A Study to Explore the Antiviral Activity, Clinical Outcomes, Safety, Tolerability, and Pharmacokinetics of JNJ-53718678 at Two Dose Levels in Non-Hospitalized Adult Participants Infected With Respiratory Syncytial Virus

Study Overview
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Brief Summary
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The purpose of this study is to explore the antiviral effect of JNJ-53718678 at 2 dose levels (80 milligrams [mg] and 500 mg) once daily for 7 days in adults with Respiratory Syncytial Virus (RSV) infection, as measured by RSV viral load in nasal secretions by quantitative reverse transcription polymerase chain reaction (qRT-PCR) assay.

Detailed Description
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This study will be performed to explore the antiviral activity, clinical outcomes, safety, tolerability, and pharmacokinetics of JNJ-53718678 in adult participants infected with RSV. The study will include both participants who are otherwise healthy (ie, without underlying condition) or who have comorbid conditions (eg, asthma, chronic obstructive pulmonary disease (COPD), cardiovascular disease, other chronic diseases), with the exception of immunocompromised participants, presenting for medical care but not requiring hospitalization. The study will include a screening period (Day -1 to Day 1), a treatment Period (Day 1 to Day 8), and a follow-up period (Day 9 to Day 28). Safety evaluations will include adverse events, laboratory tests, electrocardiogram, vital signs, physical examination, and specific toxicities.

Official Title
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A Pilot Phase 2a, Randomized, Double-blind, Placebo-controlled Study to Explore the Antiviral Activity, Clinical Outcomes, Safety, Tolerability, and Pharmacokinetics of JNJ-53718678 at Two Dose Levels in Non-Hospitalized Adult Subjects Infected With Respiratory Syncytial Virus

Conditions
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Respiratory Syncytial Virus Infections

Intervention / Treatment
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* Drug: JNJ-53718678 500 mg
* Drug: JNJ-53718678 80 mg
* Drug: Placebo


Participation Criteria
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Eligibility Criteria
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Inclusion Criteria: Participants must have an acute respiratory illness with signs and symptoms consistent with a viral infection (example, fever, cough, nasal congestion, runny nose, sore throat, myalgia, lethargy, shortness of breath, or wheezing) with onset less than or equal to 5 days from the anticipated time of randomization. Onset of symptoms is defined as the time the participant becomes aware of the first sign and/or symptom consistent with a viral infection Participant has been diagnosed with respiratory syncytial virus (RSV) infection using a rapid polymerase chain reaction (PCR) based or rapid-antigen-detection test Before randomization, a woman must be not of childbearing potential defined as: Premenarchal, Postmenopausal or Permanently sterile A male participant must agree to the use of acceptable contraceptive measures With the exception of the RSV-related illness the participant must be medically stable on the basis of physical examination, medical history, vital signs, and electrocardiogram (ECG) performed at screening Exclusion Criteria: Hospitalized participants or participants expected to be hospitalized within 24 hours of screening History of or concurrent illness (beyond a comorbid condition) that in the opinion of the investigator, might confound the results of the study or pose an additional risk in administering study drug to the participant or that could prevent, limit, or confound the protocol-specified assessments Participants who had major surgery within the 28 days prior to randomization or have planned major surgery through the course of the study Participants who are considered by the investigator to be immunocompromised within the past 12 months Participant has known or suspected chronic or acute hepatitis B or C infection Women who are pregnant or breastfeeding Participants with clinically significant abnormal ECG findings (other than QT-interval corrected for heart rate according to Fridericia [QTcF] interval greater than [>] 500 millisecond [ms]) not consistent with the underlying condition in the study population, as judged by the investigator

Ages Eligible for Study
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Minimum Age: 18 Years

Sexes Eligible for Study
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All

Accepts Healthy Volunteers
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No

Study Plan
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How is the study designed?
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Design Details

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


Arms and Interventions

| Participant Group/Arm | Intervention/Treatment |
| --- | --- |
| Experimental: Treatment A: JNJ-53718678 500 mg<br>Participants will receive 500 mg dose of JNJ-53718678 once daily for 7 days. | Drug: JNJ-53718678 500 mg<br>* Participants will receive 500 mg dose of JNJ-53718678 oral solution once daily for 7 days.<br>|
| Experimental: Treatment B: JNJ-53718678 80 mg + Placebo<br>Participants will receive 80 mg dose of JNJ-53718678 along with the matching placebo to the same total volume as for the 500 mg dose once daily for 7 days. | Drug: JNJ-53718678 80 mg<br>* Participants will receive 80 mg dose of JNJ-53718678 oral solution along with the matching placebo to the same total volume as for the 500 mg dose once daily for 7 days.<br>Drug: Placebo<br>* In treatment B, participants will receive matching placebo along with JNJ-53718678 to maintain the same total volume as for the 500 mg dose once daily for 7 days. In treatment C, participants will receive matching placebo to the same total volume as for the 500 mg dose once daily for 7 days.<br>|
| Placebo Comparator: Treatment C: Placebo<br>Participants will receive matching placebo to the same total volume as for the 500 mg dose once daily for 7 days. | Drug: Placebo<br>* In treatment B, participants will receive matching placebo along with JNJ-53718678 to maintain the same total volume as for the 500 mg dose once daily for 7 days. In treatment C, participants will receive matching placebo to the same total volume as for the 500 mg dose once daily for 7 days.<br>|

What is the study measuring?
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Primary Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| Area Under the Respiratory Syncytial Virus (RSV) Viral Load (VL)-Time Curve (AUC) From Immediately Prior to First Dose of Study Drug (Baseline) Through Day 3 | Area under the RSV VL-time curve (AUC) was determined as log10 copies*hour per milliliter (Log10 copies*hr/mL) by quantitative reverse transcription polymerase chain reaction (qRT-PCR) assay of mid turbine nasal swabs. | Baseline through Day 3 | 
| Area Under the RSV VL-time Curve (AUC) From Immediately Prior to First Dose of Study Drug (Baseline) Through Day 5 | Area under the RSV VL-time curve (AUC) was determined as Log10 copies*hr/mL by qRT-PCR assay of mid turbine nasal swabs. | Baseline through Day 5 | 
| Area Under the RSV VL-time Curve (AUC) From Immediately Prior to First Dose of Study Drug (Baseline) Through Day 8 | Area under the RSV VL-time curve (AUC) was determined as Log10 copies*hr/mL by qRT-PCR assay of mid turbine nasal swabs. | Baseline through Day 8 | 
| Area Under the RSV VL-time Curve (AUC) From Immediately Prior to First Dose of Study Drug (Baseline) Through Day 14 | Area under the RSV VL-time curve (AUC) was determined as Log10 copies*hr/mL by qRT-PCR assay of mid turbine nasal swabs. | Baseline through Day 14 | 
| Change From Baseline in RSV Viral Load at Day 3 | Change from baseline in RSV viral load at Day 3 was measured as Log10 copies/mL by qRT-PCR assay in the mid-turbinate nasal swab specimens. | Baseline to Day 3 | 
| Change From Baseline in RSV Viral Load at Day 5 | Change from baseline in RSV viral load at Day 5 was measured as Log10 copies/mL by qRT-PCR assay in the mid-turbinate nasal swab specimens. | Baseline to Day 5 | 
| Change From Baseline in RSV Viral Load at Day 8 | Change from baseline in RSV viral load at Day 8 was measured as Log10 copies/mL by qRT-PCR assay in the mid-turbinate nasal swab specimens. | Baseline to Day 8 | 
| Change From Baseline in RSV Viral Load at Day 14 | Change from baseline in RSV viral load at Day 14 was measured as Log10 copies/mL by qRT-PCR assay in the mid-turbinate nasal swab specimens. | Baseline to Day 14 | 
| Change From Baseline in RSV Viral Load at Day 21 | Change from baseline in RSV viral load oat Day 21 was measured as Log10 copies/mL by qRT-PCR assay in the mid-turbinate nasal swab specimens. | Baseline to Day 21 | 
| RSV Viral Load at Baseline | RSV viral load was measured as log10 copies/mL by qRT-PCR assay in the mid-turbinate nasal swab specimens. | Baseline | 
| RSV Viral Load at Day 3 | RSV viral load was measured as log10 copies/mL by qRT-PCR assay in the mid-turbinate nasal swab specimens. | Day 3 | 
| RSV Viral Load at Day 5 | RSV viral load was measured as log10 copies/mL by qRT-PCR assay in the mid-turbinate nasal swab specimens. | Day 5 | 
| RSV Viral Load at Day 8 | RSV viral load was measured as log10 copies/mL by qRT-PCR assay in the mid-turbinate nasal swab specimens. | Day 8 | 
| RSV Viral Load at Day 14 | RSV viral load was measured as log10 copies/mL by qRT-PCR assay in the mid-turbinate nasal swab specimens. | Day 14 | 
| RSV Viral Load at Day 21 | RSV viral load was measured as log10 copies/mL by qRT-PCR assay in the mid-turbinate nasal swab specimens. | Day 21 | 
| Time to Undetectable RSV Viral Load | The time to undetectable nasal RSV RNA viral load was defined as the time in days from initiation of study treatment until first post-baseline time point at which RSV RNA was undetectable and after which time there were no more detectable virus assessments. | Up to Day 21 | 
| Percentage of Participants With Undetectable RSV Viral Load at Day 3 | Percentage of participants with undetectable RSV viral load at Day 3 were reported. | Day 3 | 
| Percentage of Participants With Undetectable RSV Viral Load at Day 5 | Percentage of participants with undetectable RSV viral load at Day 5 were reported. | Day 5 | 
| Percentage of Participants With Undetectable RSV Viral Load at Day 8 | Percentage of participants with undetectable RSV viral load at Day 8 were reported. | Day 8 | 
| Percentage of Participants With Undetectable RSV Viral Load at Day 14 | Percentage of participants with undetectable RSV viral load at Day 14 were reported. | Day 14 | 
| Percentage of Participants With Undetectable RSV Viral Load at Day 21 | Percentage of participants with undetectable RSV viral load at Day 21 were reported. | Day 21 | 

Secondary Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| Number of Participants With Adverse Events (AEs) as a Measure of Safety and Tolerability | An adverse event is any untoward medical event that occurs in a participant administered an investigational product, and it does not necessarily indicate only events with clear causal relationship with the relevant investigational product. | Up to Day 28 | 
| Number of Participants With Worst Treatment-Emergent Laboratory Abnormalities | Number of participants with worst treatment-emergent laboratory abnormalities (serum chemistry, hematology and urinalyses) were reported based on DMID toxicity grading scale. DMID toxicity grade categorized as Grade 1=mild(mild discomfort (< 48 hours); no medical intervention/therapy required), Grade 2= moderate (Moderate Mild to moderate limitation in activity - some assistance may be needed; no or minimal medical intervention/therapy required), Grade 3= severe (severe Marked limitation in activity, some assistance usually required; medical intervention/therapy required, hospitalizations possible), and Grade 4=life threatening (extreme limitation in activity, significant assistance required; significant medical intervention/therapy required, hospitalization or hospice care probable). | Up to Day 28 | 
| Number of Participants With Worst Treatment-Emergent Vital Sign Abnormalities | Number of participants with worst treatment emergent vital sign abnormalities (including Systolic blood pressure [SBP] and diastolic blood pressure [DBP]) as abnormally low, mild increased, moderate increased and severe increased were reported. SBP: Abnormally low- Less than or equal to (<=) 50 mmHg, Grade 1 (mild)- 90 mmHg - < 100 mmHg, Grade 2 (moderate)- greater than or equal to (>=)100 mmHg to < 110 mmHg, Grade 3 (severe)- >=110 mmHg; DBP: Abnormally low- <=90 mmHg, Grade 1 (mild)- 140 mmHg - < 160 mmHg, Grade 2 (moderate)- >=160 mmHg to < 180 mmHg, Grade 3 (severe)- >=180 mmHg. | Up to Day 28 | 
| Number of Participants With Worst Treatment-Emergent (TE) Electrocardiograms (ECGs) Abnormalities | The number of participants with worst TE ECG abnormalities were reported. The ECG variables that were analyzed included heart rate, PR interval, QRS interval, QT interval, and corrected QT (QTc) interval. Parameters for abnormal ECG findings were QT interval corrected for heart rate (QTc) according to Bazett's formula (QTcB or Borderline Prolonged QTcB) Interval ([450 milliseconds {ms}, 480 ms], [480 ms, 500 ms], and [more than 500 ms]), QTc according to Fridericia's formula (QTcF or Borderline Prolonged QTcB) Interval ([450 ms, 480 ms], [480 ms, 500 ms], and [more than 500 ms]). | Up to Day 28 | 
| Peripheral Capillary Oxygen Saturation (SpO2) Over Time | Peripheral capillary oxygen saturation was measured by the investigator over time. | Baseline, Days 3, 8, 14, and 21 | 
| Change From Baseline in Peripheral Capillary Oxygen Saturation | Change from baseline in peripheral capillary oxygen saturation levels was calculated by the investigator. | Baseline to Days 3, 8, 14 and 21 | 
| Pulse Rate Over Time | Pulse rate was measured by the investigator over time. | Baseline, Days 3, 8, 14 and 21 | 
| Change From Baseline in Pulse Rate | Change from baseline in pulse rate was calculated and reported by the investigator. | Baseline to Days 3, 8, 14 and 21 | 
| Respiratory Rate Over Time | Respiratory rate was measured by the investigator over time. | Baseline, Days 3, 8, 14 and 21 | 
| Change From Baseline in Respiratory Rate | Change from baseline in respiratory rate was calculated and reported by the investigator. | Baseline to Days 3, 8, 14 and 21 | 
| Body Temperature Over Time | Body temperature was measured over time. Participants were provided a thermometer and asked to record body temperature in the electronic device. | Baseline, Days 3, 8, 14 and 21 | 
| Change From Baseline in Body Temperature | Change from baseline in body temperature was calculated and reported. Participants were provided a thermometer and asked to record body temperature in the electronic device. | Baseline to Days 3, 5, 8, 14 and 21 | 
| Area Under the Plasma Concentration-Time Curve From Time Point 0 Hours Until 24 Hours Post Dose | AUC (0-24) is defined as area under the plasma concentration-time curve from time point 0 hours until 24 hours post dose. | 0 to 24 hours post dose on Days 1 and 7 | 
| Severity of Signs and Symptoms of RSV Assessed by Respiratory Infection-Patient Reported Outcomes (RI-PRO) Questionnaire | The severity of signs and symptoms of RSV infection was assessed using the RI-PRO questionnaire. The RI-PRO questionnaire is 32-item questionnaire. It summarizes severity of 6 symptom domains: nose (4 items), throat (3 items), eyes (3 items), chest/respiratory (7 items), gastrointestinal (4 items), and body/systemic (11 items). Each RI-PRO domain score ranges from 0 (symptom free) to 4 (very severe symptoms). Domain scores were calculated as the arithmetic mean of the scores for items within the domain. | Baseline, Days 3, 5, 8, 14 and 21 | 
| Duration of Signs and Symptoms of RSV Assessed by RI-PRO | Duration of signs and symptoms of RSV infection was assessed by the time to resolution of all RSV symptoms from RI-PRO questionnaire. Resolution was defined as a score of 'Not at all/symptom-free' (score=0) or 'A little bit' (score=1) for at least 24 hours. The RI-PRO questionnaire is a 32-item questionnaire. It summarizes severity of 6 symptom domains: nose (4 items), throat (3 items), eyes (3 items), chest/respiratory (7 items), gastrointestinal (4 items) and body/systemic (11 items). Each RI-PRO score ranges from 0 (symptom-free) to 4 (very severe symptoms). | Baseline up to Day 21 | 
| Time to Resolution of Key RSV Symptoms as Assessed by RI-PRO Questionnaire | Time to resolution of key RSV symptoms (congested or stuffy nose, sore or painful throat, trouble breathing, chest tightness, coughing, coughed up mucus or phlegm, weak or tired) as assessed by RI-PRO questionnaire was reported. Resolution of RSV symptoms was defined as a score of 'Not at all/symptom free' (score = 0) or 'A little bit' (score = 1) for at least 24 hours for symptoms of the RI-PRO questionnaire. The RI-PRO questionnaire is 32-item questionnaire. It summarizes severity of 6 symptom domains: nose (4 items), throat (3 items), eyes (3 items), chest/respiratory (7 items), gastrointestinal (4 items), and body/systemic (11 items). Each RI-PRO score ranges from 0 (symptom-free) to 4 (very severe symptoms). | Up to Day 21 | 
| Time to Return to Usual Activity/Health Based on RI-PRO Questionnaire | Time from the first dose of study drug until the time to return to usual activity/health was determined. Return to usual activity/health when the response is 'Yes' on RI-PRO additional question 7 ('Have you returned to your usual activity/health today?') for at least 24 hours. | Up to Day 21 | 
| Predose Plasma Concentration (Ctrough) of JNJ-53718678 | Ctrough is the trough plasma concentration of JNJ-53718678 estimated by population PK model. | Predose on Days 1 and 7 | 
| Maximum Plasma Concentration (Cmax) of JNJ-53718678 | Cmax is the maximum plasma concentration of JNJ-53718678 estimated by population PK model. | Days 1 and 7 |