AR0-CORONA: Effect of Tenofovir/Emtricitabine in Patients Recently Infected With SARS-COV2 (Covid-19) Discharged Home

Sponsor

University Hospital, Caen (Other)

Overall Status

Completed

CT.gov ID

NCT04685512

Collaborator

(none)

Enrollment

Locations

Arms

5.4

Actual Duration (Months)

Patients Per Site

5.6

Patients Per Site Per Month

Study Details

Study Description

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.

Condition or Disease	Intervention/Treatment	Phase
Covid19	Drug: tenofovir disoproxil and emtricitabine	Phase 2/Phase 3

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.

Study Design

Study Type:

Interventional

Actual Enrollment :

60 participants

Allocation:

Randomized

Intervention Model:

Parallel Assignment

Intervention 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 patientsPhase 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 (Outcomes Assessor)

Masking Description:

Biologists in Endpoint Adjudication committee

Primary Purpose:

Treatment

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

Actual Study Start Date :

Nov 18, 2020

Actual Primary Completion Date :

Apr 1, 2021

Actual Study Completion Date :

May 1, 2021

Arms and Interventions

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

Arm

Intervention/Treatment

Experimental: TDF / FTC

2 tablets on Day-1 then 1 tablet/day for 6 days

Drug: tenofovir disoproxil and emtricitabine

Experimental drugs administration of 7-day short course TDF/FTC

No Intervention: usual care

Standard of Care

Outcome Measures

Primary Outcome Measures

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) [Day-4 after the start of study]
Nasopharyngeal swab performed at baseline and day-4 with RT-PCR for SARS-CoV2
Phase 3: Rate of non-contagious nasopharyngeal sample for SARS-CoV2 by PCR on Day-4 with Ct > or = 28 [Day-4 after the start of study]
Nasopharyngeal swab performed at day-4 with RT-PCR for SARS-CoV2

Secondary Outcome Measures

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

Eligibility Criteria

Criteria

Ages Eligible for Study:

18 Years and Older

Sexes Eligible for Study:

All

Accepts Healthy Volunteers:

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