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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 Non-Hospitalized Participants With Influenza A Infection Who Are at Risk of Developing Complications

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ClinicalTrials.gov Identifier: NCT03381196
Recruitment Status : Recruiting
First Posted : December 21, 2017
Last Update Posted : July 18, 2018
Sponsor:
Information provided by (Responsible Party):
Janssen Research & Development, LLC

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

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 (13 to 17 years), adult (18 to 65 years), and elderly (greater than [>] 65 but less than or equal to [<=] 85 years) non-hospitalized participants with influenza A infection who are at risk of developing complications. The study will be conducted in 3 phases: screening phase, double-blind treatment period (5 days), a post treatment follow-up period (23 days). Study evaluations include efficacy, clinical and virological outcomes, pharmacokinetics (PK), PK/pharmacodynamics, biomarkers, safety and tolerability. The duration of participation in the study for each participant is 28 days.

Study Type : Interventional  (Clinical Trial)
Estimated Enrollment : 720 participants
Allocation: Randomized
Intervention Model: Parallel Assignment
Masking: Double (Participant, Investigator)
Primary Purpose: Treatment
Official Title: A Phase 3 Randomized, Double-blind, Placebo-controlled, Multi-center Study to Evaluate the Efficacy and Safety of Pimodivir in Combination With the Standard-of-care Treatment in Adolescent, Adult, and Elderly Non-hospitalized Subjects With Influenza A Infection Who Are at Risk of Developing Complications
Actual Study Start Date : January 18, 2018
Estimated Primary Completion Date : May 19, 2019
Estimated Study Completion Date : October 29, 2019

Resource links provided by the National Library of Medicine

MedlinePlus related topics: Flu Flu Shot

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. The SOC treatment is determined by the investigator based on local practice, and may include influenza antivirals and/or supportive care only. The choice to use influenza antivirals as part of the SOC should be made before randomization. The influenza antiviral should be started no later than Day 2 morning (up to noon). An influenza antiviral as part of the SOC cannot be changed (for example, switching one influenza antiviral for another) during the treatment period, 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).
Other Name: JNJ-63623872

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. The choice to use influenza antivirals as part of the SOC should be made before randomization. The influenza antiviral should be started no later than Day 2 morning (up to noon).

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. The SOC treatment is determined by the investigator based on local practice, and may include influenza antivirals and/or supportive care only. The choice to use influenza antivirals as part of the SOC should be made before randomization. The influenza antiviral should be started no later than Day 2 morning (up to noon). An influenza antiviral as part of the SOC cannot be changed (for example, switching one influenza antiviral for another) during the treatment period, 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).

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. The choice to use influenza antivirals as part of the SOC should be made before randomization. The influenza antiviral should be started no later than Day 2 morning (up to noon).




Primary Outcome Measures :
  1. Time to Resolution of Influenza-Related Symptoms as Assessed by the Patient-Reported Outcome (PRO) Measure Flu-Intensity and Impact Questionnaire (Flu-iiQ) [ Time Frame: Baseline up to Day 28 ]
    The Flu-iiQ is a PRO that measures influenza symptom intensity (none, mild, moderate, or severe) on a 4 point Likert response rating scale ranging from 0 to 3, where "0" represents the absence of symptom and "3" represents the severe symptom. The resolution of influenza-related symptoms is defined as the beginning of the 24-hour period that 7 influenza symptoms (cough, sore throat, headache, nasal congestion, feeling feverish, body aches and pains, fatigue) are at most mild or at least back to previous level of symptom severity in case the participant reported the symptom as pre-existing.


Secondary Outcome Measures :
  1. Number of Participants With Adverse Events as a Measure of Safety and Tolerability [ Time Frame: Up to 28 days ]
    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 28 days ]
    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: Up to 28 days ]
    Number of participants with ECG abnormalities will be reported.

  4. Number of Participants With Vital Sign abnormalities as a Measure of Safety and Tolerability [ Time Frame: Up to 28 days ]
    Number of participants with vital sign (temperature, pulse rate, respiratory rate and blood pressure) abnormalities will be reported.

  5. Percentage of Participants Hospitalized [ Time Frame: Up to 28 days ]
    Percentage of participants hospitalized 28 days after treatment initiation will be reported.

  6. Percentage of Participants with Complications Associated with Influenza After the Start of Study Treatment [ Time Frame: Up to 28 days ]
    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]).

  7. Time to Return to Daily Activities [ Time Frame: Up to 28 days ]
    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 through 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.

  8. Time to Resolution of Fever [ Time Frame: Up to Day 14 ]
    Resolution of fever is defined as a body temperature less than (<) 37.0°C (degree centigrade) during a period of 24 hours without the use of antipyretics.

  9. Number of Participants with All-cause Mortality [ Time Frame: Up to 28 days ]
    The number of participants who died due to any cause will be assessed.

  10. Maximum Plasma Concentration (Cmax) of pimodivir [ Time Frame: Day 3, and Day 6 (12 hours post last dose on Day 5 evening) ]
    The Cmax is the maximum plasma concentration after a dose of pimodivir.

  11. Trough Plasma Concentration (Ctrough) of Pimodivir [ Time Frame: Day 6: 12 hours post last dose on Day 5 evening ]
    The (Ctrough) is the plasma concentration just prior to the beginning or at the end of a dosing interval.

  12. Time to Reach Maximum Plasma Concentration (tmax) of Pimodivir [ Time Frame: Day 3, and Day 6 (12 hours post last dose on Day 5 evening) ]
    The tmax is defined as time to reach maximum analyte plasma concentration.

  13. Area Under the Plasma Concentration- Time Curve from Time Zero to 12 Hours After Dosing AUC(0-12) [ Time Frame: Day 3, and Day 6 (12 hours post last dose on Day 5 evening) ]
    The AUC(0-12) is the area under the plasma concentration-time curve from time zero to 12 hours.

  14. 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.

  15. 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.

  16. Number of Participants with Emergence of Viral Resistance to Pimodivir [ Time Frame: Up to Day 14 ]
    Emergence of viral resistance to pimodivir will be detected by genotyping and/or phenotyping.

  17. Time to Influenza Viral Negativity [ Time Frame: Up to Day 14 ]
    Time to influenza viral negativity will be determined by quantitative real time - polymerase chain reaction (qRT-PCR) and viral culture from nasal midturbinate (MT) swabs.

  18. Viral Load Over Time [ Time Frame: Up to Day 14 ]
    Viral load over time will be measured by qRT-PCR and viral culture in the MT nasal swabs samples.

  19. Time to Resolution of Each of the 10 Individual Influenza-Related Symptoms as Assessed by the PRO Measure Flu-iiQ [ Time Frame: Up to Day 28 ]
    The resolution of each influenza-related symptom is defined as the beginning of the 24-hour period when the influenza symptom score is at most mild or at least back to previous level of symptom severity in case the participant reported the symptom as pre-existing.



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Ages Eligible for Study:   13 Years to 85 Years   (Child, Adult, Older Adult)
Sexes Eligible for Study:   All
Accepts Healthy Volunteers:   No
Criteria

Inclusion Criteria:

  • Present to the clinic with symptoms suggestive of a diagnosis of acute influenza and have at least 1 respiratory symptom and at least 1 systemic symptom, both scored as at least "moderate" if the symptom did not pre-exist before influenza onset, or scored worse than usual if the symptom pre-existed as determined by subject's ratings on Module 1 of the Flu-iiQ and the Pre-existing Symptom Questionnaire in the ePRO device. Symptoms must include the following by category: a) Respiratory symptoms: cough, sore throat, nasal congestion b) Systemic symptoms: headache, body aches or pain, feverishness, fatigue
  • Tested positive for influenza A infection after the onset of symptoms, using a rapid influenza diagnostic test (RIDT) or, if available, a polymerase chain reaction (PCR)-based or other rapid molecular diagnostic assay
  • Not be in need of hospitalized medical care at screening. Emergency room or hospital observation status for an anticipated duration of less than (<)24 hours is not considered hospitalization as long as a determination of the need for hospitalization has not been made
  • Enrollment and initiation of study drug treatment less than or equal to (<=)72 hours after onset of influenza symptoms
  • Participants 13 to 65 years of age, inclusive must also have at least 1 of the following: a) Cardiovascular or cerebrovascular disease (including congenital heart disease, chronic heart failure, coronary artery disease, or stroke; excluding isolated hypertension); b) Chronic lung disease (for example, asthma, chronic obstructive lung disease [COPD] or cystic fibrosis); c) Weakened immune system due to disease or medication (for example, participants with human immunodeficiency virus [HIV], cancer, or chronic liver or kidney disease [presence of kidney damage for >3 months, defined by structural or functional abnormalities of the kidney, with or without decreased GFR manifested by: pathological abnormalities; OR markers of kidney damage, including abnormalities in the composition of the blood or urine or abnormalities in imaging tests], or participants taking chronic systemic steroids)

Exclusion Criteria:

  • Received more than (>)1 dose of influenza antiviral medication (for example, oseltamivir [OST] or zanamivir), or any dose of ribavirin within 2 weeks, prior to first study drug intake, or received intravenous (IV) peramivir >1 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, history of a lung transplant)

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): NCT03381196


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

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Sponsors and Collaborators
Janssen Research & Development, LLC
Investigators
Study Director: Janssen Research & Development, LLC Clinical Trial Janssen Research & Development, LLC

Additional Information:
Responsible Party: Janssen Research & Development, LLC
ClinicalTrials.gov Identifier: NCT03381196     History of Changes
Other Study ID Numbers: CR108400
2017-002217-59 ( EudraCT Number )
63623872FLZ3002 ( Other Identifier: Janssen Research & Development, LLC )
First Posted: December 21, 2017    Key Record Dates
Last Update Posted: July 18, 2018
Last Verified: July 2018

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