Trial Outcomes & Findings for Study of the Use of Favipiravir in Hospitalized Subjects With COVID-19 (NCT NCT04358549)
NCT ID: NCT04358549
Last Updated: 2022-03-29
Results Overview
To determine the effect of favipiravir + SOC v. SOC on viral clearance of COVID-19 as measured by nasopharyngeal and oropharyngeal sampling
Recruitment status
COMPLETED
Study phase
PHASE2
Target enrollment
50 participants
Primary outcome timeframe
Day 29
Results posted on
2022-03-29
Participant Flow
Participant milestones
| Measure |
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
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
Standard of Care: Standard of Care for individual study site as determined by each hospital's protocol
|
|---|---|---|
|
Overall Study
STARTED
|
25
|
25
|
|
Overall Study
ITT Population (Randomized Subjects)
|
25
|
25
|
|
Overall Study
Safety Population (Patients Who Received Either Favipiravir + SOC or SOC Alone)
|
24
|
25
|
|
Overall Study
COMPLETED
|
15
|
17
|
|
Overall Study
NOT COMPLETED
|
10
|
8
|
Reasons for withdrawal
| Measure |
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
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
Standard of Care: Standard of Care for individual study site as determined by each hospital's protocol
|
|---|---|---|
|
Overall Study
Adverse Event
|
0
|
1
|
|
Overall Study
Death
|
1
|
0
|
|
Overall Study
Lost to Follow-up
|
2
|
1
|
|
Overall Study
Withdrawal by Subject
|
6
|
6
|
|
Overall Study
Start remdesivir
|
1
|
0
|
Baseline Characteristics
Study of the Use of Favipiravir in Hospitalized Subjects With COVID-19
Baseline characteristics by cohort
| Measure |
Favipiravir Treatment Arm
n=25 Participants
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 Arm
n=25 Participants
Standard of Care for 14 days
Standard of Care: Standard of Care for individual study site as determined by each hospital's protocol
|
Total
n=50 Participants
Total of all reporting groups
|
|---|---|---|---|
|
Age, Continuous
|
55.4 years
STANDARD_DEVIATION 12.37 • n=99 Participants
|
58.9 years
STANDARD_DEVIATION 13.90 • n=107 Participants
|
57.2 years
STANDARD_DEVIATION 13.14 • n=206 Participants
|
|
Sex: Female, Male
Female
|
9 Participants
n=99 Participants
|
11 Participants
n=107 Participants
|
20 Participants
n=206 Participants
|
|
Sex: Female, Male
Male
|
16 Participants
n=99 Participants
|
14 Participants
n=107 Participants
|
30 Participants
n=206 Participants
|
|
Ethnicity (NIH/OMB)
Hispanic or Latino
|
13 Participants
n=99 Participants
|
14 Participants
n=107 Participants
|
27 Participants
n=206 Participants
|
|
Ethnicity (NIH/OMB)
Not Hispanic or Latino
|
12 Participants
n=99 Participants
|
10 Participants
n=107 Participants
|
22 Participants
n=206 Participants
|
|
Ethnicity (NIH/OMB)
Unknown or Not Reported
|
0 Participants
n=99 Participants
|
1 Participants
n=107 Participants
|
1 Participants
n=206 Participants
|
|
Race (NIH/OMB)
American Indian or Alaska Native
|
0 Participants
n=99 Participants
|
0 Participants
n=107 Participants
|
0 Participants
n=206 Participants
|
|
Race (NIH/OMB)
Asian
|
1 Participants
n=99 Participants
|
0 Participants
n=107 Participants
|
1 Participants
n=206 Participants
|
|
Race (NIH/OMB)
Native Hawaiian or Other Pacific Islander
|
0 Participants
n=99 Participants
|
0 Participants
n=107 Participants
|
0 Participants
n=206 Participants
|
|
Race (NIH/OMB)
Black or African American
|
4 Participants
n=99 Participants
|
6 Participants
n=107 Participants
|
10 Participants
n=206 Participants
|
|
Race (NIH/OMB)
White
|
17 Participants
n=99 Participants
|
12 Participants
n=107 Participants
|
29 Participants
n=206 Participants
|
|
Race (NIH/OMB)
More than one race
|
3 Participants
n=99 Participants
|
7 Participants
n=107 Participants
|
10 Participants
n=206 Participants
|
|
Race (NIH/OMB)
Unknown or Not Reported
|
0 Participants
n=99 Participants
|
0 Participants
n=107 Participants
|
0 Participants
n=206 Participants
|
|
Smoking Status
Non-smoker
|
17 Participants
n=99 Participants
|
14 Participants
n=107 Participants
|
31 Participants
n=206 Participants
|
|
Smoking Status
Ex-smoker
|
6 Participants
n=99 Participants
|
11 Participants
n=107 Participants
|
17 Participants
n=206 Participants
|
|
Smoking Status
Smoker
|
2 Participants
n=99 Participants
|
0 Participants
n=107 Participants
|
2 Participants
n=206 Participants
|
PRIMARY outcome
Timeframe: Day 29Population: ITT
To determine the effect of favipiravir + SOC v. SOC on viral clearance of COVID-19 as measured by nasopharyngeal and oropharyngeal sampling
Outcome measures
| Measure |
Favipiravir Treatment Arm
n=25 Participants
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 Arm
n=25 Participants
Standard of Care for 14 days
Standard of Care: Standard of Care for individual study site as determined by each hospital's protocol
|
|---|---|---|
|
Time to Viral Clearance
|
16.0 days
Interval 12.0 to 29.0
|
30.0 days
Interval 12.0 to 31.0
|
SECONDARY outcome
Timeframe: on Day 15Population: ITT
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.
Outcome measures
| Measure |
Favipiravir Treatment Arm
n=25 Participants
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 Arm
n=25 Participants
Standard of Care for 14 days
Standard of Care: Standard of Care for individual study site as determined by each hospital's protocol
|
|---|---|---|
|
Status of Clinical Recovery as Measured by the Study-specific 6-point Ordinal Scale
Not Hospitalized
|
18 Participants
|
18 Participants
|
|
Status of Clinical Recovery as Measured by the Study-specific 6-point Ordinal Scale
Hospitalized, not requiring supplemental oxygen
|
1 Participants
|
3 Participants
|
|
Status of Clinical Recovery as Measured by the Study-specific 6-point Ordinal Scale
Hospitalized, requiring supplemental oxygen
|
4 Participants
|
1 Participants
|
|
Status of Clinical Recovery as Measured by the Study-specific 6-point Ordinal Scale
Hospitalized, on non-invasive ventilation or high flow oxygen devices
|
0 Participants
|
0 Participants
|
|
Status of Clinical Recovery as Measured by the Study-specific 6-point Ordinal Scale
Hospitalized, on invasive mechanical ventilation or ECMO
|
1 Participants
|
0 Participants
|
|
Status of Clinical Recovery as Measured by the Study-specific 6-point Ordinal Scale
Death
|
0 Participants
|
0 Participants
|
|
Status of Clinical Recovery as Measured by the Study-specific 6-point Ordinal Scale
Not available
|
1 Participants
|
3 Participants
|
SECONDARY outcome
Timeframe: through Day 29Population: ITT
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.
Outcome measures
| Measure |
Favipiravir Treatment Arm
n=25 Participants
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 Arm
n=25 Participants
Standard of Care for 14 days
Standard of Care: Standard of Care for individual study site as determined by each hospital's protocol
|
|---|---|---|
|
Time to the National Early Warning Score 2 (NEWS2) of 2 or Less, or Hospital Discharge
|
4.0 days
Interval 3.0 to 8.0
|
7.0 days
Interval 4.0 to 10.0
|
SECONDARY outcome
Timeframe: through Day 14Population: PK population: All subjects in the safety population that have at least one result that can be used in the PK summaries.
Measurement of maximum plasma concentration
Outcome measures
| Measure |
Favipiravir Treatment Arm
n=23 Participants
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 Arm
Standard of Care for 14 days
Standard of Care: Standard of Care for individual study site as determined by each hospital's protocol
|
|---|---|---|
|
Characterize the Pharmacokinetics (PK) of Favipiravir in Plasma: Cmax
Day 1
|
60.9 µg/mL
Interval 22.0 to 84.5
|
—
|
|
Characterize the Pharmacokinetics (PK) of Favipiravir in Plasma: Cmax
Day 2
|
47.1 µg/mL
Interval 16.7 to 109.0
|
—
|
|
Characterize the Pharmacokinetics (PK) of Favipiravir in Plasma: Cmax
Day 8
|
51.4 µg/mL
Interval 17.1 to 133.0
|
—
|
|
Characterize the Pharmacokinetics (PK) of Favipiravir in Plasma: Cmax
Day 14
|
50.8 µg/mL
Interval 14.2 to 134.0
|
—
|
SECONDARY outcome
Timeframe: through Day 14Population: PK population: All subjects in the safety population that have at least one result that can be used in the PK summaries.
Measurement of minimum plasma concentration
Outcome measures
| Measure |
Favipiravir Treatment Arm
n=23 Participants
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 Arm
Standard of Care for 14 days
Standard of Care: Standard of Care for individual study site as determined by each hospital's protocol
|
|---|---|---|
|
Characterized the Pharmacokinetics (PK) of Favipiravir in Plasma: Cmin
Day 1
|
3.24 µg/mL
Interval 0.12 to 36.1
|
—
|
|
Characterized the Pharmacokinetics (PK) of Favipiravir in Plasma: Cmin
Day 2
|
8.19 µg/mL
Interval 0.152 to 70.2
|
—
|
|
Characterized the Pharmacokinetics (PK) of Favipiravir in Plasma: Cmin
Day 8
|
17.1 µg/mL
Interval 1.04 to 88.4
|
—
|
|
Characterized the Pharmacokinetics (PK) of Favipiravir in Plasma: Cmin
Day 14
|
15.5 µg/mL
Interval 0.815 to 87.4
|
—
|
SECONDARY outcome
Timeframe: through Day 14Population: PK population: All subjects in the safety population that have at least one result that can be used in the PK summaries.
Measurement of the area under the curve of plasma concentration versus time profile
Outcome measures
| Measure |
Favipiravir Treatment Arm
n=23 Participants
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 Arm
Standard of Care for 14 days
Standard of Care: Standard of Care for individual study site as determined by each hospital's protocol
|
|---|---|---|
|
Characterized the Pharmacokinetics (PK) of Favipiravir in Plasma: Area Under Curve (AUC 0-24)
Day 1
|
414 hr*µg/mL
Interval 161.0 to 1240.0
|
—
|
|
Characterized the Pharmacokinetics (PK) of Favipiravir in Plasma: Area Under Curve (AUC 0-24)
Day 2
|
488 hr*µg/mL
Interval 135.0 to 2120.0
|
—
|
|
Characterized the Pharmacokinetics (PK) of Favipiravir in Plasma: Area Under Curve (AUC 0-24)
Day 8
|
786 hr*µg/mL
Interval 189.0 to 2580.0
|
—
|
|
Characterized the Pharmacokinetics (PK) of Favipiravir in Plasma: Area Under Curve (AUC 0-24)
Day 14
|
772 hr*µg/mL
Interval 151.0 to 2680.0
|
—
|
Adverse Events
Favipiravir Treatment Arm
Serious events: 2 serious events
Other events: 13 other events
Deaths: 1 deaths
Standard of Care Arm
Serious events: 3 serious events
Other events: 12 other events
Deaths: 0 deaths
Serious adverse events
| Measure |
Favipiravir Treatment Arm
n=24 participants at risk
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 Arm
n=25 participants at risk
Standard of Care for 14 days
Standard of Care: Standard of Care for individual study site as determined by each hospital's protocol
|
|---|---|---|
|
Infections and infestations
Osteomyelitis
|
4.2%
1/24 • Until 60 days from Enrollment
|
0.00%
0/25 • Until 60 days from Enrollment
|
|
Infections and infestations
Staphylococcal infection
|
4.2%
1/24 • Until 60 days from Enrollment
|
0.00%
0/25 • Until 60 days from Enrollment
|
|
Nervous system disorders
Basal ganglia hemorrhage
|
4.2%
1/24 • Until 60 days from Enrollment
|
0.00%
0/25 • Until 60 days from Enrollment
|
|
General disorders
Necrosis
|
0.00%
0/24 • Until 60 days from Enrollment
|
4.0%
1/25 • Until 60 days from Enrollment
|
|
Infections and infestations
Clostridium difficile infection
|
0.00%
0/24 • Until 60 days from Enrollment
|
4.0%
1/25 • Until 60 days from Enrollment
|
|
Infections and infestations
Urinary tract infection
|
0.00%
0/24 • Until 60 days from Enrollment
|
4.0%
1/25 • Until 60 days from Enrollment
|
|
Metabolism and nutrition disorders
Failure to thrive
|
0.00%
0/24 • Until 60 days from Enrollment
|
4.0%
1/25 • Until 60 days from Enrollment
|
Other adverse events
| Measure |
Favipiravir Treatment Arm
n=24 participants at risk
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 Arm
n=25 participants at risk
Standard of Care for 14 days
Standard of Care: Standard of Care for individual study site as determined by each hospital's protocol
|
|---|---|---|
|
Investigations
Blood lactate dehydrogenase increased
|
8.3%
2/24 • Until 60 days from Enrollment
|
0.00%
0/25 • Until 60 days from Enrollment
|
|
Investigations
Gamma-glutamyltransferase increased
|
12.5%
3/24 • Until 60 days from Enrollment
|
0.00%
0/25 • Until 60 days from Enrollment
|
|
Investigations
Inflammatory marker increased
|
4.2%
1/24 • Until 60 days from Enrollment
|
16.0%
4/25 • Until 60 days from Enrollment
|
|
Gastrointestinal disorders
Constipation
|
0.00%
0/24 • Until 60 days from Enrollment
|
8.0%
2/25 • Until 60 days from Enrollment
|
|
Gastrointestinal disorders
Dyspepsia
|
0.00%
0/24 • Until 60 days from Enrollment
|
8.0%
2/25 • Until 60 days from Enrollment
|
|
Gastrointestinal disorders
Nausea
|
8.3%
2/24 • Until 60 days from Enrollment
|
8.0%
2/25 • Until 60 days from Enrollment
|
|
Respiratory, thoracic and mediastinal disorders
Respiratory failure
|
4.2%
1/24 • Until 60 days from Enrollment
|
16.0%
4/25 • Until 60 days from Enrollment
|
|
Nervous system disorders
Dizziness
|
0.00%
0/24 • Until 60 days from Enrollment
|
8.0%
2/25 • Until 60 days from Enrollment
|
|
Nervous system disorders
Headache
|
8.3%
2/24 • Until 60 days from Enrollment
|
4.0%
1/25 • Until 60 days from Enrollment
|
|
Renal and urinary disorders
Acute kidney injury
|
12.5%
3/24 • Until 60 days from Enrollment
|
0.00%
0/25 • Until 60 days from Enrollment
|
Additional Information
Clinical Research Manager
FUJIFILM Pharmaceuticals U.S.A., Inc.
Phone: No phone at site
Email: [email protected]
Results disclosure agreements
- Principal investigator is a sponsor employee 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.
- Publication restrictions are in place
Restriction type: OTHER