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

Respiratory Syncytial Virus Infections Clinical Trial

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 Respiratory Syncytial Virus Infection in the Virus Challenge Model in Healthy Adult Subjects

Clinical Trial Details — Status: Completed

Administrative data

• NCT number: NCT02387606
• Other study ID #: CR106786
• Secondary ID: 2014-005041-4153
• Status: Completed
• Phase: Phase 2
• Start date: May 7, 2015
• Est. completion date: October 2, 2015

Study information

• Verified date: October 2022
• Source: Janssen Sciences Ireland UC
• Contact: n/a
• Is FDA regulated: No
• Study type: Interventional

Clinical Trial 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.

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.

Recruitment information / eligibility

• Status: Completed
• Enrollment: 66
• Est. completion date: October 2, 2015
• Est. primary completion date: September 21, 2015
• Accepts healthy volunteers: Accepts Healthy Volunteers
• Gender: All
• Age group: 18 Years to 45 Years

Eligibility

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)

Related Conditions & MeSH terms

• Communicable Diseases
• Infections
• Respiratory Syncytial Virus Infections
• Virus Diseases

Intervention

Drug:
• Placebo
Participants will receive placebo once daily.
• JNJ-53718678
Participants will receive JNJ-53718678 as 20 milliliter (mL) (200 mg) or 50 mL (500 mg) oral solution (containing 10 mg JNJ-53718678 per mL) in Cohort 1. JNJ-53718678 dose in Cohort 2 will be decided based on Cohort 1 results. JNJ-53718678 as 7.5 mL (75 mg) oral solution (containing 10 mg JNJ-53718678 per mL) in Cohort 3.

Locations

Country	Name	City	State
n/a

Sponsors (1)

Lead Sponsor	Collaborator
Janssen Sciences Ireland UC

Country where clinical trial is conducted

United Kingdom, 

Outcome

Type	Measure	Description	Time frame	Safety issue
Primary	Area Under the Viral Load-time Curve (VL AUC)	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.	up to Follow-up (Day 28)
Secondary	Area Under the Viral Load-time Curve (VL AUC) Determined by Plaque Forming Unit (PFU) Assay	VL AUC for RSV-A Memphis 37b will be determined by PFU assay of nasal wash.	Baseline up to Follow-up (Day 28)
Secondary	Viral Load Over Time		Baseline up to Follow-up (Day 28)
Secondary	Peak Viral Load		Baseline up to Follow-up (Day 28)
Secondary	Time To Peak Viral Load	Time to peak viral load will be reported.	Baseline up to Follow-up (Day 28)
Secondary	Area Under the Viral Load-time Curve (VL AUC) From Time 0 to 24 Hours after First Dose		24 hours after first dose
Secondary	Area Under the Viral Load-time Curve (VL AUC) From Time 0 to 48 Hours after First Dose		48 hours after first dose
Secondary	Time to Non-detectability of Virus	Time to non-detectability of virus from first administration of study drug will be assessed.	Baseline up to Follow-up (Day 28)
Secondary	Total Clinical Symptom Score	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).	Admission (Day -1 or -2) up to Day 13
Secondary	Time to Peak Symptom Score After Viral Inoculation		Admission (Day -1 or -2) up to Day 13
Secondary	Mucus Weight		Baseline up to Day 13
Secondary	Tissue Count		Baseline up to Day 13
Secondary	Sequence Analysis of the Rsv-A Memphis 37b Genome		Baseline and post-Baseline
Secondary	Forced Expiratory Volume in 1 Second (FEV1) Measured by Spirometry	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.	Baseline up to Follow-up (Day 28)
Secondary	Forced Vital Capacity (FVC) Measured by Spirometry	FVC is the total volume of air expired after a full inspiration.	Baseline up to Follow-up (Day 28)
Secondary	FEV1/FVC Ratio		Baseline up to Follow-up (Day 28)