SARS-CoV-2 (Corona virus) infection MedDRA version: 23.0 Level: LLT Classification code 10053983 Term: Corona virus infection System Organ Class: 100000004862
Conditions
Interventions
Product Name: Favipiravir
Pharmaceutical Form: Tablet
INN or Proposed INN: Favipiravir
CAS Number: 259793-96-9
Other descriptive name: Avigan
Concentration unit: mg milligram(s)
Concentration type: eq
Sponsors
University College London Comprehensive Clinical Trial Unit
Eligibility
Sex/Gender
All
Inclusion criteria
Inclusion criteria: 1. Key workers (see definition in Appendix 2) and their household members with the following: o Symptoms compatible with COVID-19 disease (Fever >37.8oC on at least one occasion AND either cough and/ or anosmia) within the first 5 days of symptom onset (date/time of enrolment must be within the first 5 days of symptom onset) o OR ANY symptoms compatible with COVID-19 disease (may include, but are not limited to fever, cough, shortness of breath, malaise, myalgia, headache, coryza) and tested positive for SARS-CoV-2 within the first 7 days of symptom onset (date/time of enrolment must be within the first 7 days of symptom onset) o OR no symptoms but tested positive for SARS-CoV-2 within the last 48 hours (date/time of test must be within 48 hours of enrolment) 2. Male or female aged 18 years to 70 years old inclusive at screening 3. Willing and able to take daily saliva samples 4. Able to provide full informed consent and willing to comply with trial-related procedures Are the trial subjects under 18? no Number of subjects for this age range: 0 F.1.2 Adults (18-64 years) yes F.1.2.1 Number of subjects for this age range 240 F.1.3 Elderly (>=65 years) yes F.1.3.1 Number of subjects for this age range 240
Exclusion criteria
Exclusion criteria: 1. Known hypersensitivity to any of the active ingredients or excipients in favipiravir and matched placebo, and in lopinavir/ritonavir and matched placebo (See Appendix 3) 2. Chronic liver disease at screening (known cirrhosis of any aetiology, chronic hepatitis (e.g. autoimmune, viral, steatohepatitis), cholangitis or any known elevation of liver aminotransferases with AST or ALT > 3 X ULN)* 3. Chronic kidney disease (stage 3 or beyond) at screening: eGFR < 60 ml/min/1.73m2* 4. HIV infection, if untreated, detectable viral load or on protease inhibitor therapy 5. Any clinical condition which the investigator considers would make the participant unsuitable for the trial 6. Concomitant medications known to interact with favipiravir and matched placebo, and with lopinavir/ritonavir and matched placebo, and carry risk of toxicity for the participant (See Appendix 4) 7. Severe illness requiring hospitalisation 8. Pregnancy and/ or breastfeeding 9. Eligible female participants of childbearing potential and male participants with a partner of childbearing potential not willing to use highly effective contraceptive measures during the trial and within the time point specified following last trial treatment dose. 10. Participants enrolled in any other interventional drug or vaccine trial (co-enrolment in observational studies is acceptable). * Considering the importance of early treatment of COVID-19 to impact viral load, the absence of chronic liver/ kidney disease will be confirmed verbally by the participant during pre-screening and Screening/Baseline visit. Safety blood samples will be collected at Screening/Baseline visit (Day 1) and test results will be examined as soon as they become available within 24 hours.
Design outcomes
Primary
| Measure | Time frame |
|---|---|
| Main Objective: The objective of this trial is to assess whether early antiviral therapy with either favipiravir + LPV/r, LPV/r or favipiravir is associated with a decrease in viral load in the upper respiratory tract after 5 days of therapy, compared with placebo.;Secondary Objective: • Percentage of participants with undetectable upper respiratory tract viral load after 5 days of therapy • Proportion of participants with undetectable stool viral load after 7 days of therapy and 14 days post-randomisation • Rate of decrease in upper respiratory tract viral load during 7 days of therapy • Duration of fever following commencement of trial medications • Proportion of participants with hepatotoxicity after 7 days of therapy and 14 days post-randomisation • Proportion of participants with other medication-related toxicity after 7 days of therapy and 14 days post-randomisation • Proportion of participants admitted to hospital with COVID-19 related illness • Proportion of participants admitted to ICU with COVID-19 related illness • Proportion of participants who have died with COVID-19 related illness • Pharmacokinetic and pharmacodynamic analysis of favipiravir • Exploratory: Proportion of participants with deleterious or resistance-conferring mutations in SARS-CoV-2;Primary end point(s): The primary outcome is the upper respiratory tract viral load at Day 5. Method of measurement: Quantitative polymerase chain reaction (PCR) performed on saliva samples at Day 5 of therapy [Time Frame: Day 5 from randomisation];Timepoint(s) of evaluation of this end point: Time Frame: Day 5 from randomisation | — |
Secondary
| Measure | Time frame |
|---|---|
| Secondary end point(s): 1) Percentage of participants with undetectable upper respiratory tract viral load after 5 days of therapy Method of measurement: Quantitative polymerase chain reaction (PCR) performed on saliva samples at Day 5 of therapy [Time Frame: 5 days from randomisation] 2) Proportion of participants with undetectable stool viral load after 7 days of therapy and 14 days post-randomisation Method of measurement: Quantitative polymerase chain reaction (PCR) performed on stool samples at Day 7 and Day 14 post-randomisation [Time Frame: Day 7 and Day 14 from randomisation] 3) Rate of decrease in upper respiratory tract viral load during 7 days of therapy Method of measurement: PCR performed on daily saliva samples collected between Day 1 and Day 7 post-randomisation [Time Frame: 7 days] 4) Duration of fever following commencement of medication Method of measurement: Daily body temperature records between Day 1 and Day 7 post-randomisation [Time Frame: 7 days] 5) Proportion of participants with hepatotoxicity after 7 days of therapy and 14 days post-randomisation Method of measurement: Standard diagnostic laboratory assays for liver transaminases, alkaline phosphatase and bilirubin [Time Frame: Day 7 and Day 14 from randomisation] 6) Proportion of participants with other medication-related toxicity after 7 days of therapy and 14 days post-randomisation Method of measurement: Determination of medication-related adverse events by investigators at Day 7 and Day 14 post-randomisation [Time Frame: Day 7 and Day 14 from randomisation] 7) Proportion of participants admitted to hospital with COVID-19 related illness Method of measurement: Participant self-report, review of hospital records and discharge summaries within 28 days of randomisation [Time Frame: 28 days] 8) Proportion of participants admitted to ICU with COVID-19 related illness Method of measurement: Participant self-report, review of hospital records and discharge summaries within 28 days of r | — |
Countries
United Kingdom
Contacts
Public ContactFelicia Ikeji
University College London Comprehensive Clinical Trial Unit
Outcome results
None listed