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.

Tracking Information

• First Submitted Date: April 16, 2020
• First Posted Date: April 24, 2020
• Results First Submitted Date: March 22, 2022
• Results First Posted Date: March 29, 2022
• Last Update Posted Date: March 29, 2022
• Actual Study Start Date: April 17, 2020
• Actual Primary Completion Date: September 30, 2020 (Final data collection date for primary outcome measure)

Current Primary Outcome Measures (submitted: March 22, 2022)

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

Original Primary Outcome Measures (submitted: April 21, 2020)

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

Current Secondary Outcome Measures (submitted: March 25, 2022)

• 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.
• 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.
• Characterize the Pharmacokinetics (PK) of Favipiravir in Plasma: Cmax [ Time Frame: through Day 14 ]
  Measurement of maximum plasma concentration
• Characterized the Pharmacokinetics (PK) of Favipiravir in Plasma: Cmin [ Time Frame: through Day 14 ]
  Measurement of minimum plasma concentration
• 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

Original Secondary Outcome Measures (submitted: April 21, 2020)

• Status of clinical recovery as measured by the study-specific 6-point ordinal scale on Day 15 [ Time Frame: through 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.
• Clinical effect of favipiravir + SOC compared to SOC measured by the National Early Warning Score 2 (NEWS2) [ Time Frame: through Day 29 ]
  The NEWS 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.
• Characterize the pharmacokinetics (PK) of favipiravir in plasma: Cmax) [ Time Frame: through Day 14 ]
  Measurement of maximum plasma concentration
• Characterized the pharmacokinetics (PK) of favipiravir in plasma: Cmin [ Time Frame: through Day 14 ]
  Measurement of minimum plasma concentration
• Characterized the pharmacokinetics (PK) of favipiravir in plasma: AUC [ Time Frame: through Day 14 ]
  Measurement of the area under the curve of plasma concentration versus time profile

• Current Other Pre-specified Outcome Measures: Not Provided
• Original Other Pre-specified Outcome Measures: Not Provided

Descriptive Information

• Brief Title: Study of the Use of Favipiravir in Hospitalized Subjects With COVID-19
• 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
• 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 Type: Interventional
• Study Phase: Phase 2

Study Design

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

• Condition: COVID-19

Intervention

• 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
  Standard of Care for individual study site as determined by each hospital's protocol

Study Arms

• 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
  Intervention: Drug: Favipiravir
• Standard of Care Arm
  Standard of Care for 14 days
  Intervention: Other: Standard of Care

• 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.

Recruitment Information

• Recruitment Status: Completed
• Actual Enrollment (submitted: April 21, 2020): 50
• Original Estimated Enrollment: Same as current
• Actual Study Completion Date: October 30, 2020
• Actual Primary Completion Date: September 30, 2020 (Final data collection date for primary outcome measure)

Eligibility 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.

Sex/Gender

• Sexes Eligible for Study: All

• Ages: 18 Years to 80 Years (Adult, Older Adult)
• Accepts Healthy Volunteers: No
• Contacts: Contact information is only displayed when the study is recruiting subjects
• Listed Location Countries: United States

Administrative Information

• NCT Number: NCT04358549
• Other Study ID Numbers: FAVI-COV-US201
• Has Data Monitoring Committee: No

U.S. FDA-regulated Product

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

IPD Sharing Statement

• Plan to Share IPD: No

• Current Responsible Party: Fujifilm Pharmaceuticals U.S.A., Inc.
• Original Responsible Party: Same as current
• Current Study Sponsor: Fujifilm Pharmaceuticals U.S.A., Inc.
• Original Study Sponsor: Same as current
• Collaborators: Not Provided
• Investigators: Not Provided
• PRS Account: Fujifilm Pharmaceuticals U.S.A., Inc.
• Verification Date: March 2022