A Two-Part Infant Study for Early Diagnosis of Respiratory Syncytial Virus (RSV) and Evaluation of JNJ-53718678 in RSV Acute Respiratory Tract Disease

Study Overview
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Brief Summary
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The purpose of this two-part designed study is to assess in the setting of a planned early interception of pediatric RSV disease, early viral and disease kinetics (observational stage) and the antiviral effects of an Respiratory Syncytial Virus (RSV) fusion inhibitor, JNJ-53718678 (interventional stage). In the observational stage the infant is closely monitored for early symptoms by the parent(s)/caregiver(s) and thus may be brought in for diagnosis earlier than in the typical setting.

Official Title
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A Two-Part Study With a Birth Cohort (Observational Stage) for Early Diagnosis of Respiratory Syncytial Virus (RSV), Followed by an Optional Phase 2a, Randomized, Double-blind, Placebo-controlled Study (Interventional Stage) to Evaluate the Antiviral Activity, Clinical Outcomes, Safety, Tolerability, and Pharmacokinetics of JNJ-53718678 in Infants With Acute Respiratory Tract Infection Due to RSV

Conditions
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Respiratory Syncytial Viruses

Intervention / Treatment
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* Other: RSV Mobile Application
* Drug: Placebo
* Drug: JNJ-53718678 2.5 mg/kg
* Drug: JNJ-53718678 3 mg/kg
* Drug: JNJ-53718678 4.5 mg/kg


Participation Criteria
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Eligibility Criteria
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Inclusion Criteria: Part 1: Observational Stage The infant is less than or equal to (<=) 4 months of age at enrollment and asymptomatic for acute respiratory illness (ARI)-like symptoms requiring medical intervention at the time of consent to participate in the study At least 1 parent/caregiver must be able to use the respiratory syncytial virus (RSV) mobile application (App) at home via his/her own Android/iOS electronic device (compatible with RSV mobile App) 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 Part 2: Interventional Stage The infant is 28 days and if prematurely born infant (that is [i.e.], less than [<] 37 weeks and 0 days of gestation at birth) is at least 3 months postnatal age The participant has been diagnosed with RSV infection using a rapid molecular-based diagnostic assay The participant weighs more than 2.4 kilogram (kg) The participant has an acute respiratory illness as evaluated by the investigator 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 SARS-CoV-2 infection during this respiratory infection Exclusion Criteria: Part 1: Observational Stage The participant has any physical abnormality which limits the ability to collect regular nasal specimens The participant is receiving chronic home oxygen therapy at enrollment (applicable to both parts) Part 2: Interventional Stage The participant is <3 months postnatal age at screening and was born prematurely (i.e., <37 weeks and 0 days of gestation) or if the participant weights <2.4 kg The participant has a QT interval with Fridericia's correction (QTcF) greater than (>) 450 milliseconds per the machine read (mean of triplicate) parameter result confirmed by repeat triplicate Electrocardiogram (ECG) recording during screening The participant is considered by the investigator to be immunocompromised, whether due to underlying medical condition or medical therapy The participant has had any of: a) Confirmed SARS-CoV-2 infection (test positive) during the four weeks prior to randomization, or b) Close contact with a person with Coronavirus Disease 2019 (COVID-19) (test confirmed or suspected SARS-CoV-2 infection) within 14 days prior to randomization

Ages Eligible for Study
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Minimum Age: 28 Days
Maximum Age: 4 Months

Sexes Eligible for Study
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All

Accepts Healthy Volunteers
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No

Study Plan
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How is the study designed?
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Design Details

Primary Purpose: Treatment
Allocation: Randomized
Intervention Model: Parallel Assignment
Masking: Double


Arms and Interventions

| Participant Group/Arm | Intervention/Treatment |
| --- | --- |
| Other: Part 1-Observational Phase<br>Participants will not receive any intervention in the observation phase. All infants will be closely monitored for early signs and symptoms of Respiratory Syncytial Virus (RSV) disease using a mobile RSV application on the parent/caregiver's mobile phone, upon an alert, the RSV will be tested, if RSV negative participants (RSV [-] diagnosed at site) will return to the pre-diagnostic phase and RSV positive participants (RSV [+] diagnosed at site) can be enrolled in the interventional stage of the study after obtaining informed consent for the interventional stage at that time. RSV (+) participants whose parent(s)/caregiver(s) do not consent for enrollment in the interventional stage and participants who are screening failures in the interventional stage will enter the post-diagnostic phase of the observational stage (hospitalized or outpatients). | Other: RSV Mobile Application<br>* Participants will not receive any intervention in observational phase of this study. Participant's respiratory symptoms will be captured by RSV mobile application installed in participant's caregiver/parent mobile phone.<br>|
| Experimental: Part 2-Interventional Phase<br>Participants will be randomized to receive either JNJ-53718678 (for Age Group 1 (greater than or equal to [>=] 28 days and less than [<] 3 months): 2.5 milligram per kilogram [mg/kg]; for Age Group 2 (>=3 and <6 months): 3 mg/kg and for Age Group 3 (>=6 months): 4.5 mg/kg) or placebo (Age Group 1, 2 and 3) twice daily for 7 days. | Drug: Placebo<br>* Participants in each Age Group (1,2,3) will receive matching placebo (volume placebo to match the calculated volume of the JNJ-53718678 dose) orally twice daily for 7 days.<br>Drug: JNJ-53718678 2.5 mg/kg<br>* JNJ-53718678 will be administered to Age Group 1 twice daily for 7 days.<br>Drug: JNJ-53718678 3 mg/kg<br>* JNJ-53718678 will be administered to Age Group 2 twice daily for 7 days.<br>Drug: JNJ-53718678 4.5 mg/kg<br>* JNJ-53718678 will be administered to Age Group 3 twice daily for 7 days.<br>|

What is the study measuring?
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Primary Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| Respiratory Syncytial Virus (RSV) Viral Load-time Curve From Immediately Prior to First Dose of JNJ-53718678 Through Day 5 (AUC [Day 1-5]) | RSV viral load AUC was determined from immediately prior to first dose of JNJ-53718678 through Day 5. The RSV viral load was measured by quantitative reverse transcription polymerase chain reaction (qRT-PCR) assay in mid-turbinate nasal swab specimens. | Baseline (Day 1) up to Day 5 | 

Secondary Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| RSV Viral Load Over Time | RSV viral load actual values over time was measured by qRT-PCR in the nasal swab specimens collected at the clinic visits and at home. | Baseline, Days 2, 3, 4, 5, 6, 7, 8, 9, 10, 11, 12, 14, and 21 | 
| Change From Baseline in RSV Viral Load Over Time | Change from baseline in RSV viral load over time was measured by qRT-PCR in the nasal swab specimens collected at the clinic visits and at home. | Baseline, Days 2, 3, 4, 5, 6, 7, 8, 9, 10, 11, 12, 14, and 21 | 
| RSV Viral Load Area Under the Curve (AUC) From Immediately Prior to First Dose of Study Drug (Baseline) Through Days 3, 8, and 14 | RSV viral load AUC was determined by qRT-PCR assay in mid-turbinate nasal swab specimens. | Baseline through Days 3, 8, and 14 | 
| Time to Undetectable RSV Viral Load | Time to undetectable RSV viral load is defined as the time in hours from initiation of study treatment until the first post-baseline time point at which the virus is confirmed undetectable. A confirmed undetectable sample is defined as the first of at least two consecutive samples that are undetectable. The last obtained sample for a participant, if undetectable, is considered confirmed. | Up to 21 days | 
| Percentage of Participants With Undetectable RSV Viral Load at Each Time Point Throughout the Study | Percentage of participants with undetectable RSV viral load at each time point throughout the study were reported. | Baseline, Days 2, 3, 4, 5, 6, 7, 8, 9, 10, 11, 12, 14, 21 | 
| Severity of Signs and Symptoms of RSV Infection Assessed by Parent(s)/Caregiver(s) Pediatric RSV Electronic Severity and Outcome Rating System (PRESORS) | The severity of signs and symptoms of RSV infection (breathing problems, retractions, tachypnea, breathing sounds, cough, tachycardia, nasal secretions, sleep disturbance, crying, illness behavior, feeding problems, and dehydration) were assessed by the PRESORS. PRESORS is a questionnaire by parent(s)/caregiver(s) recording presence and severity of signs and symptoms of RSV disease. PRESORS score consisted of 12-items, each score ranges from 0 to 3. A summary score was derived (mean of the item scores) which also ranges from 0 to 3. The higher the score, the worse the symptom. | Baseline, Days 3, 5, 8, 14, and 21 | 
| Change From Baseline in Parent(s)/Caregiver(s) PRESORS Scores | PRESORS is a questionnaire recording presence and severity of signs and symptoms of RSV disease. PRESORS score consisted of 12-items, each item score ranges from 0 to 3. A summary score was derived (mean of the item scores) which also ranges from 0 to 3. The higher the score, the worse the symptom. | Baseline, Day 3, 5, 8, 14, 21 | 
| Change From Baseline in Clinician PRESORS Score | Change from baseline in clinician (for concepts: activity level, sleep disturbance, breathing problems, retractions, tachypnea, feeding problem, cough, nasal secretions, wheezing, dehydration) PRESORS scores was reported. PRESORS is a questionnaire recording presence and severity of signs and symptoms of RSV disease. PRESORS score consisted of 10-items, each item score ranges from 0 to 3. A summary score was derived (mean of the item scores) which also ranges from 0 to 3. The higher the score, the worse the symptom. | Baseline, Day 3, 5, 8, 14, 21 | 
| Time to Resolution of RSV Symptoms | Time to resolution from first dose of study drug until the first time of resolution of all RSV Symptoms (breathing problems, retractions, tachypnea, breathing sounds, cough, tachycardia, nasal secretions, sleep disturbance, crying, illness behavior, feeding problems, and dehydration). Resolution occurs when all symptoms from the caregiver reported outcomes (ObsRO) are scored as none or mild (score of 0 or 1, respectively) for at least 24 hours. | Up to 21 days | 
| Time to Improvement on Overall Health | Time to improvement based on general questions on overall health was reported. Time from first dose of study drug until first time status of improvement of RSV symptoms reported as very much improved or much improved based on response to question 'Would you say the child's RSV symptoms have improved, are about the same or are worse than when the child entered the study'. | Up to 21 days | 
| Percentage of Participants With Worsening or Improvement of RSV Disease | Percentage of participants with worsening or improvement of RSV disease based on general questions on overall health was reported. Improvement is defined improvement of RSV symptoms reported as very much improved or much improved based on response to question 'Would you say the child's RSV symptoms have improved, are about the same or are worse than when the child entered the study'. | On Days 2, 3, 4, 5, 6, 7, 8, 9, 10, 11, 12, 13, 14, 15, 16, 17, 18, 19, 20, 21 | 
| Time to Return to Pre-RSV Health as Rated by the Parent(s)/Caregiver(s) | Time to return to pre-RSV health as rated by the parent(s)/caregiver(s) was evaluated. It is the time from first dose of study drug until the time to return to pre-RSV disease level. | Up to 21 days | 
| Percentage of Participants Who Require (re)Hospitalization During Treatment and Follow-up | Percentage of participants who require (re)hospitalization during treatment and follow-up were reported. | Up to Day 31 | 
| Percentage of Participants With Adverse Events as a Measure of Safety and Tolerability | 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. | Up to Day 31 | 
| Percentage of Participants With Abnormal Chemistry Laboratory Findings | Percentage of participants with abnormal chemistry laboratory findings (alanine aminotransferase [ALT; Grade 1 and 4], aspartate aminotransferase [AST; Grade 1], and Hyperkalemia [Grade 1 and 2]) were reported based on Division of Microbiology and Infectious Diseases (DMID) toxicity grading scale. DMID toxicity grades ranges from 1 to 4. Grade 1 = mild: transient or mild discomfort (<48 hours); no medical intervention/therapy required. Grade 2 = moderate: mild to moderate limitation in activity - some assistance may be needed; no or minimal medical intervention/therapy required. Grade 3 = severe: marked limitation in activity, some assistance usually required; medical intervention/therapy required, hospitalizations possible. Grade 4 = life-threatening or death: Extreme limitation in activity, significant assistance required; significant medical intervention/therapy required, hospitalization or hospice care probable. | Up to Day 31 | 
| Percentage of Participants With Abnormal Urinalysis Laboratory Findings | Percentage of participants with abnormal urinalysis (Hematuria- Grade 1) laboratory finding was reported based on DMID toxicity grading scale. DMID toxicity grades ranges from 1 to 4. Grade 1 = mild: transient or mild discomfort (<48 hours); no medical intervention/therapy required. Grade 2 = moderate: mild to moderate limitation in activity - some assistance may be needed; no or minimal medical intervention/therapy required. Grade 3 = severe: marked limitation in activity, some assistance usually required; medical intervention/therapy required, hospitalizations possible. Grade 4 = life-threatening or death: Extreme limitation in activity, significant assistance required; significant medical intervention/therapy required, hospitalization or hospice care probable. | Up to Day 31 | 
| Percentage of Participants With Abnormal Electrocardiograms (ECGs) Findings | Percentage of participants with abnormal ECGs findings were reported. Parameters for abnormal ECG findings were QT interval corrected for heart rate (QTc) according to Bazett's formula (QTcB) Interval ([450 milliseconds {ms}, 480 ms], [480 ms, 500 ms], and [more than 500 ms]), QTc according to Fridericia's formula (QTcF) Interval ([450 ms, 480 ms], [480 ms, 500 ms], and [more than 500 ms]), change from baseline for QTcB Interval ([30; 60] ms, and greater than [>] 60 ms), and for QTcF Interval ([30; 60] ms, and >60 ms). | Up to Day 31 | 
| Percentage of Participants With Vital Sign Abnormalities | Percentage of participants with vital signs (systolic blood pressure [SBP], diastolic blood pressure [DBP], pulse rate, respiratory rate, body temperature and peripheral capillary oxygen saturation [SpO2]) abnormalities (abnormally low [ABL] and abnormally high [ABH]) were reported. | Up to Day 31 | 
| Plasma Concentrations of JNJ-53718678 | No data was collected for pharmacokinetic (PK) analysis due to small sample size. Hence, no results are reported. | Day 1 and Day 3 |