Clinical Trial Results:
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
Summary
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EudraCT number |
2019-001509-25 |
Trial protocol |
GB BE |
Global end of trial date |
15 May 2021
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Results information
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Results version number |
v1(current) |
This version publication date |
01 Dec 2021
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First version publication date |
01 Dec 2021
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Other versions |
Trial Information
Subject Disposition
Baseline Characteristics
End Points
Adverse Events
More Information
Subject Disposition
Baseline Characteristics
End Points
Adverse Events
More Information
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Trial identification
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Sponsor protocol code |
53718678RSV2006
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Additional study identifiers
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ISRCTN number |
- | ||
US NCT number |
NCT04068792 | ||
WHO universal trial number (UTN) |
- | ||
Sponsors
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Sponsor organisation name |
Janssen Research & Development, LLC
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Sponsor organisation address |
920 US Highway 202, Raritan, NJ, United States, 08869-1420
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Public contact |
Clinical Registry Group, Janssen Research & Development, LLC, ClinicalTrialsEU@its.jnj.com
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Scientific contact |
Clinical Registry Group, Janssen Research & Development, LLC, ClinicalTrialsEU@its.jnj.com
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Paediatric regulatory details
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Is trial part of an agreed paediatric investigation plan (PIP) |
No
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Does article 45 of REGULATION (EC) No 1901/2006 apply to this trial? |
No
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Does article 46 of REGULATION (EC) No 1901/2006 apply to this trial? |
No
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Results analysis stage
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Analysis stage |
Final
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Date of interim/final analysis |
15 May 2021
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Is this the analysis of the primary completion data? |
No
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Global end of trial reached? |
Yes
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Global end of trial date |
15 May 2021
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Was the trial ended prematurely? |
No
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General information about the trial
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Main objective of the trial |
The primary objectives were as follows: In Part 1 (Observational stage) was to evaluate the onset and evolution of clinical symptoms of pediatric RSV disease and to evaluate the relationship between RSV viral load and clinical symptoms at early diagnosis of pediatric RSV disease. In Part 2:(Interventional stage) was to evaluate antiviral activity of JNJ-53718678 as measured by RSV viral load in nasal swab samples by a quantitative reverse transcription polymerase chain reaction (qRT-PCR) assay in an early intervention setting in infants (less than or equal to [<=]4 months of age at enrollment) recruited from a birth cohort.
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Protection of trial subjects |
This study was conducted in accordance with the ethical principles that have their origin in the Declaration of Helsinki and that are consistent with Good Clinical Practices and applicable regulatory requirements. Safety and tolerability, as assessed by adverse events (AEs), clinical laboratory testing, electrocardiograms (ECGs), and vital signs, were performed throughout the interventional stage of the study.
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Background therapy |
- | ||
Evidence for comparator |
- | ||
Actual start date of recruitment |
10 Oct 2019
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Long term follow-up planned |
No
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Independent data monitoring committee (IDMC) involvement? |
Yes
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Population of trial subjects
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Number of subjects enrolled per country |
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Country: Number of subjects enrolled |
Argentina: 104
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Country: Number of subjects enrolled |
Belgium: 14
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Country: Number of subjects enrolled |
United Kingdom: 11
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Country: Number of subjects enrolled |
Panama: 933
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Country: Number of subjects enrolled |
Taiwan: 148
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Worldwide total number of subjects |
1210
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EEA total number of subjects |
14
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Number of subjects enrolled per age group |
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In utero |
0
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Preterm newborn - gestational age < 37 wk |
0
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Newborns (0-27 days) |
133
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Infants and toddlers (28 days-23 months) |
1077
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Children (2-11 years) |
0
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Adolescents (12-17 years) |
0
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Adults (18-64 years) |
0
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From 65 to 84 years |
0
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85 years and over |
0
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Recruitment
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Recruitment details |
- | ||||||||||||||||||||
Pre-assignment
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Screening details |
A total of 1210 subjects were enrolled in Observational phase. Out of 1210 subjects, 22 subjects entered the Interventional phase, 11 subjects in each placebo and JNJ-53718678 arms. All subjects in the interventional phase completed the study. | ||||||||||||||||||||
Period 1
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Period 1 title |
Part 1: Observational Phase
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Is this the baseline period? |
Yes | ||||||||||||||||||||
Allocation method |
Not applicable
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Blinding used |
Not blinded | ||||||||||||||||||||
Arms
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Arm title
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Observational Stage | ||||||||||||||||||||
Arm description |
Subjects did not receive any intervention in the observational phase. Early signs and symptoms of Respiratory Syncytial Virus (RSV) disease were recorded daily using RSV app on parent/caregiver mobile phone. At a threshold score, infants received an RSV test (diagnostic phase) within 24 hours of receiving alert. RSV-negative subject (RSV[-]) returned to pre-diagnostic phase and further monitored using RSV mobile App. RSV-positive subject (RSV[+]) were enrolled in screening phase of interventional stage, after obtaining informed consent. RSV(+) subject whose parent/caregiver did not consent for enrollment in interventional stage and subject who were screen failures in interventional stage entered post-diagnostic phase of observational phase. | ||||||||||||||||||||
Arm type |
RSV Mobile App | ||||||||||||||||||||
Investigational medicinal product name |
JNJ-53718678
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Investigational medicinal product code |
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Other name |
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Pharmaceutical forms |
Oral suspension
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Routes of administration |
Oral use
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Dosage and administration details |
Subjects did not receive any intervention in Open-label phase. This phase was to only observe RSV symptoms using RSV mobile App.
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Period 2
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Period 2 title |
Part 2: Interventional Phase
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Is this the baseline period? |
No | ||||||||||||||||||||
Allocation method |
Randomised - controlled
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Blinding used |
Double blind | ||||||||||||||||||||
Roles blinded |
Subject, Investigator, Carer | ||||||||||||||||||||
Arms
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Are arms mutually exclusive |
Yes
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Arm title
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Placebo | ||||||||||||||||||||
Arm description |
As per original dosing, subjects were randomized to receive JNJ-53718678 matching placebo (for Age Group 1 greater than or equal to [>=] 28 days and less than [<] 3 months: 5 milligram per kilogram [mg/kg]; for Age Group 2 (>=3 and <6 months): 6 mg/kg and for Age Group 3 (>=6 months): 9 mg/kg) qd for 7 days. After Protocol amendment 2, subjects were randomized to receive JNJ-53718678 (for Age Group 1: 2.5 mg/kg; for Age Group 2: 3 mg/kg and for Age Group 3: 4.5 mg/kg) bid for 7 days. | ||||||||||||||||||||
Arm type |
Placebo | ||||||||||||||||||||
Investigational medicinal product name |
Placebo
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Investigational medicinal product code |
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Other name |
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Pharmaceutical forms |
Oral suspension
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Routes of administration |
Oral use
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Dosage and administration details |
Subjects in each age groups (1,2,3) were administered with JNJ-53718678 matching placebo (volume placebo to match the calculated volume of the JNJ-53718678 dose) orally once daily and twice daily (after protocol amendment 2) for 7 days.
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Arm title
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JNJ-53718678 | ||||||||||||||||||||
Arm description |
As per original dosing, subjects were randomized to receive JNJ-53718678 (for Age Group 1 greater than or equal to [>=] 28 days and less than [<] 3 months: 5 milligram per kilogram [mg/kg]; for Age Group 2 (>=3 and <6 months): 6 mg/kg and for Age Group 3 (>=6 months): 9 mg/kg) once daily for 7 days. After Protocol amendment 2, subjects were randomized to receive JNJ-53718678 (for Age Group 1: 2.5 mg/kg; for Age Group 2: 3 mg/kg and for Age Group 3: 4.5 mg/kg) twice daily for 7 days. | ||||||||||||||||||||
Arm type |
Experimental | ||||||||||||||||||||
Investigational medicinal product name |
JNJ-53718678
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Investigational medicinal product code |
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Other name |
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Pharmaceutical forms |
Oral suspension
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Routes of administration |
Oral use
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Dosage and administration details |
JNJ-53718678 5 mg/kg was administered to age group 1 once daily for 7 days. After protocol amendment 2, JNJ-53718678 2.5 mg/kg was administered to age group 1 twice daily for 7 days.
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Investigational medicinal product name |
JNJ-53718678
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Investigational medicinal product code |
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Other name |
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Pharmaceutical forms |
Oral suspension
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Routes of administration |
Oral use
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Dosage and administration details |
JNJ-53718678 9 mg/kg was administered to age group 3 once daily for 7 days. After protocol amendment 2, JNJ-53718678 4.5 mg/kg was administered to age group 3 twice daily for 7 days.
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Investigational medicinal product name |
JNJ-53718678
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Investigational medicinal product code |
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Other name |
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Pharmaceutical forms |
Oral suspension
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Routes of administration |
Oral use
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Dosage and administration details |
JNJ-53718678 6 mg/kg was administered to age group 2 one daily for 7 days. After protocol amendment 2, JNJ-53718678 3 mg/kg was administered to age group 2 twice daily for 7 days.
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Notes [1] - The number of subjects starting the period is not consistent with the number completing the preceding period. It is expected the number of subjects starting the subsequent period will be the same as the number completing the preceding period. Justification: Out of 35 subjects completed the baseline Observational period, 13 subjects completed only observational phase and 22 subjects entered and completed the interventional phase. |
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Baseline characteristics reporting groups
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Reporting group title |
Observational Stage
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Reporting group description |
Subjects did not receive any intervention in the observational phase. Early signs and symptoms of Respiratory Syncytial Virus (RSV) disease were recorded daily using RSV app on parent/caregiver mobile phone. At a threshold score, infants received an RSV test (diagnostic phase) within 24 hours of receiving alert. RSV-negative subject (RSV[-]) returned to pre-diagnostic phase and further monitored using RSV mobile App. RSV-positive subject (RSV[+]) were enrolled in screening phase of interventional stage, after obtaining informed consent. RSV(+) subject whose parent/caregiver did not consent for enrollment in interventional stage and subject who were screen failures in interventional stage entered post-diagnostic phase of observational phase. | ||||||||||||||||||||||||||||||||||||||||||
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End points reporting groups
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Reporting group title |
Observational Stage
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Reporting group description |
Subjects did not receive any intervention in the observational phase. Early signs and symptoms of Respiratory Syncytial Virus (RSV) disease were recorded daily using RSV app on parent/caregiver mobile phone. At a threshold score, infants received an RSV test (diagnostic phase) within 24 hours of receiving alert. RSV-negative subject (RSV[-]) returned to pre-diagnostic phase and further monitored using RSV mobile App. RSV-positive subject (RSV[+]) were enrolled in screening phase of interventional stage, after obtaining informed consent. RSV(+) subject whose parent/caregiver did not consent for enrollment in interventional stage and subject who were screen failures in interventional stage entered post-diagnostic phase of observational phase. | ||
Reporting group title |
Placebo
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Reporting group description |
As per original dosing, subjects were randomized to receive JNJ-53718678 matching placebo (for Age Group 1 greater than or equal to [>=] 28 days and less than [<] 3 months: 5 milligram per kilogram [mg/kg]; for Age Group 2 (>=3 and <6 months): 6 mg/kg and for Age Group 3 (>=6 months): 9 mg/kg) qd for 7 days. After Protocol amendment 2, subjects were randomized to receive JNJ-53718678 (for Age Group 1: 2.5 mg/kg; for Age Group 2: 3 mg/kg and for Age Group 3: 4.5 mg/kg) bid for 7 days. | ||
Reporting group title |
JNJ-53718678
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Reporting group description |
As per original dosing, subjects were randomized to receive JNJ-53718678 (for Age Group 1 greater than or equal to [>=] 28 days and less than [<] 3 months: 5 milligram per kilogram [mg/kg]; for Age Group 2 (>=3 and <6 months): 6 mg/kg and for Age Group 3 (>=6 months): 9 mg/kg) once daily for 7 days. After Protocol amendment 2, subjects were randomized to receive JNJ-53718678 (for Age Group 1: 2.5 mg/kg; for Age Group 2: 3 mg/kg and for Age Group 3: 4.5 mg/kg) twice daily for 7 days. |
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End point title |
Respiratory Syncytial Virus (RSV) Viral Load-time Curve from Immediately Prior to First Dose of JNJ-53718678 Through Day 5 (AUC [Day 1-5]) | ||||||||||||
End point description |
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. Intent-To-Treat-infected (ITT-i) analysis set included all randomized subjects who received at least one dose of study drug and who had a centrally confirmed RSV viral load of greater than or equal to (>=) 1 log10 copies per millilitre (mL) above the lower limit of quantification (LLOQ) of the RSV RT-qPCR assay at baseline.
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End point type |
Primary
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End point timeframe |
Baseline up to Day 5 of Interventional stage
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Statistical analysis title |
Statistical Analysis 1 | ||||||||||||
Comparison groups |
JNJ-53718678 v Placebo
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Number of subjects included in analysis |
21
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Analysis specification |
Pre-specified
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Analysis type |
other | ||||||||||||
Method |
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Parameter type |
Mean difference (final values) | ||||||||||||
Point estimate |
-1.03
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Confidence interval |
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level |
90% | ||||||||||||
sides |
2-sided
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lower limit |
-4.467 | ||||||||||||
upper limit |
2.416 |
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End point title |
Change from Baseline in RSV Viral Load Over Time | |||||||||||||||||||||||||||||||||||||||||||||||||||
End point description |
RSV viral load over time was measured by qRT-PCR in the nasal swab specimens. Log10 of the actual values as measured with qRT-PCR in nasal swab samples collected at the clinic visits and at home. ITT-i analysis set included all randomised subjects who received at least one dose of JNJ-53718678 and who had a centrally confirmed RSV viral load of >=1 log10 copies per mL above the LLOQ of the RSV RT-qPCR assay at baseline. Analyses on the ITT-i set was performed as randomised. Here 'N' (number of subjects analysed), included all subjects who were evaluable for this endpoint. Here 'n' (number analysed) included all subjects who were analysed at specified timepoints.
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End point type |
Secondary
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End point timeframe |
On Day 2, 3, 4, 5, 6, 7, 8, 9, 10, 11, 12, 14, 21 of interventional phase
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No statistical analyses for this end point |
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End point title |
RSV Viral Load Area Under the curve (AUC) from Immediately Prior to First Dose of Study Drug (Baseline) Through Days 3 and 8 | ||||||||||||||||||
End point description |
RSV viral load AUC will be determined by quantitative reverse transcriptase-polymerase chain reaction (qRT-PCR) assay in mid-turbinate nasal swab specimens. ITT-i analysis set included all randomized subjects who received at least one dose of study drug and who had a centrally confirmed RSV viral load of >=1 log10 copies per mL above the LLOQ of the RSV RT-qPCR assay at baseline. Analyses on the ITT-i set was performed as randomized.
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End point type |
Secondary
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End point timeframe |
On the day of diagnosis (Baseline) through Days 3 and 8 of interventional stage
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No statistical analyses for this end point |
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End point title |
Time to Undetectable RSV Viral Load | ||||||||||||
End point description |
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 undetectable in an assessment and after which time no detectable virus assessment follows as measured by qRT-PCR. ITT-i analysis set included all randomized subjects who received at least one dose of study drug and who had centrally confirmed RSV viral load of >=1 log10 copies per mL above the LLOQ of the RSV RT-qPCR assay at baseline. Analyses on the ITT-i set was performed as randomized. Here, 99999 refers that upper limit of confidence interval was not estimable due to low numbers.
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End point type |
Secondary
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End point timeframe |
Up to 21 days of interventional stage
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No statistical analyses for this end point |
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End point title |
Percentage of Subjects with Undetectable RSV Viral Load at each Time Point throughout the Study | ||||||||||||||||||||||||||||||||||||||||||||||||||||||
End point description |
Percentage of subjects with undetectable RSV viral load at each time point throughout the study were reported. ITT-i analysis set included all randomized subjects who received at least one dose of study drug and who had a centrally confirmed RSV viral load of >=1 log10 copies per mL above the LLOQ of the RSV RT-qPCR assay at baseline. Here 'n' (number analyzed) included all subjects who were analysed at specified timepoints.
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End point type |
Secondary
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End point timeframe |
From Baseline to Day 2, 3, 4, 5, 6, 7, 8, 9, 10, 11, 12, 14, 21 of interventional phase
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No statistical analyses for this end point |
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End point title |
Duration of Signs and Symptoms of RSV Disease Assessed by the Pediatric RSV Electronic Severity and Outcome Rating System (PRESORS) | ||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||
End point description |
Duration of signs and symptoms (sleep disturbance, crying, illness behavior, breathing problems, nasal secretions, tachypnea, tachycardia, retractions, breathing sounds, cough, feeding problems, dehydration) of RSV disease was assessed by PRESORS. PRESORS Score consisted of 5-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. ITT-i analysis set included all randomized subjects who received at least one dose of study drug and who had a centrally confirmed RSV viral load of >=1 log10 copies per mL above the LLOQ of the RSV RT-qPCR assay at baseline. Here 'n' (number analysed) included all subjects who were analysed at specified timepoints.
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End point type |
Secondary
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End point timeframe |
From baseline to Day 3, 5, 8, 14, 21 of interventional stage
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No statistical analyses for this end point |
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End point title |
Severity of Signs and Symptoms of RSV Infection Assessed by the PRESORS | |||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||
End point description |
The severity of signs and symptoms of RSV infection (fever, cough, sputum, wheezing, difficulty breathing, nasal congestion, and feeding issues) were assessed by the PRESORS. PRESORS Score consisted of 5-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. ITT-i analysis set included all randomized subjects who received at least one dose of study drug and who had a centrally confirmed RSV viral load of >=1 log10 copies per mL above the LLOQ of the RSV RT-qPCR assay at baseline. Here 'n' (number analysed) included all subjects who were analysed at specified timepoints.
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End point type |
Secondary
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End point timeframe |
Baseline up to Day 2,3,4,5,6,7,8,9,10,11,12,13,14,15,16,17,18,19,20,21 of interventional stage
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No statistical analyses for this end point |
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End point title |
Change from Baseline in Parent(s)/Caregiver(s) PRESORS Scores | |||||||||||||||||||||||||||
End point description |
Change from baseline in parent(s)/caregiver(s) PRESORS scores was reported. PRESORS Score consisted of 5-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. ITT-i analysis set included all randomized subjects who received at least one dose of study drug and who had a centrally confirmed RSV viral load of >=1 log10 copies per mL above the LLOQ of the RSV RT-qPCR assay at baseline. Here 'N' (number of subjects analysed), included all subjects who were evaluable for this endpoint. Here 'n' (number analysed) included all subjects who were analysed at specified timepoints.
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End point type |
Secondary
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End point timeframe |
Day 3, 5, 8, 14, 21 of interventional phase
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No statistical analyses for this end point |
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End point title |
Change from Baseline in Clinician PRESORS Score | ||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||
End point description |
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 Score consisted of 5-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. ITT-i analysis set included all randomized subjects who received at least one dose of study drug and who had a centrally confirmed RSV viral load of >=1 log10 copies per mL above the LLOQ of the RSV RT-qPCR assay at baseline. Here 'N' (number of subjects analysed), included all subjects who were evaluable for this endpoint. Here 'n' (number analysed) included all subjects who were analysed at specified timepoints.
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End point type |
Secondary
|
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End point timeframe |
From Baseline to Day 3, 5, 8, 14, 21 of interventional stage
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No statistical analyses for this end point |
|
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End point title |
Time to Resolution of RSV Symptoms | ||||||||||||
End point description |
Time to resolution (that is, to none or mild) of RSV symptoms (breathing problems, retractions, tachypnea, breathing sounds, cough, tachycardia, nasal secretions, sleep disturbance, crying, illness behavior, feeding problems, and dehydration) was recorded. ITT-i analysis set included all randomized subjects who received at least one dose of study drug and who had a centrally confirmed RSV viral load of>=1 log10 copies per mL above the LLOQ of the RSV RT-qPCR assay at baseline.
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End point type |
Secondary
|
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End point timeframe |
Up to 21 days of interventional stage
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No statistical analyses for this end point |
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End point title |
Time to Improvement on Overall Health | ||||||||||||
End point description |
Time to improvement based on general questions on overall health was reported. ITT-i analysis set included all randomized subjects who received at least one dose of study drug and who had a centrally confirmed RSV viral load of >=1 log10 copies per mL above the LLOQ of the RSV RT-qPCR assay at baseline. Analyses on the ITT-i set was performed as randomized.
|
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End point type |
Secondary
|
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End point timeframe |
Up to 21 days of interventional stage
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No statistical analyses for this end point |
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End point title |
Percentage of Subjects with Worsening or Improvement of RSV Disease | ||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||
End point description |
Percentage of subjects with worsening or improvement of RSV disease based on general questions on overall health was reported. ITT-i analysis set included all randomized subjects who received at least one dose of study drug and who had a centrally confirmed RSV viral load of >=1 log10 copies per mL above the LLOQ of the RSV RT-qPCR assay at baseline. Here 'n' (number analysed) included all subjects who were analysed at specified timepoints.
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End point type |
Secondary
|
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End point timeframe |
On Day 2, 3, 4, 5, 6, 7, 8, 9, 10, 11, 12, 13, 14, 15, 16, 17, 18, 19, 20, 21 of interventional phase
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No statistical analyses for this end point |
|
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End point title |
Time to Return to Pre-RSV Health as Rated by the Parent(s)/Caregiver(s) | ||||||||||||
End point description |
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. ITT-i analysis set included all randomized subjects who received at least one dose of study drug and who had a centrally confirmed RSV viral load of >=1 log10 copies per mL above the LLOQ of the RSV RT-qPCR assay at baseline.
|
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End point type |
Secondary
|
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End point timeframe |
Up to 21 days of interventional stage
|
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No statistical analyses for this end point |
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End point title |
Percentage of Subjects who Require (re)Hospitalization During Treatment and Follow-up | ||||||||||||
End point description |
Percentage of subjects who require (re)hospitalization during treatment and follow-up were reported. ITT-i analysis set included all randomized subjects who received at least one dose of study drug and who had a centrally confirmed RSV viral load of >=1 log10 copies per mL above the LLOQ of the RSV RT-qPCR assay at baseline. Analyses on the ITT-i set was performed as randomized.
|
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End point type |
Secondary
|
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End point timeframe |
Up to 28 days of interventional stage
|
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No statistical analyses for this end point |
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End point title |
Percentage of Subjects with Adverse Events as a Measure of Safety and Tolerability | ||||||||||||
End point description |
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. The Safety set (SAF) included all subjects who received at least 1 dose of study drug, and were analyzed as treated, regardless of the randomized treatment group assigned. Where ‘analyzed as treated’ is defined as: Placebo: if only placebo doses received, and JNJ-53718678: if at least one dose of the active study drug received.
|
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End point type |
Secondary
|
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End point timeframe |
From screening up to maximum of Day 31 of interventional stage
|
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No statistical analyses for this end point |
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End point title |
Percentage of Subjects with Abnormal Chemistry Laboratory Findings | |||||||||||||||||||||||||||
End point description |
Percentage of subject with abnormal chemistry laboratory findings were reported. It included alanine aminotransferase (Grade 1 and 4), aspartate aminotransferase (Grade 1). Hyperkalemia (Grade 1 and 2). The safety set (SAF) included all subjects who received at least 1 dose of study drug, and were analyzed as treated, regardless of the randomized treatment group assigned. Where ‘analyzed as treated’ is defined as: Placebo: if only placebo doses received, and JNJ-53718678: if at least one dose of the active study drug received. Here 'n' (number analyzed) included all subjects who were analyzed at specified categories.
|
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End point type |
Secondary
|
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End point timeframe |
From screening up to Day 28 of interventional stage
|
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No statistical analyses for this end point |
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End point title |
Percentage of Subjects with Abnormal Urinalysis Laboratory Findings | ||||||||||||
End point description |
Percentage of subject with abnormal urinalysis (Hematuria- Grade 1) laboratory finding was reported. The Safety set (SAF) included all subjects who received at least 1 dose of study drug, and were analyzed as treated, regardless of the randomized treatment group assigned. Where ‘analyzed as treated’ is defined as: Placebo: if only placebo doses received, and JNJ-53718678: if at least one dose of the active study drug received. Here 'N' (number of subjects analyzed), included all subjects who were evaluable for this endpoint.
|
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End point type |
Secondary
|
||||||||||||
End point timeframe |
From screening up to Day 28 of interventional stage
|
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No statistical analyses for this end point |
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End point title |
Percentage of Subjects with Abnormal Electrocardiograms (ECGs) Findings | ||||||||||||||||||||||||||||||||||||||||||||||||
End point description |
Percentage of subjects with abnormal ECGs findings were reported. Parameters for abnormal ECG finding were QTcB Interval ([450 millisecond [ms], 480 ms], [480 ms, 500 ms], and [more than 500 ms]), QTcF Interval ([450 ms, 480 ms], [480 ms, 500 ms], and [more than 500 ms]), change from baseline for QTcB Interval (less than or equal [<=] 30 ms, [30; 60] ms, and greater than [>] 60 ms), and for QTcF Interval (<=30 ms, [30; 60] ms, and >60 ms). The Safety set (SAF) included all subjects who received at least 1 dose of study drug, and were analyzed as treated, regardless of the randomized treatment group assigned. Where ‘analyzed as treated’ is defined as: Placebo: if only placebo doses received, and JNJ-53718678: if at least one dose of the active study drug received. Here 'N' (number of subjects analyzed), included all subjects who were evaluable for this endpoint. Here 'n' (number analyzed) included all subjects who were analyzed for specified categories.
|
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End point type |
Secondary
|
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End point timeframe |
From screening up to Day 28 of interventional stage
|
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No statistical analyses for this end point |
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End point title |
Percentage of Subjects with Vital Sign Abnormalities | ||||||||||||||||||||||||||||||||||||||||||||||||
End point description |
Percentage of subjects 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. The Safety set (SAF) included all subjects who received at least 1 dose of study drug, and were analyzed as treated, regardless of the randomized treatment group assigned. Where ‘analyzed as treated’ is defined as: Placebo: if only placebo doses received, and JNJ-53718678: if at least one dose of the active study drug received. Here 'n' (number analyzed) included all subjects who were analyzed for specified categories.
|
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End point type |
Secondary
|
||||||||||||||||||||||||||||||||||||||||||||||||
End point timeframe |
From screening up to Day 28 of interventional stage
|
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No statistical analyses for this end point |
|
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End point title |
Plasma Concentrations of JNJ-53718678 | ||||||||||||
End point description |
Pharmacokinetic (PK) analysis were not performed as the amount of data available was not sufficient for PK analysis.
|
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End point type |
Secondary
|
||||||||||||
End point timeframe |
Day 1 and Day 3 of interventional stage
|
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|
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Notes [1] - PK analysis not performed due to insufficient data. Hence, 'N' (number of subjects analysed) is 0. [2] - PK analysis not performed due to insufficient data. Hence, 'N' (number of subjects analysed) is 0. |
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No statistical analyses for this end point |
|
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End point title |
Part 1: RSV Symptom Score | ||||||||||||||||||||||||||||||||||||||||||||||||||
End point description |
RSV Symptom Score was captured by RSV mobile Application (App) during the pre-diagnostic phase and the post-diagnostic phase for RSV positive subjects who do not enter in the interventional stage. Respiratory symptom severity score: breathing problems, retractions, tachypnea, breathing sounds, cough, tachycardia, and nasal secretions. RSV positive (+) Analysis Set- Observational Stage: included all the subjects with a positive RSV diagnostic test who did not enter the interventional stage. Here 'N' (number of subjects analysed), included all subjects who were evaluable for this endpoint. Here 'n' (number analysed) included all subjects who were analysed at specified timepoints.
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End point type |
Secondary
|
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End point timeframe |
From baseline to Day 2, 3, 4,5,6,7,8,9,10,11,12,13,14,15,16,17,18,19,20,21 of observational stage
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No statistical analyses for this end point |
|
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End point title |
Part 1: PRESORS Scores by the Clinician (Clinician PRESORS) on the Day of RSV Diagnosis | ||||||||||||||||||||||||||||
End point description |
Clinician PRESORS scores will be reported for hospitalized RSV positive participants. Clinician PRESORS is a questionnaire recording presence and severity of signs and symptoms of RSV disease (fever, cough, sputum, wheezing, difficulty breathing, nasal congestion, and feeding issues) by clinician. RSV (+) Analysis Set- Observational Stage: included all the subjects with a positive RSV diagnostic test who did not enter the interventional stage. Here 'N' (number of subjects analysed), included all subjects who were evaluable for this endpoint. Here 'n' (number analysed) included all subjects who were analysed at specified timepoints.
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End point type |
Secondary
|
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End point timeframe |
On the day of RSV diagnosis (Baseline) up to Discharge post-diagnosis (21 Days) of observational stage
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No statistical analyses for this end point |
|
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End point title |
Part 1: RSV Viral Load During Pre-Diagnostic Phase | ||||||||
End point description |
RSV Viral load during pre-diagnostic phase was determined based on measurements of RSV viral load in nasal secretions by a qRT-PCR assay in mid-turbinate nasal swab specimens. All Enrolled Analysis Set- Observational Stage included all subjects who signed the ICF of the observational stage and were classified as eligible. Here 'N' (number of subjects analysed), included all subjects who were evaluable for this endpoint.
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End point type |
Secondary
|
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End point timeframe |
Pre-diagnostic phase: Within 24hrs of Observation Day 1
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No statistical analyses for this end point |
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End point title |
Part 1: RSV Viral Load Kinetics from Day 1 to Day 8 | ||||||||||||||||||||||||
End point description |
RSV viral load kinetics from Day 1 to Day 8 after RSV diagnosis over time (if not participating in the interventional stage) was measured by real-time qRT-PCR assay in the mid-turbinate nasal swab specimens. RSV (+) Analysis Set- Observational Stage: included all the subjects with a positive RSV diagnostic test who did not enter the interventional stage. Here 'N' (number of subjects analysed), included all subjects who were evaluable for this endpoint. Here 'n' (number analysed) included all subjects who were analysed at specified timepoints.
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End point type |
Secondary
|
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End point timeframe |
From Baseline Day 2, 3, 4, 5, 6, 7, 8 of observational stage
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No statistical analyses for this end point |
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End point title |
Part 1: Change from Baseline in Parent(s)/Caregiver(s) PRESORS Scores Over Time | ||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||
End point description |
Change from baseline in Parent(s)/Caregiver(s) (for concepts: sleep disturbance, crying, illness behavior, breathing problems, retractions, tachypnea, tachycardia, breathing sounds, feeding problem, cough, nasal secretions, dehydration) PRESORS scores was reported. PRESORS Score consisted of 5-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. RSV (+) Analysis Set- Observational Stage: included all the subjects with a positive RSV diagnostic test who did not enter the interventional stage. Here 'N' (number of subjects analysed), included all subjects who were evaluable for this endpoint. Here 'n' (number analysed) included all subjects who were analysed at specified timepoints.
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End point type |
Secondary
|
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End point timeframe |
From baseline to Day 3, 5, 8, 14, 21 of the observational stage
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No statistical analyses for this end point |
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Adverse events information
|
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Timeframe for reporting adverse events |
Up to 1 year 7 months
|
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Adverse event reporting additional description |
The Safety set (SAF) included all subjects who received at least 1 dose of study drug, and were analyzed as treated, regardless of the randomized treatment group assigned. Where ‘analysed as treated’ is defined as: Placebo: if only placebo doses received, and JNJ-53718678: if at least one dose of the active study drug received.
|
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Assessment type |
Non-systematic | |||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||
Dictionary used for adverse event reporting
|
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Dictionary name |
MedDRA | |||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||
Dictionary version |
24.0
|
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Reporting groups
|
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Reporting group title |
Interventional Phase: JNJ-53718678
|
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Reporting group description |
As per original dosing, subjects were randomized to receive JNJ-53718678 (for Age Group 1 greater than or equal to [>=] 28 days and less than [<] 3 months: 5 milligram per kilogram [mg/kg]; for Age Group 2 (>=3 and <6 months): 6 mg/kg and for Age Group 3 (>=6 months): 9 mg/kg) once daily for 7 days. After Protocol amendment 2, subjects were randomized to receive JNJ-53718678 (for Age Group 1: 2.5 mg/kg; for Age Group 2: 3 mg/kg and for Age Group 3: 4.5 mg/kg) twice daily for 7 days. | |||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||
Reporting group title |
Interventional Phase: Placebo
|
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Reporting group description |
As per original dosing, subjects were randomized to receive JNJ-53718678 matching placebo (for Age Group 1 greater than or equal to [>=] 28 days and less than [<] 3 months: 5 milligram per kilogram [mg/kg]; for Age Group 2 (>=3 and <6 months): 6 mg/kg and for Age Group 3 (>=6 months): 9 mg/kg) qd for 7 days. After Protocol amendment 2, subjects were randomized to receive JNJ-53718678 (for Age Group 1: 2.5 mg/kg; for Age Group 2: 3 mg/kg and for Age Group 3: 4.5 mg/kg) bid for 7 days. | |||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||
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Frequency threshold for reporting non-serious adverse events: 0% | ||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||
|
|
|||||||
Substantial protocol amendments (globally) |
|||||||
Were there any global substantial amendments to the protocol? Yes | |||||||
Date |
Amendment |
||||||
06 Nov 2019 |
The overall reason is to update the protocol to add the missing part of the Visit Schedule for Rash Management in Pediatric Subjects. |
||||||
05 Jun 2020 |
The overall reason for the amendment is to implement a risk mitigation plan for the newly recruited subjects in the interventional stage following identification of an exposure (Cmax)-related important potential risk of QT interval prolongation identified in the thorough QT (TQT) Study 53718678RSV1009 in healthy adult subjects. |
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13 Jul 2020 |
The overall reason is to implement recommendations from Health Authorities (HA). |
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Interruptions (globally) |
|||||||
Were there any global interruptions to the trial? Yes | |||||||
|
|||||||
Limitations and caveats |
|||||||
Limitations of the trial such as small numbers of subjects analysed or technical problems leading to unreliable data. | |||||||
The required number of subjects in the interventional phase was not reached, and hence, limiting the interpretability of the data. |