COVID-19
Conditions
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.
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
Sponsors
Fujifilm Pharmaceuticals U.S.A., Inc.
Study design
Allocation
RANDOMIZED
Intervention model
PARALLEL
Primary purpose
TREATMENT
Masking
NONE
Intervention model description
Open-label, randomized (1:1 ratio) to receive favipiravir plus standard of care or standard of care alone.
Eligibility
Sex/Gender
ALL
Age
18 Years to 80 Years
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.
Design outcomes
Primary
| Measure | Time frame | Description |
|---|---|---|
| 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
| Measure | Time frame | Description |
|---|---|---|
| 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. |
| 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. |
| Characterize the Pharmacokinetics (PK) of Favipiravir in Plasma: Cmax | through Day 14 | Measurement of maximum plasma concentration |
| Characterized the Pharmacokinetics (PK) of Favipiravir in Plasma: Cmin | through Day 14 | Measurement of minimum plasma concentration |
| 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 |
Countries
United States
Participant flow
Participants by arm
| Arm | Count |
|---|---|
| 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 | 25 |
| 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 | 25 |
| Total | 50 |
Withdrawals & dropouts
| Period | Reason | FG000 | FG001 |
|---|---|---|---|
| Overall Study | Adverse Event | 0 | 1 |
| Overall Study | Death | 1 | 0 |
| Overall Study | Lost to Follow-up | 2 | 1 |
| Overall Study | Start remdesivir | 1 | 0 |
| Overall Study | Withdrawal by Subject | 6 | 6 |
Baseline characteristics
| Characteristic | Standard of Care Arm | Total | Favipiravir Treatment Arm |
|---|---|---|---|
| Age, Continuous | 58.9 years STANDARD_DEVIATION 13.9 | 57.2 years STANDARD_DEVIATION 13.14 | 55.4 years STANDARD_DEVIATION 12.37 |
| Ethnicity (NIH/OMB) Hispanic or Latino | 14 Participants | 27 Participants | 13 Participants |
| Ethnicity (NIH/OMB) Not Hispanic or Latino | 10 Participants | 22 Participants | 12 Participants |
| Ethnicity (NIH/OMB) Unknown or Not Reported | 1 Participants | 1 Participants | 0 Participants |
| Race (NIH/OMB) American Indian or Alaska Native | 0 Participants | 0 Participants | 0 Participants |
| Race (NIH/OMB) Asian | 0 Participants | 1 Participants | 1 Participants |
| Race (NIH/OMB) Black or African American | 6 Participants | 10 Participants | 4 Participants |
| Race (NIH/OMB) More than one race | 7 Participants | 10 Participants | 3 Participants |
| Race (NIH/OMB) Native Hawaiian or Other Pacific Islander | 0 Participants | 0 Participants | 0 Participants |
| Race (NIH/OMB) Unknown or Not Reported | 0 Participants | 0 Participants | 0 Participants |
| Race (NIH/OMB) White | 12 Participants | 29 Participants | 17 Participants |
| Sex: Female, Male Female | 11 Participants | 20 Participants | 9 Participants |
| Sex: Female, Male Male | 14 Participants | 30 Participants | 16 Participants |
| Smoking Status Ex-smoker | 11 Participants | 17 Participants | 6 Participants |
| Smoking Status Non-smoker | 14 Participants | 31 Participants | 17 Participants |
| Smoking Status Smoker | 0 Participants | 2 Participants | 2 Participants |
Adverse events
| Event type | EG000 affected / at risk | EG001 affected / at risk |
|---|---|---|
| deaths Total, all-cause mortality | 1 / 24 | 0 / 25 |
| other Total, other adverse events | 13 / 24 | 12 / 25 |
| serious Total, serious adverse events | 2 / 24 | 3 / 25 |
Outcome results
Primary
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
Population: ITT
| Arm | Measure | Value (MEDIAN) |
|---|---|---|
| Favipiravir Treatment Arm | Time to Viral Clearance | 16.0 days |
| Standard of Care Arm | Time to Viral Clearance | 30.0 days |
p-value: 0.0415Log Rank
Secondary
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
Population: PK population: All subjects in the safety population that have at least one result that can be used in the PK summaries.
| Arm | Measure | Group | Value (MEDIAN) |
|---|---|---|---|
| Favipiravir Treatment Arm | Characterized the Pharmacokinetics (PK) of Favipiravir in Plasma: Area Under Curve (AUC 0-24) | Day 1 | 414 hr*µg/mL |
| Favipiravir Treatment Arm | Characterized the Pharmacokinetics (PK) of Favipiravir in Plasma: Area Under Curve (AUC 0-24) | Day 2 | 488 hr*µg/mL |
| Favipiravir Treatment Arm | Characterized the Pharmacokinetics (PK) of Favipiravir in Plasma: Area Under Curve (AUC 0-24) | Day 8 | 786 hr*µg/mL |
| Favipiravir Treatment Arm | Characterized the Pharmacokinetics (PK) of Favipiravir in Plasma: Area Under Curve (AUC 0-24) | Day 14 | 772 hr*µg/mL |
Secondary
Characterized the Pharmacokinetics (PK) of Favipiravir in Plasma: Cmin
Measurement of minimum plasma concentration
Time frame: through Day 14
Population: PK population: All subjects in the safety population that have at least one result that can be used in the PK summaries.
| Arm | Measure | Group | Value (MEDIAN) |
|---|---|---|---|
| Favipiravir Treatment Arm | Characterized the Pharmacokinetics (PK) of Favipiravir in Plasma: Cmin | Day 1 | 3.24 µg/mL |
| Favipiravir Treatment Arm | Characterized the Pharmacokinetics (PK) of Favipiravir in Plasma: Cmin | Day 2 | 8.19 µg/mL |
| Favipiravir Treatment Arm | Characterized the Pharmacokinetics (PK) of Favipiravir in Plasma: Cmin | Day 8 | 17.1 µg/mL |
| Favipiravir Treatment Arm | Characterized the Pharmacokinetics (PK) of Favipiravir in Plasma: Cmin | Day 14 | 15.5 µg/mL |
Secondary
Characterize the Pharmacokinetics (PK) of Favipiravir in Plasma: Cmax
Measurement of maximum plasma concentration
Time frame: through Day 14
Population: PK population: All subjects in the safety population that have at least one result that can be used in the PK summaries.
| Arm | Measure | Group | Value (MEDIAN) |
|---|---|---|---|
| Favipiravir Treatment Arm | Characterize the Pharmacokinetics (PK) of Favipiravir in Plasma: Cmax | Day 1 | 60.9 µg/mL |
| Favipiravir Treatment Arm | Characterize the Pharmacokinetics (PK) of Favipiravir in Plasma: Cmax | Day 2 | 47.1 µg/mL |
| Favipiravir Treatment Arm | Characterize the Pharmacokinetics (PK) of Favipiravir in Plasma: Cmax | Day 8 | 51.4 µg/mL |
| Favipiravir Treatment Arm | Characterize the Pharmacokinetics (PK) of Favipiravir in Plasma: Cmax | Day 14 | 50.8 µg/mL |
Secondary
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
Population: ITT
| Arm | Measure | Category | Value (COUNT_OF_PARTICIPANTS) |
|---|---|---|---|
| Favipiravir Treatment Arm | Status of Clinical Recovery as Measured by the Study-specific 6-point Ordinal Scale | Hospitalized, requiring supplemental oxygen | 4 Participants |
| Favipiravir Treatment Arm | Status of Clinical Recovery as Measured by the Study-specific 6-point Ordinal Scale | Hospitalized, on invasive mechanical ventilation or ECMO | 1 Participants |
| Favipiravir Treatment Arm | Status of Clinical Recovery as Measured by the Study-specific 6-point Ordinal Scale | Hospitalized, not requiring supplemental oxygen | 1 Participants |
| Favipiravir Treatment Arm | Status of Clinical Recovery as Measured by the Study-specific 6-point Ordinal Scale | Death | 0 Participants |
| Favipiravir Treatment Arm | 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 |
| Favipiravir Treatment Arm | Status of Clinical Recovery as Measured by the Study-specific 6-point Ordinal Scale | Not available | 1 Participants |
| Favipiravir Treatment Arm | Status of Clinical Recovery as Measured by the Study-specific 6-point Ordinal Scale | Not Hospitalized | 18 Participants |
| Standard of Care Arm | Status of Clinical Recovery as Measured by the Study-specific 6-point Ordinal Scale | Not available | 3 Participants |
| Standard of Care Arm | Status of Clinical Recovery as Measured by the Study-specific 6-point Ordinal Scale | Not Hospitalized | 18 Participants |
| Standard of Care Arm | Status of Clinical Recovery as Measured by the Study-specific 6-point Ordinal Scale | Hospitalized, not requiring supplemental oxygen | 3 Participants |
| Standard of Care Arm | Status of Clinical Recovery as Measured by the Study-specific 6-point Ordinal Scale | Hospitalized, requiring supplemental oxygen | 1 Participants |
| Standard of Care Arm | 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 |
| Standard of Care Arm | Status of Clinical Recovery as Measured by the Study-specific 6-point Ordinal Scale | Hospitalized, on invasive mechanical ventilation or ECMO | 0 Participants |
| Standard of Care Arm | Status of Clinical Recovery as Measured by the Study-specific 6-point Ordinal Scale | Death | 0 Participants |
90% CI: [0.19, 2.24]
Secondary
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
Population: ITT
| Arm | Measure | Value (MEDIAN) |
|---|---|---|
| Favipiravir Treatment Arm | Time to the National Early Warning Score 2 (NEWS2) of 2 or Less, or Hospital Discharge | 4.0 days |
| Standard of Care Arm | Time to the National Early Warning Score 2 (NEWS2) of 2 or Less, or Hospital Discharge | 7.0 days |
p-value: 0.9879Log Rank