FLARE: Favipiravir +/- Lopinavir: A RCT of Early Antivirals
Condition: COVID-19
MeSH terms: COVID-19
Study type: Interventional
Phase: Phase 2

Summary: 
      The current pandemic of SARS-CoV-2 causing COVID-19 disease is an unprecedented global
      emergency. COVID-19 appears to be a disease with an early phase where the virus replicates,
      coinciding with first presentation of symptoms, followed by a later 'inflammatory' phase
      which results in severe disease in some individuals. It is known from other rapidly
      progressive infections such as sepsis and influenza that early treatment with antimicrobials
      is associated with better outcome. Antiviral medications are most likely to be effective when
      administered soon after infection. There is therefore an urgent need to study subjects who
      have recently developed symptoms, or have recently been tested positive with or without
      symptoms, and who can be sampled frequently to understand changes in viral load. This cohort
      will allow us to collect detailed trajectory data on early disease and understand how
      pharmacological interventions may affect this. The objective of the FLARE trial is to assess
      whether early antiviral therapy with either favipiravir + Lopinavir/ritonavir (LPV/r), LPV/r
      or favipiravir is associated with a decrease in viral load compared with placebo. The
      hypothesis is that this holds for COVID-19 and that early antiviral treatment may prevent
      progression to the later phase of the disease.
    

Detailed description: 
      FLARE is a phase IIA randomised, double-blind, 2x2 factorial placebo-controlled,
      interventional trial in which 240 participants, aged 18 years (≥ 18 years) to 70 years old
      inclusive will be recruited. Participants will be adults who have developed the early
      symptoms of COVID-19 within the first 5 days, or tested positive for SARS-CoV-2 within the
      first 7 days of symptom onset, or not presenting symptoms but tested positive within the last
      48 hours (date/time of test must be within 48 hours of enrolment).

      Eligible participants will be randomised 1:1:1:1 to receive one of the following
      combinations:

      Favipiravir + Lopinavir/ritonavir (LPV/r) (both active); Favipiravir active +
      Lopinavir/ritonavir (LPV/r) placebo; Favipiravir placebo + Lopinavir/ritonavir (LPV/r)
      active; Favipiravir placebo + Lopinavir/ritonavir (LPV/r) placebo;

      All participants will be enrolled and followed up for 28 days. A saliva sample for
      virological analysis and safety blood samples will be collected at baseline, as well as a
      diagnostic nose and throat swab, if the participant hasn't been tested for COVID-19 yet.
      Following randomisation, participants will take trial medication for 7 days and during this
      period will take a daily saliva sample and complete a symptoms diary including four daily
      temperature measurements.

      Participants will have two follow-up visits at Day 7 and Day 14 where they will be assessed
      and undergo blood tests for toxicity and pharmacokinetic assessment (on Day 7 only) and
      provide stool samples. Participants will have a telephone follow up three (3) weeks after
      their last day of treatment (Day 7) and further information will be collected through a
      questionnaire.
    

Intervention name(s): Favipiravir; Lopinavir/ Ritonavir; Favipiravir Placebo; Lopinavir/ Ritonavir Placebo
Intervention type(s): Drug; Drug; Other; Other
Intervention description(s): Dosage and method of administration: Day 1: 1800 mg twice daily; Day 2 to Day 7: 400 mg four (4) times daily.; Dosage and method of administration: Day 1: 400mg/100 mg twice daily; Day 2 to Day 7: 200mg/50mg four (4) times daily; Dosage and method of administration: Day 1: 1800 mg twice daily; Day 2 to Day 7: 400 mg four (4) times daily.; Dosage and method of administration: Day 1: 1800 mg twice daily; Day 2 to Day 7: 400 mg four (4) times daily.
Other intervention name(s): Avigan; Kaletra
Intervention MeSH terms: Ritonavir; Lopinavir; Favipiravir
Allocation: Randomized
Intervention model: Factorial Assignment
Intervention model description: Randomised, double-blind, 2x2 factorial placebo-controlled
Masking: Triple (Participant, Care Provider, Investigator)
Primary purpose: Treatment