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

Respiratory Syncytial Virus Infections Clinical Trial

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

Clinical Trial Details — Status: Terminated

Administrative data

• NCT number: NCT02593851
• Other study ID #: CR107945
• Secondary ID: 2015-002003-2853
• Status: Terminated
• Phase: Phase 1
• Start date: December 4, 2015
• Est. completion date: November 10, 2017

Study information

• Verified date: December 2019
• 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 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.

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.

Recruitment information / eligibility

• Status: Terminated
• Enrollment: 45
• Est. completion date: November 10, 2017
• Est. primary completion date: March 21, 2017
• Accepts healthy volunteers: No
• Gender: All
• Age group: 1 Month to 24 Months

Eligibility

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

Related Conditions & MeSH terms

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

Intervention

Drug:
• JNJ-53718678
JNJ-53718678 oral solution will be administered once or twice daily for 7 days.
• Placebo
Placebo oral solution will be administered once or twice daily for 7 days.

Locations

Country	Name	City	State
n/a

Sponsors (1)

Lead Sponsor	Collaborator
Janssen Sciences Ireland UC

Countries where clinical trial is conducted

United States,  Argentina,  Australia,  Belgium,  Brazil,  Germany,  Netherlands,  Philippines,  Spain,  Sweden, 

Outcome

Type	Measure	Description	Time frame	Safety issue
Primary	Maximum Observed Plasma Concentration (Cmax) of JNJ-53718678	The Cmax is the maximum observed plasma concentration.	Days 1, 2 and 3
Primary	Trough Plasma Concentration (Ctrough) of JNJ-53718678	The Ctrough is the plasma concentration before dosing or at the end of the dosing interval of any dose other than the first dose in a multiple dosing regimen.	Days 1, 2 and 3
Primary	Area Under the Curve From Time Zero to End of Dosing Interval (AUCtau)	The AUCtau is the measure of the plasma drug concentration from time zero to end of dosing interval.	Days 1, 2 and 3
Primary	Total Apparent Clearance (CL/F) of JNJ-53718678	Clearance of a drug is a measure of the rate at which a drug is metabolized or eliminated by normal biological processes. Clearance obtained after oral dose (apparent oral clearance) is influenced by the fraction of the dose absorbed. Drug clearance is a quantitative measure of the rate at which a drug substance is removed from the blood.	Days 1, 2 and 3
Primary	Apparent Volume of Distribution (Vd/F) of JNJ-53718678	Volume of distribution is defined as the theoretical volume in which the total amount of drug would need to be uniformly distributed to produce the desired plasma concentration of a drug. Apparent volume of distribution after oral dose (Vd/F) is influenced by the fraction absorbed.	Days 1, 2 and 3
Primary	Number of Participants With Adverse Events	An adverse event is any untoward medical event that occurs in a participant administered an investigational product, and it does not necessarily indicate only events with clear causal relationship with the relevant investigational product.	Up to Follow-up (Day 28)
Secondary	Area Under the Viral Load-time Curve (VL AUC)	VL will be determined by quantitative real-time reverse transcriptase-polymerase chain reaction (qRT-PCR) assay of nasal swabs. The VL AUC (copies. hour/ml) will be calculated based on the trapezoidal method.	Up to Follow-up (Day 28)
Secondary	Amount of Viral Load Over Time	VL (copies/ml) at each assessment timepoint where a nasal sample is obtained.	Up to Follow-up (Day 28)
Secondary	Number of viral particles at Peak Viral Load	Peak viral load (copies/ml) is a measure of the maximum number of viral particles present in nasal swabs.	Up to Follow-up (Day 28)
Secondary	Time To Peak Viral Load	Time (hours) to peak viral load will be reported.	Up to Follow-up (Day 28)
Secondary	Number of Participants Reaching Undetectability of virus Between First Administration of Study Drug and Day 28	Non-detectability of virus in nasal swabs between first administration of study drug and Day 28 will be reported.	Day 1 to Day 28
Secondary	Total Number of Respiratory Syncytial Virus (RSV) Hospitalization Days from Admission to Discharge	The total number of Respiratory Syncytial Virus (RSV) hospitalization days from admission to discharge will be reported.	Up to Follow-up (Day 28)
Secondary	Total RSV Hospitalization Days with Supplemental Oxygen Requirement	The total number of RSV Hospitalization Days with Supplemental Oxygen Requirement will be reported.	Up to Follow-up (Day 28)
Secondary	The Number of days in Intensive care unit (ICU) due to RSV	The number of days stayed in ICU due to RSV will be reported.	Up to Follow-up (Day 28)
Secondary	Total Days of non-invasive ventilator support During RSV Hospitalization	The total number of days with non-invasive ventilator support during RSV hospitalization will be reported.	Up to Follow-up (Day 28)
Secondary	Total Days of Mechanical Ventilation During RSV Hospitalization	The total number of days with Mechanical Ventilation during RSV hospitalization will be reported.	Up to Follow-up (Day 28)
Secondary	Changes in Peripheral Capillary Oxygen Saturation (SpO2)	The Percentage of Peripheral Capillary Oxygen Saturation (SpO2) will be assessed by the investigator during hospitalisation.	Up to Follow-up (Day 28)
Secondary	Change from Baseline in Respiratory Rate	The Respiratory rate (number of breaths per minute) will be assessed by the investigator and caregiver during hospitalisation.	Up to Follow-up (Day 28)
Secondary	Change from Baseline in Body Temperature	The body temperature (degrees Celcius) will be assessed by the investigator and caregiver during hospitalisation.	Up to Follow-up (Day 28)
Secondary	Clinical Symptom Score	The clinical symptom score will be assessed by the investigator (Clinician Outcome Assessment) and caregiver symptom Diary for each symptom. Clinical Symptom score ranges from 0 (best) to 4 (worst).	Up to Follow-up (Day 28)