Influenza A Infection MedDRA version: 20.1 Level: LLT Classification code 10022002 Term: Influenza A virus infection System Organ Class: 100000004862
Conditions
Sponsors
Janssen-Cilag International NV
Eligibility
Sex/Gender
All
Inclusion criteria
Inclusion criteria: • Male or female, 13 to 85 years of age, inclusive. Note: Adolescent subjects (13-17 years) will be enrolled in selected countries and study sites consistent with local regulations. • Tested positive for influenza A infection after the onset of symptoms using a polymerase chain reaction (PCR)-based or other rapid molecular diagnostic assay. • Requires hospitalization to treat influenza infection and/or to treat complications of influenza infection (eg, radiological signs of lower respiratory tract disease, septic shock, central nervous system [CNS] involvement, myositis, rhabdomyolysis, acute exacerbation of chronic kidney disease, severe dehydration, myocarditis, pericarditis, ischemic heart disease, exacerbation of underlying chronic pulmonary disease, including asthma, chronic obstructive pulmonary disease [COPD], decompensation of previously controlled diabetes mellitus), including subjects admitted to the intensive care unit (ICU). Note: For the purpose of the protocol, subjects admitted under “observation” status with an anticipated length of stay beyond 24 hours are eligible for enrollment. • Enrollment and initiation of study drug treatment =96 hours after onset of influenza symptoms. • Being on invasive mechanical ventilation or having an SpO2 =65 years) yes F.1.3.1 Number of subjects for this age range 270
Exclusion criteria
Exclusion criteria: • Received more than 3 doses of influenza antiviral medication (eg, oseltamivir [OST] or zanamivir), or any dose of ribavirin within 2 weeks, prior to first study drug intake. Received intravenous (IV) peramivir more than one day prior to screening. • Unwilling to undergo regular nasal mid-turbinate (MT) swabs or has any physical abnormality which limits the ability to collect regular nasal MT specimens. • Unstable angina pectoris or myocardial infarction within 30 days prior to screening (inclusive). • Presence of clinically significant heart arrhythmias, uncontrolled, unstable atrial arrhythmia, or sustained ventricular arrhythmia, or risk factors for Torsade de Pointes syndrome. • Known severe hepatic impairment (Child Pugh C cirrhosis) or chronic hepatitis C infection undergoing hepatitis C antiviral therapy. • Severely immunocompromised in the opinion of the investigator (eg, known cluster of differentiation 4+ [CD4+] count <200 cells/mm3, absolute neutrophil count <750/mm3, first course of chemotherapy completed within 2 weeks prior to screening, history of stem cell transplant within 1 year prior to screening, any history of a lung transplant).
Design outcomes
Primary
| Measure | Time frame |
|---|---|
| Main Objective: The primary objective is to evaluate superiority of pimodivir in combination with standard-of-care (SOC) treatment compared to placebo in combination with SOC treatment on Day 6, with respect to the clinical outcome on the hospital recovery scale.;Secondary Objective: Compare pimodivir (Pi) in combination with SOC treatment (tmt) to placebo in combination with SOC tmt (Pi + SOC tmt vs. Placebo + SOC tmt) regarding: * Safety, tolerability * All-cause mortality * Incidence, duration of antibiotic tmt * No. of subjects needing extended tmt, requiring re-hospitalization, not hospitalized at Day 6 * Time to clinical response * Time to improvement of respiratory status Evaluate superiority of Pi+SOC vs.Pl+SOC with respect to: * Time in hospital, time in ICU, time on mechanical ventilation, time to return to daily activities * Clinical outcome on hospital recovery scale * Incidence of complications associated with influenza after start of study tmt * Time to viral negativity a. viral load over time by qRT-PCR and viral culture To assess PK of Pi; PK/PD relationships of Pi Investigate: * Acceptability (taste, swallowability) of Pi formulation in adolescents * Emergence of viral resistance against Pi;Primary end point(s): The primary endpoint is the hospital recovery scale as assessed on Day 6.;Timepoint(s) of evaluation of this end point: The hospital recovery scale assesses a subject’s clinical status and will be assessed as the subject’s condition on Day 6 as the primary endpoint. | — |
Secondary
| Measure | Time frame |
|---|---|
| Secondary end point(s): 1. Safety and tolerability based on assessment of adverse events (AEs), clinical laboratory assessments, 12-lead electrocardiograms (ECGs), vital signs, and peripheral capillary oxygen saturation. 2. Time from start of study drug to hospital discharge and total length of hospital stay. 3. Time from ICU admission to ICU discharge and total time in ICU. 4. Time from start to end of mechanical ventilation and total time on mechanical ventilation. 5. The hospital recovery scale as assessed each separate day from Days 2 to 14 (excluding the primary time point). 6. Time to return to daily activities. 7. Incidence of complications associated with influenza after the start of study treatment. 8. All-cause mortality. 9. Incidence and duration of antibiotic treatment. 10. The number (proportion) of subjects needing extended treatment. 11. The number (proportion) of subjects requiring re-hospitalization. 12. The number (proportion) of subjects not hospitalized at Day 6. 13. Time to clinical response. 14. Time to respiratory response. 15. PK parameters of pimodivir (ie, plasma concentration just prior to the beginning or at the end of a dosing interval [Ctrough], Cmax, tmax, and AUC12h), as determined by population PK analysis. 16. The acceptability of the pimodivir formulation in adolescents, as measured by a taste and swallowability questionnaire. 17. Time to viral negativity by qRT-PCR and viral culture. 18. Viral load over time by qRT-PCR and viral culture. 19. The emergence of viral resistance against pimodivir detected by genotyping and/or phenotyping.;Timepoint(s) of evaluation of this end point: 1-4, 6-11, 13-14: Day 33 5. Days 2-5 and 7-14 12. and 15: Day 6 16. Days 1 and 5 17 - 19: Day 19 | — |
Countries
Argentina, Australia, Austria, Belgium, Brazil, Bulgaria, Chile, Czech Republic, France, Germany, Hungary, India, Israel, Italy, Korea, Republic of, Latvia, Lithuania, Malaysia, Mexico, Netherlands, New Zealand, Peru, Poland, Romania, Russian Federation, Singapore, Slovakia, South Africa, Spain, Sweden, Taiwan, Thailand, Turkey, Ukraine, United Kingdom, United States, Vietnam
Contacts
Public ContactClinical Registry Group
Janssen-Cilag International NV
Outcome results
None listed