Clinical Trials List
Protocol Number63623872FLZ3001
NCT Number(ClinicalTrials.gov Identfier)NCT03376321
2018-01-01 - 2020-05-01
Phase III
Terminated4
ICD-10J09.X1
Influenza due to identified novel influenza A virus with pneumonia
A phase 3, randomized, double-blind, placebo-controlled, multicenter trial to evaluate the efficacy and safety of Pimodivir combined with standard care treatment in adolescents, adults, and elderly hospitalized patients with influenza A
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Trial Applicant
IQVIA RDS Taiwan Ltd.
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Sponsor
Janssen Research & Development, LLC
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Trial scale
Multi-Regional Multi-Center
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Update
2025/08/20
Investigators and Locations
Co-Principal Investigator
- Chih-Hsin Lee Division of Thoracic Medicine
- Wen-Sen Lee Division of Infectious Disease
- Han-Lin Hsu Division of Thoracic Medicine
- Fu-Lun Chen Division of Infectious Disease
- Shian-Jiun Lin Division of Thoracic Medicine
The Actual Total Number of Participants Enrolled
0 Stop recruiting
Co-Principal Investigator
- 林德宇 Division of Infectious Disease
The Actual Total Number of Participants Enrolled
0 Stop recruiting
Co-Principal Investigator
Audit
None
Co-Principal Investigator
- 楊德亮 Division of Pediatrics
- 陳立倫 Division of Pediatrics
- 李冠霖 Division of Pediatrics
- 林筱琪 Division of Pediatrics
- Luan-Yin Chang Division of Pediatrics
- 李杰明 Division of Pediatrics
- 陳婉真 Division of Pediatrics
- Chun-yi Lu Division of Pediatrics
- 邢子芸 Division of Pediatrics
The Actual Total Number of Participants Enrolled
0 Stop recruiting
Principal Investigator
Co-Principal Investigator
- Jen-Yu Hung Division of Thoracic Medicine
- 陳家閔 Division of Thoracic Medicine
- Ming-Ju Tsai Division of Thoracic Medicine
- Wei-An Chang Division of Thoracic Medicine
- Chau-Chyun Sheu Division of Thoracic Medicine
- Po-Liang Lu Division of Thoracic Medicine
The Actual Total Number of Participants Enrolled
0 Stop recruiting
Condition/Disease
Influenza A Infection
Objectives
Primary 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 Objectives
The secondary objectives are:
• To investigate the safety and tolerability of pimodivir in combination with SOC treatment compared
to placebo in combination with SOC treatment.
• To evaluate superiority with respect to the time from start of study drug to hospital discharge in
subjects treated with pimodivir in combination with SOC treatment compared to placebo in
combination with SOC treatment.
• To evaluate superiority with respect to the time from intensive care unit (ICU) admission to ICU
discharge in subjects treated with pimodivir in combination with SOC treatment compared to placebo
in combination with SOC treatment.
• To evaluate superiority with respect to the time from start to end of mechanical ventilation in subjects
treated with pimodivir in combination with SOC treatment compared to placebo in combination with SOC treatment.
• To evaluate superiority of pimodivir in combination with SOC treatment compared to placebo in
combination with SOC treatment assessed each separate day from Days 2 to 14 (excluding the primary
time point), with respect to the clinical outcome on the hospital recovery scale.
• To evaluate superiority with respect to the time to return to daily activities in subjects treated with
pimodivir in combination with SOC treatment compared to placebo in combination with SOC treatment.
• To evaluate superiority with respect to the incidence of complications associated with influenza after
the start of study treatment in subjects treated with pimodivir in combination with SOC treatment
compared to placebo in combination with SOC treatment.
• To investigate all-cause mortality in the pimodivir in combination with SOC treatment arm, compared
to the placebo in combination with SOC treatment arm.
• To investigate the incidence and duration of antibiotic treatment in the pimodivir in combination with
SOC treatment arm, compared to the placebo in combination with SOC treatment arm.
• To investigate the number (proportion) of subjects needing extended treatment in the pimodivir in
combination with SOC treatment arm, compared to the placebo in combination with SOC treatment arm.
• To investigate the number (proportion) of subjects requiring re-hospitalization in the pimodivir in
combination with SOC treatment arm, compared to the placebo in combination with SOC treatment arm.
• To investigate the number (proportion) of subjects not hospitalized at Day 6 in the pimodivir in
combination with SOC treatment arm, compared to the placebo in combination with SOC treatment arm.
• To investigate the time to clinical response in the pimodivir in combination with SOC treatment arm,
compared to the placebo in combination with SOC treatment arm.
• To investigate the time to improvement of respiratory status in the pimodivir in combination with SOC
treatment arm, compared to the placebo in combination with SOC treatment arm.
• To assess the pharmacokinetics (PK) of pimodivir and to explore the PK/pharmacodynamic (PD)
relationships of pimodivir for efficacy and safety.
• To investigate the acceptability (taste and swallowability) of the pimodivir formulation in adolescents.
• To evaluate superiority with respect to the following influenza A viral parameters in the pimodivir
treatment arm compared to the control arm by quantitative real time polymerase chain reaction
(qRT-PCR) and viral culture:
Time to viral negativity.
Viral load over time.
• To investigate the emergence of viral resistance against pimodivir detected by genotyping and/or phenotyping.
Test Drug
Pimodivir
Active Ingredient
C20H19F2N5O2.HCl.1/2 H2O
Dosage Form
film-coated oral tablets
Dosage
300
Endpoints
Primary Endpoint
The primary endpoint is the hospital recovery scale as assessed on Day 6.
Secondary Endpoints
The secondary endpoints are:
• Safety and tolerability based on assessment of adverse events (AEs), clinical laboratory assessments,
12-lead electrocardiograms (ECGs), vital signs, and peripheral capillary oxygen saturation.
• Time from start of study drug to hospital discharge and total length of hospital stay.
• Time from ICU admission to ICU discharge and total time in ICU.
• Time from start to end of mechanical ventilation and total time on mechanical ventilation.
• The hospital recovery scale as assessed each separate day from Days 2 to 14 (excluding the primary
time point).
• Time to return to daily activities.
• Incidence of complications associated with influenza after the start of study treatment.
• All-cause mortality.
• Incidence and duration of antibiotic treatment.
• The number (proportion) of subjects needing extended treatment.
• The number (proportion) of subjects requiring re-hospitalization.
• The number (proportion) of subjects not hospitalized at Day 6.
• Time to clinical response.
• Time to respiratory response.
• 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.
• The acceptability of the pimodivir formulation in adolescents, as measured by a taste and
swallowability questionnaire.
• Time to viral negativity by qRT-PCR and viral culture.
• Viral load over time by qRT-PCR and viral culture.
• The emergence of viral resistance against pimodivir detected by genotyping and/or phenotyping.
Exploratory Endpoint
• A patient-reported outcome (PRO) based on subjects’ ratings on the influenza symptom diary
will be formulated.
The primary endpoint is the hospital recovery scale as assessed on Day 6.
Secondary Endpoints
The secondary endpoints are:
• Safety and tolerability based on assessment of adverse events (AEs), clinical laboratory assessments,
12-lead electrocardiograms (ECGs), vital signs, and peripheral capillary oxygen saturation.
• Time from start of study drug to hospital discharge and total length of hospital stay.
• Time from ICU admission to ICU discharge and total time in ICU.
• Time from start to end of mechanical ventilation and total time on mechanical ventilation.
• The hospital recovery scale as assessed each separate day from Days 2 to 14 (excluding the primary
time point).
• Time to return to daily activities.
• Incidence of complications associated with influenza after the start of study treatment.
• All-cause mortality.
• Incidence and duration of antibiotic treatment.
• The number (proportion) of subjects needing extended treatment.
• The number (proportion) of subjects requiring re-hospitalization.
• The number (proportion) of subjects not hospitalized at Day 6.
• Time to clinical response.
• Time to respiratory response.
• 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.
• The acceptability of the pimodivir formulation in adolescents, as measured by a taste and
swallowability questionnaire.
• Time to viral negativity by qRT-PCR and viral culture.
• Viral load over time by qRT-PCR and viral culture.
• The emergence of viral resistance against pimodivir detected by genotyping and/or phenotyping.
Exploratory Endpoint
• A patient-reported outcome (PRO) based on subjects’ ratings on the influenza symptom diary
will be formulated.
Inclution Criteria
Key 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 <94% on room air during screening.
Subjects with known pre-influenza SpO2 <94% must have an SpO2 decline ≥3% from pre-influenza
SpO2 during screening.
• Having a screening/baseline NEWS of ≥4.
• 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 <94% on room air during screening.
Subjects with known pre-influenza SpO2 <94% must have an SpO2 decline ≥3% from pre-influenza
SpO2 during screening.
• Having a screening/baseline NEWS of ≥4.
Exclusion Criteria
Key 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).
• 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).
The Estimated Number of Participants
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Taiwan
12 participants
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Global
600 participants
