Study of the Use of Favipiravir in Hospitalized Subjects With COVID-19
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
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
- 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
- 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
Eligibility Criteria
Criteria
Inclusion Criteria:
- Adults (18 to 80 years old):
-
within 72 hours of their hospitalization for infection with Severe Acute Respiratory Syndrome - Corona Virus - 2 (SARS-CoV-2), AND,
-
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,
-
within 10 days of onset of any COVID-19 symptoms.
Exclusion Criteria:
-
Subject has a concomitant bacterial respiratory infection unless cleared by the Sponsor
-
Subject has a history of abnormalities of uric acid metabolism unless cleared by the Sponsor.
-
Subject has a history of hypersensitivity to an anti-viral nucleoside analog drug targeting a viral RNA polymerase
-
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.
-
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).
-
Has previously received favipiravir within the past 30 days
-
Has renal insufficiency requiring hemodialysis or continuous ambulatory peritoneal dialysis (CAPD) or glomerular filtration rate of less than 20 mL/min.
-
Has liver impairment greater than Child-Pugh A.
-
Has a history of alcohol or drug abuse in the previous 6 months.
-
Has a psychiatric disease that is not well controlled where controlled is defined as: stable on a regimen for more than one year.
-
Has taken another investigational drug within the past 30 days.
-
Is on another antiviral or is participating in another clinical trial for the treatment of COVID-19
-
Subject is on a ventilator at the time of study entry
-
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.- FAVI-COV-US201
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
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 |
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 |
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 |
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
|
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
|
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
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 |
fphucontact@fujifilm.com |
- FAVI-COV-US201