Clinical trial NCT02387606: Study to Evaluate Antiviral Activity, Safety, and Pharmacokinetics of Repeated Doses of Orally Administered JNJ 53718678 Against Respiratory Syncytial Virus Infection.
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
Study type: INTERVENTIONAL
Overall status: COMPLETED
Phase: PHASE2
Conditions: Respiratory Syncytial Virus Infections
Keywords: Respiratory Syncytial Virus Infections
Placebo
Antiviral activity
JNJ-53718678
Lead sponsor: Janssen Sciences Ireland UC
Sponsor class: INDUSTRY
First posted: 2015-03-13
Enrollment: 66
Sex: ALL
Minimum age (years): 18
Maximum age (years): 45
Standard ages: ADULT
Accepts healthy volunteers: yes
Allocation: RANDOMIZED
Intervention model: PARALLEL
Primary purpose: TREATMENT

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.

Eligibility criteria: 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)

Primary outcomes:
measure: Area Under the Viral Load-time Curve (VL AUC)
timeFrame: up to Follow-up (Day 28)
Secondary outcomes:
measure: Area Under the Viral Load-time Curve (VL AUC) Determined by Plaque Forming Unit (PFU) Assay
timeFrame: Baseline up to Follow-up (Day 28)
measure: Viral Load Over Time
timeFrame: Baseline up to Follow-up (Day 28)
measure: Peak Viral Load
timeFrame: Baseline up to Follow-up (Day 28)
measure: Time To Peak Viral Load
timeFrame: Baseline up to Follow-up (Day 28)
measure: Area Under the Viral Load-time Curve (VL AUC) From Time 0 to 24 Hours after First Dose
timeFrame: 24 hours after first dose
measure: Area Under the Viral Load-time Curve (VL AUC) From Time 0 to 48 Hours after First Dose
timeFrame: 48 hours after first dose
measure: Time to Non-detectability of Virus
timeFrame: Baseline up to Follow-up (Day 28)
measure: Total Clinical Symptom Score
timeFrame: Admission (Day -1 or -2) up to Day 13
measure: Time to Peak Symptom Score After Viral Inoculation
timeFrame: Admission (Day -1 or -2) up to Day 13
measure: Mucus Weight
timeFrame: Baseline up to Day 13
measure: Tissue Count
timeFrame: Baseline up to Day 13
measure: Sequence Analysis of the Rsv-A Memphis 37b Genome
timeFrame: Baseline and post-Baseline
measure: Forced Expiratory Volume in 1 Second (FEV1) Measured by Spirometry
timeFrame: Baseline up to Follow-up (Day 28)
measure: Forced Vital Capacity (FVC) Measured by Spirometry
timeFrame: Baseline up to Follow-up (Day 28)
measure: FEV1/FVC Ratio
timeFrame: Baseline up to Follow-up (Day 28)
Other outcomes:
Locations:
city: London
country: United Kingdom
Study officials:
affiliation: Janssen Sciences Ireland UC
name: Janssen Sciences Ireland UC Clinical Trial
role: STUDY_DIRECTOR
References:
citation: Stevens M, Rusch S, DeVincenzo J, Kim YI, Harrison L, Meals EA, Boyers A, Fok-Seang J, Huntjens D, Lounis N, Mari N K, Remmerie B, Roymans D, Koul A, Verloes R. Antiviral Activity of Oral JNJ-53718678 in Healthy Adult Volunteers Challenged With Respiratory Syncytial Virus: A Placebo-Controlled Study. J Infect Dis. 2018 Jul 24;218(5):748-756. doi: 10.1093/infdis/jiy227.