An Adaptive Clinical Trial of Antivirals for COVID-19 Infection

Study Overview
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Brief Summary
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This is a randomised placebo controlled phase II trial to examine the efficacy of antivirals to treat COVID-19 infection compared to placebo for virological cure and improved clinical outcomes. Individuals will be randomised to the candidate antiviral which in the first instance is Favipiravir or matched placebo and randomisation will be stratified according to whether the participant requires hospitalisation or not. This treatment will be given in addition to the usual standard of care in the participating hospital.

Official Title
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An Adaptive Randomised Placebo Controlled Phase II Trial of Antivirals for COVID-19 Infection

Conditions
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COVID

Intervention / Treatment
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* Drug: Favipiravir


Participation Criteria
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Eligibility Criteria
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Inclusion Criteria: Provision of informed consent by the participant or authorized representative Age ≥18 years Confirmed SARS-CoV-2 by nucleic acid testing in the past 5 days COVID-19 related symptom initiation within 5 days Female patients of childbearing potential must have a negative pregnancy test at Screening. Female patients of childbearing potential and fertile male patients who are sexually active with a female of childbearing potential must use highly effective methods of contraception throughout the study and for 1 week following the last dose of study treatment. Exclusion Criteria: Known allergy to the study medication Is on another antiviral for the treatment of COVID-19 Pregnancy Patients with severe hepatic dysfunction equivalent to Grade C in the Child-Pugh classification Patients with renal impairment requiring dialysis Is deemed by the Investigator to be ineligible for any reason

Ages Eligible for Study
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Minimum Age: 18 Years

Sexes Eligible for Study
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All

Accepts Healthy Volunteers
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No

Study Plan
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How is the study designed?
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Design Details

Primary Purpose: Treatment
Allocation: Randomized
Intervention Model: Parallel Assignment
Masking: Quadruple


Arms and Interventions

| Participant Group/Arm | Intervention/Treatment |
| --- | --- |
| Experimental: Favipiravir<br>1800 mg Favipiravir twice daily on Day 1 followed by 800 mg Favipiravir twice daily for the next 13 days. | Drug: Favipiravir<br>* Favipiravir<br>|
| Placebo Comparator: Placebo<br>Matched Placebo | Drug: Favipiravir<br>* Favipiravir<br>|

What is the study measuring?
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Primary Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| Time to virological cure | Time to 2 successive throat (or combined nose/throat) swabs negative for SARS-CoV-2 by nucleic acid testing | 14 days | 

Secondary Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| Safety | All adverse events definitely, probably or possibly related to study treatment. | 28 days | 
| Clinical improvement | Time from randomization to an improvement of two points (from the status at randomization) on the 7-point ordinal scale | 28 days | 
| Clinical symptoms | Time from randomization to resolution of clinical symptoms (fever, cough, shortness of breath, cough). Resolution defined as the start of the first 24 hour period when all symptoms are rated as mild or absent and remained this way for 24 hours | 28 days | 
| Biomarkers | Biomarkers taken as part of routine care including total lymphocyte count, CRP, Ferritin and LDH. | 28 days |