The Prevent Severe COVID-19 (PRESECO) Study

Study Overview
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Brief Summary
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Double-blinded, placebo control, randomized, phase-3 clinical trial to evaluate clinical efficacy of Favipiravir in patients with mild to moderate symptoms related to COVID-19 infection

Detailed Description
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COVID-19 starts as a pure viral infection and evolves into a multifactorial disease with components of hyper immune activation, end organ damage, and fibrosis. Suppression of viral replication is expected to be impactful early in the course of disease. The ability to mitigate the symptoms at an early stage will prevent progression to severe COVID-19 and can save many lives. Early treatment could also reduce viral shedding, diminishing the period of infectivity and decreasing the number of secondary cases.

Official Title
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Favipiravir for Patients With Mild to Moderate Disease From Novel Coronavirus (COVID-19)

Conditions
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Covid19

Intervention / Treatment
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* Drug: Favipiravir
* Drug: Placebo


Participation Criteria
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Eligibility Criteria
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Inclusion Criteria: Adults age 18 or older Tested positive for SARS-CoV-2 by RT-PCR assay using a respiratory tract sample (either nasopharyngeal swab OR oropharyngeal swab OR nasal aspirate OR tracheobronchial aspirate OR saliva) collected within 72 hours of randomization Stated willingness to give their written informed consent to participate in the study Stated willingness to comply with all study procedures and availability for the duration of the study Males must be sterile, OR agree not to donate semen AND agree to strictly adhere to contraceptive measures during the study and for 7 days following the last dose of study medication Females must be unable to bear children, OR ensure that their male partner is incapable of fathering a child, OR, if of childbearing potential will strictly adhere to contraceptive measures during the study and for seven days following the last dose of study medication Females must agree to stop breast-feeding prior to first dose of study drug and through seven days after completing therapy Females must have a negative pregnancy test at screening Ability to take oral medication and be willing to adhere to the favipiravir/placebo regimen Subject has access to a smart phone, tablet, or PC Minimal baseline severity score for COVID-19-related symptoms: at least two symptoms with a score of 2 or higher. COVID-19-related symptoms (excluding changes in the sense of taste or smell) include: stuffy or runny nose sore throat shortness of breath cough lack of energy or tiredness muscle or body aches headache chills or shivering feeling hot or feverish nausea diarrhea vomiting Exclusion Criteria: O2 saturation <94% Shortness of breath at rest Heart rate ≥ 125 per minute COVID-19 symptoms first presented >5 days prior to randomization Requirement for hospitalization at the time of enrollment Participation in another trial or use of any experimental treatment for COVID-19 Treatment with high steroid dose i.e. >30 mg/day prednisolone equivalent (excluding stable chronic treatment) or remdesivir or anyone receiving SARS-CoV-2 monoclonal antibodies within 3 months prior to enrollment Known sepsis or organ dysfunction/ failure Known infection with a respiratory virus other than SARS-CoV2 (e.g. Influenza) or any known bacterial infection (affecting the respiratory system or any other system) Inability to adhere to study requirements For premenopausal women: unwilling or unable to use effective birth control measures Known allergy to favipiravir Known end-stage kidney disease or requiring hemodialysis or continuous ambulatory peritoneal dialysis (CAPD) Known liver impairment greater than Child-Pugh A Psychiatric illness that is not well controlled (defined as stable on a regimen for more than one year). Known elevated uric acid levels in the past year or taking uric acid lowering medications (allopurinol, febuxostat) History of hereditary xanthinuria or history of xanthine urolithiasis. History of gout or actively being treated for gout. Current use of the following medications, which cannot be discontinued for the duration of the study: pyrazinamide, hydralazine, more than 3000 mg of acetaminophen per day.

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: Triple


Arms and Interventions

| Participant Group/Arm | Intervention/Treatment |
| --- | --- |
| Experimental: Favipiravir<br>Favipiravir 200mg tablet | Drug: Favipiravir<br>* Favipiravir<br>|
| Placebo Comparator: Placebo<br>Placebo 200mg tablet | Drug: Placebo<br>* Placebo<br>|

What is the study measuring?
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Primary Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| Time to sustained clinical recovery | The endpoint will be considered to have been met at the earliest time point at which the subject has reached Sustained Alleviation of Symptoms (Symptoms related to smell or taste are not included in the primary endpoint) reported by the patient have reached a severity of 0 - none or 1 - mild in assessments for 4-point scale assessments and not known to have redeveloped any COVID-19 associated signs and symptoms (not including reduced sense of taste or smell) in a severity beyond mild for 4 consecutive days when assessed from the start of study treatment to day 28. To meet the primary endpoint, subjects must survive with no hospitalization to day 28. | From Day 0 to Day 28 | 

Secondary Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| Proportion of subjects with COVID-19 progression (narrow progression) | Proportion of subjects with COVID-19 progression, where progression is defined as the occurrence from study day 3 onward of any emergency department (ED) visit for COVID-19 worsening or shortness of breath OR hospitalization for COVID-19 worsening or shortness of breath OR death (narrow progression) | From study day 3 to day 28 | 
| Proportion of subjects with COVID-19 progression (broad progression) | • Proportion of subjects with COVID-19 progression, defined as the occurrence from study day 3 onward of any ED visit for COVID worsening or shortness of breath OR hospitalization for COVID worsening or shortness of breath OR death OR the development of symptomatic worsening from study day 3 onward (defined as >2 additional COVID symptoms at a level of moderate or severe which have not existed on study day 1 or fever (temperature of ≥38.0ºC) which has not existed on study day 1 or oxygen desaturation (O2 saturation <94%) which has not existed on study day 1) (broad progression) | From study day 3 to day 28 | 
| Viral Shedding Sub-Study | Time (number of days) to negative conversion (defined as <100 RNA copies) of detectable SARS-CoV-2 viral RNA (defined as >100 RNA copies) in negative RT-PCR assays of saliva, from start of study treatment to study day 10. Included: all subjects with a positive PCR on study day 1 or 2 or 3. The endpoint will be evaluated from study day 3 onward. | From study day 3 to day 28 | 
| Proportion of subjects showing sustained clinical recovery by study Day 3, 5, 7, 10, 14, 21. | Proportion of subjects showing sustained clinical recovery by study Day 3, 5, 7, 10, 14, 21. | Day 3, 5, 7, 10, 14, 21. | 
| Proportion of subjects showing resolution of Symptoms by Days 3, 5, 7, 10, 14, 21 | Proportion of subjects showing resolution of Symptoms by Days 3, 5, 7, 10, 14, 21, where resolution is defined as symptom severity of 0 for all symptoms as well as temperature of <38.0 ºC as well as oxygen saturation of ≥94%. | Days 3, 5, 7, 10, 14, 21 | 
| Proportion of patients showing negative conversion of detectable SARS-CoV-2 viral RNA in saliva | Defined as SARS-CoV-2 viral load conversion from >100 on study day 1 or 2 or 3 to <100 thereafter) on Study Days 3, 5, 7, and 10. Included: all subjects with a positive PCR on study day 1 or 2 or 3. | Study Days 3, 5, 7, and 10. | 
| Proportion of patients showing negative conversion of positive SARS-CoV-2 viral culture in saliva on Study Days 3, 5, 7 and 10 | Subjects with a positive saliva SARS-CoV-2 PCR on any study day will have viral cultures performed. Subjects with a positive viral culture on day 1 or 2 or 3 will be included in this analysis. | Study Days 3, 5, 7 and 10 | 
| Proportion of subjects dying from any cause over an assessment period from start of study treatment until Day 28. | Proportion of subjects dying from any cause over an assessment period from start of study treatment until Day 28. | Until day 28 | 
| Proportion of subject with COVID-19 progression | Proportion of subject with COVID-19 progression, where progression is defined as the occurrence at any point from study day 1 to study day 28 of emergency department (ED) visit for any reason OR hospitalization for any reason. | Up to day 28 |