Clinical trial NCT02593851: A Study to Assess the Pharmacokinetics, Safety, and Tolerability of Multiple Doses of Orally Administered JNJ-53718678 in Infants Hospitalized With Respiratory Syncytial Virus (RSV) Infection
Official title: A Phase 1b, Randomized, Partially Double-blind, Placebo-controlled Study to Assess the Pharmacokinetics, Safety, and Tolerability of Multiple Doses of Orally Administered JNJ-53718678 in Infants Hospitalized With RSV Infection
Study type: INTERVENTIONAL
Overall status: TERMINATED
Phase: PHASE1
Conditions: Respiratory Syncytial Virus Infections
Virus Diseases
Keywords: Respiratory Syncytial Virus Infections
JNJ-53718678
Placebo
Infants
Lead sponsor: Janssen Sciences Ireland UC
Sponsor class: INDUSTRY
First posted: 2015-11-01
Enrollment: 45
Sex: ALL
Minimum age (years): 1
Maximum age (years): 24
Standard ages: CHILD
Accepts healthy volunteers: no
Allocation: RANDOMIZED
Intervention model: PARALLEL
Primary purpose: TREATMENT

Brief summary: The purpose of this study is to evaluate pharmacokinetics, safety, tolerability, antiviral activity, and impact on the clinical course of Respiratory Syncytial Virus (RSV) infection after multiple oral doses of JNJ-53718678 at different doses and/or dosing regimens in infants (greater than \[\>\] 1 month to less than or equal to \[\<=\] 24 months of age) who are hospitalized with RSV infection.

Detailed description: This is a Phase 1b, randomized (study medication assigned to participants by chance), partially double-blind (neither physician nor participant knows the identity of the assigned treatment), placebo-controlled, multicenter, multiple ascending dose study of JNJ 53718678 in infants (greater than \[\>\] 1 month to less than or equal to \[\<=\] 24 months of age) who are hospitalized with RSV infection. The duration of study will be approximately 4 weeks for each participant excluding screening period. In Part 1 of study, minimum total number of 42 participants will be divided in 3 cohorts: Age group 1 (Cohorts 1a-1e) (greater than or equal to \[\>=\] 6 months and less than or equal to \[\<=\] 24 months of age), Age group 2 (Cohorts 2a-2e)(\>=3 months and less than \[\<\] 6 months of age) and Age group 3 (Cohorts 3a-3e) (greater than \[\>\] 1 month and \<3 months of age). Each age group will consist of a minimum of 3 cohorts with the possibility to add 2 more per age group (Cohorts a through e) in which different doses and/or dosing regimens will be evaluated. Each cohort will consist of 5 participants (4 participants receiving JNJ-53718678 and 1 participant receiving placebo for 7 days), except for the first cohort of each age group which will contain only 4 participants (4 participants receiving JNJ 53718678). In Part 2 of the study, all age groups will be included in a single cohort, Cohort f, in which the selected dose regimen determined during Part 1 of the study will be used for each of the 3 age groups. A minimum of approximately 18 (12 participants receiving JNJ 53718678 and 6 participants receiving placebo) and a maximum of 24 participants (16 participants receiving JNJ 53718678 and 8 participants receiving placebo) will be included in this part of the study. Pharmacokinetics and safety of JNJ-53718678 will be evaluated primarily. Participants' safety will be monitored throughout the study.

Eligibility criteria: Inclusion Criteria:

* Participant has presented at the hospital for suspected Respiratory Syncytial Virus (RSV) infection within 72 hours prior to Screening completion
* Participant has been hospitalized for this suspected RSV infection
* Participant has been diagnosed with RSV infection using a polymerase chain reaction (PCR)-based assay, preferably commercially available locally
* Participant was born after a normal term pregnancy (greater than or equal to 37 weeks and 0 days)
* A legally acceptable representative of the participant must sign an Informed consent form (ICF) indicating that he or she understands the purpose of and procedures required for the study, are willing for their child to participate in the study, are willing for their child to remain in the hospital for the first 3 days of dosing (even if not clinically indicated), and are willing/able to adhere to the prohibitions and restrictions specified in the protocol and study procedures

Exclusion Criteria:

* Participant who had major surgery within the 28 days prior to randomization or planned major surgery through the course of the study
* Participant has major congenital anomalies or known cytogenetic disorders
* Participant has known or suspected immunodeficiency, such as known human immunodeficiency virus (HIV) infection
* Participant has known or suspected hepatitis B or C infection
* Participant is upon current admission initially hospitalized in the Intensive care unit (ICU) and/or in need of invasive endotracheal mechanical ventilation

Primary outcomes:
measure: Maximum Observed Plasma Concentration (Cmax) of JNJ-53718678
timeFrame: Days 1, 2 and 3
measure: Trough Plasma Concentration (Ctrough) of JNJ-53718678
timeFrame: Days 1, 2 and 3
measure: Area Under the Curve From Time Zero to End of Dosing Interval (AUCtau)
timeFrame: Days 1, 2 and 3
measure: Total Apparent Clearance (CL/F) of JNJ-53718678
timeFrame: Days 1, 2 and 3
measure: Apparent Volume of Distribution (Vd/F) of JNJ-53718678
timeFrame: Days 1, 2 and 3
measure: Number of Participants With Adverse Events
timeFrame: Up to Follow-up (Day 28)
Secondary outcomes:
measure: Area Under the Viral Load-time Curve (VL AUC)
timeFrame: Up to Follow-up (Day 28)
measure: Amount of Viral Load Over Time
timeFrame: Up to Follow-up (Day 28)
measure: Number of viral particles at Peak Viral Load
timeFrame: Up to Follow-up (Day 28)
measure: Time To Peak Viral Load
timeFrame: Up to Follow-up (Day 28)
measure: Number of Participants Reaching Undetectability of virus Between First Administration of Study Drug and Day 28
timeFrame: Day 1 to Day 28
measure: Total Number of Respiratory Syncytial Virus (RSV) Hospitalization Days from Admission to Discharge
timeFrame: Up to Follow-up (Day 28)
measure: Total RSV Hospitalization Days with Supplemental Oxygen Requirement
timeFrame: Up to Follow-up (Day 28)
measure: The Number of days in Intensive care unit (ICU) due to RSV
timeFrame: Up to Follow-up (Day 28)
measure: Total Days of non-invasive ventilator support During RSV Hospitalization
timeFrame: Up to Follow-up (Day 28)
measure: Total Days of Mechanical Ventilation During RSV Hospitalization
timeFrame: Up to Follow-up (Day 28)
measure: Changes in Peripheral Capillary Oxygen Saturation (SpO2)
timeFrame: Up to Follow-up (Day 28)
measure: Change from Baseline in Respiratory Rate
timeFrame: Up to Follow-up (Day 28)
measure: Change from Baseline in Body Temperature
timeFrame: Up to Follow-up (Day 28)
measure: Clinical Symptom Score
timeFrame: Up to Follow-up (Day 28)
Other outcomes:
Locations:
city: Kirksville
country: United States
state: Missouri
city: Bahía Blanca
country: Argentina
city: City of Buenos Aires
country: Argentina
city: Córdoba
country: Argentina
city: Geelong
country: Australia
city: Hobart
country: Australia
city: Westmead
country: Australia
city: Anderlecht
country: Belgium
city: Bruxelles
country: Belgium
city: Charleroi
country: Belgium
city: Edegem
country: Belgium
city: Leuven
country: Belgium
city: Lier
country: Belgium
city: Curitiba
country: Brazil
city: Porto Alegre
country: Brazil
city: Ribeirao Preto
country: Brazil
city: Rio de Janeiro
country: Brazil
city: São Paulo
country: Brazil
city: Freiburg
country: Germany
city: Hamm
country: Germany
city: Heidelberg
country: Germany
city: München
country: Germany
city: Hoofddorp
country: Netherlands
city: Utrecht
country: Netherlands
city: Cebu City
country: Philippines
city: Manila City
country: Philippines
city: Almeria
country: Spain
city: Barcelona
country: Spain
city: Esplugues de Llobregat
country: Spain
city: Getafe
country: Spain
city: Madrid
country: Spain
city: Malaga
country: Spain
city: Santiago de Compostela
country: Spain
city: Sevilla
country: Spain
city: Valencia
country: Spain
city: Göteborg
country: Sweden
city: Linköping
country: Sweden
city: Lund
country: Sweden
city: Malmö
country: Sweden
Study officials:
affiliation: Janssen Sciences Ireland UC
name: Janssen Sciences Ireland UC Clinical Trial
role: STUDY_DIRECTOR
References:
citation: Martinon-Torres F, Rusch S, Huntjens D, Remmerie B, Vingerhoets J, McFadyen K, Ferrero F, Baraldi E, Rojo P, Epalza C, Stevens M. Pharmacokinetics, Safety, and Antiviral Effects of Multiple Doses of the Respiratory Syncytial Virus (RSV) Fusion Protein Inhibitor, JNJ-53718678, in Infants Hospitalized With RSV Infection: A Randomized Phase 1b Study. Clin Infect Dis. 2020 Dec 17;71(10):e594-e603. doi: 10.1093/cid/ciaa283.