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.
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.
Study Type
INTERVENTIONAL
Allocation
RANDOMIZED
Purpose
TREATMENT
Masking
SINGLE
Enrollment
60
Experimental drugs administration of 7-day short course TDF/FTC
Caen University Hospital
Caen, Calvados, France
Regional Hospital
Orléans, France
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
Time frame: 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
Time frame: Day-4 after the start of study
Phase 2B/3: Incidence of Treatment-Emergent Adverse Events [Safety and Tolerability]
Number of adverse events according to the CTCAE grade
Time frame: From the start of the study to Day-7
Phase 3: Symptoms score
Self-reported COVID-19 related symptoms
Time frame: From the start of the study to Day-7
Phase 3: Proportion of secondary hospitalization
Assessed by investigators up to day-15
Time frame: 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
Time frame: Day-7 after the start of study
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