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

Phase 2

Completed

• Conditions: COVID-19
• Interventions: Other: Standard of Care; Drug: Favipiravir

• Registration Number: NCT04358549
• Lead Sponsor: Fujifilm Pharmaceuticals U.S.A., Inc.

Brief Summary

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

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 Timeline

• Study First Submitted: 2020-04-16
• Study Start: 2020-04-17
• Study First Submitted QC: 2020-04-21
• Study First Posted: 2020-04-24
• Primary Completion: 2020-09-30
• Study Completion: 2020-10-30
• Disposition First Submitted: 2021-09-30
• Status Verified: 2022-03
• Results First Submitted: 2022-03-22
• Results First Submitted QC: 2022-03-25
• Disposition First Submitted QC: 2022-03-25
• Last Update Submitted: 2022-03-25
• Results First Posted: 2022-03-29
• Disposition First Posted: 2022-03-29
• Last Update Posted: 2022-03-29

Recruitment & Eligibility

• Status: COMPLETED
• Sex: All
• Target Recruitment: 50

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 & Design

• Study Type: INTERVENTIONAL
• Study Design: PARALLEL

Arm && Interventions

Group	Intervention	Description
Standard of Care Arm	Standard of Care	Standard of Care for 14 days
Favipiravir Treatment Arm	Favipiravir	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

Primary Outcome Measures

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

Secondary Outcome Measures

Name	Time	Method
Status of Clinical Recovery as Measured by the Study-specific 6-point Ordinal Scale	on Day 15	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.
Time to the National Early Warning Score 2 (NEWS2) of 2 or Less, or Hospital Discharge	through Day 29	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.
Characterize the Pharmacokinetics (PK) of Favipiravir in Plasma: Cmax	through Day 14	Measurement of maximum plasma concentration
Characterized the Pharmacokinetics (PK) of Favipiravir in Plasma: Cmin	through Day 14	Measurement of minimum plasma concentration
Characterized the Pharmacokinetics (PK) of Favipiravir in Plasma: Area Under Curve (AUC 0-24)	through Day 14	Measurement of the area under the curve of plasma concentration versus time profile

Trial Locations

Locations (8)

University of Miami Miller School of Medicine; 🇺🇸 Miami, Florida, United States

HonorHealth; 🇺🇸 Scottsdale, Arizona, United States

Boston Medical Center; 🇺🇸 Boston, Massachusetts, United States

Brigham and Women's Hospital; 🇺🇸 Boston, Massachusetts, United States

UMass Memorial Health Care; 🇺🇸 Worcester, Massachusetts, United States

Houston Methodist Hospital; 🇺🇸 Houston, Texas, United States

Massachusetts General Hospital; 🇺🇸 Boston, Massachusetts, United States

Atlantic Health System / Morristown Medical Center; 🇺🇸 Morristown, New Jersey, United States