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

Sponsor
Fujifilm Pharmaceuticals U.S.A., Inc. (Industry)
Overall Status
Completed
CT.gov ID
NCT04358549
Collaborator
(none)
50
8
2
6.4
6.3
1

Study Details

Study Description

Brief Summary

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

Condition or Disease Intervention/Treatment Phase
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
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.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 :
Apr 17, 2020
Actual Primary Completion Date :
Sep 30, 2020
Actual Study Completion Date :
Oct 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

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

Outcome Measures

Primary Outcome Measures

  1. 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

  1. 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.

  2. 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.

  3. Characterize the Pharmacokinetics (PK) of Favipiravir in Plasma: Cmax [through Day 14]

    Measurement of maximum plasma concentration

  4. Characterized the Pharmacokinetics (PK) of Favipiravir in Plasma: Cmin [through Day 14]

    Measurement of minimum plasma concentration

  5. 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

Eligibility Criteria

Criteria

Ages Eligible for Study:
18 Years to 80 Years
Sexes Eligible for Study:
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:
  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

Site City State Country Postal Code
1 HonorHealth Scottsdale Arizona United States 85258
2 University of Miami Miller School of Medicine Miami Florida United States 33136
3 Boston Medical Center Boston Massachusetts United States 02118
4 Brigham and Women's Hospital Boston Massachusetts United States 02215
5 Massachusetts General Hospital Boston Massachusetts United States 02215
6 UMass Memorial Health Care Worcester Massachusetts United States 01605
7 Atlantic Health System / Morristown Medical Center Morristown New Jersey United States 07960
8 Houston Methodist Hospital Houston Texas United States 77030

Sponsors and Collaborators

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

Investigators

None specified.

Study Documents (Full-Text)

More Information

Publications

None provided.
Responsible Party:
Fujifilm Pharmaceuticals U.S.A., Inc.
ClinicalTrials.gov Identifier:
NCT04358549
Other Study ID Numbers:
  • FAVI-COV-US201
First Posted:
Apr 24, 2020
Last Update Posted:
Mar 29, 2022
Last Verified:
Mar 1, 2022
Individual Participant Data (IPD) Sharing Statement:
No
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:

Study Results

Participant Flow

Recruitment Details
Pre-assignment Detail
Arm/Group Title Favipiravir Treatment Arm Standard of Care Arm
Arm/Group Description 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 Favipiravir: Favipiravir to be administered as an oral tablet or made into a slurry for subjects who cannot swallow tablets Standard of Care for 14 days Standard of Care: Standard of Care for individual study site as determined by each hospital's protocol
Period Title: Overall Study
STARTED 25 25
ITT Population (Randomized Subjects) 25 25
Safety Population (Patients Who Received Either Favipiravir + SOC or SOC Alone) 24 25
COMPLETED 15 17
NOT COMPLETED 10 8

Baseline Characteristics

Arm/Group Title Favipiravir Treatment Arm Standard of Care Arm Total
Arm/Group Description 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 Favipiravir: Favipiravir to be administered as an oral tablet or made into a slurry for subjects who cannot swallow tablets Standard of Care for 14 days Standard of Care: Standard of Care for individual study site as determined by each hospital's protocol Total of all reporting groups
Overall Participants 25 25 50
Age (years) [Mean (Standard Deviation) ]
Mean (Standard Deviation) [years]
55.4
(12.37)
58.9
(13.90)
57.2
(13.14)
Sex: Female, Male (Count of Participants)
Female
9
36%
11
44%
20
40%
Male
16
64%
14
56%
30
60%
Ethnicity (NIH/OMB) (Count of Participants)
Hispanic or Latino
13
52%
14
56%
27
54%
Not Hispanic or Latino
12
48%
10
40%
22
44%
Unknown or Not Reported
0
0%
1
4%
1
2%
Race (NIH/OMB) (Count of Participants)
American Indian or Alaska Native
0
0%
0
0%
0
0%
Asian
1
4%
0
0%
1
2%
Native Hawaiian or Other Pacific Islander
0
0%
0
0%
0
0%
Black or African American
4
16%
6
24%
10
20%
White
17
68%
12
48%
29
58%
More than one race
3
12%
7
28%
10
20%
Unknown or Not Reported
0
0%
0
0%
0
0%
Smoking Status (Count of Participants)
Non-smoker
17
68%
14
56%
31
62%
Ex-smoker
6
24%
11
44%
17
34%
Smoker
2
8%
0
0%
2
4%

Outcome Measures

1. Primary Outcome
Title Time to Viral Clearance
Description 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

Outcome Measure Data

Analysis Population Description
ITT
Arm/Group Title Favipiravir Treatment Arm Standard of Care Arm
Arm/Group Description 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 Favipiravir: Favipiravir to be administered as an oral tablet or made into a slurry for subjects who cannot swallow tablets Standard of Care for 14 days Standard of Care: Standard of Care for individual study site as determined by each hospital's protocol
Measure Participants 25 25
Median (90% Confidence Interval) [days]
16.0
30.0
Statistical Analysis 1
Statistical Analysis Overview Comparison Group Selection Favipiravir Treatment Arm, Standard of Care Arm
Comments
Type of Statistical Test Superiority
Comments
Statistical Test of Hypothesis p-Value 0.0415
Comments
Method Log Rank
Comments
Method of Estimation Estimation Parameter Median Difference (Final Values)
Estimated Value 14
Confidence Interval (2-Sided) 90%
to
Parameter Dispersion Type:
Value:
Estimation Comments
2. Secondary Outcome
Title Status of Clinical Recovery as Measured by the Study-specific 6-point Ordinal Scale
Description 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

Outcome Measure Data

Analysis Population Description
ITT
Arm/Group Title Favipiravir Treatment Arm Standard of Care Arm
Arm/Group Description 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 Favipiravir: Favipiravir to be administered as an oral tablet or made into a slurry for subjects who cannot swallow tablets Standard of Care for 14 days Standard of Care: Standard of Care for individual study site as determined by each hospital's protocol
Measure Participants 25 25
Not Hospitalized
18
72%
18
72%
Hospitalized, not requiring supplemental oxygen
1
4%
3
12%
Hospitalized, requiring supplemental oxygen
4
16%
1
4%
Hospitalized, on non-invasive ventilation or high flow oxygen devices
0
0%
0
0%
Hospitalized, on invasive mechanical ventilation or ECMO
1
4%
0
0%
Death
0
0%
0
0%
Not available
1
4%
3
12%
Statistical Analysis 1
Statistical Analysis Overview Comparison Group Selection Favipiravir Treatment Arm, Standard of Care Arm
Comments
Type of Statistical Test Superiority
Comments
Statistical Test of Hypothesis p-Value
Comments
Method
Comments
Method of Estimation Estimation Parameter Odds Ratio (OR)
Estimated Value 0.653
Confidence Interval (2-Sided) 90%
0.190 to 2.240
Parameter Dispersion Type:
Value:
Estimation Comments
3. Secondary Outcome
Title Time to the National Early Warning Score 2 (NEWS2) of 2 or Less, or Hospital Discharge
Description 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

Outcome Measure Data

Analysis Population Description
ITT
Arm/Group Title Favipiravir Treatment Arm Standard of Care Arm
Arm/Group Description 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 Favipiravir: Favipiravir to be administered as an oral tablet or made into a slurry for subjects who cannot swallow tablets Standard of Care for 14 days Standard of Care: Standard of Care for individual study site as determined by each hospital's protocol
Measure Participants 25 25
Median (90% Confidence Interval) [days]
4.0
7.0
Statistical Analysis 1
Statistical Analysis Overview Comparison Group Selection Favipiravir Treatment Arm, Standard of Care Arm
Comments
Type of Statistical Test Superiority
Comments
Statistical Test of Hypothesis p-Value 0.9879
Comments
Method Log Rank
Comments
Method of Estimation Estimation Parameter Median Difference (Final Values)
Estimated Value 3
Confidence Interval (2-Sided) 90%
to
Parameter Dispersion Type:
Value:
Estimation Comments
4. Secondary Outcome
Title Characterize the Pharmacokinetics (PK) of Favipiravir in Plasma: Cmax
Description Measurement of maximum plasma concentration
Time Frame through Day 14

Outcome Measure Data

Analysis Population Description
PK population: All subjects in the safety population that have at least one result that can be used in the PK summaries.
Arm/Group Title Favipiravir Treatment Arm
Arm/Group Description 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 Favipiravir: Favipiravir to be administered as an oral tablet or made into a slurry for subjects who cannot swallow tablets
Measure Participants 23
Day 1
60.9
Day 2
47.1
Day 8
51.4
Day 14
50.8
5. Secondary Outcome
Title Characterized the Pharmacokinetics (PK) of Favipiravir in Plasma: Cmin
Description Measurement of minimum plasma concentration
Time Frame through Day 14

Outcome Measure Data

Analysis Population Description
PK population: All subjects in the safety population that have at least one result that can be used in the PK summaries.
Arm/Group Title Favipiravir Treatment Arm
Arm/Group Description 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 Favipiravir: Favipiravir to be administered as an oral tablet or made into a slurry for subjects who cannot swallow tablets
Measure Participants 23
Day 1
3.24
Day 2
8.19
Day 8
17.1
Day 14
15.5
6. Secondary Outcome
Title Characterized the Pharmacokinetics (PK) of Favipiravir in Plasma: Area Under Curve (AUC 0-24)
Description Measurement of the area under the curve of plasma concentration versus time profile
Time Frame through Day 14

Outcome Measure Data

Analysis Population Description
PK population: All subjects in the safety population that have at least one result that can be used in the PK summaries.
Arm/Group Title Favipiravir Treatment Arm
Arm/Group Description 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 Favipiravir: Favipiravir to be administered as an oral tablet or made into a slurry for subjects who cannot swallow tablets
Measure Participants 23
Day 1
414
Day 2
488
Day 8
786
Day 14
772

Adverse Events

Time Frame Until 60 days from Enrollment
Adverse Event Reporting Description
Arm/Group Title Favipiravir Treatment Arm Standard of Care Arm
Arm/Group Description 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 Favipiravir: Favipiravir to be administered as an oral tablet or made into a slurry for subjects who cannot swallow tablets Standard of Care for 14 days Standard of Care: Standard of Care for individual study site as determined by each hospital's protocol
All Cause Mortality
Favipiravir Treatment Arm Standard of Care Arm
Affected / at Risk (%) # Events Affected / at Risk (%) # Events
Total 1/24 (4.2%) 0/25 (0%)
Serious Adverse Events
Favipiravir Treatment Arm Standard of Care Arm
Affected / at Risk (%) # Events Affected / at Risk (%) # Events
Total 2/24 (8.3%) 3/25 (12%)
General disorders
Necrosis 0/24 (0%) 1/25 (4%)
Infections and infestations
Osteomyelitis 1/24 (4.2%) 0/25 (0%)
Staphylococcal infection 1/24 (4.2%) 0/25 (0%)
Clostridium difficile infection 0/24 (0%) 1/25 (4%)
Urinary tract infection 0/24 (0%) 1/25 (4%)
Metabolism and nutrition disorders
Failure to thrive 0/24 (0%) 1/25 (4%)
Nervous system disorders
Basal ganglia hemorrhage 1/24 (4.2%) 0/25 (0%)
Other (Not Including Serious) Adverse Events
Favipiravir Treatment Arm Standard of Care Arm
Affected / at Risk (%) # Events Affected / at Risk (%) # Events
Total 13/24 (54.2%) 12/25 (48%)
Gastrointestinal disorders
Constipation 0/24 (0%) 2/25 (8%)
Dyspepsia 0/24 (0%) 2/25 (8%)
Nausea 2/24 (8.3%) 2/25 (8%)
Investigations
Blood lactate dehydrogenase increased 2/24 (8.3%) 0/25 (0%)
Gamma-glutamyltransferase increased 3/24 (12.5%) 0/25 (0%)
Inflammatory marker increased 1/24 (4.2%) 4/25 (16%)
Nervous system disorders
Dizziness 0/24 (0%) 2/25 (8%)
Headache 2/24 (8.3%) 1/25 (4%)
Renal and urinary disorders
Acute kidney injury 3/24 (12.5%) 0/25 (0%)
Respiratory, thoracic and mediastinal disorders
Respiratory failure 1/24 (4.2%) 4/25 (16%)

Limitations/Caveats

[Not Specified]

More Information

Certain Agreements

Principal Investigators are NOT employed by the organization sponsoring the study.

No publication until earlier of: Sponsor publishes multisite results, Sponsor notice that multisite publication no longer planned, and 18 months after Study close. Submission to Sponsor of proposed publication for 30-45 days prior to submission for publication. Good faith consideration by Site of Sponsor's comments; deletion of any of Sponsor's confidential information. Sponsor may require up to additional 60-day delay to file patent applications for patentable subject matter in the publication.

Results Point of Contact

Name/Title Clinical Research Manager
Organization FUJIFILM Pharmaceuticals U.S.A., Inc.
Phone No phone at site
Email fphucontact@fujifilm.com
Responsible Party:
Fujifilm Pharmaceuticals U.S.A., Inc.
ClinicalTrials.gov Identifier:
NCT04358549
Other Study ID Numbers:
  • FAVI-COV-US201
First Posted:
Apr 24, 2020
Last Update Posted:
Mar 29, 2022
Last Verified:
Mar 1, 2022