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

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

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.

Study Overview

• Status: Completed
• Conditions: Covid19
• Intervention / Treatment: Drug: tenofovir disoproxil and emtricitabine

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 Type: Interventional
• Enrollment (Actual): 60
• Phase: Phase 2; Phase 3

Contacts and Locations

Study Locations

• France
  • Orléans, France, 45100
    • Regional Hospital
  • Calvados
    • Caen, Calvados, France, 14000
      • CAEN University Hospital

Participation Criteria

Eligibility Criteria

• Ages Eligible for Study: 18 years and older (ADULT, OLDER_ADULT)
• Accepts Healthy Volunteers: No
• Genders Eligible for Study: All

Description

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

Study Plan

How is the study designed?

Design Details

• Primary Purpose: TREATMENT
• Allocation: RANDOMIZED
• Interventional Model: PARALLEL
• Masking: SINGLE

Number of Arms

2

Arms and Interventions

Participant Group / 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

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

Collaborators and Investigators

• Sponsor: University Hospital, Caen
• Investigators: Principal Investigator: Jean-Jacques Parienti, University Hospital, Caen

Publications and helpful links

General Publications

• Parienti JJ et al. EClinicalMedicine 2021: https://authors.elsevier.com/sd/article/S2589-5370(21)00273-X
• Parienti JJ, Prazuck T, Peyro-Saint-Paul L, Fournier A, Valentin C, Brucato S, Verdon R, Seve A, Colin M, Lesne F, Guinard J, Ar Gouilh M, Dina J, Vabret A, Hocqueloux L. Effect of Tenofovir Disoproxil Fumarate and Emtricitabine on nasopharyngeal SARS-CoV-2 viral load burden amongst outpatients with COVID-19: A pilot, randomized, open-label phase 2 trial. EClinicalMedicine. 2021 Aug;38:100993. doi: 10.1016/j.eclinm.2021.100993. Epub 2021 Jun 27.

Study record dates

Study Major Dates

• Study Start (ACTUAL): November 18, 2020
• Primary Completion (ACTUAL): April 1, 2021
• Study Completion (ACTUAL): May 1, 2021

Study Registration Dates

• First Submitted: November 16, 2020
• First Submitted That Met QC Criteria: December 24, 2020
• First Posted (ACTUAL): December 28, 2020

Study Record Updates

• Last Update Posted (ACTUAL): July 1, 2021
• Last Update Submitted That Met QC Criteria: June 29, 2021
• Last Verified: June 1, 2021

More Information

Terms related to this study

• Keywords: COVID-19; TDF/FTC; ambulatory patients; Replication rate of the virus
• Additional Relevant MeSH Terms: Coronavirus Infections; Coronaviridae Infections; Nidovirales Infections; RNA Virus Infections; Virus Diseases; Infections; Respiratory Tract Infections; Respiratory Tract Diseases; Pneumonia, Viral; Pneumonia; Lung Diseases; COVID-19; Molecular Mechanisms of Pharmacological Action; Anti-Infective Agents; Antiviral Agents; Reverse Transcriptase Inhibitors; Nucleic Acid Synthesis Inhibitors; Enzyme Inhibitors; Anti-HIV Agents; Anti-Retroviral Agents; Tenofovir; Emtricitabine
• Other Study ID Numbers: 20-070

Plan for Individual participant data (IPD)

• Plan to Share Individual Participant Data (IPD)?: YES
• IPD Plan Description: We encourage contact the corresponding author for academic IPD sharing

Drug and device information, study documents

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