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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

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ClinicalTrials.gov Identifier: NCT03376321
Recruitment Status : Not yet recruiting
First Posted : December 18, 2017
Last Update Posted : December 18, 2017
Sponsor:
Information provided by (Responsible Party):

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.

Condition or disease Intervention/treatment Phase
Influenza A Drug: Pimodivir 600 mg Drug: Placebo Other: SOC Treatment Phase 3

Janssen Research & Development, LLC has indicated that access to an investigational treatment associated with this study is available outside the clinical trial.  

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.

Study Design

Study Type : Interventional  (Clinical Trial)
Estimated Enrollment : 600 participants
Allocation: Randomized
Intervention Model: Parallel Assignment
Masking: Double (Participant, Investigator)
Primary Purpose: Treatment
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
Anticipated Study Start Date : December 14, 2017
Estimated Primary Completion Date : April 2, 2020
Estimated Study Completion Date : May 1, 2020

Resource links provided by the National Library of Medicine

MedlinePlus related topics: Flu Flu Shot
U.S. FDA Resources

Arms and Interventions

Arm Intervention/treatment
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).
Other: 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).
Other: 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.


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.


Eligibility Criteria

Information from the National Library of Medicine

Choosing to participate in a study is an important personal decision. Talk with your doctor and family members or friends about deciding to join a study. To learn more about this study, you or your doctor may contact the study research staff using the contacts provided below. For general information, Learn About Clinical Studies.


Ages Eligible for Study:   13 Years to 85 Years   (Child, Adult, Senior)
Sexes Eligible for Study:   All
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
Contacts and Locations

Information from the National Library of Medicine

To learn more about this study, you or your doctor may contact the study research staff using the contact information provided by the sponsor.

Please refer to this study by its ClinicalTrials.gov identifier (NCT number): NCT03376321


Contacts
Contact: Study Contact 844-434-4210 JNJ.CT@sylogent.com

Locations
United States, Washington
Wenatchee Valley Hospital & Clinics Not yet recruiting
Wenatchee, Washington, United States, 98801
Sponsors and Collaborators
Janssen Research & Development, LLC
Investigators
Study Director: Janssen Research & Development, LLC Clinical Trial Janssen Research & Development, LLC
More Information

Responsible Party: Janssen Research & Development, LLC
ClinicalTrials.gov Identifier: NCT03376321     History of Changes
Other Study ID Numbers: CR108399
2017-002156-84 ( EudraCT Number )
63623872FLZ3001 ( Other Identifier: Janssen Research & Development, LLC )
First Posted: December 18, 2017    Key Record Dates
Last Update Posted: December 18, 2017
Last Verified: December 2017

Studies a U.S. FDA-regulated Drug Product: Yes
Studies a U.S. FDA-regulated Device Product: No

Additional relevant MeSH terms:
Influenza, Human
Orthomyxoviridae Infections
RNA Virus Infections
Virus Diseases
Respiratory Tract Infections
Respiratory Tract Diseases
Antiviral Agents
Anti-Infective Agents