The purpose of the study is to evaluate the safety and tolerability of single and multiple oral doses of JNJ-64417184 administered to healthy participants and the antiviral effect of multiple oral doses of JNJ-64417184 compared to placebo in participants infected through inoculation with respiratory syncytial virus (RSV)-A Memphis 37b (Part 4).
Study Type
INTERVENTIONAL
Allocation
RANDOMIZED
Purpose
TREATMENT
Masking
DOUBLE
Enrollment
130
Participants will receive JNJ-64417184 in Parts 1, 2A, 2B, 3, 4, 5 and 6.
Participants will receive matching placebo to JNJ-64417184 in Parts 1, 2A, 2B, 3, 4, 5 and 6.
hVIVO Services Limited
London, United Kingdom
Hammersmith Medicines Research Ltd
London, United Kingdom
Number of Participants With Adverse Events (AEs) as a Measure of Safety and Tolerability
An AE is any untoward medical occurrence in a participant who received study drug without regard to possibility of causal relationship.
Time frame: Approximately up to 8 months
Number of Participants With Laboratory Abnormalities
Number of participants with laboratory abnormalities will be reported.
Time frame: Approximately up to 8 months
Number of Participants With Clinically Significant Changes in Vital Signs
Number of participants with clinically significant changes in vital signs will be reported.
Time frame: Approximately up to 8 months
Number of Participants With Clinically Significant Changes in Physical Examination Findings
Number of participants with clinically significant changes in physical examination findings will be reported.
Time frame: Approximately up to 8 months
Number of Participants With ECG Abnormalities
Number of participants with electrocardiogram (ECG) abnormalities will be reported.
Time frame: Approximately up to 8 months
Change From Baseline in QT Interval Corrected According to Fridericia's Formula (QTcF) (Parts 1 and 3)
The QT interval corrected for heart rate (QTc interval) using Fridericia method will be measured by electrocardiograms (ECG) triplicates.
Time frame: Baseline up to Day 31
Change From Baseline in Forced Expiratory Volume in 1 Second (FEV1) Absolute as Measured by Spirometry (Part 4)
FEV1 is the amount of air that can be exhaled in one second. FEV1 will be measured by spirometry. A positive change from baseline in absolute FEV1 indicates improvement in lung function.
Time frame: Baseline up to Day 31
Change From Baseline in Forced Vital Capacity (FVC) Absolute as Measured by Spirometry (Part 4)
FVC is a standard pulmonary function test used to quantify respiratory muscle weakness. FVC is the volume of air that can forcibly be blown out after full inspiration in the upright position, in liters and will be measured by spirometry.
Time frame: Baseline up to Day 31
Change From Baseline in Percent-Predicted FEV1 (Part 4)
FEV1 is the amount of air, measured in liters, forcibly exhaled in 1 second. Pulmonary function tests will be performed by participants in the morning before dosing. The percent predicted FEV1 equals the participant's observed FEV1 divided by the participant's predicted FEV1 (determined by height and race) and converted to a percentage by multiplying by 100 percent (%).
Time frame: Baseline up to Day 31
Change From Baseline in Percent-Predicted FVC (Part 4)
Predicted FVC is based on a formula using sex, age and height of a person, and is an estimate of healthy lung capacity. Percent of predicted FVC = (observed value)/(predicted value) \* 100 %.
Time frame: Baseline up to Day 31
Area Under the Concentration-Time Curve Between Time of First Administration and Dosing Day 7 (AUC[0-Dosing Day 7]) of RSV-A Memphis 37b Viral Load in Participants Infected Through Inoculation With This Viral Strain (Part 4)
Area under the concentration-time curve between time of first administration and Dosing Day 7 (AUC\[0-Dosing Day 7)\] of respiratory syncytial virus (RSV)-A Memphis 37b viral load in participants infected through inoculation with this viral strain, as determined by a quantitative real-time polymerase chain reaction (qRT PCR) assay of nasal wash (Part 4) will be assessed.
Time frame: Up to Day 7
JNJ-64417184 Plasma Concentrations
Plasma concentration of JNJ-64417184 after a single oral dose and after multiple oral doses will be assessed.
Time frame: Approximately up to 67 days
JNJ-64417184 Urine Concentrations
Urine concentration of JNJ-64417184 after a single oral dose and after multiple oral doses will be assessed.
Time frame: Approximately up to 67 days
Corrected QT Interval (QTc) Duration (Parts 1 and 3)
QTc duration (as calculated from Holter extracts) after a single oral dose and after multiple oral doses administered to healthy participants will be reported.
Time frame: Up to Day 2 (Part 1); Up to Day 8 (Part 3)
AUC(0-Dosing Day 7) of RSV Viral Load From Treatment Onset (Part 4)
The AUC(0-Dosing Day 7) of RSV viral load from treatment onset, as determined by a qRT-PCR assay of nasal wash samples and by cell culture (plaque assay) will be reported.
Time frame: Up to Day 7
Time to Non-Detectability of RSV (Part 4)
Time to non-detectability of RSV as determined by a qRT-PCR assay of nasal wash samples and by cell culture (plaque assay) will be reported.
Time frame: Up to Day 31
Peak RSV Viral Load by Dosing Day (Part 4)
Peak RSV viral load by dosing day as determined by a qRT-PCR assay of nasal wash samples and by cell culture (plaque assay) will be reported.
Time frame: Up to Day 31
AUC(0-Dosing Day 7) of Total RSV Symptoms From Treatment Onset
The AUC(0-Dosing Day 7) of total RSV symptoms from treatment onset, using self reported symptoms on the symptom diary card (SDC) will be reported. Participants will assess any challenge virus-related symptoms using the symptom questionnaire in the SDC which will report the symptoms experienced by the participants at the moment on a scale of 0 to 3 where '0' implies 'no symptom' and '3' implies 'bothersome most or all of the time, stopping from participating in activities' OR 'less severe' to 'more severe' symptoms.
This platform is for informational purposes only and does not constitute medical advice. Always consult a qualified healthcare professional.
Time frame: Up to Day 7
Total Weight of Mucus (Part 4)
The total weight of mucus produced from treatment onset will be reported.
Time frame: Up to Day 12
Change From Baseline in the RSV L Protein-Encoding Gene Sequence After Treatment (Part 4)
Change from baseline in sequence of the RSV L protein encoding gene before and after treatment, for participants who show rebound, partial viral suppression or non-response to JNJ-64417184, will be assessed.
Time frame: Baseline up to Day 11