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

• ClinicalTrials.gov Identifier: NCT04358549
• Recruitment Status: Completed
• First Posted: April 24, 2020
• Results First Posted: March 29, 2022
• Last Update Posted: March 29, 2022
• Sponsor: Fujifilm Pharmaceuticals U.S.A., Inc.
• Information provided by (Responsible Party): Fujifilm Pharmaceuticals U.S.A., Inc.

Study Description

Brief Summary:

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

Condition or disease	Intervention/treatment	Phase
COVID-19	Drug: Favipiravir; Other: Standard of Care	Phase 2

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 Design

• Study Type: Interventional (Clinical Trial)
• Actual Enrollment: 50 participants
• Allocation: Randomized
• Intervention Model: Parallel Assignment
• Intervention Model Description: Open-label, randomized (1:1 ratio) to receive favipiravir plus standard of care or standard of care alone.
• Masking: None (Open Label)
• Primary Purpose: Treatment
• Official Title: 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
• Actual Study Start Date: April 17, 2020
• Actual Primary Completion Date: September 30, 2020
• Actual Study Completion Date: October 30, 2020

Arms and Interventions

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
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

Outcome Measures

Primary Outcome Measures :

1. Time to Viral Clearance [ Time Frame: 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 :

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

Eligibility Criteria

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

Criteria

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.

Contacts and Locations

Locations

United States, Arizona

HonorHealth

Scottsdale, Arizona, United States, 85258

United States, Florida

University of Miami Miller School of Medicine

Miami, Florida, United States, 33136

United States, Massachusetts

Boston Medical Center

Boston, Massachusetts, United States, 02118

Brigham and Women's Hospital

Boston, Massachusetts, United States, 02215

Massachusetts General Hospital

Boston, Massachusetts, United States, 02215

UMass Memorial Health Care

Worcester, Massachusetts, United States, 01605

United States, New Jersey

Atlantic Health System / Morristown Medical Center

Morristown, New Jersey, United States, 07960

United States, Texas

Houston Methodist Hospital

Houston, Texas, United States, 77030

Sponsors and Collaborators

Fujifilm Pharmaceuticals U.S.A., Inc.

  Study Documents (Full-Text)

Documents provided by Fujifilm Pharmaceuticals U.S.A., Inc.:

Study Protocol  [PDF] July 15, 2020

Statistical Analysis Plan  [PDF] December 15, 2020

More Information

Publications automatically indexed to this study by ClinicalTrials.gov Identifier (NCT Number):

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.

• Responsible Party: Fujifilm Pharmaceuticals U.S.A., Inc.
• ClinicalTrials.gov Identifier: NCT04358549
• Other Study ID Numbers: FAVI-COV-US201
• First Posted: April 24, 2020
• Results First Posted: March 29, 2022
• Last Update Posted: March 29, 2022
• Last Verified: March 2022

Individual Participant Data (IPD) Sharing Statement:

• Plan to Share IPD: No

• Studies a U.S. FDA-regulated Drug Product: Yes
• Studies a U.S. FDA-regulated Device Product: No

Additional relevant MeSH terms:

COVID-19; Pneumonia, Viral; Pneumonia; Respiratory Tract Infections; Infections; Virus Diseases; Coronavirus Infections; Coronaviridae Infections; Nidovirales Infections; RNA Virus Infections; Lung Diseases; Respiratory Tract Diseases; Favipiravir; Antiviral Agents; Anti-Infective Agents