None listed
Conditions
Interventions
Treatment Arm 1: Pimodivir 600 mg twice daily for 5 days + standard of care treatment. Type of group
Treatment Arm 1:
Pimodivir 300mg Oral tablets. Dosage: 2 tablets combined with standard of care treatment 2 twice daily by 5 days.
Treatment Extension Arm 1:
Pimodivir 300mg Oral tablets. Dosage: 2 tablets combined with standard of care treatment 2 twice daily by 5 days from sixth to tenth day.
Group name:Treatment Arm 2: pimodivir placebo twice daily for 5 days + standard of care treatment. Type of group
Treatment Arm 2:
Pimodivir placebo Oral tablets. Dosage: 2 tablets combined with standard of care treatment 2 twice daily by 5 days.
Treatment Extension Arm 2:
Pimodivir placebo Oral tablets. Dosage: 2 tablets combined with standard of care treatment 2 twice daily by 5 days from sixth to tenth day.
Sponsors
Janssen Research & Develoment, LLC,
Eligibility
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 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. • Having an SpO2 <94% on room air. Subjects with known pre influenza SpO2 <94% must have an SpO2 decline ≥3% from pre-influenza SpO2. • Having a screening/baseline NEWS of ≥4.
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. • Chronic hepatitis C infection undergoing antiviral therapy. • Severely immunocompromised in the opinion of the investigator (eg, 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 |
|---|---|
| Outcome name:The primary efficacy analysis will consist of the analysis of the hospital recovery scale outcome on Day 6 using a proportional odds model, including treatment, and the stratification factors (baseline NEWS, type of baseline SOC, and time since onset of influenza symptoms). In case of missing data, multiple imputation will be employed as sensitivity analyses, under the missing at-random assumption and missing-not-at-random assumption. Measure:The primary endpoint is the hospital recovery scale as assessed on Day 6. Timepoints: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. The hospital recovery scale will be assessed on Days 4 to 14 (excluding the primary time point) as secondary endpoints. | — |
Secondary
| Measure | Time frame |
|---|---|
| Outcome name:The time to hospital discharge will consist of a stratified Gehan-Wilcoxon test (using the randomization stratification factors, ie, type of baseline SOC, time of onset of symptoms and baseline NEWS). Kaplan Meier curves, overall and by stratum, and a stratified log-rank test for time to symptom resolution will also be provided. Additionally, the data will be analyzed using an accelerated failure time model. If this model fit is poor, a Cox proportional hazards model will be applied. Both models will be adjusted for stratification factors. The length of time in the ICU and the length of time on mechanical ventilation will be analyzed analogous to that of time to hospital discharge, only including subjects that were admitted to the ICU. Measure:1. Hospital recovery scale, ie, primary endpoint (Day 6) 2. Reduction in post-baseline complications 3. Length of hospital stay 4. Time to return to daily activities 5. Length of time in the ICU 6. Length of time on mechanical ventilation 7. Rate of re-hospitalization Timepoints:If superiority is shown on the primary endpoint, the first secondary endpoint will be tested and so forth. In case superiority is not shown for an endpoint, no further endpoints in the sequence will be tested for superiority. | — |
Countries
Argentina, Australia, Belgium, Brazil, Bulgaria, Chile, Czech Republic, France, Germany, Hungary, India, Israel, Italy, Korea South, Latvia, Lithuania, Malasya, Mexico, New Zealand, Poland, Romania, Russian Federation, Singapore, Slovakia, South Africa, Spain, Switzerland, Taiwan, Thailand, Turkey, Ukraine, United States, Vietnam
Contacts
Public ContactElvira Mogrovejo
IQVIA RDS Peru S.R.L
Outcome results
None listed