Influenza
Conditions
Keywords
Influenza
Brief summary
This is a Phase 2, randomized, double-blind, placebo-controlled multicenter study evaluating the efficacy and safety of two doses of favipiravir in adult patients with uncomplicated influenza.
Detailed description
This is a Phase 2, randomized, double-blind, placebo-controlled, multicenter study designed to evaluate the efficacy and safety of a 5-day regimen of favipiravir in influenza patients aged 20-80 years. Enrolled patients will be randomly assigned to 1 of 3 parallel treatment dose groups:Placebo; Low-dose favipiravir (1000 mg favipiravir BID for 1 day, followed by 400 mg favipiravir BID for 4 days); High-dose favipiravir (1200 mg favipiravir BID for 1 day, followed by 800 mg favipiravir BID for 4 days).
Interventions
DRUGFavipiravir
1000 mg favipiravir BID x 1 day, and 400 mg favipiravir BID x 4 days
DRUGPlacebo comparator
Placebo BID x 1 day, and Placebo BID x 4 days
Sponsors
MDVI, LLC
Study design
Allocation
RANDOMIZED
Intervention model
FACTORIAL
Primary purpose
TREATMENT
Masking
QUADRUPLE (Subject, Caregiver, Investigator, Outcomes Assessor)
Eligibility
Sex/Gender
ALL
Age
20 Years to 80 Years
Healthy volunteers
No
Inclusion criteria
1. Patients who test positive for influenza A or B by a commercially available Rapid Antigen Test (RAT) of the nasopharynx. A patient with a negative RAT result may still enroll if the sponsor and investigator agree that there is a known influenza outbreak circulating in the community. 2. Patients ≥ 20 but \< 65 years of age with a temperature (oral) of 100.4°F (38.0°C) or more; patients ≥ 65 years of age with a temperature (oral) of 100.0°F (37.8°C) or more at the first visit, or in the 6 hours prior if antipyretics were taken. 3. Patients with 2 or more of the following symptoms (moderate to severe in intensity) at the time of enrollment: * Cough * Sore throat * Headache * Nasal congestion * Feeling feverish * Body aches and pains * Fatigue (tiredness)
Exclusion criteria
1. Patients who have had influenza symptoms or fever (i.e., one of the symptoms listed under the inclusion criteria) for 36 hours or more prior to study screening. 2. Patients who have underlying chronic respiratory disease (e.g., chronic obstructive pulmonary disease \[COPD\], chronic bronchitis, diffuse panbronchiolitis, bronchiectasis, pulmonary emphysema, pulmonary fibrosis, bronchial asthma, or old tuberculosis). 3. Patients who at the beginning of the study are suspected of having bacterial respiratory infection (i.e., expectoration of purulent or mucopurulent sputum and/or infiltrate in lung in a chest x-ray, etc.). 4. Patients who have serious chronic diseases. For example, patients with HIV, cancer (i.e., requiring chemotherapy within the preceding 6 months), cirrhosis (end-stage), and/or unstable renal, cardiac, pulmonary, neurologic, vascular, or endocrinologic disease states requiring medication dose adjustments within the last 30 days.
Design outcomes
Primary
| Measure | Time frame | Description |
|---|---|---|
| Clinical Efficacy of 2 Dose Regimens of Favipiravir Compared With Placebo in Treating Patients With Influenza | 22 weeks | Overall time required from first study drug administration to alleviation of the 6 primary influenza symptoms and for temperature (oral) measurements to be less than 38.0°C for patients aged 20 to less than 65 years and less than 37.8°C for patients aged 65 years or older. Alleviated was defined as all 6 symptom scores had to be decreased to 1 or below and the decrease remain unchanged for 21.5 hours. |
Countries
Australia, Chile, New Zealand, Paraguay, Peru, South Africa, United States
Participant flow
Participants by arm
| Arm | Count |
|---|---|
| 1: Low Dose Favipiravir Favipiravir: 1000 mg favipiravir BID x 1 day, and 400 mg favipiravir BID x 4 days | 132 |
| 2: High Dose Favipiravir Favipiravir: 1200 mg favipiravir BID x 1 day, and 800 mg favipiravir BID x 4 days | 189 |
| Placebo Placebo comparator: Placebo BID x 1 day, and Placebo BID x 4 days | 197 |
| Total | 518 |
Withdrawals & dropouts
| Period | Reason | FG000 | FG001 | FG002 |
|---|---|---|---|---|
| Overall Study | Adverse Event | 2 | 3 | 2 |
| Overall Study | aggravation influenza | 1 | 1 | 1 |
| Overall Study | Lost to Follow-up | 3 | 7 | 3 |
| Overall Study | other underlying illness | 0 | 3 | 3 |
| Overall Study | Protocol Violation | 0 | 2 | 0 |
| Overall Study | Withdrawal by Subject | 5 | 6 | 6 |
Baseline characteristics
| Characteristic | 2: High Dose Favipiravir | Placebo | 1: Low Dose Favipiravir | Total |
|---|---|---|---|---|
| Age, Continuous | 42.6 years | 42.7 years | 42.2 years | 42.5 years |
| Race/Ethnicity, Customized Asian | 7 participants | 4 participants | 3 participants | 14 participants |
| Race/Ethnicity, Customized Black or African American | 22 participants | 23 participants | 17 participants | 62 participants |
| Race/Ethnicity, Customized Hispanic or Latino | 25 participants | 29 participants | 15 participants | 69 participants |
| Race/Ethnicity, Customized Mestizo | 20 participants | 17 participants | 14 participants | 51 participants |
| Race/Ethnicity, Customized More than one race, excluding Hispanic or Latino | 0 participants | 0 participants | 2 participants | 2 participants |
| Race/Ethnicity, Customized More than one race, including Hispanic or Latino | 3 participants | 2 participants | 0 participants | 5 participants |
| Race/Ethnicity, Customized Native Hawaiian or other Pacific Islander | 2 participants | 1 participants | 2 participants | 5 participants |
| Race/Ethnicity, Customized Other | 7 participants | 6 participants | 7 participants | 20 participants |
| Race/Ethnicity, Customized White | 103 participants | 115 participants | 72 participants | 290 participants |
| Rapid Antigen Test Result Influenza negative | 26 participants | 28 participants | 19 participants | 73 participants |
| Rapid Antigen Test Result Type A and B positive | 5 participants | 2 participants | 6 participants | 13 participants |
| Rapid Antigen Test Result Type A Positive | 113 participants | 124 participants | 77 participants | 314 participants |
| Rapid Antigen Test Result Type B positive | 45 participants | 43 participants | 30 participants | 118 participants |
| Region of Enrollment Australia | 9 participants | 8 participants | 7 participants | 24 participants |
| Region of Enrollment Chile | 9 participants | 7 participants | 2 participants | 18 participants |
| Region of Enrollment New Zealand | 5 participants | 10 participants | 6 participants | 21 participants |
| Region of Enrollment Peru | 36 participants | 36 participants | 24 participants | 96 participants |
| Region of Enrollment South Africa | 10 participants | 8 participants | 8 participants | 26 participants |
| Region of Enrollment United States | 120 participants | 128 participants | 85 participants | 333 participants |
| Sex: Female, Male Female | 102 Participants | 109 Participants | 73 Participants | 284 Participants |
| Sex: Female, Male Male | 87 Participants | 88 Participants | 59 Participants | 234 Participants |
| Virus type identification A (H1N1) pdm | 32 participants | 39 participants | 39 participants | 110 participants |
| Virus type identification A (H3N2) | 67 participants | 66 participants | 29 participants | 162 participants |
| Virus type identification B | 23 participants | 20 participants | 20 participants | 63 participants |
| Virus type identification Neither | 67 participants | 72 participants | 43 participants | 182 participants |
| Virus type identification Other | 0 participants | 0 participants | 1 participants | 1 participants |
Adverse events
| Event type | EG000 affected / at risk | EG001 affected / at risk | EG002 affected / at risk |
|---|---|---|---|
| deaths Total, all-cause mortality | — / — | — / — | — / — |
| other Total, other adverse events | 47 / 132 | 65 / 189 | 79 / 197 |
| serious Total, serious adverse events | 2 / 132 | 0 / 189 | 1 / 197 |
Outcome results
Primary
Clinical Efficacy of 2 Dose Regimens of Favipiravir Compared With Placebo in Treating Patients With Influenza
Overall time required from first study drug administration to alleviation of the 6 primary influenza symptoms and for temperature (oral) measurements to be less than 38.0°C for patients aged 20 to less than 65 years and less than 37.8°C for patients aged 65 years or older. Alleviated was defined as all 6 symptom scores had to be decreased to 1 or below and the decrease remain unchanged for 21.5 hours.
Time frame: 22 weeks
Population: The primary analysis population for efficacy analyses was the ITTI Population (N=333), defined as all patients who received at least 1 dose of study drug with any available efficacy data after randomization and who tested positive for influenza A or B by PCR assay or culture tests on Day 1 using determinations.
| Arm | Measure | Value (MEDIAN) |
|---|---|---|
| 1: Low Dose Favipiravir | Clinical Efficacy of 2 Dose Regimens of Favipiravir Compared With Placebo in Treating Patients With Influenza | 100.4 hours |
| 2: High Dose Favipiravir | Clinical Efficacy of 2 Dose Regimens of Favipiravir Compared With Placebo in Treating Patients With Influenza | 86.5 hours |
| Placebo | Clinical Efficacy of 2 Dose Regimens of Favipiravir Compared With Placebo in Treating Patients With Influenza | 91.9 hours |
Comparison: Time required from first study drug administration to alleviation of the 6 primary influenza symptoms and fever. The primary influenza symptoms included cough, sore throat, headache, nasal congestion, body aches and pains, and fatigue. Symptoms were considered alleviated when all were decreased to ≤1 and decrease persisted unchanged ≥ 21.5 hours. Fever was considered alleviated when maintained at \< 38.0°C (age 20 to \< 65 years) or \< 37.8°C (age ≥ 65 years) ≥ 21.5 hours.p-value: 0.05Gehan-Wilcoxon