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

Study Status: Completed
Recruit Status: Completed
Study Type: Interventional

Official Title: A Phase 2a, Randomized, Double-blinded, Placebo-Controlled Study to Evaluate the Antiviral Activity, Safety, and Pharmacokinetics of Repeated Doses of Orally Administered JNJ 53718678 Against

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 Summary: 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.
Sponsor: Janssen Sciences Ireland UC

Current Primary Outcome: Area Under the Viral Load-time Curve (VL AUC) [ Time Frame: 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.


Original Primary Outcome: Same as current

Current Secondary Outcome:

  • Area Under the Viral Load-time Curve (VL AUC) Determined by Plaque Forming Unit (PFU) Assay [ Time Frame: 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 [ Time Frame: Baseline up to Follow-up (Day 28) ]
  • Peak Viral Load [ Time Frame: Baseline up to Follow-up (Day 28) ]
  • Time To Peak Viral Load [ Time Frame: 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 [ Time Frame: 24 hours after first dose ]
  • Area Under the Viral Load-time Curve (VL AUC) From Time 0 to 48 Hours after First Dose [ Time Frame: 48 hours after first dose ]
  • Time to Non-detectability of Virus [ Time Frame: Baseline up to Follow-up (Day 28) ]
    Time to non-detectability of virus from first administration of study drug will be assessed.
  • Total Clinical Symptom Score [ Time Frame: 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).
  • Time to Peak Symptom Score After Viral Inoculation [ Time Frame: Admission (Day -1 or -2) up to Day 13 ]
  • Mucus Weight [ Time Frame: Baseline up to Day 13 ]
  • Tissue Count [ Time Frame: Baseline up to Day 13 ]
  • Sequence Analysis of the Rsv-A Memphis 37b Genome [ Time Frame: Baseline and post-Baseline ]
  • Forced Expiratory Volume in 1 Second (FEV1) Measured by Spirometry [ Time Frame: 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 [ Time Frame: Baseline up to Follow-up (Day 28) ]
    FVC is the total volume of air expired after a full inspiration.
  • FEV1/FVC Ratio [ Time Frame: Baseline up to Follow-up (Day 28) ]


Original Secondary Outcome: Same as current

Information By: Janssen Sciences Ireland UC

Dates:
Date Received: March 9, 2015
Date Started: May 2015
Date Completion:
Last Updated: June 8, 2016
Last Verified: June 2016