Influenza Infection
Conditions
Brief summary
This multicenter, randomized, double-blind, placebo-controlled, parallel-group Phase 3 study will evaluate the efficacy and safety of peramivir inhalation solution in adults with uncomplicated influenza. Approximately 600 participants aged 18 to 64 years with laboratory-confirmed influenza and symptom onset within 48 hours will be randomized in a 2:1 ratio to receive a single nebulized dose of peramivir inhalation solution 80 mg or matching placebo. The primary efficacy outcome is the time to alleviation of all seven influenza symptoms. Secondary outcomes include changes in influenza viral RNA and infectious viral titers, time to viral clearance, alleviation of respiratory and systemic symptoms, resolution of fever, influenza-related complications, and use of rescue medication. Safety will be assessed through adverse events, clinical laboratory tests, vital signs, physical examinations, and electrocardiograms. Pharmacokinetics will also be evaluated in a subset of approximately 90 participants. Participants will be followed for approximately 15 days.
Interventions
DRUGPeramivir Inhalation Solution
Participants will receive a single nebulized dose of matching placebo on Day 1. The placebo will be administered as two 2-mL ampules containing no active peramivir. Nebulization will last at least 15 minutes. Participants will remain under observation at the study site for 30 minutes after completion of administration.
DRUGPlacebo for Peramivir Inhalation Solution
Participants will receive a single nebulized administration of matching placebo on Day 1. Two 2-mL placebo ampules containing no active peramivir will be placed in the nebulizer, for a total volume of 4 mL. Nebulization will last at least 15 minutes. Participants will remain under observation at the study site for 30 minutes after completion of administration.
Sponsors
Capital Medical University
Study design
Allocation
RANDOMIZED
Intervention model
PARALLEL
Primary purpose
TREATMENT
Masking
QUADRUPLE (Subject, Caregiver, Investigator, Outcomes Assessor)
Eligibility
Sex/Gender
ALL
Age
18 Years to 64 Years
Healthy volunteers
No
Inclusion criteria
* Participants must meet all of the following criteria: The participant or the participant's legally authorized representative understands the study and voluntarily signs the informed consent form. The participant must be 18 to 64 years of age, inclusive, at the time of informed consent. At screening, the participant meets all of the following criteria: Positive result from a rapid influenza diagnostic test (antigen test) or polymerase chain reaction (PCR) test. Axillary temperature of at least 37.3°C at screening. If an antipyretic has been taken, the axillary temperature must be at least 37.3°C at least 4 hours after administration. At least one influenza-related systemic symptom of moderate or greater severity: muscle or joint pain, fatigue, headache, or feverishness/chills. At least one influenza-related respiratory symptom of moderate or greater severity: nasal congestion, sore throat, or cough. The interval between the onset of the first influenza symptom and initiation of study treatment is no more than 48 hours. Symptom onset is defined as either: The first occurrence of a temperature of at least 37.3°C measured axillary, 37.5°C measured orally, or 38.0°C measured rectally or tympanically; or The onset of at least one systemic or respiratory symptom: nasal congestion, sore throat, cough, muscle or joint pain, fatigue, headache, or feverishness/chills. The participant is able to comply with all study procedures and complete the participant diary as required. A female participant must meet either of the following criteria: Not of childbearing potential, defined as having undergone hysterectomy or bilateral oophorectomy, having medically documented ovarian failure, or being postmenopausal. Postmenopausal status is defined as age greater than 50 years with amenorrhea for at least 12 months; or Of childbearing potential, with a negative pregnancy test at screening, and not pregnant, in the peripartum period, or breastfeeding. The participant and the participant's partner agree to remain completely abstinent or use effective contraception from screening through 3 months after completion of study treatment. Acceptable methods include: For a female participant or the female partner of a male participant, one of the following methods together with correct condom use by the male partner: an intrauterine device with an annual failure rate of less than 1%, a female barrier method consisting of a cervical cap or diaphragm with spermicide, or tubal sterilization; or Prior vasectomy of the male participant or the male partner of a female participant. Male participants agree not to donate sperm from screening through 3 months after completion of study treatment.
Exclusion criteria
* Participants meeting any of the following criteria will be excluded: * Influenza requiring hospitalization, as indicated by any of the following: * Severe influenza characterized by one or more of the following: * Persistent fever accompanied by severe cough, purulent sputum, bloody sputum, or chest pain. * Tachypnea, difficulty breathing, or cyanosis of the lips. * Altered mental status, including reduced responsiveness, somnolence, or agitation, or the occurrence of seizures. * Severe vomiting or diarrhea with evidence of dehydration. * Pneumonia. * Marked exacerbation of a pre-existing underlying disease. * Any other clinical condition requiring hospitalization. * Critical influenza characterized by one or more of the following: * Respiratory failure. * Acute necrotizing encephalopathy. * Shock. * Multiple organ dysfunction. * Any other serious clinical condition requiring intensive monitoring or care. * High risk of severe influenza, as indicated by any of the following: * A serious or poorly controlled underlying condition, such as chronic pulmonary disease, liver disease, chronic kidney disease, severe hematologic disease, chronic congestive heart failure classified as New York Heart Association functional class III or IV, neurologic or neuromuscular disease, or metabolic disease. * Clinically significant QT interval abnormality on electrocardiography, defined as a Fridericia-corrected QT interval (QTcF) greater than 450 milliseconds for males or greater than 470 milliseconds for females. * Immunodeficiency, including malignancy, organ or bone marrow transplantation, human immunodeficiency virus infection, or use of immunosuppressive therapy within the previous 3 months. * A concomitant condition requiring treatment with aspirin- or salicylate-containing medication. * Bronchitis, pneumonia, pleural effusion, or interstitial lung abnormality that is clinically suspected or confirmed by chest imaging (posteroanterior or posteroanterior and lateral chest radiography, or computed tomography) at screening and considered clinically significant by the investigator. * Previous diagnosis of chronic obstructive pulmonary disease, severe allergic rhinitis, or asthma. * Acute respiratory tract infection, otitis media, or sinusitis within 2 weeks before screening. * A concomitant infection requiring systemic anti-infective treatment, or a white blood cell count greater than 10.0 × 10\^9/L at screening. * Purulent sputum or suppurative tonsillitis at screening. * Suspected hypersensitivity to any active ingredient or excipient of the investigational product or acetaminophen. * Use of any anti-influenza antiviral medication within 7 days before screening, including but not limited to neuraminidase inhibitors, hemagglutinin inhibitors, M2 ion-channel blockers, or RNA polymerase inhibitors, such as oseltamivir, zanamivir, peramivir, umifenovir (Arbidol), favipiravir, rimantadine, amantadine, baloxavir marboxil, onradivir, suraxavir marboxil, seloxavir marboxil, or pixavir marboxil. * Receipt of an influenza vaccine within 6 months before screening. * Suspected or confirmed history of alcohol or drug abuse. * Participation in another interventional drug or medical device clinical trial within 28 days before screening. * Positive test for SARS-CoV-2 at screening. * Any other condition that, in the investigator's judgment, makes the participant unsuitable for participation in the study
Design outcomes
Primary
| Measure | Time frame | Description |
|---|---|---|
| Time to Alleviation of All Influenza Symptoms | From initiation of study treatment through 336 hours after treatment | Time in hours from initiation of study treatment to alleviation of all seven influenza symptoms recorded in the participant diary. The seven symptoms are nasal congestion, sore throat, cough, muscle or joint pain, fatigue, headache, and feverishness or chills. Alleviation is defined as a score of 0 (absent) or 1 (mild) for all seven symptoms, maintained for at least 21.5 hours. |
Secondary
| Measure | Time frame | Description |
|---|---|---|
| Change From Baseline in Influenza Virus RNA and Viral Titer | Baseline (pre-dose), Days 2, 3, 4, 5, Day 9 ± 2 days, and Day 15 (+3 days)/early withdrawal. | Change from baseline in influenza virus RNA measured by quantitative PCR (qPCR; log10 copies/mL) and influenza viral titer (log10 TCID50/mL) at scheduled visits. |
| Weighted Time to Alleviation of Five Core Influenza Symptoms | From initiation of study treatment through 336 hours after treatment | Weighted time in hours from initiation of study treatment to alleviation of all five core influenza symptoms: feverishness or chills, cough, nasal congestion, sore throat, and headache. Alleviation is defined as a score of 0 (absent) or 1 (mild) for all five symptoms, maintained for at least 21.5 hours. Symptom-specific weights will be applied as prespecified in the statistical analysis plan. |
| Time to Influenza Viral RNA Negativity | From initiation of study treatment through Day 15 (+3 days) | Time in hours from initiation of study treatment to the first respiratory specimen in which influenza viral RNA is below the assay limit of detection, as measured by quantitative polymerase chain reaction. |
| Time to Influenza Virus Titer Negativity | From initiation of study treatment through Day 15 (+3 days) | Time in hours from initiation of study treatment to the first respiratory specimen in which the infectious influenza virus titer is below the assay lower limit of quantification. |
| Proportion of Participants With Influenza Virus RNA Below the LOD and Viral Titer Below the LLOQ | Baseline, Days 2, 3, 4, 5, Day 9 ± 2 days, and Day 15 (+3 days)/early withdrawal. | Proportion of participants with influenza virus RNA below the qPCR LOD and influenza viral titer below the LLOQ at each scheduled visit. |
| Percentage of Participants With Alleviation of All Influenza Symptoms | Assessed repeatedly from initiation of study treatment through 336 hours after treatment | Percentage of participants with scores of 0 (absent) or 1 (mild) for all seven influenza symptoms, maintained for at least 21.5 hours. |
| Percentage of Participants With Alleviation of All Respiratory Symptoms | Assessed repeatedly from initiation of study treatment through 336 hours after treatment | Percentage of participants with scores of 0 (absent) or 1 (mild) for all three respiratory symptoms-nasal congestion, sore throat, and cough-maintained for at least 21.5 hours. |
| Time to Alleviation of All Respiratory Symptoms | From initiation of study treatment through 336 hours after treatment | Time in hours from initiation of study treatment to alleviation of nasal congestion, sore throat, and cough. Alleviation is defined as a score of 0 (absent) or 1 (mild) for all three symptoms, maintained for at least 21.5 hours. |
| Percentage of Participants With Alleviation of All Systemic Symptoms | Assessed repeatedly from initiation of study treatment through 336 hours after treatment | Percentage of participants with scores of 0 (absent) or 1 (mild) for all four systemic symptoms-muscle or joint pain, fatigue, headache, and feverishness or chills-maintained for at least 21.5 hours. |
| Time to Alleviation of All Systemic Symptoms | From initiation of study treatment through 336 hours after treatment | Time in hours from initiation of study treatment to alleviation of muscle or joint pain, fatigue, headache, and feverishness or chills. Alleviation is defined as a score of 0 (absent) or 1 (mild) for all four symptoms, maintained for at least 21.5 hours. |
| Time to Alleviation of Each Individual Influenza Symptom | From initiation of study treatment through 336 hours after treatment | Time in hours from initiation of study treatment to alleviation of each of the seven influenza symptoms, assessed separately: nasal congestion, sore throat, cough, muscle or joint pain, fatigue, headache, and feverishness or chills. Alleviation is defined as a score of 0 (absent) or 1 (mild), maintained for at least 21.5 hours. |
| Time to Alleviation of Fever | From initiation of study treatment through 336 hours after treatment | Time in hours from initiation of study treatment to the first axillary temperature below 37.0°C that is maintained for at least 12 hours. |
| Percentage of Participants With Normalization of Body Temperature | At 24, 48, 72, 96, 120, 144, and 168 hours after initiation of study treatment | Percentage of participants with an axillary temperature below 37.0°C that is maintained for at least 12 hours. |
| Percentage of Participants With Influenza-Related Complications | From initiation of study treatment through Day 15 (+3 days) | Percentage of participants experiencing one or more influenza-related complications, including hospitalization, death, sinusitis, bronchitis, otitis media, or radiographically confirmed pneumonia. |
| Use of Acetaminophen for Influenza-Related Symptoms | From initiation of study treatment through 336h. | Proportion of participants using acetaminophen and frequency of acetaminophen use during the study treatment period. |
Countries
China
Contacts
CONTACTYeming Wang, PhD
Outcome results
None listed