Effect of Tenofovir/Emtricitabine in Patients Recently Infected With SARS-COV2 (Covid-19) Discharged Home

Study Overview
=================
Brief Summary
-----------------
COVID-19 pandemic is currently affecting the globe. To date, there is no effective oral therapy against SARS-CoV2 infection. The investigators propose to test as a repurposing drug combination, a short course of tenofovir disoproxil and emtricitabine (TDF/FTC), as a proof-of-concept randomized open-label study to test its viral efficacy against SARS-CoV2.

Detailed Description
-----------------
The SARS-CoV2 pandemic is causing morbidity and mortality. There is no cure. Remdesivir is a nucleotide analogue that has demonstrated its efficacy in vitro against SARS-CoV2 and in humans (shorten symptoms duration by 2 days without improving survival), but it is used parenterally. TDF belongs to the same therapeutic class, represents a promising avenue of research. TDF/FTC demonstrated in vivo efficacy against SARS-CoV2 in preclinical animal models and its use is associated with reduced risk of SARS-CoV2 infection in 2 large cohorts of HIV infected patients.The objective of this work is to evaluate the anti-viral efficacy of the TDF/FTC combination in short course in patients infected with SARS-CoV2 on an outpatient basis. The investigators propose a multicenter, open-label, phase 2B/3 randomized trial of a 7-day treatment with TDF / FTC (2 tablets on Day-1 then 1 tablet / day for 6 days) according to the dosage used in pre-exposure prophylaxis for HIV. This study should include 60 outpatients (Phase 2B) and 120 additional outpatients (Phase III) who were diagnosed with SARS-CoV2 positive and with no contraindication to TDF / FTC and without criteria for hospitalization. The primary endpoint of the phase 2B will be the SARS-CoV2 antiviral efficacy quantified by RT-PCR nasopharyngeal sample Ct increase on Day-4 compared to baseline. The primary endpoint of the phase 3 will be the rate of non-contagious PCR on Day-4 from a nasopharyngeal sample. Secondary endpoints will be tolerance, symptoms resolution, percentage of hospitalization and the rate of non-contagious PCR on Day-7 from a nasopharyngeal sample. The investigators hypothesize that compared to no treatment, treatment with TDF/FTC reduces at Day-4: SARS-CoV2 viral load corresponding to a 4-point +/-5 increase in Ct (Phase 2B) contagious carriage from 80% to 60% (Phase 3). The AR0-CORONA investigators hope, through this study, to be able to validate an anti-viral treatment making it possible to reduce the duration of contagiousness and thus contribute to attenuating the R0 of recently infected patients carrying SARS-CoV2 who are isolated at home.

Official Title
-----------------
Effect of Tenofovir/Emtricitabine Short Course on Viral Clearance in Patients Recently Infected With SARS-COV2 (Covid-19) Not Requiring Hospitalization: a Phase IIB/III Multicenter Open-label Randomized Controlled Trial

Conditions
-----------------
Covid19

Intervention / Treatment
-----------------
* Drug: tenofovir disoproxil and emtricitabine


Participation Criteria
=================
Eligibility Criteria
-----------------
Inclusion Criteria: Patients 18 years and over SARS-CoV2 Infection confirmed by PCR Patients who do not require immediate hospitalization Signed informed consent Non-Inclusion criteria: Patients with HIV or Hepatitis B Symptoms suggestive of a SARS-CoV2 infection that has been progressing for more than 7 days Asympomatic patients with unknown date of infection or date of infection>7 days Chronic HCV infection Contraindication to the use of TDF/FTC Hypersensitivity to tenofovir, to emtricitabine or to any of the excipients (especially lactose) Glomerular filtration rate <80mL / min Recent (less than 7 days) or concomitant use of NSAIDs or other nephrotoxic drugs (antiinfectives, immunosuppressants, allopurinol, lithium need for hospitalization for contemporary decompensation of a comorbidity need for hospitalization due to SARS-CoV2 infection: Capillary oximetry less than 95% clinical evaluation by the investigating doctor leading to hospitalization Pregnant or breastfeeding women Exclusion Criteria: - Diagnosis of pregnancy during treatment

Ages Eligible for Study
-----------------
Minimum Age: 18 Years

Sexes Eligible for Study
-----------------
All

Accepts Healthy Volunteers
-----------------
No

Study Plan
=================
How is the study designed?
-----------------

Design Details

Primary Purpose: Treatment
Allocation: Randomized
Intervention Model: Parallel Assignment
Interventional Model Description: Phase 2B: 30 treated, 30 untreated - 1 interim analysis planned after inclusion of 30 patients / Phase 3: 90 treated, 90 untreated - 2 interim analyses planned after inclusion of 60 and 120 patients
Masking: Single


Arms and Interventions

| Participant Group/Arm | Intervention/Treatment |
| --- | --- |
| Experimental: TDF / FTC<br>2 tablets on Day-1 then 1 tablet/day for 6 days | Drug: tenofovir disoproxil and emtricitabine<br>* Experimental drugs administration of 7-day short course TDF/FTC<br>|
| No Intervention: usual care<br>Standard of Care | |

What is the study measuring?
-----------------
Primary Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| Phase 2B: Reduction of SARS-CoV2 viral load assessed by Ct PCR at day-4 adjusted on Ct PCR SARS-CoV2 viral load at baseline (ANCOVA) | Nasopharyngeal swab performed at baseline and day-4 with RT-PCR for SARS-CoV2 | Day-4 after the start of study | 
| Phase 3: Rate of non-contagious nasopharyngeal sample for SARS-CoV2 by PCR on Day-4 with Ct > or = 28 | Nasopharyngeal swab performed at day-4 with RT-PCR for SARS-CoV2 | Day-4 after the start of study | 

Secondary Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| Phase 2B/3: Incidence of Treatment-Emergent Adverse Events [Safety and Tolerability] | Number of adverse events according to the CTCAE grade | From the start of the study to Day-7 | 
| Phase 3: Symptoms score | Self-reported COVID-19 related symptoms | From the start of the study to Day-7 | 
| Phase 3: Proportion of secondary hospitalization | Assessed by investigators up to day-15 | Day-15 | 
| Phase 3: Rate of non-contagious nasopharyngeal sample for SARS-CoV2 by PCR on Day-7 with Ct > or = 28 | Nasopharyngeal swab performed at day-7 with RT-PCR for SARS-CoV2 | Day-7 after the start of study | 

 Terms related to the study
=================
Keywords Provided by Centre Hospitalier Valida
-----------------
COVID-19, TDF/FTC, ambulatory patients, Replication rate of the virus