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CompletedNCT04358549Updated Mar 29, 2022Results posted

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

A Phase 2 interventional study of Favipiravir and Standard of Care in COVID-19, sponsored by Fujifilm Pharmaceuticals U.S.A., Inc.. Completed at 8 sites in United States. Open to participants aged 18 Years to 80 Years. Per ClinicalTrials.gov, last updated 2022-03-29.

Sponsored by Fujifilm Pharmaceuticals U.S.A., Inc. · Phase 2, Interventional, and Treatment

Phase
Phase 2
Study type
Interventional
Enrollment
50
Allocation
Randomized
Ages
18 Years to 80 Years
Sex
All
01

Study summary

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

Read the 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.

02

Conditions studied

  • COVID-19

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03

In context

COVID-19

7,640 studies on the registry are indexed under COVID-19; 488 are open to participants now.

This study's enrollment of 50 is below the median of 100 across 4,099 interventional studies indexed under COVID-19.

Browse COVID-19 studies →

Lead sponsor

Fujifilm Pharmaceuticals U.S.A., Inc. is the lead sponsor of 9 studies on the registry; none are open to participants now.

Counted across the registry records on this site, refreshed daily.

04

Who can participate

Ages eligible
18 Years to 80 Years
Sexes eligible
All
Accepts healthy volunteers
No

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

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.
05

Study design

Phase
Phase 2
Primary purpose
Treatment
Allocation
Randomized
Intervention model
Parallel assignment
Masking
None (open label)
Enrollment
50 participants (actual)

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

    Drug: Favipiravir

  • Other
    Standard of Care Arm

    Standard of Care for 14 days

    Other: Standard of Care

Interventions

  • DrugFavipiravir

    Favipiravir to be administered as an oral tablet or made into a slurry for subjects who cannot swallow tablets

  • OtherStandard of Care

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

06

What researchers measure

Primary outcomes

  1. 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

    Time frame: Day 29

Secondary outcomes

  1. 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.

    Time frame: on Day 15

  2. 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.

    Time frame: through Day 29

  3. Characterize the Pharmacokinetics (PK) of Favipiravir in Plasma: Cmax

    Measurement of maximum plasma concentration

    Time frame: through Day 14

  4. Characterized the Pharmacokinetics (PK) of Favipiravir in Plasma: Cmin

    Measurement of minimum plasma concentration

    Time frame: through Day 14

  5. 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

    Time frame: through Day 14

07

Results

Posted Mar 29, 2022

Participant flow

Participant flow — Overall Study
MilestoneFavipiravir Treatment ArmStandard of Care Arm
Started2525
Itt population (randomized subjects)2525
Safety population (patients who received either favipiravir + soc or soc alone)2425
Completed1517
Not completed108
Withdrew: Adverse event01
Withdrew: Death10
Withdrew: Lost to follow-up21
Withdrew: Withdrawal by subject66
Withdrew: Start remdesivir10

Outcome measures

PrimaryTime 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

Time frame:
Day 29
Reported as:
Median · days
Time to Viral Clearance
daysFavipiravir Treatment ArmStandard of Care Arm
Time to Viral Clearance16.0 (12.0 to 29.0)30.0 (12.0 to 31.0)
Statistical analysis
  • Favipiravir Treatment Arm vs Standard of Care Arm · Log Rank · p = 0.0415 · Median difference (final values): 14
SecondaryStatus 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.

Time frame:
on Day 15
Reported as:
Count of participants · Participants
Status of Clinical Recovery as Measured by the Study-specific 6-point Ordinal Scale
ParticipantsFavipiravir Treatment ArmStandard of Care Arm
Not Hospitalized1818
Hospitalized, not requiring supplemental oxygen13
Hospitalized, requiring supplemental oxygen41
Hospitalized, on non-invasive ventilation or high flow oxygen devices00
Hospitalized, on invasive mechanical ventilation or ECMO10
Death00
Not available13
Statistical analysis
  • Favipiravir Treatment Arm vs Standard of Care Arm · Odds ratio (or): 0.653 · 90% CI 0.190 to 2.240
SecondaryTime 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.

Time frame:
through Day 29
Reported as:
Median · days
Time to the National Early Warning Score 2 (NEWS2) of 2 or Less, or Hospital Discharge
daysFavipiravir Treatment ArmStandard of Care Arm
Time to the National Early Warning Score 2 (NEWS2) of 2 or Less, or Hospital Discharge4.0 (3.0 to 8.0)7.0 (4.0 to 10.0)
Statistical analysis
  • Favipiravir Treatment Arm vs Standard of Care Arm · Log Rank · p = 0.9879 · Median difference (final values): 3
SecondaryCharacterize the Pharmacokinetics (PK) of Favipiravir in Plasma: Cmax

Measurement of maximum plasma concentration

Time frame:
through Day 14
Reported as:
Median · µg/mL
Characterize the Pharmacokinetics (PK) of Favipiravir in Plasma: Cmax
µg/mLFavipiravir Treatment Arm
Day 160.9 (22.0 to 84.5)
Day 247.1 (16.7 to 109)
Day 851.4 (17.1 to 133)
Day 1450.8 (14.2 to 134)
SecondaryCharacterized the Pharmacokinetics (PK) of Favipiravir in Plasma: Cmin

Measurement of minimum plasma concentration

Time frame:
through Day 14
Reported as:
Median · µg/mL
Characterized the Pharmacokinetics (PK) of Favipiravir in Plasma: Cmin
µg/mLFavipiravir Treatment Arm
Day 13.24 (0.120 to 36.1)
Day 28.19 (0.152 to 70.2)
Day 817.1 (1.04 to 88.4)
Day 1415.5 (0.815 to 87.4)
SecondaryCharacterized 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

Time frame:
through Day 14
Reported as:
Median · hr*µg/mL
Characterized the Pharmacokinetics (PK) of Favipiravir in Plasma: Area Under Curve (AUC 0-24)
hr*µg/mLFavipiravir Treatment Arm
Day 1414 (161 to 1240)
Day 2488 (135 to 2120)
Day 8786 (189 to 2580)
Day 14772 (151 to 2680)

Adverse events

Collected over Until 60 days from Enrollment. Non-serious events are listed at a 4% frequency threshold.

Adverse event summary by group
GroupDeathsSeriousOther
Favipiravir Treatment Arm1/24 (4.2%)2/24 (8.3%)13/24 (54.2%)
Standard of Care Arm0/25 (0%)3/25 (12%)12/25 (48%)
Most frequent serious events
Most frequent serious events
EventFavipiravir Treatment ArmStandard of Care Arm
OsteomyelitisInfections and infestations1/240/25
Staphylococcal infectionInfections and infestations1/240/25
Basal ganglia hemorrhageNervous system disorders1/240/25
NecrosisGeneral disorders0/241/25
Clostridium difficile infectionInfections and infestations0/241/25
Urinary tract infectionInfections and infestations0/241/25
Failure to thriveMetabolism and nutrition disorders0/241/25
Most frequent other events
Most frequent other events
EventFavipiravir Treatment ArmStandard of Care Arm
Inflammatory marker increasedInvestigations1/244/25
Respiratory failureRespiratory, thoracic and mediastinal disorders1/244/25
Gamma-glutamyltransferase increasedInvestigations3/240/25
Acute kidney injuryRenal and urinary disorders3/240/25
Blood lactate dehydrogenase increasedInvestigations2/240/25
NauseaGastrointestinal disorders2/242/25
HeadacheNervous system disorders2/241/25
ConstipationGastrointestinal disorders0/242/25
DyspepsiaGastrointestinal disorders0/242/25
DizzinessNervous system disorders0/242/25

Baseline characteristics

Intent-to-Treat (ITT) population

Age, Continuous
Age, Continuous(years)Favipiravir Treatment ArmStandard of Care ArmTotal
Mean55.4 ± 12.3758.9 ± 13.9057.2 ± 13.14
Sex: Female, Male
Sex: Female, Male(Participants)Favipiravir Treatment ArmStandard of Care ArmTotal
Female91120
Male161430
Ethnicity (NIH/OMB)
Ethnicity (NIH/OMB)(Participants)Favipiravir Treatment ArmStandard of Care ArmTotal
Hispanic or Latino131427
Not Hispanic or Latino121022
Unknown or Not Reported011
Race (NIH/OMB)
Race (NIH/OMB)(Participants)Favipiravir Treatment ArmStandard of Care ArmTotal
American Indian or Alaska Native000
Asian101
Native Hawaiian or Other Pacific Islander000
Black or African American4610
White171229
More than one race3710
Unknown or Not Reported000
Smoking Status
Smoking Status(Participants)Favipiravir Treatment ArmStandard of Care ArmTotal
Non-smoker171431
Ex-smoker61117
Smoker202
08

Study locations

8 sites
  • HonorHealth
    Scottsdale, Arizona 85258, United States
  • University of Miami Miller School of Medicine
    Miami, Florida 33136, United States
  • Boston Medical Center
    Boston, Massachusetts 02118, United States
  • Brigham and Women's Hospital
    Boston, Massachusetts 02215, United States
  • Massachusetts General Hospital
    Boston, Massachusetts 02215, United States
  • UMass Memorial Health Care
    Worcester, Massachusetts 01605, United States
  • Atlantic Health System / Morristown Medical Center
    Morristown, New Jersey 07960, United States
  • Houston Methodist Hospital
    Houston, Texas 77030, United States
09

References and documents

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. PubMed 34888401 ↗

Study documents

  • Study protocol · Jul 15, 2020
  • Statistical analysis plan · Dec 15, 2020

Documents are hosted by the registry — open the source record to download them.

Individual participant data

Plan to share: No

10

Updates

Tracking since Sep 25, 2026
No changes since tracking began. The registry record was last updated on Mar 29, 2022, before this site started recording changes on Sep 25, 2026. Its history is on ClinicalTrials.gov ↗
11

Registry details

Key details

Study ID
NCT04358549
Lead sponsor
Fujifilm Pharmaceuticals U.S.A., Inc.
Responsible party
Sponsor
First posted
Apr 24, 2020
Start date
Apr 17, 2020
Primary completion
Sep 30, 2020
Completion
Oct 30, 2020
Results posted
Mar 29, 2022
Last update
Mar 29, 2022

Oversight

Data monitoring committee
No
FDA-regulated drug
Yes
FDA-regulated device
No
View the source record on ClinicalTrials.gov ↗

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