25, 2022
• Last Verified: April 2022

Individual Participant Data (IPD) Sharing Statement:

• Plan to Share IPD: Yes
• 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

• Studies a U.S. FDA-regulated Drug Product: Yes
• Studies a U.S. FDA-regulated Device Product: No

Additional relevant MeSH terms:

Coronavirus Infections; Coronaviridae Infections; Nidovirales Infections; RNA Virus Infections; Virus Diseases; Infections; Hydroxychloroquine; Antimalarials; Antiprotozoal Agents; Antiparasitic Agents; Anti-Infective Agents; Enzyme Inhibitors; Molecular Mechanisms of Pharmacological Action; Antirheumatic Agents