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Clinical Trial Results:
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

Summary
EudraCT number	2016-003642-93
Trial protocol	GB BE ES HU SE FR DE PL BG Outside EU/EEA IT
Global end of trial date	18 Apr 2022

Results information
Results version number	v2(current)
This version publication date	18 Nov 2023
First version publication date	03 Nov 2022
Other versions	v1
Version creation reason

Trial Information
Subject Disposition
Baseline Characteristics
End Points
Adverse Events
More Information

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Trial information

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Sponsor protocol code

53718678RSV2002

ISRCTN number

US NCT number

NCT03656510

WHO universal trial number (UTN)

Sponsor organisation name

Janssen Research & Development LLC

Sponsor organisation address

920 Route 202, South Raritan, New Jersey, United States, 08869

Public contact

Clinical Registry Group, Janssen Research & Development LLC, ClinicalTrialsEU@its.jnj.com

Scientific contact

Clinical Registry Group, Janssen Research & Development LLC, ClinicalTrialsEU@its.jnj.com

Is trial part of an agreed paediatric investigation plan (PIP)

Yes

EMA paediatric investigation plan number(s)

EMEA-001838-PIP01-15

Does article 45 of REGULATION (EC) No 1901/2006 apply to this trial?

Does article 46 of REGULATION (EC) No 1901/2006 apply to this trial?

Analysis stage

Final

Date of interim/final analysis

29 Jun 2022

Is this the analysis of the primary completion data?

Global end of trial reached?

Yes

Global end of trial date

18 Apr 2022

Was the trial ended prematurely?

Yes

Main objective of the trial

The main objective of this trial was to establish antiviral activity of JNJ-53718678 as measured by respiratory syncytial virus (RSV) viral load in nasal swab samples by a quantitative reverse transcription polymerase chain reaction (qRT-PCR) assay in children greater than or equal to (>=) 28 days and less than or equal to (<=) 3 years of age with RSV disease.

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.

Background therapy

Evidence for comparator

Actual start date of recruitment

03 Dec 2018

Long term follow-up planned

Independent data monitoring committee (IDMC) involvement?

Yes

Number of subjects enrolled per country

Country: Number of subjects enrolled

Argentina: 16

Country: Number of subjects enrolled

Bulgaria: 24

Country: Number of subjects enrolled

Brazil: 26

Country: Number of subjects enrolled

Germany: 3

Country: Number of subjects enrolled

Spain: 65

Country: Number of subjects enrolled

United Kingdom: 2

Country: Number of subjects enrolled

Hungary: 13

Country: Number of subjects enrolled

Italy: 3

Country: Number of subjects enrolled

Japan: 39

Country: Number of subjects enrolled

Korea, Republic of: 2

Country: Number of subjects enrolled

Mexico: 3

Country: Number of subjects enrolled

Malaysia: 12

Country: Number of subjects enrolled

Poland: 2

Country: Number of subjects enrolled

Russian Federation: 2

Country: Number of subjects enrolled

Sweden: 3

Country: Number of subjects enrolled

Thailand: 10

Country: Number of subjects enrolled

Turkey: 4

Country: Number of subjects enrolled

Taiwan: 12

Country: Number of subjects enrolled

United States: 4

Country: Number of subjects enrolled

South Africa: 1

Worldwide total number of subjects

246

EEA total number of subjects

113

Number of subjects enrolled per age group

In utero

Preterm newborn - gestational age < 37 wk

Newborns (0-27 days)

Infants and toddlers (28 days-23 months)

215

Children (2-11 years)

Adolescents (12-17 years)

Adults (18-64 years)

From 65 to 84 years

85 years and over

Subject disposition

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Recruitment details

Screening details

A total of 246 subjects were enrolled in the study out of which 242 subjects completed the study.

Period 1 title

Overall Study (overall period)

Is this the baseline period?

Yes

Allocation method

Randomised - controlled

Blinding used

Double blind

Roles blinded

Subject, Investigator

Are arms mutually exclusive

Yes

Cohort 1: Placebo

Arm description

Subjects of age groups (age group 1: greater than or equal to [>=] 28 days to less than [<] 3 months, age group 2: >=3 months to <6 months, and age group 3: >=6 months to less than or equal to [<=] 3 years), who were hospitalised or expected to be hospitalised within 24 hours after presentation to the hospital received placebo matching to JNJ-53718678 (high volume placebo or low volume placebo to match the calculated volume of the JNJ-53718678 for the high dose or low dose, respectively) orally once daily for 7 days.

Arm type

Experimental

Investigational medicinal product name

Placebo

Investigational medicinal product code

Other name

Pharmaceutical forms

Concentrate for oral suspension

Routes of administration

Oral use

Dosage and administration details

Subjects received placebo matching to JNJ-53718678 orally once daily for 7 days.

Cohort 1: JNJ-53718678 Low Dose

Arm description

Subjects who were hospitalised or expected to be hospitalised within 24 hours after presentation to the hospital, received JNJ-53718678 1.7 milligrams per kilogram (mg/kg) for age group 1: >=28 days to <3 months; 2 mg/kg for age group 2: >=3 months to <6 months; and 3 mg/kg for age group 3: >=6 months to <=3 years, orally once daily for 7 days.

Arm type

Experimental

Investigational medicinal product name

JNJ-53718678

Investigational medicinal product code

Other name

Rilematovir

Pharmaceutical forms

Concentrate for oral suspension

Routes of administration

Oral use

Dosage and administration details

Subjects received JNJ-53718678 low dose, orally once daily for 7 days.

Cohort 1: JNJ-53718678 High Dose

Arm description

Subjects who were hospitalised or expected to be hospitalised within 24 hours after presentation to the hospital received JNJ-53718678 5 mg/kg for age group 1: >=28 days to <3 months; 6 mg/kg for age group 2: >=3 months to <6 months; and 9 mg/kg for age group 3: >=6 months to <=3 years, orally once daily for 7 days.

Arm type

Experimental

Investigational medicinal product name

JNJ-53718678

Investigational medicinal product code

Other name

Rilematovir

Pharmaceutical forms

Concentrate for oral suspension

Routes of administration

Oral use

Dosage and administration details

Subjects received JNJ-53718678 high dose, orally once daily for 7 days.

Cohort 2: Placebo

Arm description

As per the original dosing, outpatient subjects of age groups (age group 1: >=28 days to <3 months, age group 2: >=3 months to <6 months, and age group 3: >=6 months to <=3 years) were randomised to receive placebo matching to JNJ-53718678 (high volume placebo or low volume placebo to match the calculated volume of the JNJ-53718678 for the high dose or low dose, respectively) orally once daily for 7 days. After protocol amendment 4, subjects received placebo matching to JNJ-53718678 (high dose or low dose) orally twice daily for 7 days.

Arm type

Experimental

Investigational medicinal product name

Placebo

Investigational medicinal product code

Other name

Pharmaceutical forms

Concentrate for oral suspension

Routes of administration

Oral use

Dosage and administration details

Subjects received placebo matching to JNJ-53718678 orally once daily for 7 days. After protocol amendment 4, subjects received placebo matching to JNJ-53718678 (high dose or low dose) orally twice daily for 7 days.

Cohort 2: JNJ-53718678 Low Dose

Arm description

As per the original dosing, outpatient subjects were randomised to receive JNJ-53718678 1.7 mg/kg for age group 1: >=28 days to <3 months; 2 mg/kg for age group 2: >=3 months to <6 months; and 3 mg/kg for age group 3: >=6 months to <=3 years, orally once daily for 7 days. After protocol amendment 4, subjects were randomised to receive JNJ-53718678 0.85 mg/kg for age group 1, JNJ-53718678 1.0 mg/kg for age group 2, and JNJ-53718678 1.5 mg/kg for age group 3, orally twice daily for 7 days.

Arm type

Experimental

Investigational medicinal product name

JNJ-53718678

Investigational medicinal product code

Other name

Rilematovir

Pharmaceutical forms

Concentrate for oral suspension

Routes of administration

Oral use

Dosage and administration details

Subjects received JNJ-53718678 low dose, orally once daily for 7 days. After protocol amendment 4, subjects were randomised to receive JNJ-53718678 0.85 mg/kg for age group 1, JNJ-53718678 1.0 mg/kg for age group 2, and JNJ-53718678 1.5 mg/kg for age group 3, orally twice daily for 7 days.

Cohort 2: JNJ-53718678 High Dose

Arm description

As per the original dosing, outpatient subjects were randomised to receive JNJ-53718678 5 mg/kg for age group 1: >=28 days to <3 months; 6 mg/kg for age group 2: >=3 months to <6 months; and 9 mg/kg for age group 3: >=6 months to <=3 years, orally once daily for 7 days. After protocol amendment 4, subjects were randomised to receive JNJ-53718678 2.5 mg/kg for age group 1, JNJ-53718678 3.0 mg/kg for age group 2, and JNJ-53718678 4.5 mg/kg for age group 3, orally twice daily for 7 days.

Arm type

Experimental

Investigational medicinal product name

JNJ-53718678

Investigational medicinal product code

Other name

Rilematovir

Pharmaceutical forms

Concentrate for oral suspension

Routes of administration

Oral use

Dosage and administration details

Subjects received JNJ-53718678 high dose, orally once daily for 7 days. After protocol amendment 4, subjects were randomised to receive JNJ-53718678 2.5 mg/kg for age group 1, JNJ-53718678 3.0 mg/kg for age group 2, and JNJ-53718678 4.5 mg/kg for age group 3, orally twice daily for 7 days.

Number of subjects in period 1	Cohort 1: Placebo	Cohort 1: JNJ-53718678 Low Dose	Cohort 1: JNJ-53718678 High Dose	Cohort 2: Placebo	Cohort 2: JNJ-53718678 Low Dose	Cohort 2: JNJ-53718678 High Dose
Started	50	49	48	34	34	31
Completed	48	48	48	33	34	31
Not completed	2	1	0	1	0	0
Consent withdrawn by subject	1	1	-	1	-	-
Lost to follow-up	1	-	-	-	-	-

Baseline characteristics

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Reporting group title

Cohort 1: Placebo

Reporting group description

Reporting group title

Cohort 1: JNJ-53718678 Low Dose

Reporting group description

Reporting group title

Cohort 1: JNJ-53718678 High Dose

Reporting group description

Reporting group title

Cohort 2: Placebo

Reporting group description

Reporting group title

Cohort 2: JNJ-53718678 Low Dose

Reporting group description

Reporting group title

Cohort 2: JNJ-53718678 High Dose

Reporting group description

Reporting group values	Cohort 1: Placebo	Cohort 1: JNJ-53718678 Low Dose	Cohort 1: JNJ-53718678 High Dose	Cohort 2: Placebo	Cohort 2: JNJ-53718678 Low Dose	Cohort 2: JNJ-53718678 High Dose	Total
Number of subjects	50	49	48	34	34	31	246
Age categorical
Units: Subjects
Infants and toddlers (28 days-23 months)	47	45	45	27	26	25	215
Children (2-11 years)	3	4	3	7	8	6	31
Age continuous
Units: months
arithmetic mean (standard deviation)	8.4 ± 8.59	8.6 ± 8.74	8.5 ± 8.21	13.8 ± 10.31	14.8 ± 10.9	17.2 ± 8.81	-
Sex: Female, Male
Units: Subjects
Female	23	20	23	13	8	14	101
Male	27	29	25	21	26	17	145

End points

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Reporting group title

Cohort 1: Placebo

Reporting group description

Reporting group title

Cohort 1: JNJ-53718678 Low Dose

Reporting group description

Reporting group title

Cohort 1: JNJ-53718678 High Dose

Reporting group description

Reporting group title

Cohort 2: Placebo

Reporting group description

Reporting group title

Cohort 2: JNJ-53718678 Low Dose

Reporting group description

Reporting group title

Cohort 2: JNJ-53718678 High Dose

Reporting group description

Subject analysis set title

Cohorts 1 and 2: Placebo

Subject analysis set type

Intention-to-treat

Subject analysis set description

As per the original dosing, subjects of age groups (age group 1: >=28 days to <3 months, age group 2: >=3 months to <6 months, and age group 3: >=6 months to less than or equal to [<=3] years) were randomised to receive placebo matching to JNJ-53718678 (high volume placebo or low volume placebo to match the calculated volume of the JNJ-53718678 for the high dose or low dose, respectively) orally once daily for 7 days in Cohorts 1 and 2. After protocol amendment 4, subjects in Cohort 2 were randomised to receive placebo matching to JNJ-53718678 (high dose or low dose) orally twice daily for 7 days.

Subject analysis set title

Cohorts 1 and 2: JNJ-53718678 Low Dose

Subject analysis set type

Intention-to-treat

Subject analysis set description

As per the original dosing, subjects were randomised to receive JNJ-53718678 1.7 mg/kg for age group 1: >=28 days to <3 months; 2 mg/kg for age group 2: >=3 months to <6 months; and 3 mg/kg for age group 3: >=6 months to <=3 years, orally once daily for 7 days in Cohorts 1 and 2. After protocol amendment 4, subjects in Cohort 2 were randomised to receive JNJ-53718678 0.85 mg/kg for age group 1, JNJ-53718678 1.0 mg/kg for age group 2, and JNJ-53718678 1.5 mg/kg for age group 3, orally twice daily for 7 days.

Subject analysis set title

Cohorts 1 and 2: JNJ-53718678 High Dose

Subject analysis set type

Intention-to-treat

Subject analysis set description

As per the original dosing, subjects were randomised to receive JNJ-53718678 5 mg/kg for age group 1: >=28 days to <3 months; 6 mg/kg for age group 2: >=3 months to <6 months; and 9 mg/kg for age group 3: >=6 months to <=3 years, orally once daily for 7 days in Cohorts 1 and 2. After protocol amendment 4, subjects in Cohort 2 were randomised to receive JNJ-53718678 2.5 mg/kg for age group 1, JNJ-53718678 3.0 mg/kg for age group 2, and JNJ-53718678 4.5 mg/kg for age group 3, orally twice daily for 7 days.

Primary: 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])

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End point title

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]) ^[1]

End point description

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, analysed and reported for this endpoint. Intent-to-Treat-infected (ITT-i) analysis set included all randomised subjects who received at least one dose of study drug and who had a centrally confirmed RSV RNA viral load of greater than or equal to (>=) 1 log10 copies/mL above the lower limit of quantification (LLOQ) of the RSV RT-qPCR assay at baseline. Analyses on the ITT-i set were performed as randomised.

End point type

Primary

End point timeframe

Baseline through Day 5

Notes
[1] - No statistical analyses have been specified for this primary end point. It is expected there is at least one statistical analysis for each primary end point.
Justification: Only descriptive data was planned to be reported for this endpoint.

End point values	Cohorts 1 and 2: Placebo	Cohorts 1 and 2: JNJ-53718678 Low Dose	Cohorts 1 and 2: JNJ-53718678 High Dose
Number of subjects analysed	79	80	72
Units: log10 copies*day per millilitre (mL)
arithmetic mean (confidence interval 95%)	22.74 (21.677 to 23.800)	21.48 (20.402 to 22.566)	21.51 (20.374 to 22.650)

No statistical analyses for this end point

Secondary: RSV Viral Load Over Time

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End point title

RSV Viral Load Over Time

End point description

RSV viral load actual values over time were measured by qRT-PCR in the nasal swab specimens collected at the clinic visits and at home. As planned, combined data for both the cohorts was collected, analysed and reported for this endpoint. ITT-i analysis set included all randomised subjects who received at least one dose of study drug and who had centrally confirmed RSV RNA viral load of >=1 log10 copies/mL above the LLOQ of the RSV RT-qPCR assay at baseline. Analyses on ITT-i set were performed as randomised. Here, 'n' (number analysed) represents number of subjects who were evaluable at specified timepoints.

End point type

Secondary

End point timeframe

Baseline, Days 3, 5, 8, 14, and 21

End point values	Cohorts 1 and 2: Placebo	Cohorts 1 and 2: JNJ-53718678 Low Dose	Cohorts 1 and 2: JNJ-53718678 High Dose
Number of subjects analysed	79	80	72
Units: log10 copies/mL
arithmetic mean (standard deviation)
Baseline (n=79, 80, 72)	6.913 ± 1.3449	7.113 ± 1.3667	7.004 ± 1.4709
Day 3 (n=77, 79, 71)	5.398 ± 1.5834	5.432 ± 1.8952	5.271 ± 1.7710
Day 5 (n=77, 77, 72)	4.146 ± 1.8508	4.079 ± 1.8760	3.883 ± 1.9815
Day 8 (n=78, 73,70)	2.604 ± 2.0857	2.108 ± 1.8538	2.078 ± 1.8319
Day 14 (n=73, 74, 67)	1.640 ± 1.9515	1.636 ± 2.2221	1.440 ± 1.8768
Day 21 (n=74, 78, 68)	1.150 ± 1.7752	0.817 ± 1.5347	0.810 ± 1.6699

No statistical analyses for this end point

Secondary: Change From Baseline in RSV Viral Load Over Time

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End point title

Change From Baseline in RSV Viral Load Over Time

End point description

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. As planned, combined data for both the cohorts was collected, analysed and reported for this endpoint. ITT-i analysis set included all randomised subjects who received at least one dose of study drug and who had centrally confirmed RSV RNA viral load of >=1 log10 copies/mL above the LLOQ of the RSV RT-qPCR assay at baseline. Analyses on ITT-i set were performed as randomised. Here, 'n' (number analysed) represents number of subjects who were evaluable at specified timepoints.

End point type

Secondary

End point timeframe

Baseline up to Days 3, 5, 8, 14, and 21

End point values	Cohorts 1 and 2: Placebo	Cohorts 1 and 2: JNJ-53718678 Low Dose	Cohorts 1 and 2: JNJ-53718678 High Dose
Number of subjects analysed	79	80	72
Units: log10 copies/mL
arithmetic mean (standard deviation)
Day 3 (n=77, 79, 71)	-1.502 ± 1.3290	-1.690 ± 1.6225	-1.694 ± 1.5134
Day 5 (n=77, 77, 72)	-2.754 ± 1.7699	-3.049 ± 1.6493	-3.121 ± 1.8453
Day 8 (n=78, 73, 70)	-4.308 ± 2.2435	-5.017 ± 1.8563	-4.948 ± 1.8428
Day 14 (n=73, 74, 67)	-5.292 ± 2.2968	-5.471 ± 2.4289	-5.578 ± 2.2707
Day 21 (n=74, 78, 68)	-5.801 ± 2.1652	-6.302 ± 2.0439	-6.268 ± 1.9394

No statistical analyses for this end point

Secondary: Least Squares (LS) Mean RSV Viral Load on Days 3, 8, and 14

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End point title

Least Squares (LS) Mean RSV Viral Load on Days 3, 8, and 14

End point description

LS mean RSV viral load on Days 3, 8, and 14 was reported. LS mean viral load (log10 copies/mL) was estimated per time point. The difference in RSV viral Load AUC (log10 copies*day/mL) from immediately prior to first dose of study drug (baseline) through Days 3, 8, and 14 was determined from the model estimating LS Mean Viral Load per time point and is presented in statistical analysis. RSV viral load was measured by qRT-PCR assay in mid-turbinate nasal swab specimens. As planned, combined data for both cohorts was collected and analysed at Days 3 and 8. 99999: data were not analysed at Day 14 due to the premature study termination. ITT-i analysis set: all randomised subjects who received at least one dose of study drug and who had centrally confirmed RSV RNA viral load of >=1 log10 copies/mL above the LLOQ of the RSV RT-qPCR assay at baseline. Here, 'n' (number analysed): subjects who were evaluable at specified timepoints.

End point type

Secondary

End point timeframe

Baseline through Days 3, 8, and 14

End point values	Cohorts 1 and 2: Placebo	Cohorts 1 and 2: JNJ-53718678 Low Dose	Cohorts 1 and 2: JNJ-53718678 High Dose
Number of subjects analysed	79	80	72
Units: log10 copies*day/mL
least squares mean (confidence interval 95%)
Day 3 (n=79, 80, 72)	5.48 (5.129 to 5.834)	5.36 (5.009 to 5.717)	5.32 (4.949 to 5.695)
Day 8 (n=79, 80, 72)	2.66 (2.307 to 3.011)	2.08 (1.716 to 2.444)	2.08 (1.701 to 2.450)
Day 14 (n=0, 0, 0)	99999 (-99999 to 99999)	99999 (-99999 to 99999)	99999 (-99999 to 99999)

Statistical Analysis 1

Comparison groups

Cohorts 1 and 2: Placebo v Cohorts 1 and 2: JNJ-53718678 Low Dose

Number of subjects included in analysis

159

Analysis specification

Pre-specified

Analysis type

other ^[2]

Method

Parameter type

Mean difference (final values)

Point estimate

-0.6

Confidence interval

level

95%

sides

2-sided

lower limit

-1.382

upper limit

0.185

Notes
[2] - Difference versus placebo in mean RSV viral load AUC on Day 3

Statistical Analysis 3

Comparison groups

Cohorts 1 and 2: Placebo v Cohorts 1 and 2: JNJ-53718678 Low Dose

Number of subjects included in analysis

159

Analysis specification

Pre-specified

Analysis type

other ^[3]

Method

Parameter type

Mean difference (final values)

Point estimate

-2.46

Confidence interval

level

95%

sides

2-sided

lower limit

-4.674

upper limit

-0.25

Notes
[3] - Difference versus placebo in mean RSV viral load AUC on Day 8

Statistical Analysis 4

Comparison groups

Cohorts 1 and 2: Placebo v Cohorts 1 and 2: JNJ-53718678 High Dose

Number of subjects included in analysis

151

Analysis specification

Pre-specified

Analysis type

other ^[4]

Method

Parameter type

Mean difference (final values)

Point estimate

-2.38

Confidence interval

level

95%

sides

2-sided

lower limit

-4.645

upper limit

-0.114

Notes
[4] - Difference versus placebo in mean RSV viral load AUC on Day 8

Statistical Analysis 2

Comparison groups

Cohorts 1 and 2: Placebo v Cohorts 1 and 2: JNJ-53718678 High Dose

Number of subjects included in analysis

151

Analysis specification

Pre-specified

Analysis type

other ^[5]

Method

Parameter type

Mean difference (final values)

Point estimate

-0.39

Confidence interval

level

95%

sides

2-sided

lower limit

-1.19

upper limit

0.418

Notes
[5] - Difference versus placebo in mean RSV viral load AUC on Day 3

Secondary: Time to Undetectable RSV Viral Load

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End point title

Time to Undetectable RSV Viral Load

End point description

Time to undetectable RSV viral load (as measured by qRT-PCR) was defined as the time in hours from first dose of study drug to first post-baseline timepoint at which the virus was undetectable and after which there were no more detectable virus assessments. As planned, combined data for both the cohorts was collected, analysed and reported for this endpoint. ITT-i analysis set included all randomised subjects who received at least one dose of study drug and who had centrally confirmed RSV RNA viral load of >=1 log10 copies/mL above the LLOQ of the RSV RT-qPCR assay at baseline. Analyses on ITT-i set were performed as randomised.

End point type

Secondary

End point timeframe

Up to Day 21

End point values	Cohorts 1 and 2: Placebo	Cohorts 1 and 2: JNJ-53718678 Low Dose	Cohorts 1 and 2: JNJ-53718678 High Dose
Number of subjects analysed	79	80	72
Units: Hours
median (confidence interval 95%)	467.0 (332.90 to 478.40)	428.3 (309.50 to 480.40)	330.7 (308.28 to 476.00)

No statistical analyses for this end point

Secondary: Percentage of Subjects with Undetectable RSV Viral Load at Each Timepoint Throughout the Study

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End point title

Percentage of Subjects with Undetectable RSV Viral Load at Each Timepoint Throughout the Study

End point description

Percentage of subjects with undetectable RSV viral load (as measured by qRT-PCR) at each timepoint throughout the study was reported. As planned, combined data for both the cohorts were collected, analysed and reported for this endpoint. ITT-i analysis set included all randomised subjects who received at least one dose of study drug and who had centrally confirmed RSV RNA viral load of >=1 log10 copies/mL above the LLOQ of the RSV RT-qPCR assay at baseline. Analyses on ITT-i set were performed as randomised. Here, 'n' (number analysed) represents number of subjects who were evaluable at specified timepoints

End point type

Secondary

End point timeframe

Baseline, Days 3, 5, 8, 14, and 21

End point values	Cohorts 1 and 2: Placebo	Cohorts 1 and 2: JNJ-53718678 Low Dose	Cohorts 1 and 2: JNJ-53718678 High Dose
Number of subjects analysed	79	80	72
Units: percentage of subjects
number (not applicable)
Baseline (n=79, 80, 72)	0	0	0
Day 3 (n=77, 79, 71)	1.3	3.8	2.8
Day 5 (n=77, 77, 72)	7.8	9.1	11.1
Day 8 (n=78, 73, 70)	33.3	38.4	38.6
Day 14 (n=73, 74, 67)	54.8	58.1	58.2
Day 21 (n=74, 78, 68)	67.6	76.9	77.9

No statistical analyses for this end point

Secondary: Change from Baseline in Parent(s)/Caregiver(s) Pediatric RSV Electronic Severity and Outcomes Rating System (PRESORS) Scores

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End point title

Change from Baseline in Parent(s)/Caregiver(s) Pediatric RSV Electronic Severity and Outcomes Rating System (PRESORS) Scores

End point description

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). PRESORS overall RSV symptoms summary parameter 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. ITT-i analysis set included all randomised subjects who received at least one dose of study drug and who had centrally confirmed RSV RNA viral load of >=1 log10 copies/mL above the LLOQ of the RSV RT-qPCR assay at baseline. Analyses on ITT-i set were performed as randomised. Here, 'n' (number analysed) represents number of subjects who were evaluable at specified timepoints.

End point type

Secondary

End point timeframe

Baseline up to Days 3, 5, 8, 14, and 21

End point values	Cohort 1: Placebo	Cohort 1: JNJ-53718678 Low Dose	Cohort 1: JNJ-53718678 High Dose	Cohort 2: Placebo	Cohort 2: JNJ-53718678 Low Dose	Cohort 2: JNJ-53718678 High Dose
Number of subjects analysed	47	47	44	32	33	28
Units: Units on a scale
arithmetic mean (standard deviation)
Day 3 (n=45, 40, 41, 25, 27, 26)	-0.51 ± 0.571	-0.55 ± 0.618	-0.70 ± 0.594	-0.25 ± 0.576	-0.15 ± 0.427	-0.21 ± 0.537
Day 5 (n=45, 41, 41, 28, 27, 26)	-0.91 ± 0.585	-0.88 ± 0.542	-1.11 ± 0.581	-0.48 ± 0.572	-0.52 ± 0.558	-0.58 ± 0.644
Day 8 (n=44, 41, 41, 28, 27, 26)	-1.15 ± 0.581	-1.25 ± 0.537	-1.39 ± 0.514	-0.85 ± 0.526	-0.83 ± 0.582	-1.04 ± 0.628
Day 14 (n=44, 39, 40, 28, 27, 26)	-1.40 ± 0.591	-1.39 ± 0.582	-1.59 ± 0.458	-1.06 ± 0.529	-1.08 ± 0.568	-1.24 ± 0.681
Day 21 (n=42, 40, 41, 28, 26, 26)	-1.41 ± 0.637	-1.33 ± 0.559	-1.56 ± 0.468	-1.12 ± 0.529	-1.15 ± 0.496	-1.29 ± 0.596

No statistical analyses for this end point

Secondary: Change from Baseline in Clinician PRESORS Score

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End point title

Change from Baseline in Clinician PRESORS Score

End point description

Change from baseline in clinician PRESORS scores (for concepts: activity level, sleep disturbance, breathing problems, retractions, tachypnea, feeding problem, cough, nasal secretions, wheezing, dehydration) was assessed. Clinician PRESORS is a questionnaire recording presence and severity of signs and symptoms of RSV disease and consisted of 10-items, each item score ranges from 0 to 3. Overall RSV symptoms summary parameter was derived (mean of the item scores) which also ranges from 0 to 3. The higher the score, the worse the symptom. ITT-i analysis set included all randomised subjects who received at least one dose of study drug and who had centrally confirmed RSV RNA viral load of >=1 log10 copies/mL above the LLOQ of the RSV RT-qPCR assay at baseline. Analyses on ITT-i set were performed as randomised. Here, 'n' (number analysed) represents number of subjects who were evaluable at specified timepoints.

End point type

Secondary

End point timeframe

Baseline up to Days 3, 5, 8, 14, and 21

End point values	Cohort 1: Placebo	Cohort 1: JNJ-53718678 Low Dose	Cohort 1: JNJ-53718678 High Dose	Cohort 2: Placebo	Cohort 2: JNJ-53718678 Low Dose	Cohort 2: JNJ-53718678 High Dose
Number of subjects analysed	47	47	44	32	33	28
Units: Units on a scale
arithmetic mean (standard deviation)
Day 3 (n=43, 41, 42, 29, 29, 26)	-0.45 ± 0.441	-0.45 ± 0.517	-0.48 ± 0.469	-0.25 ± 0.424	-0.21 ± 0.378	-0.29 ± 0.338
Day 5 (n=42, 38, 41, 28, 28, 25)	-0.73 ± 0.582	-0.71 ± 0.424	-0.83 ± 0.483	-0.38 ± 0.415	-0.37 ± 0.462	-0.60 ± 0.516
Day 8 (n=41, 38, 38, 30, 29, 26)	-0.92 ± 0.461	-1.04 ± 0.396	-1.04 ± 0.449	-0.71 ± 0.529	-0.63 ± 0.423	-0.85 ± 0.552
Day 14 (n=40, 37, 34, 28, 27, 23)	-1.10 ± 0.466	-1.11 ± 0.428	-1.14 ± 0.369	-0.81 ± 0.497	-0.77 ± 0.436	-0.91 ± 0.541
Day 21 (n=35, 40, 33, 29, 28, 27)	-1.13 ± 0.424	-1.12 ± 0.433	-1.17 ± 0.336	-0.87 ± 0.455	-0.81 ± 0.411	-0.93 ± 0.524

No statistical analyses for this end point

Secondary: Time to Improvement on Overall Health

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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 assessed. 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'. ITT-i analysis set included all randomised subjects who received at least one dose of study drug and who had centrally confirmed RSV RNA viral load of >=1 log10 copies/mL above the LLOQ of the RSV RT-qPCR assay at baseline. Analyses on ITT-i set were performed as randomised. Here, 'N' (number of subjects analysed) signifies number of subjects who were evaluable for this endpoint.

End point type

Secondary

End point timeframe

Up to Day 21

End point values	Cohort 1: Placebo	Cohort 1: JNJ-53718678 Low Dose	Cohort 1: JNJ-53718678 High Dose	Cohort 2: Placebo	Cohort 2: JNJ-53718678 Low Dose	Cohort 2: JNJ-53718678 High Dose
Number of subjects analysed	45	44	43	32	32	28
Units: Hours
median (confidence interval 95%)	189.6 (187.80 to 192.50)	190.2 (188.70 to 200.00)	189.1 (186.90 to 191.90)	186.8 (184.30 to 190.40)	198.2 (185.30 to 237.30)	187.9 (185.90 to 189.80)

No statistical analyses for this end point

Secondary: Time to Resolution of RSV Symptoms Based on PRESORS Caregiver (ObsRO)

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End point title

Time to Resolution of RSV Symptoms Based on PRESORS Caregiver (ObsRO)

End point description

Time to resolution is defined as time 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. ITT-i analysis set included all randomised subjects who received at least one dose of study drug and who had centrally confirmed RSV RNA viral load of >=1 log10 copies/mL above the LLOQ of the RSV RT-qPCR assay at baseline. Analyses on ITT-i set were performed as randomised.

End point type

Secondary

End point timeframe

Up to Day 21

End point values	Cohort 1: Placebo	Cohort 1: JNJ-53718678 Low Dose	Cohort 1: JNJ-53718678 High Dose	Cohort 2: Placebo	Cohort 2: JNJ-53718678 Low Dose	Cohort 2: JNJ-53718678 High Dose
Number of subjects analysed	47	47	44	32	33	28
Units: Hours
median (confidence interval 95%)	193.5 (161.80 to 243.80)	163.6 (108.70 to 198.70)	151.8 (114.70 to 223.70)	166.6 (141.50 to 207.20)	206.1 (159.20 to 232.80)	176.9 (148.30 to 264.20)

No statistical analyses for this end point

Secondary: Percentage of Subjects by Status of RSV Symptoms Based on PRESORS Caregiver (ObsRO) General Question Over Time

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End point title

Percentage of Subjects by Status of RSV Symptoms Based on PRESORS Caregiver (ObsRO) General Question Over Time

End point description

Percentage of subjects by status of RSV symptoms based on PRESORS caregiver (ObsRO) general question over time was assessed. PRESORS is a questionnaire recording presence and severity of signs and symptoms of RSV disease (fever, cough, sputum, wheezing, difficulty breathing, nasal congestion, feeding issues). Status of RSV symptoms was assessed by a question (how would you rate the child's RSV symptoms now?) of PRESORS questionnaire and responses were categorized as: 1) none, 2) very mild, 3) mild, 4) moderate, 5) severe, 6) very severe. ITT-i set: all randomised subjects who received at least one dose of study drug and who had centrally confirmed RSV RNA viral load of >=1 log10 copies/mL above LLOQ of RSV RT-qPCR assay at baseline. Analyses on ITT-i set were performed as randomised. Here, N (number of subjects analysed) signifies number of subjects who were evaluable for this endpoint and n (number analysed) represents number of subjects who were evaluable at specified timepoints.

End point type

Secondary

End point timeframe

Baseline, Days 3, 5, 8, 14, and 21

End point values	Cohort 1: Placebo	Cohort 1: JNJ-53718678 Low Dose	Cohort 1: JNJ-53718678 High Dose	Cohort 2: Placebo	Cohort 2: JNJ-53718678 Low Dose	Cohort 2: JNJ-53718678 High Dose
Number of subjects analysed	47	47	44	32	33	28
Units: percentage of subjects
number (not applicable)
Baseline: None (n=45,43,41, 28, 27, 26)	0	0	0	0	0	0
Baseline: Very mild (n=45,43,41, 28, 27, 26)	0	0	2.4	7.1	7.4	3.8
Baseline: Mild (n=45,43,41, 28, 27, 26)	6.7	7.0	4.9	32.1	22.2	19.2
Baseline: Moderate (n=45,43,41, 28, 27, 26)	51.1	55.8	51.2	53.6	55.6	46.2
Baseline: Severe (n=45,43,41, 28, 27, 26)	37.8	27.9	41.5	7.1	14.8	30.8
Baseline: Very severe (n=45,43,41, 28, 27, 26)	4.4	9.3	0	0	0	0
Day 3: None (n=47,43,44,29,31,28)	0	2.3	0	3.4	0	0
Day 3: Very mild (n=47,43,44)	6.4	9.3	6.8	0	3.2	0
Day 3: Mild (n=47,43,44,29,31,28)	23.4	18.6	36.4	27.6	19.4	25.0
Day 3: Moderate (n=47,43,44,29,31,28)	46.8	48.8	43.2	62.1	64.5	64.3
Day 3: Severe (n=47,43,44,29,31,28)	17.0	18.6	9.1	6.9	12.9	10.7
Day 3: Very severe (n=47,43,44,29,31,28)	6.4	2.3	4.5	0	0	0
Day 5: None (n=47,43,43,30,32,28)	2.1	0	7.0	3.3	0	3.6
Day 5: Very mild (n=47,43,43,30,32,28)	23.4	23.3	16.3	10.0	12.5	10.7
Day 5: Mild (n=47,43,43,30,32,28)	38.3	27.9	32.6	36.7	43.8	32.1
Day 5: Moderate (n=47,43,43,30,32,28)	21.3	39.5	41.9	46.7	43.8	46.4
Day 5: Severe (n=47,43,43,30,32,28)	10.6	9.3	2.3	3.3	0	7.1
Day 5: Very severe (n=47,43,43,30,32,28)	4.3	0	0	0	0	0
Day 8: None (n=46,43,42,31,33,27)	13.0	16.3	26.2	12.9	6.1	7.4
Day 8: Very mild (n=46,43,42,31,33,27)	30.4	37.2	28.6	35.5	45.5	25.9
Day 8: Mild (n=46,43,42,31,33,27)	34.8	23.3	28.6	38.7	27.3	48.1
Day 8: Moderate (n=46,43,42,31,33,27)	17.4	23.3	16.7	12.9	21.2	14.8
Day 8: Severe (n=46,43,42,31,33,27)	2.2	0	0	0	0	0
Day 8: Very severe (n=46,43,42,31,33,27)	2.2	0	0	0	0	3.7
Day 14: None (n=41,40,41,30,30,28)	48.8	55.0	58.5	70.0	63.3	67.9
Day 14: Very mild (n=41,40,41,30,30,28)	36.6	30.0	26.8	20.0	13.3	17.9
Day 14: Mild (n=41,40,41,30,30,28)	12.2	2.5	7.3	6.7	16.7	10.7
Day 14: Moderate (n=41,40,41,30,30,28)	2.4	10.0	7.3	3.3	6.7	0
Day 14: Severe (n=41,40,41,30,30,28)	0	2.5	0	0	0	3.6
Day 14: Very severe (n=41,40,41,30,30,28)	0	0	0	0	0	0
Day 21: None (n=27,37,33,25,24,22)	66.7	67.6	57.6	84.0	83.3	86.4
Day 21: Very mild (n=27,37,33,25,24,22)	18.5	18.9	24.2	8.0	12.5	4.5
Day 21: Mild (n=27,37,33,25,24,22)	11.1	2.7	12.1	0	4.2	9.1
Day 21: Moderate (n=27,37,33,25,24,22)	3.7	8.1	6.1	8.0	0	0
Day 21: Severe (n=27,37,33,25,24,22)	0	2.7	0	0	0	0
Day 21: Very severe (n=27,37,33,25,24,22)	0	0	0	0	0	0

No statistical analyses for this end point

Secondary: Percentage of Subjects by Health Status Assessment Based on PRESORS Caregiver (ObsRO) General Question Over Time

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End point title

Percentage of Subjects by Health Status Assessment Based on PRESORS Caregiver (ObsRO) General Question Over Time

End point description

Percentage of subjects by health status assessment based on PRESORS caregiver (ObsRO) general question over time was assessed. 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). Health status was assessed by a question (how is the child's health now) of PRESORS questionnaire and responses were categorized as: 1) excellent, 2) very good, 3) good, 4) fair, 5) poor, and 6) very poor. ITT-i analysis set included all randomised subjects who received at least one dose of study drug and who had centrally confirmed RSV RNA viral load of >=1 log10 copies/mL above LLOQ of RSV RT-qPCR assay at baseline. Analyses on ITT-i set were performed as randomised. Here, 'N' (number of subjects analysed) signifies number of subjects who were evaluable for this endpoint and 'n' (number analysed) represents number of subjects who were evaluable at specified timepoints.

End point type

Secondary

End point timeframe

Baseline, Days 3, 5, 8, 14, and 21

End point values	Cohort 1: Placebo	Cohort 1: JNJ-53718678 Low Dose	Cohort 1: JNJ-53718678 High Dose	Cohort 2: Placebo	Cohort 2: JNJ-53718678 Low Dose	Cohort 2: JNJ-53718678 High Dose
Number of subjects analysed	47	47	44	32	33	28
Units: Percentage of subjects
number (not applicable)
Baseline: Excellent (n= 45, 43, 41, 28,27,26)	0	2.3	0	0	3.7	0
Baseline: Very good (n= 45,43,41, 28,27,26)	0	4.7	0	3.6	0	7.7
Baseline: Good (n= 45, 43, 41, 28,27,26)	4.4	7.0	7.3	14.3	11.1	3.8
Baseline: Fair (n= 45, 43, 41, 28,27,26)	42.2	51.2	43.9	57.1	40.7	23.1
Baseline: poor (n= 45, 43, 41, 28,27,26)	48.9	30.2	48.8	25.0	44.4	65.4
Baseline: Very poor (n= 45, 43, 41, 28,27,26)	4.4	4.7	0	0	0	0
Day 3: Excellent (n= 47, 44, 43, 29,31,28)	0	0	0	3.4	0	0
Day 3: Very good (n= 47, 44, 43, 29,31,28)	8.5	9.3	2.3	0	0	0
Day 3: Good (n= 47, 44, 43, 29,31,28)	23.4	20.9	34.1	17.2	12.9	10.7
Day 3: Fair (n= 47, 44, 43, 29,31,28)	38.3	46.5	45.5	58.6	41.9	53.6
Day 3: Poor (n= 47, 44, 43, 29,31,28)	21.3	23.3	13.6	20.7	45.2	35.7
Day 3: Very poor (n= 47, 44, 43, 29,31,28)	8.5	0	4.5	0	0	0
Day 5: Excellent (n= 47, 43, 43, 30,32,28)	2.1	0	0	6.7	0	0
Day 5: Very good (n= 47, 43, 43, 30,32,28)	19.1	9.3	20.9	0	6.3	3.6
Day 5: Good (n= 47, 43, 43, 30,32,28)	23.4	41.9	37.2	26.7	31.3	28.6
Day 5: Fair (n= 47, 43, 43, 30,32,28)	36.2	39.5	34.9	63.3	40.6	42.9
Day 5: Poor (n= 47, 43, 43, 30,32,28)	12.8	9.3	7.0	3.3	21.9	25.0
Day 5: Very poor (n= 47, 43, 43, 30,32,28)	6.4	0	0	0	0	0
Day 8: Excellent (n= 46, 43, 42, 31, 33,27)	13.0	9.3	16.7	6.5	3.0	3.7
Day 8: Very Good (n= 46, 43, 42, 31, 33,27)	23.9	32.6	21.4	19.4	21.2	22.2
Day 8: Good (n= 46, 43, 42, 31, 33,27)	32.6	32.6	38.1	48.4	36.4	33.3
Day 8: Fair (n= 46, 43, 42, 31, 33,27)	23.9	25.6	21.4	22.6	36.4	33.3
Day 8: Poor (n= 46, 43, 42, 31, 33,27)	4.3	0	2.4	3.2	3.0	3.7
Day 8: Very poor (n=46, 43, 42, 31, 33,27)	2.2	0	0	0	0	3.7
Day 14: Excellent (n= 41, 40, 41, 30, 30,28)	24.4	42.5	43.9	50.0	56.7	53.6
Day 14: Very good (n= 41, 40, 41, 30, 30,28)	43.9	47.5	36.6	23.3	16.7	28.6
Day 14: Good (n= 41, 40, 41, 30, 30,28)	19.5	5.0	9.8	20.0	16.7	7.1
Day 14: fair (n=41, 40, 41, 30, 30,28)	9.8	5.0	7.3	6.7	6.7	3.6
Day 14: Poor (n= 41, 40, 41, 30, 30,28)	2.4	0	2.4	0	3.3	3.6
Day 14: Very poor (n= 41, 40, 41, 30, 30,28)	0	0	0	0	0	3.6
Day 21: Excellent (n= 27,37, 33, 25,24,22)	55.6	45.9	45.5	60.0	79.2	68.2
Day 21: Very Good (n= 27,37, 33, 25,24,22)	22.2	32.4	33.3	28.0	12.5	9.1
Day 21: Good (n= 27,37, 33)	11.1	13.5	15.2	8.0	4.2	13.6
Day 21: Fair (n= 27,37, 33, 25,24,22)	11.1	5.4	6.1	0	4.2	9.1
Day 21: Poor (n= 27,37, 33, 25,24,22)	0	2.7	0	4.0	0	0
Day 21: Very poor (n=27,37, 33, 25,24,22)	0	0	0	0	0	0

No statistical analyses for this end point

Secondary: Percentage of Subjects with Worsening or Improvement Status of RSV Disease

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End point title

Percentage of Subjects with Worsening or Improvement Status of RSV Disease

End point description

Percentage of subjects with worsening or improvement of RSV disease based on general questions of overall health was assessed. Improvement or worsening was assessed by a 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' and responses were categorised as: 1) very much improved, 2) much improved, 3) a little improved, 4) about the same, 5) a little worse, 6) much worse, and 7) very much worse. ITT-i analysis set included all randomised subjects who received at least one dose of study drug and who had centrally confirmed RSV RNA viral load of >=1 log10 copies/mL above the LLOQ of the RSV RT-qPCR assay at baseline. Analyses on ITT-i set were performed as randomised. Here, 'n' (number analysed) represents number of subjects who were evaluable at specified timepoints.

End point type

Secondary

End point timeframe

Days 14 and 21

End point values	Cohort 1: Placebo	Cohort 1: JNJ-53718678 Low Dose	Cohort 1: JNJ-53718678 High Dose	Cohort 2: Placebo	Cohort 2: JNJ-53718678 Low Dose	Cohort 2: JNJ-53718678 High Dose
Number of subjects analysed	47	47	44	32	33	28
Units: Percentage of subjects
number (not applicable)
Day 14: Very much improved (n=41,40,40,30,29,28)	58.5	57.5	67.5	76.7	51.7	64.3
Day 14: Much improved (n=41,40,40,30,29,28)	34.1	40.0	30.0	20.0	37.9	32.1
Day 14: A little improved (n=41,40,40,30,29,28)	7.3	2.5	2.5	0	3.4	0
Day 14: About the same (n=41,40,40,30,29,28)	0	0	0	3.3	3.4	3.6
Day 14: A little worse (n=41,40,40,30,29,28)	0	0	0	0	3.4	0
Day 14: Much worse (n=41,40,40,30,29,28)	0	0	0	0	0	0
Day 14: Very much worse (n=41,40,40,30,29,28)	0	0	0	0	0	0
Day 21: Very much improved (n=27,36,32,25,23,22)	77.8	63.9	56.3	76.0	78.3	77.3
Day 21: Much improved (n=27,36,32,25,23,22)	14.8	30.6	37.5	24.0	21.7	13.6
Day 21: A little improved (n=27,36,32,25,23,22)	3.7	2.8	3.1	0	0	0
Day 21: About the same (n=27,36, 32,25,23,22)	3.7	2.8	3.1	0	0	0
Day 21: A little worse (n=27,36,32,25,23,22)	0	0	0	0	0	9.1
Day 21: Much worse (n=27, 36, 32, 25,23, 22)	0	0	0	0	0	0
Day 21: Very much worse (n=27,36,32,25,23,22)	0	0	0	0	0	0

No statistical analyses for this end point

Secondary: Percentage of Subjects by Return to Pre-RSV Disease Health Status Assessment Based on PRESORS Caregiver (ObsRO) General Question Over Time

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End point title

Percentage of Subjects by Return to Pre-RSV Disease Health Status Assessment Based on PRESORS Caregiver (ObsRO) General Question Over Time

End point description

Percentage of subjects by return to pre-RSV disease health status assessment based on PRESORS caregiver (ObsRO) general question over time was assessed by a question (Has the child’s health returned to normal [how it was before RSV?]) of PRESORS score that was categorized as: 1) No, and 2) Yes. 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). Below results are reported for category 'Yes'. ITT-i analysis set included all randomised subjects who received at least one dose of study drug and who had centrally confirmed RSV RNA viral load of >=1 log10 copies/mL above the LLOQ of the RSV RT-qPCR assay at baseline. Analyses on ITT-i set were performed as randomised. Here, 'n' (number analysed) represents number of subjects evaluable at specified timepoints.

End point type

Secondary

End point timeframe

Baseline, Days 3, 5, 8, 14, and 21

End point values	Cohort 1: Placebo	Cohort 1: JNJ-53718678 Low Dose	Cohort 1: JNJ-53718678 High Dose	Cohort 2: Placebo	Cohort 2: JNJ-53718678 Low Dose	Cohort 2: JNJ-53718678 High Dose
Number of subjects analysed	47	47	44	32	33	28
Units: percentage of subjects
number (not applicable)
Baseline (n=11, 4,9,9,9,8)	0	0	0	22.2	0	12.5
Day 3 (n=39, 35, 32, 25,25,23)	15.4	8.6	28.1	12.0	12.0	4.3
Day 5 (n=42, 37, 39, 25,23,23)	23.8	16.2	25.6	16.0	4.3	0
Day 8 (n= 40, 38, 34,27,25,20)	37.5	44.7	58.8	51.9	36.0	10.0
Day 14 (n=29, 36, 32, 27, 21,26 )	72.4	77.8	84.4	81.5	85.7	73.1
Day 21 (n=27, 36, 32,25,23,22)	81.5	86.1	84.4	92.0	95.7	95.5

No statistical analyses for this end point

Secondary: Respiratory Rate Over Time

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End point title

Respiratory Rate Over Time

End point description

Respiratory rate was measured by the investigator over time. The safety analysis set included all subjects who received at least 1 dose of study agent, and were analysed as treated, regardless of the randomised treatment group assigned. Here, 'n' (number analysed) represents number of subjects who were evaluable at specified timepoints.

End point type

Secondary

End point timeframe

Baseline, Days 3, 5, 8, 14, and 21

End point values	Cohort 1: Placebo	Cohort 1: JNJ-53718678 Low Dose	Cohort 1: JNJ-53718678 High Dose	Cohort 2: Placebo	Cohort 2: JNJ-53718678 Low Dose	Cohort 2: JNJ-53718678 High Dose
Number of subjects analysed	50	49	48	34	34	31
Units: Breaths/minute
arithmetic mean (standard deviation)
Baseline (n=50, 49, 48, 34, 34, 31)	45.0 ± 10.60	45.6 ± 11.82	45.7 ± 10.85	41.3 ± 13.66	41.3 ± 11.76	37.0 ± 8.77
Day 3 (n=48, 48, 48, 33, 34, 31)	44.1 ± 11.44	41.8 ± 10.13	42.7 ± 10.04	37.9 ± 10.16	37.3 ± 9.54	34.4 ± 9.19
Day 5 (n=47, 45, 46, 33, 34, 31)	38.3 ± 9.36	38.1 ± 9.57	39.1 ± 8.81	38.2 ± 13.37	38.1 ± 8.89	35.4 ± 9.53
Day 8 (n=47, 44, 46, 32, 34, 31)	35.5 ± 7.90	34.4 ± 7.87	39.2 ± 9.45	37.4 ± 11.70	36.9 ± 9.75	34.0 ± 10.54
Day 14 (n=47, 45, 46, 30, 32, 29)	35.6 ± 7.13	34.9 ± 8.89	35.2 ± 7.45	35.7 ± 9.27	35.6 ± 10.53	32.6 ± 8.38
Day 21 (n=46, 48, 44, 31, 34, 31)	36.07 ± 10.21	34.9 ± 8.96	36.6 ± 7.43	36.4 ± 9.61	35.5 ± 9.65	34.7 ± 11.09

No statistical analyses for this end point

Secondary: Change from Baseline in Respiratory Rate

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End point title

Change from Baseline in Respiratory Rate

End point description

Change from baseline in respiratory rate was derived based on the reported measurements of respiratory rate over time. The respiratory rate over time was reported by the investigator. The safety analysis set included all subjects who received at least 1 dose of study agent, and were analysed as treated, regardless of the randomised treatment group assigned. Here, 'n' (number analysed) represents number of subjects who were evaluable at specified timepoints.

End point type

Secondary

End point timeframe

Baseline to Days 3, 5, 8, 14 and 21

End point values	Cohort 1: Placebo	Cohort 1: JNJ-53718678 Low Dose	Cohort 1: JNJ-53718678 High Dose	Cohort 2: Placebo	Cohort 2: JNJ-53718678 Low Dose	Cohort 2: JNJ-53718678 High Dose
Number of subjects analysed	50	49	48	34	34	31
Units: Breaths/minute
arithmetic mean (standard deviation)
Day 3 (n=48, 48, 48, 33, 34, 31)	-0.8 ± 10.88	-3.5 ± 11.99	-3.0 ± 12.43	-3.7 ± 12.47	-4.0 ± 9.54	-2.6 ± 9.20
Day 5 (n=47, 45, 46, 33, 34, 31)	-6.5 ± 9.41	-7.1 ± 11.13	-7.0 ± 11.94	-3.4 ± 8.59	-3.3 ± 8.40	-1.5 ± 9.62
Day 8 (n=47,44, 46, 32, 34, 31)	-9.4 ± 9.19	-11.4 ± 12.96	-6.3 ± 12.69	-4.4 ± 11.56	-4.4 ± 10.39	-2.9 ± 10.54
Day 14 (n=47, 45, 46, 30, 32, 29)	-9.3 ± 9.96	-10.3 ± 12.59	-10.2 ± 10.92	-6.4 ± 3.13	-5.8 ± 12.82	-4.0 ± 9.92
Day 21 (n=46, 48, 44, 31, 34, 31)	-8.4 ± 10.84	-10.4 ± 13.01	-9.8 ± 12.36	-5.5 ± 14.15	-5.8 ± 11.95	-2.3 ± 13.25

No statistical analyses for this end point

Secondary: Heart Rate Over Time

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End point title

Heart Rate Over Time

End point description

Heart rate was measured by the investigator over time. The safety analysis set included all subjects who received at least 1 dose of study agent, and were analysed as treated, regardless of the randomised treatment group assigned. Here, 'n' (number analysed) represents number of subjects who were evaluable at specified timepoints.

End point type

Secondary

End point timeframe

Baseline, Days 3, 5, 8, 14, and 21

End point values	Cohort 1: Placebo	Cohort 1: JNJ-53718678 Low Dose	Cohort 1: JNJ-53718678 High Dose	Cohort 2: Placebo	Cohort 2: JNJ-53718678 Low Dose	Cohort 2: JNJ-53718678 High Dose
Number of subjects analysed	50	49	48	34	34	31
Units: Beats/minute
arithmetic mean (standard deviation)
Baseline (n=50,49,48,34, 34, 31)	143.2 ± 17.40	138.9 ± 17.57	139.0 ± 18.57	131.2 ± 24.28	135.6 ± 19.35	126.1 ± 22.55
Day 3 (n=48, 48, 48, 33, 34, 31)	138.8 ± 16.82	137.5 ± 18.25	138.5 ± 17.06	127.8 ± 20.99	128.3 ± 17.97	118.8 ± 28.10
Day 5 (n=47, 46, 47, 33, 34, 31)	136.0 ± 15.81	132.7 ± 18.28	136.1 ± 19.68	119.2 ± 14.75	122.6 ± 19.85	120.4 ± 23.31
Day 8 (n=48, 44, 46, 32, 34, 31)	133.3 ± 17.59	127.9 ± 18.13	134.0 ± 19.14	118.7 ± 20.25	120.0 ± 19.61	118.9 ± 27.04
Day 14 (n=47, 45, 46, 30, 32, 29)	131.7 ± 19.81	132.4 ± 19.33	134.4 ± 20.70	117.4 ± 18.17	118.0 ± 19.17	115.2 ± 18.82
Day 21 (n=46, 48, 44, 31, 34, 31)	128.2 ± 20.27	131.5 ± 15.74	132.5 ± 19.14	117.2 ± 22.56	125.3 ± 20.95	115.2 ± 19.78

No statistical analyses for this end point

Secondary: Change from Baseline in Heart Rate

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End point title

Change from Baseline in Heart Rate

End point description

Change from baseline in heart rate was derived based on the reported measurements of heart rate over time. The safety analysis set included all subjects who received at least 1 dose of study agent, and were analysed as treated, regardless of the randomised treatment group assigned. Here, 'n' (number analysed) represents number of subjects who were evaluable at specified timepoints.

End point type

Secondary

End point timeframe

Baseline to Days 3, 5, 8, 14, and 21

End point values	Cohort 1: Placebo	Cohort 1: JNJ-53718678 Low Dose	Cohort 1: JNJ-53718678 High Dose	Cohort 2: Placebo	Cohort 2: JNJ-53718678 Low Dose	Cohort 2: JNJ-53718678 High Dose
Number of subjects analysed	50	49	48	34	34	31
Units: Beats/minute
arithmetic mean (standard deviation)
Day 3 (n=48, 48, 48, 33, 34, 31)	-4.9 ± 19.36	-1.6 ± 19.82	-0.6 ± 18.84	-3.0 ± 24.71	-7.4 ± 16.83	-7.3 ± 28.39
Day 5 (n=47, 46, 47, 33, 34, 31)	-7.9 ± 20.31	-5.8 ± 22.94	-2.9 ± 20.56	-11.6 ± 18.55	-13.0 ± 17.11	-5.6 ± 28.53
Day 8 (n=48,44, 46, 32, 34, 31)	-10.4 ± 18.45	-12.2 ± 23.20	-5.2 ± 22.02	-12.7 ± 26.09	-15.6 ± 20.67	-7.2 ± 35.90
Day 14 (n=47, 45, 46, 30, 32, 29)	-12.0 ± 21.79	-6.5 ± 23.99	-5.1 ± 22.44	-14.4 ± 24.62	-17.7 ± 17.69	-10.1 ± 28.02
Day 21 (n=46, 48, 44, 31, 34, 31)	-15.0 ± 23.80	-7.7 ± 25.88	-6.5 ± 19.52	-14.0 ± 25.38	-10.4 ± 21.02	-10.9 ± 28.63

No statistical analyses for this end point

Secondary: Body Temperature Over Time

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End point title

Body Temperature Over Time

End point description

Body temperature was reported over time (either investigator or caregiver measured). The safety analysis set included all subjects who received at least 1 dose of study agent, and were analysed as treated, regardless of the randomised treatment group assigned. Here, 'n' (number analysed) represents number of subjects who were evaluable at specified timepoints.

End point type

Secondary

End point timeframe

Baseline, Days 3, 5, 8, 14 and 21

End point values	Cohort 1: Placebo	Cohort 1: JNJ-53718678 Low Dose	Cohort 1: JNJ-53718678 High Dose	Cohort 2: Placebo	Cohort 2: JNJ-53718678 Low Dose	Cohort 2: JNJ-53718678 High Dose
Number of subjects analysed	50	49	48	34	34	31
Units: Degree celsius
arithmetic mean (standard deviation)
Baseline (n=50, 49, 48, 34, 34, 31)	36.84 ± 0.635	36.64 ± 0.468	36.82 ± 0.623	36.84 ± 0.613	36.94 ± 0.845	36.79 ± 0.785
Day 3 (n=48, 48, 48, 33, 34, 31)	36.77 ± 0.464	36.87 ± 0.524	36.80 ± 0.601	37.14 ± 0.725	37.20 ± 0.694	36.98 ± 0.817
Day 5 (n=49, 48, 48, 33, 34, 31)	36.75 ± 0.407	36.54 ± 0.557	36.70 ± 0.408	36.87 ± 0.567	36.71 ± 0.348	36.84 ± 0.718
Day 8 (n=48, 47, 48, 33, 34, 31)	36.70 ± 0.416	36.73 ± 0.513	36.65 ± 0.441	36.67 ± 0.369	36.76 ± 0.536	36.74 ± 0.559
Day 14 (n=47, 45, 47, 33, 34, 31)	36.86 ± 0.315	36.68 ± 0.440	36.60 ± 0.396	36.63 ± 0.357	36.72 ± 0.364	36.59 ± 0.377
Day 21 (n=47, 48, 47, 33, 34, 31)	36.76 ± 0.577	36.67 ± 0.407	36.66 ± 0.573	36.74 ± 0.615	36.64 ± 0.292	36.62 ± 0.418

No statistical analyses for this end point

Secondary: Change from Baseline in Body Temperature

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End point title

Change from Baseline in Body Temperature

End point description

Change from baseline in body temperature was derived based on the reported measurements of body temperature over time (either investigator or caregiver measured). The safety analysis set included all subjects who received at least 1 dose of study agent, and were analysed as treated, regardless of the randomised treatment group assigned. Here, 'n' (number analysed) represents number of subjects who were evaluable at specified timepoints.

End point type

Secondary

End point timeframe

Baseline to Days 3, 5, 8, 14, and 21

End point values	Cohort 1: Placebo	Cohort 1: JNJ-53718678 Low Dose	Cohort 1: JNJ-53718678 High Dose	Cohort 2: Placebo	Cohort 2: JNJ-53718678 Low Dose	Cohort 2: JNJ-53718678 High Dose
Number of subjects analysed	50	49	48	34	34	31
Units: Degree celsius
arithmetic mean (standard deviation)
Day 3 (n=48, 48, 48, 33, 34, 30)	-0.08 ± 0.697	0.23 ± 0.541	-0.02 ± 0.629	0.33 ± 0.768	0.26 ± 0.835	0.21 ± 0.724
Day 5 (n=49, 48, 48, 33, 34, 30)	-0.10 ± 0.713	-0.09 ± 0.532	-0.12 ± 0.627	0.07 ± 0.700	-0.22 ± 0.767	-0.04 ± 0.627
Day 8 (n=48, 47, 48, 33, 34, 30)	-0.13 ± 0.659	0.10 ± 0.600	-0.17 ± 0.596	-0.13 ± 0.588	-0.17 ± 1.016	-0.11 ± 0.772
Day 14 (n=47, 45, 47, 33, 34, 30)	0.01 ± 0.594	0.04 ± 0.528	-0.21 ± 0.609	-0.17 ± 0.687	-0.21 ± 0.866	-0.19 ± 0.843
Day 21 (n=47, 48, 47, 33, 34, 30)	-0.09 ± 0.758	0.03 ± 0.519	-0.17 ± 0.724	-0.06 ± 0.704	-0.30 ± 0.826	-0.18 ± 0.913

No statistical analyses for this end point

Secondary: Peripheral Capillary Oxygen Saturation (SpO2) Over Time

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End point title

Peripheral Capillary Oxygen Saturation (SpO2) Over Time

End point description

Peripheral capillary oxygen saturation was measured by the investigator over time. The safety analysis set included all subjects who received at least 1 dose of study agent, and were analysed as treated, regardless of the randomised treatment group assigned. Here, 'n' (number analysed) represents number of subjects who were evaluable at specified timepoints.

End point type

Secondary

End point timeframe

Baseline, Days 3, 5, 8, 14 and 21

End point values	Cohort 1: Placebo	Cohort 1: JNJ-53718678 Low Dose	Cohort 1: JNJ-53718678 High Dose	Cohort 2: Placebo	Cohort 2: JNJ-53718678 Low Dose	Cohort 2: JNJ-53718678 High Dose
Number of subjects analysed	50	49	48	32	32	30
Units: Percentage of SpO2
arithmetic mean (standard deviation)
Baseline (n=50, 49, 48, 32, 32, 30)	97.3 ± 2.47	96.5 ± 3.44	96.6 ± 2.10	96.8 ± 2.07	96.7 ± 1.91	95.9 ± 2.92
Day 3 (n=47,48, 48, 31, 32, 29)	96.8 ± 2.46	96.3 ± 2.72	96.0 ± 2.43	96.9 ± 1.77	96.3 ± 3.12	96.5 ± 2.96
Day 5 (n=47,46, 47, 32, 32, 30)	97.3 ± 1.67	96.8 ± 3.74	96.7 ± 2.25	96.9 ± 1.68	97.1 ± 2.12	97.1 ± 2.43
Day 8 (n=46, 44, 46, 30, 32, 30)	97.3 ± 1.99	97.3 ± 2.47	97.5 ± 1.74	97.8 ± 1.48	97.4 ± 2.69	97.9 ± 1.83
Day 14 (n=44, 43, 45, 29, 29, 28)	98.1 ± 1.42	98.3 ± 1.84	98.1 ± 1.64	98.6 ± 2.03	98.6 ± 1.53	98.4 ± 1.73
Day 21 (n=45, 47, 43, 30, 32, 30)	98.4 ± 1.47	98.2 ± 1.80	98.0 ± 2.12	98.5 ± 1.74	98.7 ± 1.36	98.9 ± 1.25

No statistical analyses for this end point

Secondary: Change from Baseline in Peripheral Capillary Oxygen Saturation (SpO2)

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End point title

Change from Baseline in Peripheral Capillary Oxygen Saturation (SpO2)

End point description

Change from baseline in peripheral capillary oxygen saturation levels was derived based on reported values over time. The safety analysis set included all subjects who received at least 1 dose of study agent, and were analysed as treated, regardless of the randomised treatment group assigned. Here, 'n' (number analysed) represents number of subjects who were evaluable at specified timepoints.

End point type

Secondary

End point timeframe

Baseline to Days 3, 5, 8, 14, and 21

End point values	Cohort 1: Placebo	Cohort 1: JNJ-53718678 Low Dose	Cohort 1: JNJ-53718678 High Dose	Cohort 2: Placebo	Cohort 2: JNJ-53718678 Low Dose	Cohort 2: JNJ-53718678 High Dose
Number of subjects analysed	50	49	48	34	34	31
Units: Percentage of SpO2
arithmetic mean (standard deviation)
Day 3 (n=47, 48, 48, 31, 32, 29)	-0.5 ± 2.93	-0.2 ± 3.09	-0.6 ± 2.72	0.2 ± 2.31	-0.4 ± 2.45	0.7 ± 1.63
Day 5 (n=47, 46, 47, 31, 32, 30)	0.0 ± 2.92	0.4 ± 2.93	0.1 ± 2.38	0.1 ± 2.49	0.4 ± 2.41	1.2 ± 2.54
Day 8 (n=46, 44, 46, 30, 32, 30)	0.1 ± 3.02	0.9 ± 3.53	0.8 ± 2.47	0.9 ± 2.59	0.8 ± 2.86	2.0 ± 3.36
Day 14 (n=44, 43, 45, 29, 29, 28)	1.0 ± 2.28	1.7 ± 3.08	1.4 ± 2.32	2.0 ± 2.72	1.8 ± 2.05	2.6 ± 3.06
Day 21 (n=45, 47, 43, 29, 32, 30)	1.1 ± 2.45	1.7 ± 3.38	1.3 ± 2.40	1.8 ± 2.57	2.0 ± 2.12	3.0 ± 2.80

No statistical analyses for this end point

Secondary: Cohort 1: Time to Return to Age-adjusted Normal Values for Vital Signs

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End point title

Cohort 1: Time to Return to Age-adjusted Normal Values for Vital Signs ^[6]

End point description

Time to return to age-adjusted normal values from first dose of study drug based on the reported vital signs (respiratory rate, heart rate, SpO2 >=92%, and SpO2 >=95%) values was assessed. As per the study protocol and study design, this endpoint was planned to be analysed for subjects who were hospitalised only. Only subjects in Cohort 1 were hospitalised, hence this endpoint is only reported for Cohort 1. ITT-i analysis set included all randomised subjects who received at least one dose of study drug and who had centrally confirmed RSV RNA viral load of >=1 log10 copies/mL above the LLOQ of the RSV RT-qPCR assay at baseline. Analyses on ITT-i set were performed as randomised.

End point type

Secondary

End point timeframe

Up to Day 28

Notes
[6] - The end point is not reporting statistics for all the arms in the baseline period. It is expected all the baseline period arms will be reported on when providing values for an end point on the baseline period.
Justification: This endpoint was planned to be analysed for specified arms only.

End point values	Cohort 1: Placebo	Cohort 1: JNJ-53718678 Low Dose	Cohort 1: JNJ-53718678 High Dose
Number of subjects analysed	47	47	44
Units: Hours
median (confidence interval 95%)
Respiratory Rate (n=47, 47, 44)	13.6 (0.001 to 70.10)	20.0 (0.001 to 43.50)	30.2 (0.001 to 84.50)
Heart Rate (n=47, 47, 44)	37.3 (0.001 to 51.50)	17.0 (0.001 to 67.50)	10.2 (0.001 to 160.50)
SpO2 >=92% on Room Air (n=47, 47, 44)	65.4 (30.30 to 95.10)	86.6 (45.30 to 119.20)	68.9 (42.40 to 105.50)
SpO2 >=95% on Room Air (n=47, 47, 44)	71.3 (47.70 to 99.30)	87.0 (47.80 to 120.00)	92.5 (48.50 to 141.10)

No statistical analyses for this end point

Secondary: Percentage of Subjects who Require (re)Hospitalisation During Treatment and Follow-up

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End point title

Percentage of Subjects who Require (re)Hospitalisation During Treatment and Follow-up

End point description

Percentage of subjects who require (re)hospitalisation during treatment and follow-up was assessed. Percentage of subjects requiring re-hospitalisation following the initial hospital discharge was assessed in Cohort 1 subjects (hospitalised cohort) whilst percentage of subjects requiring hospitalisation after first dose of study drug was assessed in Cohort 2 subjects (outpatient cohort). ITT-i analysis set included all randomised subjects who received at least one dose of study drug and who had centrally confirmed RSV RNA viral load of >=1 log10 copies/mL above the LLOQ of the RSV RT-qPCR assay at baseline. Analyses on ITT-i set were performed as randomised.

End point type

Secondary

End point timeframe

Up to Day 28

End point values	Cohort 1: Placebo	Cohort 1: JNJ-53718678 Low Dose	Cohort 1: JNJ-53718678 High Dose	Cohort 2: Placebo	Cohort 2: JNJ-53718678 Low Dose	Cohort 2: JNJ-53718678 High Dose
Number of subjects analysed	47	47	44	32	33	28
Units: percentage of subjects
number (not applicable)	6.4	4.3	2.3	6.3	6.1	14.3

No statistical analyses for this end point

Secondary: Cohort 1: Time to Discharge From Hospital

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End point title

Cohort 1: Time to Discharge From Hospital ^[7]

End point description

Time to discharge from hospital was derived from the reported discharge date/time and from first dose date/time. As per the study protocol and study design, this endpoint was planned to be analysed for subjects who were hospitalised only. Only subjects in Cohort 1 were hospitalised, hence this endpoint is only reported for Cohort 1. ITT-i analysis set included all randomised subjects who received at least one dose of study drug and who had centrally confirmed RSV RNA viral load of >=1 log10 copies/mL above the LLOQ of the RSV RT-qPCR assay at baseline. Analyses on ITT-i set were performed as randomised.

End point type

Secondary

End point timeframe

Up to Day 28

Notes
[7] - The end point is not reporting statistics for all the arms in the baseline period. It is expected all the baseline period arms will be reported on when providing values for an end point on the baseline period.
Justification: This endpoint was planned to be analysed for specified arms only.

End point values	Cohort 1: Placebo	Cohort 1: JNJ-53718678 Low Dose	Cohort 1: JNJ-53718678 High Dose
Number of subjects analysed	47	47	44
Units: Hours
median (confidence interval 95%)	96.2 (88.80 to 118.00)	95.3 (67.20 to 140.30)	96.2 (72.10 to 144.90)

No statistical analyses for this end point

Secondary: Cohort 1: Percentage of Subjects who Required Admission to the Intensive Care Unit (ICU)

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End point title

Cohort 1: Percentage of Subjects who Required Admission to the Intensive Care Unit (ICU) ^[8]

End point description

Percentage of subjects who required admission to the ICU was assessed. This endpoint was applicable for those subjects that were not in ICU before first dose of study drug. As per the study protocol and study design, this endpoint was planned to be analysed for subjects who were hospitalised only. Only subjects in Cohort 1 were hospitalised, hence this endpoint is only reported for Cohort 1. ITT-i analysis set included all randomised subjects who received at least one dose of study drug and who had centrally confirmed RSV RNA viral load of >=1 log10 copies/mL above the LLOQ of the RSV RT-qPCR assay at baseline. Analyses on ITT-i set were performed as randomised. Here, 'N' (number of subjects analysed) signifies number of subjects who were evaluable for this endpoint.

End point type

Secondary

End point timeframe

Up to Day 21

Notes
[8] - The end point is not reporting statistics for all the arms in the baseline period. It is expected all the baseline period arms will be reported on when providing values for an end point on the baseline period.
Justification: This endpoint was planned to be analysed for specified arms only.

End point values	Cohort 1: Placebo	Cohort 1: JNJ-53718678 Low Dose	Cohort 1: JNJ-53718678 High Dose
Number of subjects analysed	42	44	39
Units: Percentage of subjects
number (not applicable)	2.4	4.5	2.6

No statistical analyses for this end point

Secondary: Cohort 1: Time to Clinical Stability Evaluated by the Investigator

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End point title

Cohort 1: Time to Clinical Stability Evaluated by the Investigator ^[9]

End point description

Time to clinical stability was derived based on vital signs (SpO2>=92%,SpO2>=95% on room air) assessments and supplementation end dates as collected. Time to clinical stability=time from initiation of study treatment until time at which following criteria were met:Time to return to age-adjusted normal value for otherwise healthy subject, pre-RSV infection status for subject with risk factor for severe RSV disease, no more oxygen supplementation in otherwise healthy subject, subject with risk factor for severe RSV disease and no more IV administered/nasogastric tube feeding/hydration supplementation in otherwise healthy subject or pre-RSV status of IV/nasogastric tube feeding/hydration in subject with risk factor for severe RSV disease. ITT-i:all randomised subjects who received at least one dose of study drug and who had centrally confirmed RSV RNA viral load of >=1 log10 copies/mL above the LLOQ of the RSV RT-qPCR assay at baseline.Analyses on ITT-i set were performed as randomised.

End point type

Secondary

End point timeframe

Up to Day 21

Notes
[9] - The end point is not reporting statistics for all the arms in the baseline period. It is expected all the baseline period arms will be reported on when providing values for an end point on the baseline period.
Justification: This endpoint was planned to be analysed for specified arms only.

End point values	Cohort 1: Placebo	Cohort 1: JNJ-53718678 Low Dose	Cohort 1: JNJ-53718678 High Dose
Number of subjects analysed	47	47	44
Units: Hours
median (confidence interval 95%)
SpO2 >=92% on Room Air(n=47,47,44)	95.8 (63.50 to 165.80)	123.3 (82.00 to 169.10)	176.5 (77.80 to 309.50)
SpO2 >=95% on Room Air(n=47,47,44)	95.8 (71.20 to 165.90)	134.8 (82.00 to 311.50)	180.5 (85.70 to 315.40)

No statistical analyses for this end point

Secondary: Cohort 1: Duration of ICU Stay

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End point title

Cohort 1: Duration of ICU Stay ^[10]

End point description

Duration of ICU stay was derived based on the reported admission/discharge date/times for ICU. Duration defined as total number of hours a subject was in ICU from first dose of study drug until study termination. As per the study protocol and study design, this endpoint was planned to be analysed for subjects who were hospitalised only. Only subjects in Cohort 1 were hospitalised, hence this endpoint is only reported for Cohort 1. ITT-i analysis set included all randomised subjects who were admitted to ICU and received at least one dose of study drug and who had centrally confirmed RSV RNA viral load of >=1 log10 copies/mL above the LLOQ of the RSV RT-qPCR assay at baseline. Analyses on ITT-i set were performed as randomised. Here, 'N' (number of subjects analysed) signifies number of subjects who were evaluable for this endpoint.

End point type

Secondary

End point timeframe

Up to Day 21

Notes
[10] - The end point is not reporting statistics for all the arms in the baseline period. It is expected all the baseline period arms will be reported on when providing values for an end point on the baseline period.
Justification: This endpoint was planned to be analysed for specified arms only.

End point values	Cohort 1: Placebo	Cohort 1: JNJ-53718678 Low Dose	Cohort 1: JNJ-53718678 High Dose
Number of subjects analysed	6	5	6
Units: Hours
arithmetic mean (standard deviation)	238.22 ± 70.570	206.94 ± 204.940	127.72 ± 89.389

No statistical analyses for this end point

Secondary: Cohort 1: Percentage of Subjects who Required Supplemental Oxygen

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End point title

Cohort 1: Percentage of Subjects who Required Supplemental Oxygen ^[11]

End point description

Percentage of subjects who required supplemental oxygen after first dose of study drug was reported. This parameter was only for subjects that did not require oxygen supplementation before first dose of study drug. As per the study protocol and study design, this endpoint was planned to be analysed for subjects who were hospitalised only. Only subjects in Cohort 1 were hospitalised, hence this endpoint was only reported for Cohort 1. ITT-i analysis set included all randomised subjects who received at least one dose of study drug and who had centrally confirmed RSV RNA viral load of >=1 log10 copies/mL above the LLOQ of the RSV RT-qPCR assay at baseline. Analyses on ITT-i set were performed as randomised. Here, 'N' (number of subjects analysed) signifies number of subjects who were evaluable for this endpoint.

End point type

Secondary

End point timeframe

Up to Day 21

Notes
[11] - The end point is not reporting statistics for all the arms in the baseline period. It is expected all the baseline period arms will be reported on when providing values for an end point on the baseline period.
Justification: This endpoint was planned to be analysed for specified arms only.

End point values	Cohort 1: Placebo	Cohort 1: JNJ-53718678 Low Dose	Cohort 1: JNJ-53718678 High Dose
Number of subjects analysed	14	12	7
Units: Percentage of subjects
number (not applicable)	21.4	25.0	28.6

No statistical analyses for this end point

Secondary: Cohort 1: Percentage of Subjects who Required Non-invasive Mechanical Ventilation Support

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End point title

Cohort 1: Percentage of Subjects who Required Non-invasive Mechanical Ventilation Support ^[12]

End point description

Percentage of subjects who required non-invasive mechanical ventilation support (example: continuous positive airway pressure) after first dose of study drug was assessed. This parameter was only for subjects who did not require non-invasive mechanical ventilation support before first dose of study drug. As per the study protocol and study design, this endpoint was planned to be analysed for subjects who were hospitalised only. Only subjects in Cohort 1 were hospitalised, hence this endpoint is only reported for Cohort 1. ITT-i analysis set included all randomised subjects who received at least one dose of study drug and who had centrally confirmed RSV RNA viral load of >=1 log10 copies/mL above the LLOQ of the RSV RT-qPCR assay at baseline. Analyses on ITT-i set were performed as randomised. Here, 'N' (number of subjects analysed) signifies number of subjects who were evaluable for this endpoint.

End point type

Secondary

End point timeframe

Up to Day 21

Notes
[12] - The end point is not reporting statistics for all the arms in the baseline period. It is expected all the baseline period arms will be reported on when providing values for an end point on the baseline period.
Justification: This endpoint was planned to be analysed for specified arms only.

End point values	Cohort 1: Placebo	Cohort 1: JNJ-53718678 Low Dose	Cohort 1: JNJ-53718678 High Dose
Number of subjects analysed	45	44	38
Units: Percentage of subjects
number (not applicable)	2.2	6.8	2.6

No statistical analyses for this end point

Secondary: Cohort 1: Duration of Supplemental Oxygen

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End point title

Cohort 1: Duration of Supplemental Oxygen ^[13]

End point description

Duration of supplemental oxygen was assessed. Duration was defined as total number of hours a subject used supplemental oxygen from first dose of study drug until study termination. As per the study protocol and study design, this endpoint was planned to be analysed for subjects who were hospitalised only. Only subjects in Cohort 1 were hospitalised, hence this endpoint was only reported for Cohort 1. ITT-i analysis set included all randomised subjects who received at least one dose of study drug and who had centrally confirmed RSV RNA viral load of >=1 log10 copies/mL above the LLOQ of the RSV RT-qPCR assay at baseline. Analyses on ITT-i set were performed as randomised. Here, 'N' (number of subjects analysed) signifies number of subjects who were evaluable for this endpoint.

End point type

Secondary

End point timeframe

Up to Day 28

Notes
[13] - The end point is not reporting statistics for all the arms in the baseline period. It is expected all the baseline period arms will be reported on when providing values for an end point on the baseline period.
Justification: This endpoint was planned to be analysed for specified arms only.

End point values	Cohort 1: Placebo	Cohort 1: JNJ-53718678 Low Dose	Cohort 1: JNJ-53718678 High Dose
Number of subjects analysed	34	38	38
Units: Hours
median (full range (min-max))	74.25 (1.0 to 337.3)	74.60 (0.2 to 573.5)	68.05 (1.2 to 348.5)

No statistical analyses for this end point

Secondary: Cohort 1: Duration of Non-invasive Ventilation Support

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End point title

Cohort 1: Duration of Non-invasive Ventilation Support ^[14]

End point description

As per the protocol study design, this endpoint was planned to be analysed for subjects who were hospitalised only. ITT-i set: all randomised subjects who received at least one dose of study drug and who had centrally confirmed RSV RNA viral load of >=1 log10 copies/mL above the LLOQ of the RSV RT-qPCR assay at baseline. Analyses on ITT-i set were performed as randomised. N (number of subjects analysed): subjects who were evaluable for this endpoint and n (number analysed): subjects who were evaluable at specified categories. 99999: For the subset of subjects who received non-invasive ventilation post dose, duration for non-invasive ventilation could not be derived by individual type as start/end dates and times were not collected in full to allow breakdown of duration derivation by ventilation type and only overall duration of oxygen supplementation (overall ventilation support) could be derived which is reported in the endpoint "Duration of Supplemental Oxygen".

End point type

Secondary

End point timeframe

Up to Day 21

Notes
[14] - The end point is not reporting statistics for all the arms in the baseline period. It is expected all the baseline period arms will be reported on when providing values for an end point on the baseline period.
Justification: This endpoint was planned to be analysed for specified arms only.

End point values	Cohort 1: Placebo	Cohort 1: JNJ-53718678 Low Dose	Cohort 1: JNJ-53718678 High Dose
Number of subjects analysed	47	47	44
Units: Hours
median (full range (min-max))	99999 (-99999 to 99999)	99999 (-99999 to 99999)	99999 (-99999 to 99999)

No statistical analyses for this end point

Secondary: Cohort 1: Percentage of Subjects who Required Invasive Mechanical Ventilation Support

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End point title

Cohort 1: Percentage of Subjects who Required Invasive Mechanical Ventilation Support ^[15]

End point description

Percentage of subjects who required invasive mechanical ventilation support (example: endotracheal-mechanical ventilation) after first dose of study drug was assessed. This parameter was only for subjects who did not require invasive mechanical ventilation support before first dose of study drug. As per the study protocol and study design, this endpoint was planned to be analysed for subjects who were hospitalised only. Only subjects in Cohort 1 were hospitalised, hence this endpoint is only reported for Cohort 1. ITT-i analysis set included all randomised subjects who received at least one dose of study drug and who had centrally confirmed RSV RNA viral load of >=1 log10 copies/mL above the LLOQ of the RSV RT-qPCR assay at baseline. Analyses on ITT-i set were performed as randomised.

End point type

Secondary

End point timeframe

Up to Day 21

Notes
[15] - The end point is not reporting statistics for all the arms in the baseline period. It is expected all the baseline period arms will be reported on when providing values for an end point on the baseline period.
Justification: This endpoint was planned to be analysed for specified arms only.

End point values	Cohort 1: Placebo	Cohort 1: JNJ-53718678 Low Dose	Cohort 1: JNJ-53718678 High Dose
Number of subjects analysed	47	47	44
Units: Percentage of subjects
number (not applicable)	4.3	2.1	2.3

No statistical analyses for this end point

Secondary: Cohort 1: Percentage of Subjects who Required Non-invasive Non-mechanical Ventilation Support

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End point title

Cohort 1: Percentage of Subjects who Required Non-invasive Non-mechanical Ventilation Support ^[16]

End point description

Percentage of subjects who required non-invasive non-mechanical ventilation support (example: nasal cannula) after first dose of study drug was assessed. This parameter was only for subjects who did not require non-invasive non-mechanical ventilation support before first dose of study drug. As per the study protocol and study design, this endpoint was planned to be analysed for subjects who were hospitalised only. Only subjects in Cohort 1 were hospitalised, hence this endpoint is only reported for Cohort 1. ITT-i analysis set included all randomised subjects who received at least one dose of study drug and who had centrally confirmed RSV RNA viral load of >=1 log10 copies/mL above the LLOQ of the RSV RT-qPCR assay at baseline. Analyses on ITT-i set were performed as randomised. Here, 'N' (number of subjects analysed) signifies number of subjects who were evaluable for this endpoint.

End point type

Secondary

End point timeframe

Up to Day 21

Notes
[16] - The end point is not reporting statistics for all the arms in the baseline period. It is expected all the baseline period arms will be reported on when providing values for an end point on the baseline period.
Justification: This endpoint was planned to be analysed for specified arms only.

End point values	Cohort 1: Placebo	Cohort 1: JNJ-53718678 Low Dose	Cohort 1: JNJ-53718678 High Dose
Number of subjects analysed	16	14	11
Units: Percentage of subjects
number (not applicable)	31.3	35.7	45.5

No statistical analyses for this end point

Secondary: Cohort 1: Percentage of Subjects who Needed Hydration and/or Feeding by Intravenous (IV) Administration or Nasogastric Tube

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End point title

Cohort 1: Percentage of Subjects who Needed Hydration and/or Feeding by Intravenous (IV) Administration or Nasogastric Tube ^[17]

End point description

Percentage of subjects who needed hydration and/or feeding by IV Administration or nasogastric tube after the first dose of study drug was assessed. This parameter was only for subjects who didnot require supplemental feeding/hydration before first dose of study drug. As per the planned analysis, this endpoint was analysed for subjects who were hospitalised only. Only subjects in Cohort 1 were hospitalised, hence this endpoint is only reported for Cohort 1. ITT-i analysis set included all randomised subjects who received at least one dose of study drug and who had centrally confirmed RSV RNA viral load of >=1 log10 copies/mL above the LLOQ of the RSV RT-qPCR assay at baseline. Analyses on ITT-i set were performed as randomised. Here, 'N' (number of subjects analysed) signifies number of subjects who were evaluable for this endpoint.

End point type

Secondary

End point timeframe

Up to Day 28

Notes
[17] - The end point is not reporting statistics for all the arms in the baseline period. It is expected all the baseline period arms will be reported on when providing values for an end point on the baseline period.
Justification: This endpoint was planned to be analysed for specified arms only.

End point values	Cohort 1: Placebo	Cohort 1: JNJ-53718678 Low Dose	Cohort 1: JNJ-53718678 High Dose
Number of subjects analysed	32	32	26
Units: percentage of subjects
number (not applicable)	6.3	15.6	19.2

No statistical analyses for this end point

Secondary: Cohort 1: Time to End of Supplemental Oxygen up to 72 Hours From First Hospital Discharge

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End point title

Cohort 1: Time to End of Supplemental Oxygen up to 72 Hours From First Hospital Discharge ^[18]

End point description

Time to end of supplemental oxygen up to 72 hours from first hospital discharge was assessed. Time to end of supplemental oxygen was defined as time (hours) from first dose of study drug to last end date/time of any oxygen supplementation received, but within 72 hours following first hospital discharge. As per the study planned analysis, this endpoint was analysed for subjects who were hospitalised only. Only subjects in Cohort 1 were hospitalised, hence this endpoint is only reported for Cohort 1. ITT-i analysis set included all randomised subjects who received at least one dose of study drug and who had centrally confirmed RSV RNA viral load of >=1 log10 copies/mL above the LLOQ of the RSV RT-qPCR assay at baseline. Analyses on ITT-i set were performed as randomised.

End point type

Secondary

End point timeframe

Up to end of supplemental oxygen including supplemental oxygen within 72 hours after first hospital discharge (up to Day 28)

Notes
[18] - The end point is not reporting statistics for all the arms in the baseline period. It is expected all the baseline period arms will be reported on when providing values for an end point on the baseline period.
Justification: This endpoint was planned to be analysed for specified arms only.

End point values	Cohort 1: Placebo	Cohort 1: JNJ-53718678 Low Dose	Cohort 1: JNJ-53718678 High Dose
Number of subjects analysed	47	47	44
Units: Hours
median (confidence interval 95%)	58.1 (22.90 to 75.90)	57.9 (35.30 to 85.50)	63.0 (31.80 to 92.00)

No statistical analyses for this end point

Secondary: Cohort 1: Duration of Invasive Ventilation Support

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End point title

Cohort 1: Duration of Invasive Ventilation Support ^[19]

End point description

As per the study protocol and study design, this endpoint was planned to be analysed for subjects who were hospitalised only. Only subjects in Cohort 1 were hospitalised, hence this endpoint could only have been reported for Cohort 1. ITT-i analysis set included all randomised subjects who received at least one dose of study drug and who had centrally confirmed RSV RNA viral load of >=1 log10 copies/mL above LLOQ of RSV RT-qPCR assay at baseline. Analyses on ITT-i set were performed as randomised. 99999: For the subset of subjects who received invasive ventilation post dose, duration for invasive ventilation could not be derived by individual type as start/end dates and times were not collected in full to allow breakdown of duration derivation by ventilation type and only overall duration of oxygen supplementation (overall ventilation support) could be derived which is reported in the endpoint "Duration of Supplemental Oxygen".

End point type

Secondary

End point timeframe

Up to Day 21

Notes
[19] - The end point is not reporting statistics for all the arms in the baseline period. It is expected all the baseline period arms will be reported on when providing values for an end point on the baseline period.
Justification: This endpoint was planned to be analysed for specified arms only.

End point values	Cohort 1: Placebo	Cohort 1: JNJ-53718678 Low Dose	Cohort 1: JNJ-53718678 High Dose
Number of subjects analysed	47	47	44
Units: Hours
median (full range (min-max))	99999 (-99999 to 99999)	99999 (-99999 to 99999)	99999 (-99999 to 99999)

No statistical analyses for this end point

Secondary: Percentage of Subjects with Abnormal Laboratory Findings

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End point title

Percentage of Subjects with Abnormal Laboratory Findings

End point description

Percentage of subjects with abnormal laboratory findings (chemistry [CH] and hematology [H]) worst toxicity grade was assessed based on Division of Microbiology and Infectious Diseases (DMID) toxicity grading scale which ranges from 1 to 4. Grade 1=mild:transient or mild discomfort (<48 hours); no medical therapy required. Grade 2=moderate:mild to moderate limitation in activity-some assistance may be needed; no or minimal medical therapy required. Grade 3=severe: marked limitation in activity, some assistance usually required; medical therapy required, hospitalisations possible. Grade 4=life-threatening or death: Extreme limitation in activity, significant assistance required; significant medical therapy required, hospitalisation or hospice care probable. Safety set:all subjects who received at least 1 dose of study agent and were analysed as treated, regardless of the randomised treatment group assigned. Here, n (number analysed): subjects evaluable for the specified categories.

End point type

Secondary

End point timeframe

Up to Day 28

End point values	Cohort 1: Placebo	Cohort 1: JNJ-53718678 Low Dose	Cohort 1: JNJ-53718678 High Dose	Cohort 2: Placebo	Cohort 2: JNJ-53718678 Low Dose	Cohort 2: JNJ-53718678 High Dose
Number of subjects analysed	50	49	48	34	34	31
Units: percentage of subjects
number (not applicable)
CH: ALT:G1 (n=22,27,22,32,28,29)	13.6	0	0	0	3.6	3.4
CH: ALT: G 2 (n=22,27,22,32,28,29)	0	0	4.5	0	0	0
CH: ALT: G3 (n=22,27,22,32,28,29)	4.5	0	0	0	0	0
CH: AST: G1(n=22,25,22,31,29,30)	0	0	4.5	0	0	3.3
CH: AST:G3(n=22,25,22,31,29,30)	4.5	0	0	0	0	0
CH:Hyperbilirubinemia:G2(n=37,37,34,34,34,31)	2.7	0	0	0	0	0
CH:Hyperglycemia:G1(n=22,26,23,32,29,30)	13.6	0	4.3	6.3	3.4	10.0
CH:Hyperkalemia:G1(n=22,27,23,32,29,30)	59.1	22.2	39.1	21.9	55.2	36.7
CH:Hyperkalemia:G2(n=22,27,23,32,29,30)	0	0	4.3	3.1	3.4	3.3
CH:Hyperkalemia:G4(n=22, 27,23,32, 29,30)	0	0	8.7	0	0	0
CH:Hypernatremia:G2(n=22, 27,23,32,29,30)	4.5	3.7	0	3.1	3.4	3.3
CH:Hypernatremia:G3(n=22, 27,23,32,29, 30)	4.5	0	0	0	0	0
CH:Hyperuricemia:G1(n=22,27,23,34,34,31)	0	0	4.3	0	0	0
CH:Hypoglycemia:G1(n=22,26,23,32,29,30)	4.5	0	4.3	6.3	3.4	0
CH:H.Mg:G1(n=22,27,23,32,29,30)	0	3.7	4.3	3.1	0	0
CH:H.Mg:G2(n=22,27,23,32,29,30)	0	0	4.3	0	0	0
CH:H.Mg:G3(n=22,27,23,32,29,30)	0	0	4.3	0	0	0
CH:Hyponatremia:G2(n=22, 27,23,32,29,30)	4.5	3.7	0	0	0	10.0
H:ANC: G1(n=37,35,36,33,33,28)	13.5	11.4	2.8	3.0	9.1	0
H:ANC:G3 (n=37,35,36,33,33,28)	0	2.9	0	0	0	0
H: APTT: Grade 1(n=9,10,15,1,3,3)	11.1	0	0	0	0	33.3
H:Hemoglobin: G1(n=38,36,35,34,34,31)	7.9	5.6	2.9	0	0	0
H:Hemoglobin:G2(n=38,36,35,34,34,31)	2.6	2.8	0	0	0	0
H:Prothrombin Time:G1(n=9,10,15,34,34,31)	0	10.0	0	0	0	0
H:Prothrombin Time:G3(n=9,10,15,34,34,31)	11.1	0	6.7	0	0	0
C:Hyperglycemia:G2(n=22, 26, 23,32,29,30)	0	0	0	0	0	3.3

No statistical analyses for this end point

Secondary: Percentage of Subjects with Adverse Events

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End point title

Percentage of Subjects with Adverse Events

End point description

Percentage of subjects with adverse events was assessed. An AE is any untoward medical occurrence in clinical study subjects administered a medicinal (investigational or non-investigational) product. An adverse event does not necessarily have a causal relationship with the intervention. The safety analysis set included all subjects who received at least 1 dose of study agent, and were analysed as treated, regardless of the randomised treatment group assigned.

End point type

Secondary

End point timeframe

Up to Day 28

End point values	Cohort 1: Placebo	Cohort 1: JNJ-53718678 Low Dose	Cohort 1: JNJ-53718678 High Dose	Cohort 2: Placebo	Cohort 2: JNJ-53718678 Low Dose	Cohort 2: JNJ-53718678 High Dose
Number of subjects analysed	50	49	48	34	34	31
Units: Percentage of subjects
number (not applicable)	58.0	59.2	64.6	47.1	58.8	41.9

No statistical analyses for this end point

Secondary: Percentage of Subjects With Abnormal Electrocardiograms (ECGs) Findings

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End point title

Percentage of Subjects With Abnormal Electrocardiograms (ECGs) Findings

End point description

Percentage of subjects with abnormal ECG (PR interval; QRS interval; QT interval; RR interval) findings were assessed. The safety analysis set included all subjects who received at least 1 dose of study agent, and were analysed as treated, regardless of the randomised treatment group assigned. Here, 'n' (number analysed) represents number of subjects who were evaluable for specified categories (per ECG parameters).

End point type

Secondary

End point timeframe

Up to Day 28

End point values	Cohort 1: Placebo	Cohort 1: JNJ-53718678 Low Dose	Cohort 1: JNJ-53718678 High Dose	Cohort 2: Placebo	Cohort 2: JNJ-53718678 Low Dose	Cohort 2: JNJ-53718678 High Dose
Number of subjects analysed	50	49	48	34	34	31
Units: percentage of subjects
number (not applicable)
QRS Duration: Abnormally High(n=49,48,48,33,33,31)	4.1	4.2	4.2	6.1	6.1	9.7
RR Interval: Abnormally Low(n=49,48,48,33,33,31)	12.2	8.3	12.5	21.2	15.2	9.7
PR Interval: Abnormally Low(n=49,48,48,33,33,31)	0	2.1	2.1	0	3.0	0
QT Interval: Abnormally Low(n=49,48,48,33,33,31)	2.0	4.2	2.1	3.0	9.1	3.2

No statistical analyses for this end point

Secondary: Percentage of Subjects with Categorized Change from Baseline in ECG Parameters (QT, QTcB, QTcF)

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End point title

Percentage of Subjects with Categorized Change from Baseline in ECG Parameters (QT, QTcB, QTcF)

End point description

Percentage of subjects with categorized change from baseline in ECG parameters (QT/ QTcB/ QTcF interval) was assessed. Abnormal ECG change from baseline in QT, QTcB, and QTcF interval is categorized as borderline QT/QTc change: 30 ms (milliseconds) to <60 ms, and abnormally high QT/QTc change: greater than [>] 60 ms). The safety analysis set included all subjects who received at least 1 dose of study agent, and were analysed as treated, regardless of the randomised treatment group assigned. Here, 'n' (number analysed) represents number of subjects who were evaluable per ECG parameter.

End point type

Secondary

End point timeframe

Baseline to Day 28

End point values	Cohort 1: Placebo	Cohort 1: JNJ-53718678 Low Dose	Cohort 1: JNJ-53718678 High Dose	Cohort 2: Placebo	Cohort 2: JNJ-53718678 Low Dose	Cohort 2: JNJ-53718678 High Dose
Number of subjects analysed	50	49	48	34	34	31
Units: Percentage of subjects
number (not applicable)
QT Interval:Normal QT change(n=48,48,48,33,33,29)	66.7	70.8	68.8	66.7	57.6	58.6
QT Interval:Borderline QT (n=48,48,48,33,33,29)	29.2	25.0	27.1	27.3	33.3	37.9
QT Interval:AbnormallyhighQT(n=48,48,48,33,33,29)	4.2	4.2	4.2	6.1	9.1	3.4
QTcB Interval:Normal QTc(n=48,48,48,33,33,29)	83.8	87.5	93.8	90.9	90.9	93.1
QTcB Interval:Borderline QTc(n=48,48,48,33,33,29)	14.6	12.5	6.3	9.1	9.1	6.9
QTcB: Abnormally high QTc(n=48,48,48,33,33,29)	2.1	0	0	0	0	0
QTcF Interval:Normal QTc(n=48,48,48,33,33,29)	81.3	83.3	83.3	90.9	78.8	86.3
QTcF Interval:Borderline QTc(n=48,48,48,33,33,29)	16.7	16.7	16.7	9.1	21.2	13.8
QTcF: Abnormally high QTc(n=48,48,48,33,33,29)	2.1	0	0	0	0	0

No statistical analyses for this end point

Secondary: Percentage of Subjects With Vital Signs Abnormalities

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End point title

Percentage of Subjects With Vital Signs Abnormalities

End point description

Percentage of subjects with vital signs (SBP,DBP,pulse rate,respiratory rate,body temperature,andSpO2) abnormalities (abnormally low [ABL] and abnormally high [ABH]) were reported. Safety analysis set: all subjects who received at least 1 dose of study agent, and were analysed as treated, regardless of the randomised treatment group assigned. Here, n (number analysed) represents number of subjects evaluable per vital signs parameter. As per change in planned analysis, the upper limit for the last age group was 3.5 years instead of 3 years.

End point type

Secondary

End point timeframe

Up to Day 28

End point values	Cohort 1: Placebo	Cohort 1: JNJ-53718678 Low Dose	Cohort 1: JNJ-53718678 High Dose	Cohort 2: Placebo	Cohort 2: JNJ-53718678 Low Dose	Cohort 2: JNJ-53718678 High Dose
Number of subjects analysed	50	49	48	34	34	31
Units: percentage of subjects
number (not applicable)
SBP:ABL(n=49,48,48,33,34,31)	2.0	2.1	8.3	12.1	8.8	9.7
SBP:ABH(n=49,48,48,33,34,31)	42.9	45.8	35.4	18.2	17.6	12.9
DBP:ABL(n=49,48,48,33,34,31)	8.2	18.8	25.0	15.2	2.9	0
DBP:ABH(n=49,48,48,33,34,31)	28.6	35.4	27.1	9.1	17.6	6.5
Pulse rate:ABH(n=49,48,48,33,34,31)	30.6	27.1	27.1	12.1	20.6	16.1
Pulse rate:ABL(n=49,48,48,33,34,31)	0.0	2.1	0	6.1	5.9	16.1
RR:ABH(n=49,48,48,34,34,31)	4.1	12.5	18.8	3.1	2.9	6.5
RR:ABL(n=49,48,48,34,34,31)	12.2	10.4	0.0	0	0	0
Temperature: ABH(n=50,49,48,34,34,31)	30.6	41.7	22.9	50.0	52.9	54.8
SpO2:ABL(n=50,49,48,32,32,30)	8.2	12.5	6.3	3.1	9.4	0

No statistical analyses for this end point

Secondary: Cohort 1: Area Under the Plasma Concentration-Time Curve From Timepoint 0 Hours Until 24 Hours Post Dose (AUC[0-24 Hours])

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End point title

Cohort 1: Area Under the Plasma Concentration-Time Curve From Timepoint 0 Hours Until 24 Hours Post Dose (AUC[0-24 Hours]) ^[20]

End point description

AUC (0-24) was defined as area under the plasma concentration-time curve from timepoint 0 hours until 24 hours post dose estimated by population pharmacokinetic (PK) model. PK analysis set included all subjects from Cohort 1 who received JNJ-53718678 and for whom at least one PK concentration was reported. Here, 'n' (number analysed) represents number of subjects who were evaluable for specified timepoints.

End point type

Secondary

End point timeframe

0 to 24 hours post dose on Days 1 and 7

Notes
[20] - The end point is not reporting statistics for all the arms in the baseline period. It is expected all the baseline period arms will be reported on when providing values for an end point on the baseline period.
Justification: This endpoint was planned to be analysed for specified arms only.

End point values	Cohort 1: JNJ-53718678 Low Dose	Cohort 1: JNJ-53718678 High Dose
Number of subjects analysed	30	32
Units: nanogramshours per millilitre (ngh/mL)
arithmetic mean (standard deviation)
>=28 days and <3 months: Day 1 (n=6,7)	6690 ± 1950	20600 ± 3990
>=28 days and <3 months: Day 7 (n=6,7)	11400 ± 3930	36000 ± 8140
>=3 months and <6 months: Day 1 (n=6,4)	5340 ± 2670	23600 ± 12500
>=3 months and <6 months: Day 7 (n=6,4)	7370 ± 4270	35000 ± 20100
>=6 months and <=3 years: Day 1 (n=11,17)	6910 ± 2900	25000 ± 11600
>=6 months and <=3 years: Day 7 (n=11,17)	8160 ± 3950	31000 ± 16300

No statistical analyses for this end point

Secondary: Cohort 1: Maximum Plasma Concentration (Cmax) of JNJ-53718678

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End point title

Cohort 1: Maximum Plasma Concentration (Cmax) of JNJ-53718678 ^[21]

End point description

Cmax is the maximum plasma concentration of JNJ-53718678 estimated by population PK model. PK analysis set included all subjects from Cohort 1 who received JNJ-53718678 and for whom at least one PK concentration was reported. Here, 'n' (number analysed) represents number of subjects who were evaluable for specified timepoints.

End point type

Secondary

End point timeframe

Days 1 and 7

Notes
[21] - The end point is not reporting statistics for all the arms in the baseline period. It is expected all the baseline period arms will be reported on when providing values for an end point on the baseline period.
Justification: This endpoint was planned to be analysed for specified arms only.

End point values	Cohort 1: JNJ-53718678 Low Dose	Cohort 1: JNJ-53718678 High Dose
Number of subjects analysed	30	32
Units: nanograms per millilitre (ng/mL)
arithmetic mean (standard deviation)
>=28 days and <3 months: Day 1 (n=6, 7)	531 ± 193	1590 ± 345
>=28 days and <3 months: Day 7 (n=6, 7)	843 ± 255	2550 ± 550
>=3 months and <6 months: Day 1 (n=6, 4)	497 ± 256	2070 ± 1200
>=3 months and <6 months: Day 7 (n=6, 4)	691 ± 306	2920 ± 1500
>=6 months and <=3 years: Day 1 (n=12, 18)	846 ± 268	2720 ± 1040
>=6 months and <=3 years: Day 7 (n=11, 17)	1030 ± 310	3560 ± 1330

No statistical analyses for this end point

Secondary: Cohort 1: Trough Plasma Concentration (Ctrough) of JNJ-53718678

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End point title

Cohort 1: Trough Plasma Concentration (Ctrough) of JNJ-53718678 ^[22]

End point description

Ctrough is the trough plasma concentration of JNJ-53718678 estimated by population PK model. PK analysis set included all subjects from Cohort 1 who received JNJ-53718678 and for whom at least one PK concentration was reported. Here, 'n' (number analysed) represents number of subjects who were evaluable for specified timepoints.

End point type

Secondary

End point timeframe

Days 1 and 7

Notes
[22] - The end point is not reporting statistics for all the arms in the baseline period. It is expected all the baseline period arms will be reported on when providing values for an end point on the baseline period.
Justification: This endpoint was planned to be analysed for specified arms only.

End point values	Cohort 1: JNJ-53718678 Low Dose	Cohort 1: JNJ-53718678 High Dose
Number of subjects analysed	30	32
Units: ng/mL
arithmetic mean (standard deviation)
>=28 days and <3 months: Day 1 (n=6, 7)	64 ± 31.3	167 ± 147
>=28 days and <3 months: Day 7 (n=6, 7)	267 ± 111	885 ± 239
>=3 months and <6 months: Day 1 (n=6, 4)	55.5 ± 33.5	204 ± 58.5
>=3 months and <6 months: Day 7 (n=6, 4)	126 ± 103	702 ± 487
>=6 months and <=3 years: Day 1 (n=11, 17)	59.9 ± 43	227 ± 149
>=6 months and <=3 years: Day 7 (n=11, 17)	89 ± 73.6	386 ± 331

No statistical analyses for this end point

Secondary: Percentage of Subjects With Medical Resource Utilization (MRU)

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End point title

Percentage of Subjects With Medical Resource Utilization (MRU)

End point description

Percentage of subjects with MRU (any medical care encounters) was reported. ITT-i analysis set included all randomised subjects who received at least one dose of study drug and who had centrally confirmed RSV RNA viral load of >=1 log10 copies/mL above the LLOQ of the RSV RT-qPCR assay at baseline. Analyses on ITT-i set were performed as randomised.

End point type

Secondary

End point timeframe

Up to Day 28

End point values	Cohort 1: Placebo	Cohort 1: JNJ-53718678 Low Dose	Cohort 1: JNJ-53718678 High Dose	Cohort 2: Placebo	Cohort 2: JNJ-53718678 Low Dose	Cohort 2: JNJ-53718678 High Dose
Number of subjects analysed	47	47	44	32	33	28
Units: percentage of subjects
number (not applicable)	100.0	100.0	100.0	9.4	15.2	25.0

No statistical analyses for this end point

Secondary: Cohort 2: Plasma Concentration of JNJ-53718678

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End point title

Cohort 2: Plasma Concentration of JNJ-53718678 ^[23]

End point description

Plasma concentration of JNJ-53718678 was measured for Cohort 2. As per planned analysis in the protocol, PK sampling was performed on either Day 3 or Day 5 for subjects receiving twice daily dosing, resulting in one combined timepoint of Day 3 or Day 5. Hence, the data collected on either Day 3 or Day 5 was pooled and is reported here collectively. PK analysis set included all subjects from Cohort 2 who received JNJ-53718678 and for whom at least one PK concentration was reported. Here, 'n' (number analyzed) represents number of subjects who were evaluable at specified timepoints.

End point type

Secondary

End point timeframe

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

Notes
[23] - The end point is not reporting statistics for all the arms in the baseline period. It is expected all the baseline period arms will be reported on when providing values for an end point on the baseline period.
Justification: This endpoint was planned to be analysed for specified arms only.

End point values	Cohort 2: JNJ-53718678 Low Dose	Cohort 2: JNJ-53718678 High Dose
Number of subjects analysed	33	30
Units: ng/mL
arithmetic mean (standard deviation)
Day 3 (Once daily) (n=22,21)	392.97 ± 638.253	931.66 ± 1757.958
Day 8 (Once daily) (n=22,20)	59.05 ± 84.552	364.73 ± 951.896
Day 1 (Twice daily) (n=10,7)	394.58 ± 297.539	1539.43 ± 602.591
Day 3 or Day 5 (Twice daily) (n=10,9)	441.13 ± 305.450	1050.44 ± 663.166

No statistical analyses for this end point

Secondary: Number of Subjects with Emerging Variations in the Viral Genome Potentially Associated with Resistance to JNJ-53718678

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End point title

Number of Subjects with Emerging Variations in the Viral Genome Potentially Associated with Resistance to JNJ-53718678

End point description

Number of subjects with emerging variations in the viral genome potentially associated with resistance to JNJ-53718678 was reported. Number of subjects with F gene sequencing data available and with emerging genetic variations post-baseline as compared to baseline, considering 24 RSV F protein positions of interest (positions 127, 137, 138, 140, 141, 143, 144, 323, 338, 339, 392, 394, 396, 397, 398, 399, 400, 401, 474, 486, 487, 488, 489, and 517) was reported. ITT-i analysis set included all randomised subjects who received at least one dose of study drug and who had centrally confirmed RSV RNA viral load of >=1 log10 copies/mL above the LLOQ of the RSV RT-qPCR assay at baseline. Analyses on ITT-i set were performed as randomised. Here, ‘N’ (number of subjects analysed) signifies number of subjects who were evaluable for this endpoint.

End point type

Secondary

End point timeframe

Up to Day 21

End point values	Cohort 1: Placebo	Cohort 1: JNJ-53718678 Low Dose	Cohort 1: JNJ-53718678 High Dose	Cohort 2: Placebo	Cohort 2: JNJ-53718678 Low Dose	Cohort 2: JNJ-53718678 High Dose
Number of subjects analysed	44	43	40	32	29	28
Units: Subjects	0	0	2	0	0	2

No statistical analyses for this end point

Secondary: Percentage of Subjects with Acceptability and Palatability of the JNJ-53718678 Formulation as Assessed by Parent(s)/Caregiver(s)

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End point title

Percentage of Subjects with Acceptability and Palatability of the JNJ-53718678 Formulation as Assessed by Parent(s)/Caregiver(s)

End point description

Percentage of subjects with acceptability and palatability of the JNJ-53718678 formulation was assessed through a questionnaire asking about the child's reaction when given the medicine, completed by parent(s)/caregiver(s) after last dosing that categorized as 1) child took medicine easily, 2) disgusted expressions after tasting medicine, 3) cried after tasting medicine, 4) would not open mouth or turned head away to avoid medicine, 5) spit out or coughed out medicine, 6) gagged, and 7) vomited (within 2 minutes of swallowing medicine). Below results are based on response to "child took medicine easily". ITT-i analysis set included all randomised subjects who received at least one dose of study drug and who had centrally confirmed RSV RNA viral load of >=1 log10 copies/mL above the LLOQ of the RSV RT-qPCR assay at baseline. Analyses on ITT-i set were performed as randomised. Here, 'N' (number of subjects analysed) signifies number of subjects who were evaluable for this endpoint.

End point type

Secondary

End point timeframe

Day 8

End point values	Cohort 1: Placebo	Cohort 1: JNJ-53718678 Low Dose	Cohort 1: JNJ-53718678 High Dose	Cohort 2: Placebo	Cohort 2: JNJ-53718678 Low Dose	Cohort 2: JNJ-53718678 High Dose
Number of subjects analysed	34	32	37	24	21	21
Units: percentage of subjects
number (not applicable)	67.6	84.4	73.0	70.8	90.5	85.7

No statistical analyses for this end point

Adverse events

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Timeframe for reporting adverse events

Up to Day 28

Adverse event reporting additional description

The safety analysis set included all subjects who received at least 1 dose of study agent, and were analysed as treated, regardless of the randomised treatment group assigned.

Assessment type

Non-systematic

Dictionary name

MedDRA

Dictionary version

23.124.1

Reporting group title

Cohort 1: Placebo

Reporting group description

Reporting group title

Cohort 2: JNJ-53718678 High Dose

Reporting group description

Reporting group title

Cohort 2: Placebo

Reporting group description

Reporting group title

Cohort 2: JNJ-53718678 Low Dose

Reporting group description

Reporting group title

Cohort 1: JNJ-53718678 Low Dose

Reporting group description

Reporting group title

Cohort 1: JNJ-53718678 High Dose

Reporting group description

Serious adverse events	Cohort 1: Placebo	Cohort 2: JNJ-53718678 High Dose	Cohort 2: Placebo	Cohort 2: JNJ-53718678 Low Dose	Cohort 1: JNJ-53718678 Low Dose	Cohort 1: JNJ-53718678 High Dose
Total subjects affected by serious adverse events
subjects affected / exposed	4 / 50 (8.00%)	3 / 31 (9.68%)	2 / 34 (5.88%)	2 / 34 (5.88%)	5 / 49 (10.20%)	2 / 48 (4.17%)
number of deaths (all causes)	0	0	0	0	0	0
number of deaths resulting from adverse events
Respiratory, thoracic and mediastinal disorders
Acute Respiratory Failure
subjects affected / exposed	0 / 50 (0.00%)	0 / 31 (0.00%)	0 / 34 (0.00%)	0 / 34 (0.00%)	1 / 49 (2.04%)	0 / 48 (0.00%)
occurrences causally related to treatment / all	0 / 0	0 / 0	0 / 0	0 / 0	0 / 1	0 / 0
deaths causally related to treatment / all	0 / 0	0 / 0	0 / 0	0 / 0	0 / 0	0 / 0
Asthma
subjects affected / exposed	0 / 50 (0.00%)	1 / 31 (3.23%)	0 / 34 (0.00%)	0 / 34 (0.00%)	0 / 49 (0.00%)	0 / 48 (0.00%)
occurrences causally related to treatment / all	0 / 0	0 / 1	0 / 0	0 / 0	0 / 0	0 / 0
deaths causally related to treatment / all	0 / 0	0 / 0	0 / 0	0 / 0	0 / 0	0 / 0
Respiratory Failure
subjects affected / exposed	2 / 50 (4.00%)	0 / 31 (0.00%)	0 / 34 (0.00%)	0 / 34 (0.00%)	1 / 49 (2.04%)	1 / 48 (2.08%)
occurrences causally related to treatment / all	0 / 2	0 / 0	0 / 0	0 / 0	0 / 1	0 / 1
deaths causally related to treatment / all	0 / 0	0 / 0	0 / 0	0 / 0	0 / 0	0 / 0
Hypoxia
subjects affected / exposed	1 / 50 (2.00%)	0 / 31 (0.00%)	0 / 34 (0.00%)	0 / 34 (0.00%)	0 / 49 (0.00%)	0 / 48 (0.00%)
occurrences causally related to treatment / all	0 / 1	0 / 0	0 / 0	0 / 0	0 / 0	0 / 0
deaths causally related to treatment / all	0 / 0	0 / 0	0 / 0	0 / 0	0 / 0	0 / 0
Wheezing
subjects affected / exposed	1 / 50 (2.00%)	0 / 31 (0.00%)	0 / 34 (0.00%)	1 / 34 (2.94%)	0 / 49 (0.00%)	0 / 48 (0.00%)
occurrences causally related to treatment / all	0 / 1	0 / 0	0 / 0	0 / 1	0 / 0	0 / 0
deaths causally related to treatment / all	0 / 0	0 / 0	0 / 0	0 / 0	0 / 0	0 / 0
Infections and infestations
Bronchiolitis
subjects affected / exposed	0 / 50 (0.00%)	0 / 31 (0.00%)	1 / 34 (2.94%)	0 / 34 (0.00%)	0 / 49 (0.00%)	0 / 48 (0.00%)
occurrences causally related to treatment / all	0 / 0	0 / 0	0 / 1	0 / 0	0 / 0	0 / 0
deaths causally related to treatment / all	0 / 0	0 / 0	0 / 0	0 / 0	0 / 0	0 / 0
Coronavirus Infection
subjects affected / exposed	0 / 50 (0.00%)	0 / 31 (0.00%)	1 / 34 (2.94%)	0 / 34 (0.00%)	0 / 49 (0.00%)	0 / 48 (0.00%)
occurrences causally related to treatment / all	0 / 0	0 / 0	0 / 1	0 / 0	0 / 0	0 / 0
deaths causally related to treatment / all	0 / 0	0 / 0	0 / 0	0 / 0	0 / 0	0 / 0
Bronchitis
subjects affected / exposed	0 / 50 (0.00%)	1 / 31 (3.23%)	0 / 34 (0.00%)	0 / 34 (0.00%)	1 / 49 (2.04%)	0 / 48 (0.00%)
occurrences causally related to treatment / all	0 / 0	0 / 1	0 / 0	0 / 0	0 / 1	0 / 0
deaths causally related to treatment / all	0 / 0	0 / 0	0 / 0	0 / 0	0 / 0	0 / 0
Pneumonia Respiratory Syncytial Viral
subjects affected / exposed	0 / 50 (0.00%)	0 / 31 (0.00%)	0 / 34 (0.00%)	1 / 34 (2.94%)	0 / 49 (0.00%)	0 / 48 (0.00%)
occurrences causally related to treatment / all	0 / 0	0 / 0	0 / 0	0 / 1	0 / 0	0 / 0
deaths causally related to treatment / all	0 / 0	0 / 0	0 / 0	0 / 0	0 / 0	0 / 0
Pneumonia
subjects affected / exposed	0 / 50 (0.00%)	0 / 31 (0.00%)	0 / 34 (0.00%)	0 / 34 (0.00%)	0 / 49 (0.00%)	1 / 48 (2.08%)
occurrences causally related to treatment / all	0 / 0	0 / 0	0 / 0	0 / 0	0 / 0	0 / 1
deaths causally related to treatment / all	0 / 0	0 / 0	0 / 0	0 / 0	0 / 0	0 / 0
Influenza
subjects affected / exposed	0 / 50 (0.00%)	0 / 31 (0.00%)	0 / 34 (0.00%)	1 / 34 (2.94%)	0 / 49 (0.00%)	0 / 48 (0.00%)
occurrences causally related to treatment / all	0 / 0	0 / 0	0 / 0	0 / 1	0 / 0	0 / 0
deaths causally related to treatment / all	0 / 0	0 / 0	0 / 0	0 / 0	0 / 0	0 / 0
Gastroenteritis
subjects affected / exposed	0 / 50 (0.00%)	1 / 31 (3.23%)	0 / 34 (0.00%)	0 / 34 (0.00%)	0 / 49 (0.00%)	0 / 48 (0.00%)
occurrences causally related to treatment / all	0 / 0	0 / 1	0 / 0	0 / 0	0 / 0	0 / 0
deaths causally related to treatment / all	0 / 0	0 / 0	0 / 0	0 / 0	0 / 0	0 / 0
Respiratory Syncytial Virus Bronchiolitis
subjects affected / exposed	0 / 50 (0.00%)	0 / 31 (0.00%)	0 / 34 (0.00%)	0 / 34 (0.00%)	1 / 49 (2.04%)	0 / 48 (0.00%)
occurrences causally related to treatment / all	0 / 0	0 / 0	0 / 0	0 / 0	0 / 1	0 / 0
deaths causally related to treatment / all	0 / 0	0 / 0	0 / 0	0 / 0	0 / 0	0 / 0
Respiratory Tract Infection
subjects affected / exposed	0 / 50 (0.00%)	0 / 31 (0.00%)	0 / 34 (0.00%)	0 / 34 (0.00%)	1 / 49 (2.04%)	0 / 48 (0.00%)
occurrences causally related to treatment / all	0 / 0	0 / 0	0 / 0	0 / 0	0 / 1	0 / 0
deaths causally related to treatment / all	0 / 0	0 / 0	0 / 0	0 / 0	0 / 0	0 / 0
Metabolism and nutrition disorders
Feeding Disorder
subjects affected / exposed	0 / 50 (0.00%)	0 / 31 (0.00%)	0 / 34 (0.00%)	0 / 34 (0.00%)	1 / 49 (2.04%)	0 / 48 (0.00%)
occurrences causally related to treatment / all	0 / 0	0 / 0	0 / 0	0 / 0	0 / 1	0 / 0
deaths causally related to treatment / all	0 / 0	0 / 0	0 / 0	0 / 0	0 / 0	0 / 0

Frequency threshold for reporting non-serious adverse events: 0%

Non-serious adverse events	Cohort 1: Placebo	Cohort 2: JNJ-53718678 High Dose	Cohort 2: Placebo	Cohort 2: JNJ-53718678 Low Dose	Cohort 1: JNJ-53718678 Low Dose	Cohort 1: JNJ-53718678 High Dose
Total subjects affected by non serious adverse events
subjects affected / exposed	28 / 50 (56.00%)	13 / 31 (41.94%)	14 / 34 (41.18%)	20 / 34 (58.82%)	29 / 49 (59.18%)	30 / 48 (62.50%)
Vascular disorders
Haematoma
subjects affected / exposed	1 / 50 (2.00%)	0 / 31 (0.00%)	0 / 34 (0.00%)	0 / 34 (0.00%)	0 / 49 (0.00%)	0 / 48 (0.00%)
occurrences all number	1	0	0	0	0	0
Hyperaemia
subjects affected / exposed	0 / 50 (0.00%)	0 / 31 (0.00%)	0 / 34 (0.00%)	0 / 34 (0.00%)	0 / 49 (0.00%)	1 / 48 (2.08%)
occurrences all number	0	0	0	0	0	1
General disorders and administration site conditions
Pyrexia
subjects affected / exposed	2 / 50 (4.00%)	1 / 31 (3.23%)	0 / 34 (0.00%)	1 / 34 (2.94%)	3 / 49 (6.12%)	3 / 48 (6.25%)
occurrences all number	2	1	0	1	3	3
Oedema Peripheral
subjects affected / exposed	1 / 50 (2.00%)	0 / 31 (0.00%)	0 / 34 (0.00%)	0 / 34 (0.00%)	0 / 49 (0.00%)	0 / 48 (0.00%)
occurrences all number	1	0	0	0	0	0
Hyperthermia
subjects affected / exposed	1 / 50 (2.00%)	0 / 31 (0.00%)	0 / 34 (0.00%)	0 / 34 (0.00%)	0 / 49 (0.00%)	0 / 48 (0.00%)
occurrences all number	1	0	0	0	0	0
Face Oedema
subjects affected / exposed	1 / 50 (2.00%)	0 / 31 (0.00%)	0 / 34 (0.00%)	0 / 34 (0.00%)	0 / 49 (0.00%)	0 / 48 (0.00%)
occurrences all number	1	0	0	0	0	0
Respiratory, thoracic and mediastinal disorders
Dyspnoea
subjects affected / exposed	0 / 50 (0.00%)	0 / 31 (0.00%)	0 / 34 (0.00%)	1 / 34 (2.94%)	0 / 49 (0.00%)	0 / 48 (0.00%)
occurrences all number	0	0	0	1	0	0
Dysphonia
subjects affected / exposed	1 / 50 (2.00%)	0 / 31 (0.00%)	0 / 34 (0.00%)	0 / 34 (0.00%)	0 / 49 (0.00%)	0 / 48 (0.00%)
occurrences all number	1	0	0	0	0	0
Cough
subjects affected / exposed	2 / 50 (4.00%)	1 / 31 (3.23%)	0 / 34 (0.00%)	0 / 34 (0.00%)	1 / 49 (2.04%)	0 / 48 (0.00%)
occurrences all number	2	1	0	0	1	0
Catarrh
subjects affected / exposed	0 / 50 (0.00%)	1 / 31 (3.23%)	0 / 34 (0.00%)	0 / 34 (0.00%)	1 / 49 (2.04%)	0 / 48 (0.00%)
occurrences all number	0	1	0	0	1	0
Bronchospasm
subjects affected / exposed	2 / 50 (4.00%)	0 / 31 (0.00%)	0 / 34 (0.00%)	0 / 34 (0.00%)	1 / 49 (2.04%)	1 / 48 (2.08%)
occurrences all number	2	0	0	0	1	1
Bronchial Secretion Retention
subjects affected / exposed	1 / 50 (2.00%)	0 / 31 (0.00%)	0 / 34 (0.00%)	0 / 34 (0.00%)	0 / 49 (0.00%)	0 / 48 (0.00%)
occurrences all number	1	0	0	0	0	0
Bronchial Obstruction
subjects affected / exposed	0 / 50 (0.00%)	0 / 31 (0.00%)	0 / 34 (0.00%)	0 / 34 (0.00%)	0 / 49 (0.00%)	1 / 48 (2.08%)
occurrences all number	0	0	0	0	0	1
Atelectasis
subjects affected / exposed	1 / 50 (2.00%)	0 / 31 (0.00%)	0 / 34 (0.00%)	0 / 34 (0.00%)	1 / 49 (2.04%)	1 / 48 (2.08%)
occurrences all number	1	0	0	0	1	1
Asthma
subjects affected / exposed	0 / 50 (0.00%)	1 / 31 (3.23%)	0 / 34 (0.00%)	0 / 34 (0.00%)	0 / 49 (0.00%)	0 / 48 (0.00%)
occurrences all number	0	1	0	0	0	0
Epistaxis
subjects affected / exposed	0 / 50 (0.00%)	0 / 31 (0.00%)	0 / 34 (0.00%)	1 / 34 (2.94%)	0 / 49 (0.00%)	1 / 48 (2.08%)
occurrences all number	0	0	0	1	0	1
Nasal Discomfort
subjects affected / exposed	0 / 50 (0.00%)	0 / 31 (0.00%)	0 / 34 (0.00%)	0 / 34 (0.00%)	1 / 49 (2.04%)	0 / 48 (0.00%)
occurrences all number	0	0	0	0	1	0
Lung Consolidation
subjects affected / exposed	0 / 50 (0.00%)	0 / 31 (0.00%)	0 / 34 (0.00%)	0 / 34 (0.00%)	0 / 49 (0.00%)	1 / 48 (2.08%)
occurrences all number	0	0	0	0	0	1
Respiratory Depth Increased
subjects affected / exposed	0 / 50 (0.00%)	0 / 31 (0.00%)	0 / 34 (0.00%)	0 / 34 (0.00%)	1 / 49 (2.04%)	0 / 48 (0.00%)
occurrences all number	0	0	0	0	1	0
Respiratory Distress
subjects affected / exposed	2 / 50 (4.00%)	0 / 31 (0.00%)	0 / 34 (0.00%)	0 / 34 (0.00%)	0 / 49 (0.00%)	0 / 48 (0.00%)
occurrences all number	2	0	0	0	0	0
Wheezing
subjects affected / exposed	0 / 50 (0.00%)	0 / 31 (0.00%)	0 / 34 (0.00%)	0 / 34 (0.00%)	1 / 49 (2.04%)	0 / 48 (0.00%)
occurrences all number	0	0	0	0	1	0
Rhinorrhoea
subjects affected / exposed	0 / 50 (0.00%)	0 / 31 (0.00%)	1 / 34 (2.94%)	1 / 34 (2.94%)	0 / 49 (0.00%)	0 / 48 (0.00%)
occurrences all number	0	0	1	1	0	0
Sinus Disorder
subjects affected / exposed	0 / 50 (0.00%)	0 / 31 (0.00%)	0 / 34 (0.00%)	0 / 34 (0.00%)	0 / 49 (0.00%)	1 / 48 (2.08%)
occurrences all number	0	0	0	0	0	1
Upper Respiratory Tract Congestion
subjects affected / exposed	1 / 50 (2.00%)	0 / 31 (0.00%)	0 / 34 (0.00%)	0 / 34 (0.00%)	0 / 49 (0.00%)	0 / 48 (0.00%)
occurrences all number	1	0	0	0	0	0
Upper Respiratory Tract Inflammation
subjects affected / exposed	0 / 50 (0.00%)	0 / 31 (0.00%)	0 / 34 (0.00%)	0 / 34 (0.00%)	0 / 49 (0.00%)	1 / 48 (2.08%)
occurrences all number	0	0	0	0	0	1
Psychiatric disorders
Restlessness
subjects affected / exposed	0 / 50 (0.00%)	0 / 31 (0.00%)	0 / 34 (0.00%)	0 / 34 (0.00%)	0 / 49 (0.00%)	1 / 48 (2.08%)
occurrences all number	0	0	0	0	0	1
Investigations
Alanine Aminotransferase Increased
subjects affected / exposed	0 / 50 (0.00%)	0 / 31 (0.00%)	0 / 34 (0.00%)	1 / 34 (2.94%)	0 / 49 (0.00%)	1 / 48 (2.08%)
occurrences all number	0	0	0	1	0	1
Transaminases Increased
subjects affected / exposed	1 / 50 (2.00%)	0 / 31 (0.00%)	0 / 34 (0.00%)	0 / 34 (0.00%)	0 / 49 (0.00%)	0 / 48 (0.00%)
occurrences all number	1	0	0	0	0	0
Platelet Count Increased
subjects affected / exposed	0 / 50 (0.00%)	0 / 31 (0.00%)	1 / 34 (2.94%)	0 / 34 (0.00%)	1 / 49 (2.04%)	0 / 48 (0.00%)
occurrences all number	0	0	1	0	1	0
Blood Potassium Increased
subjects affected / exposed	0 / 50 (0.00%)	0 / 31 (0.00%)	0 / 34 (0.00%)	0 / 34 (0.00%)	1 / 49 (2.04%)	0 / 48 (0.00%)
occurrences all number	0	0	0	0	1	0
Blood Creatinine Increased
subjects affected / exposed	0 / 50 (0.00%)	0 / 31 (0.00%)	0 / 34 (0.00%)	1 / 34 (2.94%)	0 / 49 (0.00%)	0 / 48 (0.00%)
occurrences all number	0	0	0	1	0	0
Aspartate Aminotransferase Increased
subjects affected / exposed	0 / 50 (0.00%)	0 / 31 (0.00%)	0 / 34 (0.00%)	0 / 34 (0.00%)	0 / 49 (0.00%)	1 / 48 (2.08%)
occurrences all number	0	0	0	0	0	1
Oxygen Saturation Decreased
subjects affected / exposed	0 / 50 (0.00%)	0 / 31 (0.00%)	0 / 34 (0.00%)	0 / 34 (0.00%)	1 / 49 (2.04%)	0 / 48 (0.00%)
occurrences all number	0	0	0	0	1	0
Injury, poisoning and procedural complications
Arthropod Sting
subjects affected / exposed	0 / 50 (0.00%)	0 / 31 (0.00%)	0 / 34 (0.00%)	1 / 34 (2.94%)	0 / 49 (0.00%)	0 / 48 (0.00%)
occurrences all number	0	0	0	1	0	0
Contusion
subjects affected / exposed	1 / 50 (2.00%)	0 / 31 (0.00%)	0 / 34 (0.00%)	0 / 34 (0.00%)	1 / 49 (2.04%)	0 / 48 (0.00%)
occurrences all number	1	0	0	0	1	0
Head Injury
subjects affected / exposed	0 / 50 (0.00%)	0 / 31 (0.00%)	0 / 34 (0.00%)	0 / 34 (0.00%)	0 / 49 (0.00%)	1 / 48 (2.08%)
occurrences all number	0	0	0	0	0	1
Radial Head Dislocation
subjects affected / exposed	0 / 50 (0.00%)	0 / 31 (0.00%)	0 / 34 (0.00%)	0 / 34 (0.00%)	1 / 49 (2.04%)	0 / 48 (0.00%)
occurrences all number	0	0	0	0	1	0
Skin Wound
subjects affected / exposed	0 / 50 (0.00%)	0 / 31 (0.00%)	0 / 34 (0.00%)	0 / 34 (0.00%)	1 / 49 (2.04%)	0 / 48 (0.00%)
occurrences all number	0	0	0	0	1	0
Blood and lymphatic system disorders
Leukopenia
subjects affected / exposed	0 / 50 (0.00%)	0 / 31 (0.00%)	0 / 34 (0.00%)	0 / 34 (0.00%)	1 / 49 (2.04%)	0 / 48 (0.00%)
occurrences all number	0	0	0	0	1	0
Anaemia
subjects affected / exposed	0 / 50 (0.00%)	0 / 31 (0.00%)	0 / 34 (0.00%)	0 / 34 (0.00%)	2 / 49 (4.08%)	1 / 48 (2.08%)
occurrences all number	0	0	0	0	2	1
Eosinophilia
subjects affected / exposed	0 / 50 (0.00%)	0 / 31 (0.00%)	0 / 34 (0.00%)	0 / 34 (0.00%)	0 / 49 (0.00%)	1 / 48 (2.08%)
occurrences all number	0	0	0	0	0	1
Lymphadenopathy
subjects affected / exposed	1 / 50 (2.00%)	0 / 31 (0.00%)	0 / 34 (0.00%)	0 / 34 (0.00%)	0 / 49 (0.00%)	0 / 48 (0.00%)
occurrences all number	1	0	0	0	0	0
Lymphocytosis
subjects affected / exposed	1 / 50 (2.00%)	0 / 31 (0.00%)	0 / 34 (0.00%)	1 / 34 (2.94%)	1 / 49 (2.04%)	1 / 48 (2.08%)
occurrences all number	1	0	0	1	1	1
Neutropenia
subjects affected / exposed	1 / 50 (2.00%)	0 / 31 (0.00%)	0 / 34 (0.00%)	0 / 34 (0.00%)	0 / 49 (0.00%)	2 / 48 (4.17%)
occurrences all number	1	0	0	0	0	2
Thrombocytosis
subjects affected / exposed	2 / 50 (4.00%)	0 / 31 (0.00%)	0 / 34 (0.00%)	2 / 34 (5.88%)	2 / 49 (4.08%)	3 / 48 (6.25%)
occurrences all number	2	0	0	2	2	3
Eye disorders
Eye Discharge
subjects affected / exposed	0 / 50 (0.00%)	0 / 31 (0.00%)	0 / 34 (0.00%)	0 / 34 (0.00%)	1 / 49 (2.04%)	0 / 48 (0.00%)
occurrences all number	0	0	0	0	1	0
Ocular Hyperaemia
subjects affected / exposed	0 / 50 (0.00%)	0 / 31 (0.00%)	1 / 34 (2.94%)	0 / 34 (0.00%)	0 / 49 (0.00%)	0 / 48 (0.00%)
occurrences all number	0	0	1	0	0	0
Gastrointestinal disorders
Faeces Soft
subjects affected / exposed	3 / 50 (6.00%)	0 / 31 (0.00%)	0 / 34 (0.00%)	0 / 34 (0.00%)	0 / 49 (0.00%)	2 / 48 (4.17%)
occurrences all number	4	0	0	0	0	3
Anorectal Discomfort
subjects affected / exposed	0 / 50 (0.00%)	0 / 31 (0.00%)	0 / 34 (0.00%)	0 / 34 (0.00%)	0 / 49 (0.00%)	1 / 48 (2.08%)
occurrences all number	0	0	0	0	0	1
Anal Erythema
subjects affected / exposed	0 / 50 (0.00%)	0 / 31 (0.00%)	0 / 34 (0.00%)	0 / 34 (0.00%)	1 / 49 (2.04%)	0 / 48 (0.00%)
occurrences all number	0	0	0	0	1	0
Diarrhoea
subjects affected / exposed	1 / 50 (2.00%)	4 / 31 (12.90%)	5 / 34 (14.71%)	3 / 34 (8.82%)	2 / 49 (4.08%)	5 / 48 (10.42%)
occurrences all number	1	4	5	3	2	5
Constipation
subjects affected / exposed	0 / 50 (0.00%)	0 / 31 (0.00%)	0 / 34 (0.00%)	0 / 34 (0.00%)	1 / 49 (2.04%)	0 / 48 (0.00%)
occurrences all number	0	0	0	0	1	0
Vomiting
subjects affected / exposed	1 / 50 (2.00%)	0 / 31 (0.00%)	4 / 34 (11.76%)	1 / 34 (2.94%)	3 / 49 (6.12%)	3 / 48 (6.25%)
occurrences all number	1	0	4	1	3	3
Post-Tussive Vomiting
subjects affected / exposed	0 / 50 (0.00%)	0 / 31 (0.00%)	0 / 34 (0.00%)	0 / 34 (0.00%)	0 / 49 (0.00%)	1 / 48 (2.08%)
occurrences all number	0	0	0	0	0	1
Noninfective Gingivitis
subjects affected / exposed	0 / 50 (0.00%)	0 / 31 (0.00%)	0 / 34 (0.00%)	0 / 34 (0.00%)	0 / 49 (0.00%)	1 / 48 (2.08%)
occurrences all number	0	0	0	0	0	1
Gastrooesophageal Reflux Disease
subjects affected / exposed	0 / 50 (0.00%)	0 / 31 (0.00%)	0 / 34 (0.00%)	0 / 34 (0.00%)	1 / 49 (2.04%)	0 / 48 (0.00%)
occurrences all number	0	0	0	0	1	0
Hepatobiliary disorders
Hepatosplenomegaly
subjects affected / exposed	0 / 50 (0.00%)	0 / 31 (0.00%)	0 / 34 (0.00%)	1 / 34 (2.94%)	0 / 49 (0.00%)	0 / 48 (0.00%)
occurrences all number	0	0	0	1	0	0
Hypertransaminasaemia
subjects affected / exposed	1 / 50 (2.00%)	0 / 31 (0.00%)	0 / 34 (0.00%)	0 / 34 (0.00%)	0 / 49 (0.00%)	0 / 48 (0.00%)
occurrences all number	2	0	0	0	0	0
Skin and subcutaneous tissue disorders
Miliaria
subjects affected / exposed	0 / 50 (0.00%)	1 / 31 (3.23%)	0 / 34 (0.00%)	0 / 34 (0.00%)	1 / 49 (2.04%)	0 / 48 (0.00%)
occurrences all number	0	1	0	0	1	0
Erythema
subjects affected / exposed	0 / 50 (0.00%)	0 / 31 (0.00%)	0 / 34 (0.00%)	0 / 34 (0.00%)	1 / 49 (2.04%)	1 / 48 (2.08%)
occurrences all number	0	0	0	0	1	1
Eczema
subjects affected / exposed	0 / 50 (0.00%)	0 / 31 (0.00%)	0 / 34 (0.00%)	1 / 34 (2.94%)	0 / 49 (0.00%)	0 / 48 (0.00%)
occurrences all number	0	0	0	1	0	0
Dermatitis Diaper
subjects affected / exposed	0 / 50 (0.00%)	1 / 31 (3.23%)	0 / 34 (0.00%)	1 / 34 (2.94%)	1 / 49 (2.04%)	3 / 48 (6.25%)
occurrences all number	0	1	0	1	1	3
Dermatitis Atopic
subjects affected / exposed	0 / 50 (0.00%)	1 / 31 (3.23%)	0 / 34 (0.00%)	0 / 34 (0.00%)	0 / 49 (0.00%)	1 / 48 (2.08%)
occurrences all number	0	1	0	0	0	1
Asteatosis
subjects affected / exposed	0 / 50 (0.00%)	0 / 31 (0.00%)	0 / 34 (0.00%)	1 / 34 (2.94%)	0 / 49 (0.00%)	0 / 48 (0.00%)
occurrences all number	0	0	0	1	0	0
Rash Macular
subjects affected / exposed	1 / 50 (2.00%)	0 / 31 (0.00%)	0 / 34 (0.00%)	0 / 34 (0.00%)	0 / 49 (0.00%)	0 / 48 (0.00%)
occurrences all number	1	0	0	0	0	0
Rash Erythematous
subjects affected / exposed	0 / 50 (0.00%)	0 / 31 (0.00%)	0 / 34 (0.00%)	0 / 34 (0.00%)	1 / 49 (2.04%)	0 / 48 (0.00%)
occurrences all number	0	0	0	0	2	0
Rash
subjects affected / exposed	3 / 50 (6.00%)	0 / 31 (0.00%)	0 / 34 (0.00%)	2 / 34 (5.88%)	1 / 49 (2.04%)	3 / 48 (6.25%)
occurrences all number	3	0	0	2	1	3
Urticaria
subjects affected / exposed	1 / 50 (2.00%)	0 / 31 (0.00%)	0 / 34 (0.00%)	0 / 34 (0.00%)	0 / 49 (0.00%)	1 / 48 (2.08%)
occurrences all number	1	0	0	0	0	1
Skin Lesion
subjects affected / exposed	0 / 50 (0.00%)	0 / 31 (0.00%)	0 / 34 (0.00%)	0 / 34 (0.00%)	0 / 49 (0.00%)	1 / 48 (2.08%)
occurrences all number	0	0	0	0	0	1
Rash Papular
subjects affected / exposed	0 / 50 (0.00%)	0 / 31 (0.00%)	0 / 34 (0.00%)	1 / 34 (2.94%)	0 / 49 (0.00%)	1 / 48 (2.08%)
occurrences all number	0	0	0	1	0	1
Renal and urinary disorders
Oliguria
subjects affected / exposed	1 / 50 (2.00%)	0 / 31 (0.00%)	0 / 34 (0.00%)	0 / 34 (0.00%)	0 / 49 (0.00%)	0 / 48 (0.00%)
occurrences all number	1	0	0	0	0	0
Polyuria
subjects affected / exposed	1 / 50 (2.00%)	1 / 31 (3.23%)	0 / 34 (0.00%)	0 / 34 (0.00%)	0 / 49 (0.00%)	0 / 48 (0.00%)
occurrences all number	1	1	0	0	0	0
Musculoskeletal and connective tissue disorders
Musculoskeletal Stiffness
subjects affected / exposed	0 / 50 (0.00%)	0 / 31 (0.00%)	0 / 34 (0.00%)	0 / 34 (0.00%)	0 / 49 (0.00%)	1 / 48 (2.08%)
occurrences all number	0	0	0	0	0	1
Infections and infestations
Bronchitis
subjects affected / exposed	0 / 50 (0.00%)	1 / 31 (3.23%)	0 / 34 (0.00%)	1 / 34 (2.94%)	0 / 49 (0.00%)	0 / 48 (0.00%)
occurrences all number	0	1	0	1	0	0
Bronchiolitis
subjects affected / exposed	0 / 50 (0.00%)	0 / 31 (0.00%)	0 / 34 (0.00%)	0 / 34 (0.00%)	0 / 49 (0.00%)	1 / 48 (2.08%)
occurrences all number	0	0	0	0	0	1
Candida Nappy Rash
subjects affected / exposed	0 / 50 (0.00%)	0 / 31 (0.00%)	0 / 34 (0.00%)	0 / 34 (0.00%)	0 / 49 (0.00%)	1 / 48 (2.08%)
occurrences all number	0	0	0	0	0	1
Lower Respiratory Tract Infection Bacterial
subjects affected / exposed	1 / 50 (2.00%)	0 / 31 (0.00%)	0 / 34 (0.00%)	0 / 34 (0.00%)	0 / 49 (0.00%)	0 / 48 (0.00%)
occurrences all number	1	0	0	0	0	0
Localised Infection
subjects affected / exposed	0 / 50 (0.00%)	0 / 31 (0.00%)	0 / 34 (0.00%)	0 / 34 (0.00%)	0 / 49 (0.00%)	1 / 48 (2.08%)
occurrences all number	0	0	0	0	0	1
Influenza
subjects affected / exposed	1 / 50 (2.00%)	0 / 31 (0.00%)	0 / 34 (0.00%)	2 / 34 (5.88%)	0 / 49 (0.00%)	0 / 48 (0.00%)
occurrences all number	1	0	0	2	0	0
Conjunctivitis
subjects affected / exposed	2 / 50 (4.00%)	0 / 31 (0.00%)	0 / 34 (0.00%)	0 / 34 (0.00%)	2 / 49 (4.08%)	0 / 48 (0.00%)
occurrences all number	2	0	0	0	2	0
Gastroenteritis
subjects affected / exposed	0 / 50 (0.00%)	0 / 31 (0.00%)	0 / 34 (0.00%)	0 / 34 (0.00%)	2 / 49 (4.08%)	2 / 48 (4.17%)
occurrences all number	0	0	0	0	2	2
Fungal Infection
subjects affected / exposed	1 / 50 (2.00%)	0 / 31 (0.00%)	0 / 34 (0.00%)	0 / 34 (0.00%)	0 / 49 (0.00%)	0 / 48 (0.00%)
occurrences all number	1	0	0	0	0	0
Exanthema Subitum
subjects affected / exposed	0 / 50 (0.00%)	0 / 31 (0.00%)	1 / 34 (2.94%)	0 / 34 (0.00%)	0 / 49 (0.00%)	0 / 48 (0.00%)
occurrences all number	0	0	1	0	0	0
Ear Infection
subjects affected / exposed	1 / 50 (2.00%)	1 / 31 (3.23%)	0 / 34 (0.00%)	0 / 34 (0.00%)	0 / 49 (0.00%)	0 / 48 (0.00%)
occurrences all number	1	1	0	0	0	0
Hand-Foot-And-Mouth Disease
subjects affected / exposed	0 / 50 (0.00%)	0 / 31 (0.00%)	1 / 34 (2.94%)	0 / 34 (0.00%)	2 / 49 (4.08%)	0 / 48 (0.00%)
occurrences all number	0	0	1	0	2	0
Respiratory Tract Infection Viral
subjects affected / exposed	0 / 50 (0.00%)	0 / 31 (0.00%)	1 / 34 (2.94%)	0 / 34 (0.00%)	0 / 49 (0.00%)	0 / 48 (0.00%)
occurrences all number	0	0	1	0	0	0
Rhinovirus Infection
subjects affected / exposed	1 / 50 (2.00%)	0 / 31 (0.00%)	0 / 34 (0.00%)	0 / 34 (0.00%)	1 / 49 (2.04%)	0 / 48 (0.00%)
occurrences all number	1	0	0	0	1	0
Respiratory Tract Infection Bacterial
subjects affected / exposed	0 / 50 (0.00%)	0 / 31 (0.00%)	0 / 34 (0.00%)	0 / 34 (0.00%)	1 / 49 (2.04%)	0 / 48 (0.00%)
occurrences all number	0	0	0	0	1	0
Respiratory Tract Infection
subjects affected / exposed	1 / 50 (2.00%)	0 / 31 (0.00%)	0 / 34 (0.00%)	0 / 34 (0.00%)	1 / 49 (2.04%)	1 / 48 (2.08%)
occurrences all number	1	0	0	0	1	1
Pneumonia Bacterial
subjects affected / exposed	0 / 50 (0.00%)	0 / 31 (0.00%)	0 / 34 (0.00%)	0 / 34 (0.00%)	1 / 49 (2.04%)	1 / 48 (2.08%)
occurrences all number	0	0	0	0	1	1
Pneumonia
subjects affected / exposed	2 / 50 (4.00%)	1 / 31 (3.23%)	0 / 34 (0.00%)	0 / 34 (0.00%)	0 / 49 (0.00%)	1 / 48 (2.08%)
occurrences all number	2	1	0	0	0	1
Parainfluenzae Virus Infection
subjects affected / exposed	1 / 50 (2.00%)	0 / 31 (0.00%)	0 / 34 (0.00%)	0 / 34 (0.00%)	0 / 49 (0.00%)	0 / 48 (0.00%)
occurrences all number	1	0	0	0	0	0
Otitis Media Acute
subjects affected / exposed	1 / 50 (2.00%)	1 / 31 (3.23%)	1 / 34 (2.94%)	0 / 34 (0.00%)	2 / 49 (4.08%)	1 / 48 (2.08%)
occurrences all number	1	1	1	0	2	1
Otitis Media
subjects affected / exposed	1 / 50 (2.00%)	1 / 31 (3.23%)	1 / 34 (2.94%)	0 / 34 (0.00%)	0 / 49 (0.00%)	1 / 48 (2.08%)
occurrences all number	1	1	1	0	0	1
Oral Candidiasis
subjects affected / exposed	2 / 50 (4.00%)	0 / 31 (0.00%)	0 / 34 (0.00%)	0 / 34 (0.00%)	2 / 49 (4.08%)	0 / 48 (0.00%)
occurrences all number	2	0	0	0	2	0
Sinusitis
subjects affected / exposed	0 / 50 (0.00%)	0 / 31 (0.00%)	0 / 34 (0.00%)	0 / 34 (0.00%)	1 / 49 (2.04%)	0 / 48 (0.00%)
occurrences all number	0	0	0	0	1	0
Nasopharyngitis
subjects affected / exposed	1 / 50 (2.00%)	1 / 31 (3.23%)	0 / 34 (0.00%)	2 / 34 (5.88%)	2 / 49 (4.08%)	6 / 48 (12.50%)
occurrences all number	1	1	0	2	2	6
Tonsillitis
subjects affected / exposed	0 / 50 (0.00%)	0 / 31 (0.00%)	1 / 34 (2.94%)	1 / 34 (2.94%)	0 / 49 (0.00%)	0 / 48 (0.00%)
occurrences all number	0	0	1	1	0	0
Upper Respiratory Tract Infection
subjects affected / exposed	4 / 50 (8.00%)	1 / 31 (3.23%)	1 / 34 (2.94%)	0 / 34 (0.00%)	3 / 49 (6.12%)	1 / 48 (2.08%)
occurrences all number	4	1	1	0	3	1
Urinary Tract Infection
subjects affected / exposed	0 / 50 (0.00%)	0 / 31 (0.00%)	0 / 34 (0.00%)	0 / 34 (0.00%)	2 / 49 (4.08%)	1 / 48 (2.08%)
occurrences all number	0	0	0	0	2	1
Viral Infection
subjects affected / exposed	1 / 50 (2.00%)	0 / 31 (0.00%)	0 / 34 (0.00%)	0 / 34 (0.00%)	0 / 49 (0.00%)	0 / 48 (0.00%)
occurrences all number	1	0	0	0	0	0
Viral Rash
subjects affected / exposed	0 / 50 (0.00%)	1 / 31 (3.23%)	0 / 34 (0.00%)	0 / 34 (0.00%)	0 / 49 (0.00%)	1 / 48 (2.08%)
occurrences all number	0	1	0	0	0	1
Metabolism and nutrition disorders
Zinc Deficiency
subjects affected / exposed	0 / 50 (0.00%)	0 / 31 (0.00%)	0 / 34 (0.00%)	0 / 34 (0.00%)	1 / 49 (2.04%)	0 / 48 (0.00%)
occurrences all number	0	0	0	0	1	0
Metabolic Alkalosis
subjects affected / exposed	1 / 50 (2.00%)	0 / 31 (0.00%)	0 / 34 (0.00%)	0 / 34 (0.00%)	0 / 49 (0.00%)	0 / 48 (0.00%)
occurrences all number	1	0	0	0	0	0
Hyperuricaemia
subjects affected / exposed	1 / 50 (2.00%)	0 / 31 (0.00%)	0 / 34 (0.00%)	0 / 34 (0.00%)	0 / 49 (0.00%)	0 / 48 (0.00%)
occurrences all number	1	0	0	0	0	0
Hyperkalaemia
subjects affected / exposed	1 / 50 (2.00%)	0 / 31 (0.00%)	0 / 34 (0.00%)	0 / 34 (0.00%)	0 / 49 (0.00%)	0 / 48 (0.00%)
occurrences all number	1	0	0	0	0	0

More information

Top of page

Were there any global substantial amendments to the protocol? Yes

14 May 2019

The purpose of this amendment was to increase the sample size of Cohort 1 (hospitalised cohort) from 24 to 48 subjects per treatment arm to increase the precision on the estimates for the clinical course related endpoints in this cohort.

05 Jul 2019

The purpose of this amendment was to clarify how the required balance within the symptom onset randomisation strata (symptom onset less than or equal to (<=) 3 days and greater than (>) 3 days to <=5 days) for each of the interim analyses as well as for the final analysis will be achieved while allowing some flexibility in view of respiratory syncytial virus (RSV) seasonality and reducing the recruitment impact of a (temporary) pause in enrollment in one of the strata.

20 Dec 2019

The purpose of this amendment was to allow unblinding of the central sponsor team and selected local sponsor representatives from Japan to the data included in the second interim analysis and to allow unblinding of the sponsor, including the study team, and selected local sponsor representatives from Japan to all interim analyses planned after the second interim analysis.

26 May 2020

The purpose of this amendment was to implement a risk mitigation plan following identification of an exposure (Cmax)-related important potential risk of QT interval prolongation identified in the throughout QT (TQT) Study 53718678RSV1009 in healthy adult subjects. Given that Cohort 1 enrollment has completed and no more Cohort 1 subjects were ongoing in the study.

10 Jul 2020

The purpose of this amendment was to implement recommendations from Health Authorities (HA). Given that Cohort 1 enrollment had completed and no more Cohort 1 subjects were ongoing in the study, the changes were only applicable for the newly to be recruited Cohort 2 subjects.

01 Dec 2020

The purpose of this amendment was to maximize enrollment of subjects with at least moderate RSV disease severity, where potentially greater treatment benefit was achieved.

Were there any global interruptions to the trial? No

Limitations of the trial such as small numbers of subjects analysed or technical problems leading to unreliable data.

None reported

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Clinical trials

Trial information

Trial information

Subject disposition

Subject disposition

Baseline characteristics

Baseline characteristics

End points

End points

Primary: 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])

Primary: 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])

Secondary: RSV Viral Load Over Time

Secondary: RSV Viral Load Over Time

Secondary: Change From Baseline in RSV Viral Load Over Time

Secondary: Change From Baseline in RSV Viral Load Over Time

Secondary: Least Squares (LS) Mean RSV Viral Load on Days 3, 8, and 14

Secondary: Least Squares (LS) Mean RSV Viral Load on Days 3, 8, and 14

Secondary: Time to Undetectable RSV Viral Load

Secondary: Time to Undetectable RSV Viral Load

Secondary: Percentage of Subjects with Undetectable RSV Viral Load at Each Timepoint Throughout the Study

Secondary: Percentage of Subjects with Undetectable RSV Viral Load at Each Timepoint Throughout the Study

Secondary: Change from Baseline in Parent(s)/Caregiver(s) Pediatric RSV Electronic Severity and Outcomes Rating System (PRESORS) Scores

Secondary: Change from Baseline in Parent(s)/Caregiver(s) Pediatric RSV Electronic Severity and Outcomes Rating System (PRESORS) Scores

Secondary: Change from Baseline in Clinician PRESORS Score

Secondary: Change from Baseline in Clinician PRESORS Score

Secondary: Time to Improvement on Overall Health

Secondary: Time to Improvement on Overall Health

Secondary: Time to Resolution of RSV Symptoms Based on PRESORS Caregiver (ObsRO)

Secondary: Time to Resolution of RSV Symptoms Based on PRESORS Caregiver (ObsRO)

Secondary: Percentage of Subjects by Status of RSV Symptoms Based on PRESORS Caregiver (ObsRO) General Question Over Time

Secondary: Percentage of Subjects by Status of RSV Symptoms Based on PRESORS Caregiver (ObsRO) General Question Over Time

Secondary: Percentage of Subjects by Health Status Assessment Based on PRESORS Caregiver (ObsRO) General Question Over Time

Secondary: Percentage of Subjects by Health Status Assessment Based on PRESORS Caregiver (ObsRO) General Question Over Time

Secondary: Percentage of Subjects with Worsening or Improvement Status of RSV Disease

Secondary: Percentage of Subjects with Worsening or Improvement Status of RSV Disease

Secondary: Percentage of Subjects by Return to Pre-RSV Disease Health Status Assessment Based on PRESORS Caregiver (ObsRO) General Question Over Time

Secondary: Percentage of Subjects by Return to Pre-RSV Disease Health Status Assessment Based on PRESORS Caregiver (ObsRO) General Question Over Time

Secondary: Respiratory Rate Over Time

Secondary: Respiratory Rate Over Time

Secondary: Change from Baseline in Respiratory Rate

Secondary: Change from Baseline in Respiratory Rate

Secondary: Heart Rate Over Time

Secondary: Heart Rate Over Time

Secondary: Change from Baseline in Heart Rate

Secondary: Change from Baseline in Heart Rate

Secondary: Body Temperature Over Time

Secondary: Body Temperature Over Time

Secondary: Change from Baseline in Body Temperature

Secondary: Change from Baseline in Body Temperature

Secondary: Peripheral Capillary Oxygen Saturation (SpO2) Over Time

Secondary: Peripheral Capillary Oxygen Saturation (SpO2) Over Time

Secondary: Change from Baseline in Peripheral Capillary Oxygen Saturation (SpO2)

Secondary: Change from Baseline in Peripheral Capillary Oxygen Saturation (SpO2)

Secondary: Cohort 1: Time to Return to Age-adjusted Normal Values for Vital Signs

Secondary: Cohort 1: Time to Return to Age-adjusted Normal Values for Vital Signs

Secondary: Percentage of Subjects who Require (re)Hospitalisation During Treatment and Follow-up

Secondary: Percentage of Subjects who Require (re)Hospitalisation During Treatment and Follow-up

Secondary: Cohort 1: Time to Discharge From Hospital

Secondary: Cohort 1: Time to Discharge From Hospital

Secondary: Cohort 1: Percentage of Subjects who Required Admission to the Intensive Care Unit (ICU)

Secondary: Cohort 1: Percentage of Subjects who Required Admission to the Intensive Care Unit (ICU)

Secondary: Cohort 1: Time to Clinical Stability Evaluated by the Investigator

Secondary: Cohort 1: Time to Clinical Stability Evaluated by the Investigator

Secondary: Cohort 1: Duration of ICU Stay

Secondary: Cohort 1: Duration of ICU Stay

Secondary: Cohort 1: Percentage of Subjects who Required Supplemental Oxygen

Secondary: Cohort 1: Percentage of Subjects who Required Supplemental Oxygen

Secondary: Cohort 1: Percentage of Subjects who Required Non-invasive Mechanical Ventilation Support

Secondary: Cohort 1: Percentage of Subjects who Required Non-invasive Mechanical Ventilation Support

Secondary: Cohort 1: Duration of Supplemental Oxygen

Secondary: Cohort 1: Duration of Supplemental Oxygen

Secondary: Cohort 1: Duration of Non-invasive Ventilation Support

Secondary: Cohort 1: Duration of Non-invasive Ventilation Support

Secondary: Cohort 1: Percentage of Subjects who Required Invasive Mechanical Ventilation Support

Secondary: Cohort 1: Percentage of Subjects who Required Invasive Mechanical Ventilation Support

Secondary: Cohort 1: Percentage of Subjects who Required Non-invasive Non-mechanical Ventilation Support

Secondary: Cohort 1: Percentage of Subjects who Required Non-invasive Non-mechanical Ventilation Support

Secondary: Cohort 1: Percentage of Subjects who Needed Hydration and/or Feeding by Intravenous (IV) Administration or Nasogastric Tube

Secondary: Cohort 1: Percentage of Subjects who Needed Hydration and/or Feeding by Intravenous (IV) Administration or Nasogastric Tube

Secondary: Cohort 1: Time to End of Supplemental Oxygen up to 72 Hours From First Hospital Discharge