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History of Changes for Study: NCT03376321
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
Latest version (submitted March 19, 2021) on ClinicalTrials.gov
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Study Record Versions
Version A B Submitted Date Changes
1 December 12, 2017 None (earliest Version on record)
2 February 1, 2018 Recruitment Status, Study Status, Contacts/Locations and Oversight
3 February 28, 2018 Outcome Measures, Arms and Interventions, Study Status, Contacts/Locations and Eligibility
4 April 6, 2018 Contacts/Locations, Arms and Interventions, Study Status and Eligibility
5 April 24, 2018 Contacts/Locations and Study Status
6 May 3, 2018 Study Status and Contacts/Locations
7 May 22, 2018 Contacts/Locations and Study Status
8 June 19, 2018 Contacts/Locations and Study Status
9 July 17, 2018 Study Status and Contacts/Locations
10 October 3, 2018 Contacts/Locations and Study Status
11 October 17, 2018 Contacts/Locations and Study Status
12 November 6, 2018 Study Status and Contacts/Locations
13 December 4, 2018 Contacts/Locations and Study Status
14 December 27, 2018 Contacts/Locations and Study Status
15 January 22, 2019 Contacts/Locations and Study Status
16 February 18, 2019 Contacts/Locations and Study Status
17 March 15, 2019 Study Status and Contacts/Locations
18 March 19, 2019 Contacts/Locations and Study Status
19 April 16, 2019 Contacts/Locations and Study Status
20 May 14, 2019 Contacts/Locations and Study Status
21 June 11, 2019 Contacts/Locations and Study Status
22 July 10, 2019 Contacts/Locations, Study Status, Eligibility and Outcome Measures
23 August 6, 2019 Contacts/Locations and Study Status
24 September 3, 2019 Contacts/Locations and Study Status
25 October 1, 2019 Study Status and Contacts/Locations
26 October 29, 2019 Contacts/Locations and Study Status
27 November 26, 2019 Contacts/Locations and Study Status
28 December 24, 2019 Contacts/Locations and Study Status
29 January 21, 2020 Study Status and Contacts/Locations
30 February 18, 2020 Study Status and Contacts/Locations
31 March 17, 2020 Study Status and Contacts/Locations
32 April 14, 2020 Contacts/Locations and Study Status
33 May 12, 2020 Study Status and Contacts/Locations
34 June 9, 2020 Study Status and Contacts/Locations
35 July 7, 2020 Study Status and Contacts/Locations
36 August 4, 2020 Study Status and Contacts/Locations
37 September 1, 2020 Study Status and Contacts/Locations
38 October 16, 2020 Recruitment Status, Contacts/Locations, Study Status and Study Design
39 March 19, 2021 Study Status, Outcome Measures, Document Section, Results and Contacts/Locations
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Study NCT03376321
Submitted Date:  December 12, 2017 (v1)

Open or close this module Study Identification
Unique Protocol ID: CR108399
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
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
Secondary IDs: 2017-002156-84 [EudraCT Number]
63623872FLZ3001 [Janssen Research & Development, LLC]
Open or close this module Study Status
Record Verification: December 2017
Overall Status: Not yet recruiting
Study Start: December 14, 2017
Primary Completion: April 2, 2020 [Anticipated]
Study Completion: May 1, 2020 [Anticipated]
First Submitted: December 12, 2017
First Submitted that
Met QC Criteria:
December 12, 2017
First Posted: December 18, 2017 [Actual]
Last Update Submitted that
Met QC Criteria:
December 12, 2017
Last Update Posted: December 18, 2017 [Actual]
Open or close this module Sponsor/Collaborators
Sponsor: Janssen Research & Development, LLC
Responsible Party: Sponsor
Collaborators:
Open or close this module Oversight
U.S. FDA-regulated Drug: Yes
U.S. FDA-regulated Device: No
Data Monitoring: Yes
Open or close this module Study Description
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.
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.
Open or close this module Conditions
Conditions: Influenza A
Keywords:
Open or close this module Study Design
Study Type: Interventional
Primary Purpose: Treatment
Study Phase: Phase 3
Interventional Study Model: Parallel Assignment
Number of Arms: 2
Masking: Double (Participant, Investigator)
Allocation: Randomized
Enrollment: 600 [Anticipated]
Open or close this module Arms and Interventions
Arms Assigned Interventions
Experimental: Treatment Arm 1 (pimodivir + SOC treatment)
Participants will receive pimodivir 600 milligram (mg) orally twice daily for 5 days (on Days 1 through 5; for participants who will receive only 1 dose of pimodivir on Day 1 [evening], dosing will continue until the morning of Day 6) along with Standard-of-Care (SOC) treatment. Participants who meet all treatment extension criteria as defined in the protocol may receive an additional 5 day course of the same treatment as received at study start. The SOC treatment is determined by the investigator based on local practice, may include influenza antivirals and/or supportive care only. An influenza antiviral as part of the SOC cannot be changed (for example, switching one influenza antiviral for another) or started during either the treatment period or extension phase, with the exception that an influenza antiviral may be discontinued in the case of a suspected adverse event (AE).
Drug: Pimodivir 600 mg
Participants will receive pimodivir 600 mg orally twice daily for 5 days (on Days 1 through 5; for participants who will receive only 1 dose of pimodivir on Day 1 [evening], dosing will continue until the morning of Day 6). Participants who meet treatment extension criteria may receive an additional 5 day course of the same treatment as received at study start (on Days 6 through 10).
SOC Treatment
Participants may receive SOC treatment as a part of background therapy. The SOC treatment is determined by the investigator based on local practice, and may include influenza antivirals and/or supportive care only. An influenza antiviral as part of the SOC cannot be changed (for example, switching one influenza antiviral for another) or started during either the treatment period or extension phase, with the exception that an influenza antiviral may be discontinued in the case of a suspected AE.
Placebo Comparator: Treatment Arm 2 (placebo + SOC treatment)
Participants will receive placebo matching to pimodivir orally twice daily for 5 days (on Days 1 through 5; for participants who will receive only 1 dose of placebo on Day 1 [evening], dosing will continue until the morning of Day 6) along with SOC treatment. Participants who meet all treatment extension criteria as defined in the protocol may receive an additional 5 day course of the same treatment as received at study start. The SOC treatment is determined by the investigator based on local practice, may include influenza antivirals and/or supportive care only. An influenza antiviral as part of the SOC cannot be changed (for example, switching one influenza antiviral for another) or started during either the treatment period or extension phase, with the exception that an influenza antiviral may be discontinued in the case of a suspected AE.
Drug: Placebo
Participants will receive placebo matching to pimodivir, orally twice daily for 5 days (on Days 1 through 5; for participants who will receive only 1 dose of placebo on Day 1 [evening], dosing will continue until the morning of Day 6). Participants who meet treatment extension criteria may receive an additional 5 day course of the same treatment as received at study start (on Days 6 through 10).
SOC Treatment
Participants may receive SOC treatment as a part of background therapy. The SOC treatment is determined by the investigator based on local practice, and may include influenza antivirals and/or supportive care only. An influenza antiviral as part of the SOC cannot be changed (for example, switching one influenza antiviral for another) or started during either the treatment period or extension phase, with the exception that an influenza antiviral may be discontinued in the case of a suspected AE.
Open or close this module Outcome Measures
Primary Outcome Measures:
1. Participant's Clinical Status Assessed by Hospital Recovery Scale
[ Time Frame: Day 6 ]

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.
Secondary Outcome Measures:
1. Number of Participants With Adverse Events as a Measure of Safety and Tolerability
[ Time Frame: Up to 33 days (up to 28 days if no treatment extension) ]

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.
2. Number of Participants With Laboratory Abnormalities as a Measure of Safety and Tolerability
[ Time Frame: Up to 33 days (up to 28 days if no treatment extension) ]

Blood samples for hematology, serum chemistry, and urinalysis will be collected at predefined time points for clinical laboratory testing.
3. Number of Participants With Electrocardiogram (ECG) Abnormalities as a Measure of Safety and Tolerability
[ Time Frame: Screening, Days 28 and 33 ]

A 12-lead ECG will be performed.
4. Number of Participants With Vital Signs abnormalities as a Measure of Safety and Tolerability
[ Time Frame: Up to 33 days (up to 28 days if no treatment extension) ]

Number of participants with vital signs (temperature, pulse rate, respiratory rate and blood pressure) abnormalities will be reported.
5. Number of Participants With Peripheral Capillary Oxygen Saturation (SpO2) Abnormalities as a Measure of Safety and Tolerability
[ Time Frame: Up to 33 days (up to 28 days if no treatment extension) ]

Number of participants with SpO2 abnormalities will be reported.
6. Length of Hospital Stay
[ Time Frame: Up to 33 days (up to 28 days if no treatment extension) ]

Length of hospital stay includes total days length of hospital stay from admission to discharge.
7. Length of Time in the Intensive Care Unit (ICU)
[ Time Frame: Up to 33 days (up to 28 days if no treatment extension) ]

In the event that a participant required intensive care, the duration for how long the participant remained in the ICU will be measured.
8. Length of Time on Mechanical Ventilation
[ Time Frame: Up to 33 days (up to 28 days if no treatment extension) ]

Length of time requiring mechanical ventilation will be measured.
9. Participant's Clinical Status Assessed by Hospital Recovery Scale
[ Time Frame: Days 4 to 5 and 7 to 14 ]

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.
10. Time to Return to Daily Activities
[ Time Frame: Up to 33 days (up to 28 days if no treatment extension) ]

Time to return to daily activities will be assessed by means of the participant's response to the question 'Over the past 24 hours, how much has influenza interfered with your ability to carry out your daily activities'. Participants will respond to the above question via an electronic Patient-reported Outcome (ePRO) device by means of the following response scale: Not at all; A little bit; Somewhat; Quite a bit; Very much.
11. Percentage of Participants with Complications Associated with Influenza After the Start of Study Treatment
[ Time Frame: Up to 33 days (up to 28 days if no treatment extension) ]

Percentage of participants with complications associated with influenza after the start of study will be reported. 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, severe dehydration, decompensation of previously controlled diabetes mellitus, other infections [for example, sinusitis and otitis]).
12. Number of Participants with All-cause Mortality
[ Time Frame: Up to 33 days (up to 28 days if no treatment extension) ]

The number of participants who died due to any cause while on treatment will be assessed.
13. Percentage of Participants Receiving Antibiotic Treatment
[ Time Frame: Up to 33 days (up to 28 days if no treatment extension) ]

Percentage of participants receiving antibiotic treatment will be reported.
14. Duration of Antibiotic Treatment
[ Time Frame: Up to 33 days (up to 28 days if no treatment extension) ]

Duration of antibiotic treatment taken will be reported.
15. Number of Participants Receiving Extended Treatment
[ Time Frame: Day 6 ]

Number of participants receiving extended treatment will be reported.
16. Number of Participants Requiring Re-hospitalization
[ Time Frame: Up to 33 days (up to 28 days if no treatment extension) ]

Number of participants requiring re-hospitalization will be reported.
17. Number of Participants not Hospitalized at Day 6
[ Time Frame: Day 6 ]

Number of participants not hospitalized at Day 6 will be reported.
18. Time to Clinical Response
[ Time Frame: Up to 33 days (up to 28 days if no treatment extension) ]

Time to achieve the clinical response will be determined. Clinical response is defined as achieving 4 of the 5 following vital signs resolution criteria, including at least the fever and oxygen saturation criteria, maintained for at least 24 hours: having no fever (without the use of antipyretics within 8 hours), oxygen saturation of at least 94 percent (%) without oxygen supplementation for at least 24 hours, improved respiratory status (return to pre- influenza infection oxygen requirement in participants with chronic oxygen use, or a respiratory rate less than or equal to 24 breaths per min without supplemental oxygen), heart rate 100 beats per minute or lower, systolic blood pressure of 90 millimeter of mercury (mmHg) or higher without inotropic support given within 2 hours of assessment.
19. Time to Respiratory Response
[ Time Frame: Up to 33 days (up to 28 days if no treatment extension) ]

Time to improvement of respiratory response will be determined. Improvement of respiratory response is defined as meeting both the oxygen saturation and respiration status criterion.
20. Maximum Plasma Concentration (Cmax) of pimodivir
[ Time Frame: Day 1: 1.5 to 6 hours post dose; Day 3: pre-dose; Day 5: pre-dose and 1.5 to 6 hours post dose; and Day 6: 12 hours post dose ]

The Cmax is the maximum plasma concentration after a dose of pimodivir.
21. Trough Plasma Concentration (Ctrough) of Pimodivir
[ Time Frame: Day 3: pre-dose; Day 5: pre-dose; and Day 6: 12 hours post dose ]

The (Ctrough) is the plasma concentration just prior to the beginning or at the end of a dosing interval.
22. Time to Reach Maximum Plasma Concentration (tmax) of Pimodivir
[ Time Frame: Day 1: 1.5 to 6 hours post dose; Day 3: pre-dose; Day 5: pre-dose and 1.5 to 6 hours post dose; and Day 6: 12 hours post dose ]

The tmax is defined as time to reach maximum analyte plasma concentration.
23. Area Under the Plasma Concentration-Time Curve from Time Zero to 12 Hours After Dosing AUC(0-12)
[ Time Frame: Day 1: 1.5 to 6 hours post dose; Day 3: pre-dose; Day 5: pre-dose and 1.5 to 6 hours post dose; and Day 6: 12 hours post dose ]

The AUC(0-12) is the area under the plasma concentration-time curve from time zero to 12 hours.
24. Time to Influenza Viral Negativity
[ Time Frame: Up to Day 19 (up to Day 14, if no treatment extension) ]

Time to influenza viral negativity will be determined by quantitative real time - polymerase chain reaction (qRT-PCR) and viral culture from nasal mid-turbinate (MT) swabs.
25. Viral Load Over Time
[ Time Frame: Up to Day 19 (up to Day 14, if no treatment extension) ]

Viral load over time will be measured by qRT-PCR and viral culture in the MT nasal swabs and endotracheal samples.
26. Number of Participants with Emergence of Viral Resistance to Pimodivir
[ Time Frame: Up to Day 19 (up to Day 14, if no treatment extension) ]

Emergence of viral resistance to pimodivir will be detected by genotyping and/or phenotyping.
27. Acceptability of the Pimodivir Formulation in Adolescents as Measured by a Taste Questionnaire
[ Time Frame: Days 1 and 5 (evening) or 6 (morning) ]

Acceptability of the pimodivir formulation in adolescents will be measured by a taste questionnaire. For overall taste, questions will be answered on a following response scale: No taste, Weak taste, Moderate taste, and Strong taste.
28. Acceptability of the Pimodivir Formulation in Adolescents as Measured by a Swallowability Questionnaire
[ Time Frame: Days 1 and 5 (evening) or 6 (morning) ]

Acceptability of the pimodivir formulation in adolescents will be measured by a swallowability questionnaire. Swallowability questions will be answered on a response scale of 1 to 7: 1. Very difficult; 2. Moderately difficult; 3. Slightly difficult; 4. Neither difficult or easy; 5. Slightly easy; 6. Moderately easy; and 7. Very easy.
29. Virologic Response by Baseline Viral Resistance to Pimodivir/Other Antivirals
[ Time Frame: Up to Day 19 (up to Day 14, if no treatment extension) ]

Virologic response by baseline viral resistance to pimodivir/other antivirals will be determined by qRT-PCR and viral culture.
Open or close this module Eligibility
Minimum Age: 13 Years
Maximum Age: 85 Years
Sex: All
Gender Based:
Accepts Healthy Volunteers: No
Criteria:

Inclusion Criteria:

  • 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 (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
  • Having a peripheral capillary oxygen saturation (SpO2) less than (<)94 percent (%) on room air. Participants with known pre-influenza SpO2 <94% must have an SpO2 decline greater than or equal to (>=)3% from pre-influenza SpO2
  • Having a screening/baseline National Early Warning Score (NEWS) 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
  • Chronic hepatitis C infection undergoing antiviral therapy
  • Severely immunocompromised in the opinion of the investigator (for example, 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
Open or close this module Contacts/Locations
Central Contact Person: Study Contact
Telephone: 844-434-4210
Email: JNJ.CT@sylogent.com
Study Officials: Janssen Research & Development, LLC Clinical Trial
Study Director
Janssen Research & Development, LLC
Locations: United States, Washington
Wenatchee Valley Hospital & Clinics
Wenatchee, Washington, United States, 98801
Open or close this module IPDSharing
Plan to Share IPD:
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