Study to Evaluate Antiviral Activity, Safety, and Pharmacokinetics of Repeated Doses of Orally Administered JNJ 53718678 Against Respiratory Syncytial Virus Infection.

Phase 2

Completed

• Conditions: Respiratory Syncytial Virus Infections
• Interventions: Drug: Placebo; Drug: JNJ-53718678

• Registration Number: NCT02387606
• Lead Sponsor: Janssen Sciences Ireland UC

Brief Summary

The purpose of this study is to evaluate the antiviral effect of repeated oral dosing of JNJ 53718678 compared to placebo in healthy adult participants infected through inoculation with respiratory syncytial virus (RSV)-A Memphis 37b virus.

Detailed Description

This is a randomized (study medication assigned to participants by chance), double-blind (neither physician nor participant knows the identity of the assigned treatment), placebo-controlled, single-center study of JNJ 53718678 in healthy adult participants. Study consists of 3 phases: Screening (Day -56 and Study Day -3 prior to the planned date of virus inoculation/challenge on Study Day 0), quarantine (includes challenge on Day -1 or -2 and treatment for 7 days), and follow-up (Day 15 and 28). Participants will be admitted to the quarantine unit on Study Day -1 or - 2 and will be inoculated (intranasal) with the RSV-A Memphis 37b virus on Study Day 0. Participants will be evaluated in 3 cohorts: Cohort 1 and Cohort 3 (participants will be dosed with JNJ-53718678 or placebo for 7 days) and Cohort 2 (for up to 7 days \[Dosing Days 1-x\] \[x will be determined based on the results from Cohort 1\]). Participants will be randomized and JNJ-53718678/placebo dosing will be started after RSV presence in nasal wash has been detected by polymerase chain reaction (PCR). After completion of Cohort 1, data will be reviewed (unblinded) and the antiviral activity, safety, pharmacokinetic, clinical symptom and mucus weight data will be evaluated, based on which Cohort 2 will be initiated. Participants' safety will be monitored throughout the study.

Study Timeline

• Study First Submitted: 2015-03-09
• Study First Submitted QC: 2015-03-09
• Study First Posted: 2015-03-13
• Study Start: 2015-05-07
• Primary Completion: 2015-09-21
• Study Completion: 2015-10-02
• Disposition First Submitted: 2016-06-08
• Disposition First Submitted QC: 2016-06-08
• Disposition First Posted: 2016-06-10
• Status Verified: 2022-10
• Last Update Submitted: 2022-10-25
• Last Update Posted: 2022-10-26

Recruitment & Eligibility

• Status: COMPLETED
• Sex: All
• Target Recruitment: 66

Inclusion Criteria

• Female participants must be of non-childbearing potential: postmenopausal for at least 2 years or surgically sterile or otherwise incapable of becoming pregnant
• Female participants, except for postmenopausal women, must have a negative serum pregnancy test at screening
• Participants must agree to comply with contraceptive measures as mentioned in protocol
• Participants must be sero-suitable for respiratory syncytial virus (RSV) within 57 days prior to inoculation
• Participants must be non-smokers for at least one month prior to screening and participants must have a negative cotinine test at screening

Exclusion Criteria

• Participants with a past history of heart arrhythmias (extrasystoli, tachycardia at rest) or of risk factors for Torsade de Pointes syndrome
• Participants with a history or evidence of abuse of alcohol, barbiturates, amphetamines, recreational or narcotic drug use within the past 3 months, which in the Investigator's opinion would compromise participant's safety and/or compliance with the study procedures
• Participants with current human immunodeficiency virus type 1 (HIV-1) or HIV-2 infection at screening
• Participants with current hepatitis A infection, or hepatitis B virus (HBV) infection, or hepatitis C virus (HCV) infection (confirmed by HCV antibody) at screening
• Participants with active acute respiratory infection at admission (Study Day -1 or -2)

Study & Design

• Study Type: INTERVENTIONAL
• Study Design: PARALLEL

Arm && Interventions

Group	Intervention	Description
Cohort 3	Placebo	Participants will receive placebo or JNJ-53718678, 75 mg once daily for 7 days.
Cohort 2	Placebo	Participants will receive placebo or JNJ-53718678; dosing regimen in Cohort 2 will be decided based on Cohort 1 results.
Cohort 1	Placebo	Participants will receive placebo or JNJ-53718678 500 milligram (mg) or 200 mg once daily for 7 days.
Cohort 1	JNJ-53718678	Participants will receive placebo or JNJ-53718678 500 milligram (mg) or 200 mg once daily for 7 days.
Cohort 2	JNJ-53718678	Participants will receive placebo or JNJ-53718678; dosing regimen in Cohort 2 will be decided based on Cohort 1 results.
Cohort 3	JNJ-53718678	Participants will receive placebo or JNJ-53718678, 75 mg once daily for 7 days.

Primary Outcome Measures

Name	Time	Method
Area Under the Viral Load-time Curve (VL AUC)	up to Follow-up (Day 28)	VL AUC for RSV-A Memphis 37b will be determined by quantitative reverse transcriptase -polymerase chain reaction (qRT-PCR) assay of nasal wash. The VL AUC will be calculated based on the viral load values measured 2 times per day, starting with the last value prior to first dosing, and ending with the last available value before discharge.

Secondary Outcome Measures

Name	Time	Method
Area Under the Viral Load-time Curve (VL AUC) Determined by Plaque Forming Unit (PFU) Assay	Baseline up to Follow-up (Day 28)	VL AUC for RSV-A Memphis 37b will be determined by PFU assay of nasal wash.
Viral Load Over Time	Baseline up to Follow-up (Day 28)
Time To Peak Viral Load	Baseline up to Follow-up (Day 28)	Time to peak viral load will be reported.
Area Under the Viral Load-time Curve (VL AUC) From Time 0 to 24 Hours after First Dose	24 hours after first dose
Tissue Count	Baseline up to Day 13
Peak Viral Load	Baseline up to Follow-up (Day 28)
Area Under the Viral Load-time Curve (VL AUC) From Time 0 to 48 Hours after First Dose	48 hours after first dose
Sequence Analysis of the Rsv-A Memphis 37b Genome	Baseline and post-Baseline
Total Clinical Symptom Score	Admission (Day -1 or -2) up to Day 13	Total clinical symptom score will be assessed using a composite of 10 self-reported symptoms on the Symptom Diary Card. The Investigator will review the participant's SDC entries on a daily basis after the administration of challenge virus inoculum. Total Clinical Symptom Score ranges from 0 (no symptoms) to 3 (not well).
FEV1/FVC Ratio	Baseline up to Follow-up (Day 28)
Time to Non-detectability of Virus	Baseline up to Follow-up (Day 28)	Time to non-detectability of virus from first administration of study drug will be assessed.
Time to Peak Symptom Score After Viral Inoculation	Admission (Day -1 or -2) up to Day 13
Mucus Weight	Baseline up to Day 13
Forced Expiratory Volume in 1 Second (FEV1) Measured by Spirometry	Baseline up to Follow-up (Day 28)	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 FEV1 indicates improvement in lung function.
Forced Vital Capacity (FVC) Measured by Spirometry	Baseline up to Follow-up (Day 28)	FVC is the total volume of air expired after a full inspiration.