Brief Summary
The purpose of this study is to evaluate the clinical and virologic benefit of pimodivir in combination with Standard-of-Care (SOC) treatment compared to placebo in combination with SOC treatment.
Brief Title
A Study to Evaluate the Efficacy and Safety of Pimodivir in Combination With the Standard-of-Care Treatment in Adolescent, Adult, and Elderly Hospitalized Participants With Influenza A Infection
Detailed Description
This double-blind (neither researchers nor participants know what treatment participant is receiving) study will evaluate efficacy/safety of pimodivir in combination with SOC treatment versus placebo in combination with SOC treatment in adolescent, adult, and elderly hospitalized participants with influenza A infection. The study will be conducted in 3 phases: screening phase, double-blind treatment period of 5 days (with the possibility to extend treatment period by 5 days for participants who will enter an optional double-blind extension treatment arm), and post treatment follow-up period of 23 days. Study evaluations will include efficacy, pharmacokinetic, biomarkers, safety and tolerability. The duration of participation in study for each participant is 28 days, except for participants receiving extended treatment, for whom study duration will be up to 33 days.
Categories
Completion Date
Completion Date Type
Actual
Conditions
Influenza A
Eligibility Criteria
Inclusion Criteria:
* 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 (for example, 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 participants admitted to the Intensive Care Unit (ICU)
* Enrollment and initiation of study drug treatment less than or equal to (\<=)96 hours after onset of influenza symptoms
* Being on invasive mechanical ventilation or having a peripheral capillary oxygen saturation (SpO2) less than (\<)94 percent (%) on room air during screening. Participants with known pre-influenza SpO2 \<94% must have an SpO2 decline greater than or equal to (\>=)3% from pre-influenza SpO2 during screening
* Having a screening/baseline National Early Warning Score 2 (NEWS2) of \>=4
Exclusion Criteria:
* Received more than 3 doses of influenza antiviral medication (for example, oseltamivir \[OST\] or zanamivir), or any dose of ribavarin (RBV) within 2 weeks, prior to first study drug intake. Received intravenous (IV) peramivir more than one day prior to screening
* 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 (for example, known cluster of differentiation 4 plus \[CD4+\] count \<200 cells per cubic millimeter \[cells/mm\^3\], absolute neutrophil count \<750/mm\^3, 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)
* Known allergies, hypersensitivity, or intolerance to pimodivir or its excipients
* 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 (for example, 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 participants admitted to the Intensive Care Unit (ICU)
* Enrollment and initiation of study drug treatment less than or equal to (\<=)96 hours after onset of influenza symptoms
* Being on invasive mechanical ventilation or having a peripheral capillary oxygen saturation (SpO2) less than (\<)94 percent (%) on room air during screening. Participants with known pre-influenza SpO2 \<94% must have an SpO2 decline greater than or equal to (\>=)3% from pre-influenza SpO2 during screening
* Having a screening/baseline National Early Warning Score 2 (NEWS2) of \>=4
Exclusion Criteria:
* Received more than 3 doses of influenza antiviral medication (for example, oseltamivir \[OST\] or zanamivir), or any dose of ribavarin (RBV) within 2 weeks, prior to first study drug intake. Received intravenous (IV) peramivir more than one day prior to screening
* 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 (for example, known cluster of differentiation 4 plus \[CD4+\] count \<200 cells per cubic millimeter \[cells/mm\^3\], absolute neutrophil count \<750/mm\^3, 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)
* Known allergies, hypersensitivity, or intolerance to pimodivir or its excipients
Inclusion Criteria
Inclusion Criteria:
* 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 (for example, 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 participants admitted to the Intensive Care Unit (ICU)
* Enrollment and initiation of study drug treatment less than or equal to (\<=)96 hours after onset of influenza symptoms
* Being on invasive mechanical ventilation or having a peripheral capillary oxygen saturation (SpO2) less than (\<)94 percent (%) on room air during screening. Participants with known pre-influenza SpO2 \<94% must have an SpO2 decline greater than or equal to (\>=)3% from pre-influenza SpO2 during screening
* Having a screening/baseline National Early Warning Score 2 (NEWS2) of \>=4
* 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 (for example, 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 participants admitted to the Intensive Care Unit (ICU)
* Enrollment and initiation of study drug treatment less than or equal to (\<=)96 hours after onset of influenza symptoms
* Being on invasive mechanical ventilation or having a peripheral capillary oxygen saturation (SpO2) less than (\<)94 percent (%) on room air during screening. Participants with known pre-influenza SpO2 \<94% must have an SpO2 decline greater than or equal to (\>=)3% from pre-influenza SpO2 during screening
* Having a screening/baseline National Early Warning Score 2 (NEWS2) of \>=4
Gender
All
Gender Based
false
Healthy Volunteers
No
Last Update Post Date
Last Update Post Date Type
Actual
Last Update Submit Date
Maximum Age
85 Years
Minimum Age
13 Years
NCT Id
NCT03376321
Org Class
Industry
Org Full Name
Janssen Research & Development, LLC
Org Study Id
CR108399
Overall Status
Terminated
Phases
Phase 3
Primary Completion Date
Primary Completion Date Type
Actual
Official Title
A Phase 3 Randomized, Double-blind, Placebo-controlled, Multicenter Study to Evaluate the Efficacy and Safety of Pimodivir in Combination With the Standard-of-Care Treatment in Adolescent, Adult, and Elderly Hospitalized Patients With Influenza A Infection
Primary Outcomes
Outcome Description
The hospital recovery scale assesses a participant's clinical status. The scale provides 6 mutually exclusive conditions ordered from best to worst: 1) not hospitalized; 2) non-ICU hospitalization, not requiring supplemental oxygen; 3) non-ICU hospitalization, requiring supplemental oxygen; 4) admitted to the ICU, not requiring invasive mechanical ventilation; 5) requiring invasive mechanical ventilation; and 6) death.
Outcome Measure
Number of Participants With Hospital Recovery Scale on Day 6
Outcome Time Frame
Day 6
Secondary Ids
Secondary Id
2017-002156-84
Secondary Id
63623872FLZ3001
Secondary Outcomes
Outcome Description
The time to hospital discharge was defined as the time from start of study drug to hospital discharge.
Outcome Time Frame
Up to Day 33
Outcome Measure
Time to Hospital Discharge
Outcome Description
Influenza complications include pulmonary complications (such as respiratory failure, primary viral pneumonia, secondary bacterial pneumonia \[including pneumonia attributable to unusual pathogens\], exacerbations of chronic underlying pulmonary diseases such as chronic obstructive pulmonary disease \[COPD\] and asthma) and extrapulmonary complications (such as cardiovascular and cerebrovascular diseases \[for example, myocardial infarction, congestive heart failure, arrhythmia, stroke\], muscular disorders \[for example, myositis, rhabdomyolysis\], central nervous system \[CNS\] involvement, acute exacerbation of chronic kidney disease, decompensation of previously controlled diabetes mellitus, other infections \[for example, sinusitis and otitis\]).
Outcome Time Frame
Up to Day 33
Outcome Measure
Number of Participants With Adjudicated Influenza Complications
Outcome Description
Viral load over time was measured by quantitative real time polymerase chain reaction (qRT-PCR) and viral culture in the mid-turbinate (MT) nasal swabs and endotracheal samples.
Outcome Time Frame
Baseline, Days 1, 2, 3, 4, 5, 6, 7, 8, 9, 10, 11, 14 and 19
Outcome Measure
Viral Load Over Time
Outcome Description
An adverse event is any untoward medical event that occurs in a participant administered an investigational product, and it does not necessarily indicate only events with clear causal relationship with the relevant investigational product.
Outcome Time Frame
Up to Day 33
Outcome Measure
Number of Participants With Adverse Events as a Measure of Safety and Tolerability
Outcome Description
Emergence of viral resistance to Pimodivir was detected by genotyping and/or phenotyping. Nasal MT swabs and endotracheal samples were used for sequence analysis of the polymerase basic protein (PB)2 region of the influenza polymerase gene, and of neuraminidase (NA) genes for participants using an NA inhibitor (NAI) as part of their Standard of Care (SOC).
Outcome Time Frame
Up to Day 33
Outcome Measure
Number of Participants With Emergence of Viral Resistance to Pimodivir
Outcome Description
Plasma concentration of Pimodivir was reported.
Outcome Time Frame
Day 1: 1 hour30minutes to 6 hours postdose, Day 3: Predose, Day 5: Predose and 1 hour30minutes to 6 hours postdose, Day 6: 12 hours postdose
Outcome Measure
Plasma Concentration of Pimodivir
Outcome Description
Number of participants with clinically significant changes in laboratory tests were reported. Blood samples for hematology, serum chemistry, and urinalysis were collected at predefined time points for clinical laboratory testing.
Outcome Time Frame
Up to Day 33
Outcome Measure
Number of Participants With Clinically Significant Changes in Laboratory Tests
Outcome Description
Number of participants with clinically significant changes in Electrocardiogram (ECG) was reported.
Outcome Time Frame
Up to Day 33
Outcome Measure
Number of Participants With Clinically Significant Changes in Electrocardiogram (ECG)
Outcome Description
Number of participants with clinically significant changes in vital signs (temperature, pulse rate, respiratory rate and blood pressure) was reported.
Outcome Time Frame
Up to Day 33
Outcome Measure
Number of Participants With Clinically Significant Changes in Vital Signs
Start Date
Start Date Type
Actual
Status Verified Date
First Post Date
First Post Date Type
Actual
First Submit Date
First Submit QC Date
Std Ages
Child
Adult
Older Adult
Maximum Age Number (converted to Years and rounded down)
85
Minimum Age Number (converted to Years and rounded down)
13
Investigators
Investigator Type
Principal Investigator
Investigator Name
Paul Riska
Investigator Email
priska@montefiore.org
Investigator Phone
718-020-6494