Favipiravir Therapy in Adults With Mild COVID-19 (Avi-Mild)

A Trial of Favipiravir Therapy in Adults With Mild Coronavirus Disease COVID-19

Favipiravir is a selective and potent inhibitor of influenza viral RNA polymerase. It acts as a purine analogue, which selectively inhibits viral RNA-dependent RNA polymerase (RdRps). It has the characteristic of acting on RNA viruses including Ebola and Coronaviruses especially novel coronavirus (2019-nCoV). The purpose of this study is to evaluate the clinical efficacy and safety of Favipiravir in comparison to placebo in the treatment of mild COVID-19 cases. It is a Multicenter, randomized double-blinded, parallel-group trial.

Study Overview

• Status: Completed
• Conditions: COVID-19
• Intervention / Treatment: Drug: Favipiravir; Drug: Placebo

• Study Type: Interventional
• Enrollment (Actual): 231
• Phase: Phase 2; Phase 3

Contacts and Locations

Study Locations

• Saudi Arabia
  • Al Madinah, Saudi Arabia
    • Prince Mohammed Bin Abdul Aziz Hospital - Al Madinah
  • Al Madīnah, Saudi Arabia
    • King Fahad Hospital - Madinah
  • Al Madīnah, Saudi Arabia
    • Primary Health Care-Safiyah
  • Mecca, Saudi Arabia
    • King Abdullah Medical City - Makkah
  • Riyadh, Saudi Arabia
    • King Abdulaziz Medical City - Riyadh
  • Riyadh, Saudi Arabia
    • Primary Health Care-Al Mansoura
  • Riyadh, Saudi Arabia
    • Primary Health Care-Al Urijah

Participation Criteria

Eligibility Criteria

• Ages Eligible for Study: 18 years to 100 years (Adult, Older Adult)
• Accepts Healthy Volunteers: No
• Genders Eligible for Study: All

Description

Inclusion Criteria

Patients must be eligible according to the following criteria for enrollment

1. Should be at least 18 years of age
2. Male or non-pregnant female (pregnancy testing is not mandatory. If the patient requests or is not sure, the study team will provide it)
3. Diagnosed with mild COVID-19* confirmed by positive PCR test for SARS-CoV-2 at the time of recruitment, a result within the last five days
4. Patients have to be enrolled within 5 days of disease onset.

Exclusion criteria

Patients meeting any of the following criteria will be excluded from trial enrolment:

1. Patients with concomitant documented bacterial pneumonia established through positive sputum cultures
2. Patients who are pregnant or breastfeeding
3. Known sensitivity/allergy to Favipiravir (If Faviparavir was used for COVID-19 in the patient previously for influenza)

4. Major comorbidities increasing the risk of study drug including

   • Hematologic malignancy
   • Advanced (stage 4-5) chronic kidney disease or dialysis therapy
   • Severe liver damage (Child-Pugh score C, AST> 5 times the upper limit)
   • HIV
   • Gout/history of Gout or hyperuricemia (two times above the ULN)

(6) Having used Favipiravir or participated in any other interventional drug clinical study within 30 days before the first dose of study drug (i.e., the patient received it for influenza previously) (7) The investigator believes that participating in the trial is not in the best interests of the patient, or the investigator considers unsuitable for enrollment (such as unpredictable risks or subject compliance issues) (8) Clinical prognostic non-survival, palliative care, or in a deep coma and have no response to supportive treatment within three hours of admission.

(9) Hospitalized patients for mild, moderate, or severe COVID-19

Study Plan

How is the study designed?

Design Details

• Primary Purpose: Treatment
• Allocation: Randomized
• Interventional Model: Parallel Assignment
• Masking: Double

Number of Arms

2

Arms and Interventions

Participant Group / Arm	Intervention / Treatment
Experimental: Favipiravir; Favipiravir: 1800 mg (9 tablets) by mouth twice daily for one day, followed by 800mg (4 tablets) twice daily (Maximum days of therapy is 7 days)	Drug: Favipiravir; 1800 mg twice daily for one day, followed by 800mg (4 tablets) twice daily
Placebo Comparator: Placebo; 9 tablets by mouth twice daily for one day, followed by 4 tablets twice daily (Maximum days of therapy is 7 days).	Drug: Placebo; (9 tablets) by mouth twice daily for one day, followed by (4 tablets) twice daily (Maximum days of therapy is 7 days)

What is the study measuring?

Primary Outcome Measures

Outcome Measure	Measure Description	Time Frame
PCR negative	Time from randomization to negativity in RT-PCR nucleic acid test for COVID-19 within 15 days of randomization	15 days

Secondary Outcome Measures

Outcome Measure	Measure Description	Time Frame
Time from randomization to clinical recovery	The duration from start of treatment (Favipiravir or placebo) to normalization of pyrexia, respiratory symptoms, and relief of cough (or other relevant symptoms at enrollment) that is maintained for at least 72 hours.	15 days
Evaluate symptoms progression	Evaluate symptoms severity and the disease course progression in both arms till 28 days after starting the medicine.	28 days
Evaluate Faviparivirs effect	To evaluate Favipiravir's effect on the requirement of the use of antipyretics, analgesics, or antibiotics within 15 days after starting medicine.	15 days
Evaluate Favipiravir's effect	To evaluate Favipiravir's effect on disease complications within 28 days after starting medicine (hospitalization, ICU admission, or Mechanical ventilation )	28 days
Evaluate the safety of Favipiravir	Evaluate the safety of investigational drug compared to the control arm within 15 days after starting the medicine. This is assessed by allergic reactions, medication intolerance, liver toxicity, and hyperuricemia in subjects	28 days

Collaborators and Investigators

• Sponsor: King Abdullah International Medical Research Center
• Collaborators: Ministry of Health, Saudi Arabia
• Investigators: Principal Investigator: Mohammad Bosaeed, KAMC-RD, Ministry of National Guard Health Affairs (MNGHA), Saudi Arabia

Publications and helpful links

General Publications

• Bosaeed M, Alharbi A, Hussein M, Abalkhail M, Sultana K, Musattat A, Alqahtani H, Alshamrani M, Mahmoud E, Alothman A, Alsaedy A, Aldibasi O, Alhagan K, Asiri AM, AlJohani S, Al-Jeraisy M, Alaskar A. Multicentre randomised double-blinded placebo-controlled trial of favipiravir in adults with mild COVID-19. BMJ Open. 2021 Apr 14;11(4):e047495. doi: 10.1136/bmjopen-2020-047495.

Study record dates

Study Major Dates

• Study Start (Actual): July 23, 2020
• Primary Completion (Actual): August 4, 2021
• Study Completion (Actual): August 4, 2021

Study Registration Dates

• First Submitted: June 28, 2020
• First Submitted That Met QC Criteria: July 8, 2020
• First Posted (Actual): July 9, 2020

Study Record Updates

• Last Update Posted (Actual): November 5, 2021
• Last Update Submitted That Met QC Criteria: November 4, 2021
• Last Verified: November 1, 2021

More Information

Terms related to this study

• Keywords: COVID19; Favipiravir; Mild illness; Saudi Arabia
• 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; Anti-Infective Agents; Antiviral Agents; Favipiravir
• Other Study ID Numbers: RC 20/220/R

Plan for Individual participant data (IPD)

• Plan to Share Individual Participant Data (IPD)?: No

Drug and device information, study documents

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