Study of the Use of Favipiravir in Hospitalized Subjects With COVID-19

Open Label, Randomized, Controlled Phase 2 Proof-of-Concept Study of the Use of Favipiravir Compared to Standard of Care in Hospitalized Subjects With COVID-19

To determine the effect of favipiravir + SOC v. SOC on COVID-19 viral clearance.

Study Overview

• Status: Completed
• Conditions: COVID-19
• Intervention / Treatment: Drug: Favipiravir; Other: Standard of Care

Detailed Description

This is an open label, randomized, controlled, multicenter Phase 2 proof-of-concept study of favipiravir in hospitalized subjects with Corona Virus Disease (COVID) -19. Subjects will be randomized within their study site and stratified by the severity of their disease to receive either favipiravir + standard of care (SOC) or SOC alone.

The dose regimen will be 1800 mg favipiravir bis in die (BID) plus SOC or SOC alone on Day 1 followed by 1000 mg BID favipiravir (800 mg BID for subjects with Child-Pugh A liver impairment) plus SOC or SOC for the next 13 days.

The study will have 14 days of treatment and 46 days of follow-up.

Approximately 50 patients are planned to be enrolled in the trial at approximately 8 study sites in the US.

• Study Type: Interventional
• Enrollment (Actual): 50
• Phase: Phase 2

Contacts and Locations

Study Locations

• United States
  • Arizona
    • Scottsdale, Arizona, United States, 85258
      • Honorhealth
  • Florida
    • Miami, Florida, United States, 33136
      • University of Miami Miller School of Medicine
  • Massachusetts
    • Boston, Massachusetts, United States, 02118
      • Boston Medical Center
    • Boston, Massachusetts, United States, 02215
      • Brigham and Women's Hospital
    • Boston, Massachusetts, United States, 02215
      • Massachusetts General Hospital
    • Worcester, Massachusetts, United States, 01605
      • UMass Memorial Health Care
  • New Jersey
    • Morristown, New Jersey, United States, 07960
      • Atlantic Health System / Morristown Medical Center
  • Texas
    • Houston, Texas, United States, 77030
      • Houston Methodist Hospital

Participation Criteria

Eligibility Criteria

• Ages Eligible for Study: 18 years to 80 years (Adult, Older Adult)
• Accepts Healthy Volunteers: No
• Genders Eligible for Study: All

Description

Inclusion Criteria:

1) Adults (18 to 80 years old):

1. within 72 hours of their hospitalization for infection with Severe Acute Respiratory Syndrome - Corona Virus - 2 (SARS-CoV-2), AND,
2. within 72 hours of the latest Polymerase Chain Reaction (PCR) positive result and within 7 days of the 1st PCR positive result for SARS-CoV-2. (The latest PCR could be the only PCR result.), AND,
3. within 10 days of onset of any COVID-19 symptoms.

Exclusion Criteria:

1. Subject has a concomitant bacterial respiratory infection unless cleared by the Sponsor
2. Subject has a history of abnormalities of uric acid metabolism unless cleared by the Sponsor.
3. Subject has a history of hypersensitivity to an anti-viral nucleoside analog drug targeting a viral RNA polymerase
4. Subject is using adrenocorticosteroids (except topical or inhaled preparations or oral preparations equivalent to or less than 10 mg of oral prednisone) or immunosuppressive or immunomodulatory drugs (e.g., immunosuppressants, anticancer drugs, interleukins, interleukin antagonists or interleukin receptor blockers). Dexamethasone 6 mg daily (PO or IV) for 10 days is permitted.
5. Subject has a serious chronic disease (e.g., human immunodeficiency virus (HIV), cancer requiring chemotherapy within the preceding 6 months, moderate or severe hepatic insufficiency and/or unstable renal, cardiac, pulmonary, neurologic, vascular, or endocrinologic disease states requiring medication dose adjustments within the last 30 days).
6. Has previously received favipiravir within the past 30 days
7. Has renal insufficiency requiring hemodialysis or continuous ambulatory peritoneal dialysis (CAPD) or glomerular filtration rate of less than 20 mL/min.
8. Has liver impairment greater than Child-Pugh A.
9. Has a history of alcohol or drug abuse in the previous 6 months.
10. Has a psychiatric disease that is not well controlled where controlled is defined as: stable on a regimen for more than one year.
11. Has taken another investigational drug within the past 30 days.
12. Is on another antiviral or is participating in another clinical trial for the treatment of COVID-19
13. Subject is on a ventilator at the time of study entry
14. Is deemed by the Investigator to be ineligible for any reason.

Study Plan

How is the study designed?

Design Details

• Primary Purpose: Treatment
• Allocation: Randomized
• Interventional Model: Parallel Assignment
• Masking: None (Open Label)

Number of Arms

2

Arms and Interventions

Participant Group / Arm	Intervention / Treatment
Experimental: Favipiravir Treatment Arm; Day 1: favipiravir 1800 mg BID plus Standard of Care (SOC) Days 2-14: 1000 mg BID plus SOC. For subjects with Child-Pugh A liver impairment: Days 2-14: 800 mg BID plus SOC	Drug: Favipiravir; Favipiravir to be administered as an oral tablet or made into a slurry for subjects who cannot swallow tablets
Other: Standard of Care Arm; Standard of Care for 14 days	Other: Standard of Care; Standard of Care for individual study site as determined by each hospital's protocol

What is the study measuring?

Primary Outcome Measures

Outcome Measure	Measure Description	Time Frame
Time to Viral Clearance	To determine the effect of favipiravir + SOC v. SOC on viral clearance of COVID-19 as measured by nasopharyngeal and oropharyngeal sampling	Day 29

Secondary Outcome Measures

Outcome Measure	Measure Description	Time Frame
Status of Clinical Recovery as Measured by the Study-specific 6-point Ordinal Scale	To determine the clinical benefit of administering favipiravir plus SOC compared to SOC alone, clinical benefit will be measured using a study-specified ordinal scale on Day 15 in adult patients hospitalized with COVID-19.	on Day 15
Time to the National Early Warning Score 2 (NEWS2) of 2 or Less, or Hospital Discharge	The NEWS2 is based on a simple aggregate scoring system in which a score is allocated to physiological measurements, already recorded in routine practice, when patients present to, or are being monitored in hospital. Six simple physiological parameters form the basis of the scoring system: respiration rate, oxygen saturation, systolic blood pressure, pulse rate, level of consciousness or new confusion, temperature. The time to aggregate NEWS2 score of ≤ 2 (sustained for at least 72 hours) or hospital discharge is analyzed.	through Day 29
Characterize the Pharmacokinetics (PK) of Favipiravir in Plasma: Cmax	Measurement of maximum plasma concentration	through Day 14
Characterized the Pharmacokinetics (PK) of Favipiravir in Plasma: Cmin	Measurement of minimum plasma concentration	through Day 14
Characterized the Pharmacokinetics (PK) of Favipiravir in Plasma: Area Under Curve (AUC 0-24)	Measurement of the area under the curve of plasma concentration versus time profile	through Day 14

Collaborators and Investigators

• Sponsor: Fujifilm Pharmaceuticals U.S.A., Inc.

Publications and helpful links

General Publications

• Finberg RW, Ashraf M, Julg B, Ayoade F, Marathe JG, Issa NC, Wang JP, Jaijakul S, Baden LR, Epstein C. US201 Study: A Phase 2, Randomized Proof-of-Concept Trial of Favipiravir for the Treatment of COVID-19. Open Forum Infect Dis. 2021 Dec 7;8(12):ofab563. doi: 10.1093/ofid/ofab563. eCollection 2021 Dec.

Study record dates

Study Major Dates

• Study Start (Actual): April 17, 2020
• Primary Completion (Actual): September 30, 2020
• Study Completion (Actual): October 30, 2020

Study Registration Dates

• First Submitted: April 16, 2020
• First Submitted That Met QC Criteria: April 21, 2020
• First Posted (Actual): April 24, 2020

Study Record Updates

• Last Update Posted (Actual): March 29, 2022
• Last Update Submitted That Met QC Criteria: March 25, 2022
• Last Verified: March 1, 2022

More Information

Terms related to this study

• 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: FAVI-COV-US201

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