A Phase 2, Double-blind, Placebo-controlled Study to Evaluate the Antiviral Activity, Clinical Outcomes, Safety, Tolerability, and Pharmacokinetic/Pharmacodynamic Relationships of Different Doses of JNJ-53718678 in Children >=28 Days and <=3 Years of Age With Acute Respiratory Tract Infection Due to Respiratory Syncytial Virus Infection
Overview
- Phase
- Phase 2
- Intervention
- JNJ-53718678
- Conditions
- Respiratory Syncytial Virus Infections
- Sponsor
- Janssen Research & Development, LLC
- Enrollment
- 246
- Locations
- 169
- Primary Endpoint
- Respiratory Syncytial Virus (RSV) Viral Load Area Under Curve (AUC) From Immediately Prior to First Dose of Study Drug (Baseline) Through Day 5 (AUC[Day 5])
- Status
- Terminated
- Last Updated
- last year
Overview
Brief Summary
The purpose of this study is to evaluate the antiviral activity, clinical outcomes, safety, tolerability, and pharmacokinetic/pharmacodynamic relationships of different oral dose levels of JNJ-53718678 in children greater than or equal to 28 days and less than or equal to 3 years of age with respiratory syncytial virus (RSV) disease (hospitalized participants [Cohort 1] or outpatients [Cohort 2]).
Detailed Description
JNJ-53718678 is an investigational respiratory syncytial virus (RSV) specific fusion inhibitor and is under development for the treatment of RSV infection, which results in an upper and/or lower respiratory tract illness. The primary hypothesis of this study is that JNJ-53718678 has antiviral activity against RSV (that is, results in a decrease in RSV nasal viral load from immediately prior to first dose of study drug until Day 5). This will be assessed by a positive dose-response relationship of JNJ-53718678 compared to placebo. Besides the RSV nasal viral load through day 5, other timepoints will also be evaluated as well as other nasal viral load related parameters. In addition, the evolution of signs and symptoms of RSV disease will be evaluated. Participants' safety will be monitored throughout the study by evaluating the occurrence and severity of adverse events and by laboratory and electrocardiogram measurements. Study participants will be identified when they are hospitalized or expected to be hospitalized within 24 hours after presentation to the hospital (Cohort 1) or present for medical care as outpatients (Cohort 2) with symptoms of an acute respiratory illness supporting a diagnosis of RSV infection. Eligible participants will be randomized 1:1:1 to receive either a low or a high dose of JNJ 53718678 or placebo and will be receiving study treatment for 7 days. They will be followed up for 3 weeks after the last dose. The total study duration for each participant will be approximately 29 days.
Investigators
Eligibility Criteria
Inclusion Criteria
- •Informed consent form (ICF) must be given
- •Laboratory diagnosis of respiratory syncytial virus (RSV) infection
- •The participant has an acute respiratory illness
- •The time of onset of RSV symptoms to the anticipated time of randomization must be less than or equal to (\<=) 5 days
- •Except for the RSV-related illness, the Participant must be medically stable in case of allowed co-morbid conditions
- •The participant must have been assessed per local public health practice and considered not to have Severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) infection during this respiratory infection
Exclusion Criteria
- •The participant is less than (\<) 3 months postnatal age at screening and was born prematurely (i.e, \<37 weeks and 0 days of gestation) OR if the participant weighs \<2.4 kilogram (kg) or greater than (\>) 16.8 kg
- •Participant is considered by the investigator to be immunocompromised within the past 12 months
- •Participant unwilling or unable to undergo mid-turbinate nasal swab procedures
- •Participant is receiving chronic home oxygen therapy at screening
- •Participant has other clinically significant abnormal electrocardiogram (ECG) findings not consistent with the present risk factor for severe RSV disease (if applicable) in the study population, as judged by the investigator based on the machine read ECG results at screening
- •The participant has a QTcF interval greater than (\>)450 millisecond (ms) per the machine read (mean of triplicate) parameter result confirmed by repeat triplicate ECG recording during screening
Arms & Interventions
High Dose: JNJ-53718678
Participants will be randomized to receive JNJ-53718678 2.5 milligram per kilogram (mg/kg) (Age Group 1: greater than or equal to \[\>=\] 28 days and less than \[\<\] 3 months of age), 3 mg/kg (Age Group 2: \>=3 months and \<6 months of age) and 4.5 mg/kg (Age Group 3: \>=6 months and less than or equal to \[\<=3\] years of age) orally twice daily for 7 days.
Intervention: JNJ-53718678
Low Dose: JNJ-53718678
Participants will be randomized to receive JNJ-53718678 0.85 mg/kg (Age Group 1: \>=28 days and \<3 months of age), 1 mg/kg (Age Group 2: \>=3 months and \<6 months of age) and 1.5 mg/kg (Age Group 3: \>=6 months and 3 years of age) orally twice daily for 7 days.
Intervention: JNJ-53718678
Placebo
Participants will be randomized to receive matching placebo (i.e. high volume placebo or low volume placebo to match the calculated volume of the JNJ-53718678 for the high dose or low dose) orally twice daily for 7 days.
Intervention: Placebo
Outcomes
Primary Outcomes
Respiratory Syncytial Virus (RSV) Viral Load Area Under Curve (AUC) From Immediately Prior to First Dose of Study Drug (Baseline) Through Day 5 (AUC[Day 5])
Time Frame: Baseline through Day 5
RSV viral load AUC from immediately prior to first dose of study drug through Day 5 was determined. The RSV viral load was measured by quantitative reverse transcription polymerase chain reaction (qRT-PCR) assay in mid-turbinate nasal swab specimens. As planned, combined data for both the cohorts was collected, analyzed and reported for this outcome measure.
Secondary Outcomes
- RSV Viral Load Over Time(Baseline, Days 3, 5, 8, 14, and 21)
- Change From Baseline in RSV Viral Load Over Time(Baseline up to Days 3, 5, 8, 14, and 21)
- Least Squares (LS) Mean RSV Viral Load on Days 3, 8 and 14(Baseline through Days 3, 8, and 14)
- Time to Undetectable RSV Viral Load(Up to Day 21)
- Percentage of Participants With Undetectable RSV Viral Load at Each Timepoint Throughout the Study(Baseline, Days 3, 5, 8, 14 and 21)
- Change From Baseline in Parent(s)/Caregiver(s) Pediatric RSV Electronic Severity and Outcomes Rating System (PRESORS) Scores(Baseline up to Days 3, 5, 8, 14 and 21)
- Change From Baseline in Clinician PRESORS Score(Baseline, up to Days 3, 5, 8, 14 and 21)
- Time to Resolution of RSV Symptoms Based on PRESORS Caregiver (ObsRO)(Up to Day 21)
- Time to Improvement on Overall Health(Up to Day 21)
- Percentage of Participants by Status of RSV Symptoms Based on PRESORS Caregiver (ObsRO) General Question Over Time(Baseline, Days 3, 5, 8, 14, and 21)
- Percentage of Participants by Health Status Assessment Based on PRESORS Caregiver (ObsRO) General Question Over Time(Baseline, Days 3, 5, 8, 14, and 21)
- Percentage of Participants With Worsening or Improvement Status of RSV Disease(Days 14 and 21)
- Percentage of Participants by Return to Pre-RSV Disease Health Status Assessment Based on PRESORS Caregiver (ObsRO) General Question Over Time(Baseline, Days 3, 5, 8, 14, and 21)
- Change From Baseline in Heart Rate(Baseline to Days 3, 5, 8, 14 and 21)
- Respiratory Rate (RR) Over Time(Baseline, Days 3, 5, 8, 14 and 21)
- Change From Baseline in Respiratory Rate(Baseline to Days 3, 5, 8, 14 and 21)
- Heart Rate Over Time(Baseline, Days 3, 5, 8, 14 and 21)
- Peripheral Capillary Oxygen Saturation (SpO2) Over Time(Baseline, Days 3, 5, 8, 14 and 21)
- Percentage of Participants Who Required (re)Hospitalization During Treatment and Follow-up(Up to Day 28)
- Cohort 1: Time to Return to Age-adjusted Normal Values for Vital Signs(Up to Day 28)
- Cohort 1: Time to Clinical Stability Evaluated by the Investigator(Up to Day 21)
- Body Temperature Over Time(Baseline, Days 3, 5, 8, 14 and 21)
- Change From Baseline in Body Temperature(Baseline to Days 3, 5, 8, 14 and 21)
- Change From Baseline in Peripheral Capillary Oxygen Saturation (SpO2)(Baseline to Days 3, 5, 8, 14, and 21)
- Cohort 1: Time to Discharge From Hospital(Up to Day 28)
- Cohort 1: Percentage of Participants Who Required Admission to the Intensive Care Unit (ICU)(Up to Day 21)
- Cohort 1: Duration of ICU Stay(Up to Day 21)
- Cohort 1: Percentage of Participants Who Required Supplemental Oxygen(Up to Day 21)
- Cohort 1: Duration of Supplemental Oxygen(Up to Day 28)
- Cohort 1: Percentage of Participants Who Required Non-invasive Mechanical Ventilation Support(Up to Day 21)
- Cohort 1: Percentage of Participants Who Required Invasive Mechanical Ventilation Support(Up to Day 21)
- Cohort 1: Percentage of Participants Who Required Non-invasive Non-mechanical Ventilation Support(Up to Day 21)
- Cohort 1: Time to End of Supplemental Oxygen up to 72 Hours From First Hospital Discharge(Up to end of supplemental oxygen including supplemental oxygen within 72 hours after first hospital discharge (up to Day 28))
- Percentage of Participants With Categorized Change From Baseline in ECG Parameters (QT, QTcB, QTcF)(Baseline to Day 28)
- Cohort 1: Area Under the Plasma Concentration-Time Curve From Timepoint 0 Hours Until 24 Hours Post Dose (AUC[0-24 Hours])(0 to 24 hours post dose on Days 1 and 7)
- Cohort 1: Maximum Plasma Concentration (Cmax) of JNJ-53718678(Days 1 and 7)
- Cohort 1: Trough Plasma Concentration (Ctrough) of JNJ-53718678(Days 1 and 7)
- Cohort 2: Plasma Concentration of JNJ-53718678(Once daily dosing: Day 3 and Day 8 pre- or post-dose. Twice daily dosing: Day 1 at least 1 hour post-dose, and Days 3 or 5 (combined in one timepoint) at least 4 hours after morning dose but prior to evening dose)
- Number of Participants With Emerging Variations in the Viral Genome Potentially Associated With Resistance to JNJ-53718678(Up to Day 21)
- Cohort 1: Duration of Non-invasive Ventilation Support(Up to Day 21)
- Percentage of Participants With Vital Signs Abnormalities(Up to Day 28)
- Cohort 1: Duration of Invasive Ventilation Support(Up to Day 21)
- Cohort 1: Percentage of Participants Who Needed Hydration and/or Feeding by Intravenous (IV) Administration or Nasogastric Tube(Up to Day 28)
- Percentage of Participants With Adverse Events(Up to Day 28)
- Percentage of Participants With Abnormal Laboratory Findings(Up to Day 28)
- Percentage of Participants With Abnormal Electrocardiograms (ECGs) Findings(Up to Day 28)
- Percentage of Participants With Medical Resource Utilization (MRU)(Up to Day 28)
- Percentage of Participants With Acceptability and Palatability of the JNJ-53718678 Formulation as Assessed by Parent(s)/Caregiver(s)(Day 8)