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
Overview
- Phase
- Phase 1
- Intervention
- JNJ-53718678
- Conditions
- Respiratory Syncytial Virus Infections
- Sponsor
- Janssen Sciences Ireland UC
- Enrollment
- 45
- Primary Endpoint
- Area Under the Curve From Time Zero to End of Dosing Interval (AUCtau)
- Status
- Terminated
- Last Updated
- 6 years ago
Overview
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.
Investigators
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
Arms & Interventions
Part 1: Cohort 1a
Participants (greater than or equal to \[\>=\] 6 months and less than or equal to \[\<=\] 24 months of age) will receive JNJ-53718678, 2 milligram per kilogram body weight (mg/kg) oral solution once daily on Day 1 to Day 7. Dose and/or dosing regimen may be adapted in subsequent cohorts based on the review of the safety/tolerability and full pharmacokinetic data from Cohort 1a.
Intervention: JNJ-53718678
Part 1: Cohort 1b
Participants (\>= 6 months and \<= 24 months of age) will receive total daily dose of 6 mg/kg JNJ-53718678 oral solution or placebo \[either in once daily \[qd\] or twice daily \[bid\]) on Day 1 to Day 7.
Intervention: JNJ-53718678
Part 1: Cohort 1b
Participants (\>= 6 months and \<= 24 months of age) will receive total daily dose of 6 mg/kg JNJ-53718678 oral solution or placebo \[either in once daily \[qd\] or twice daily \[bid\]) on Day 1 to Day 7.
Intervention: Placebo
Part 1: Cohort 1c
Participants (\>= 6 months and \<= 24 months of age) will receive total daily dose of 18 mg/kg JNJ-53718678 oral solution or placebo \[either in a qd or a bid regimen\] on Day 1 to Day 7.
Intervention: JNJ-53718678
Part 1: Cohort 1c
Participants (\>= 6 months and \<= 24 months of age) will receive total daily dose of 18 mg/kg JNJ-53718678 oral solution or placebo \[either in a qd or a bid regimen\] on Day 1 to Day 7.
Intervention: Placebo
Part 1: Cohort 1d
Participants (\>= 6 months and \<= 24 months of age) will receive JNJ-53718678 oral solution or placebo \[either in a qd or a bid regimen\] on Day 1 to Day 7. The cohort 1d is optional and may be included at the discretion of the sponsor.
Intervention: JNJ-53718678
Part 1: Cohort 1d
Participants (\>= 6 months and \<= 24 months of age) will receive JNJ-53718678 oral solution or placebo \[either in a qd or a bid regimen\] on Day 1 to Day 7. The cohort 1d is optional and may be included at the discretion of the sponsor.
Intervention: Placebo
Part 1: Cohort 1e
Participants (\>= 6 months and \<= 24 months of age) will receive JNJ-53718678 oral solution or placebo \[either in a qd or a bid regimen\] on Day 1 to Day 7. The cohort 1e is optional and may be included at the discretion of the sponsor.
Intervention: JNJ-53718678
Part 1: Cohort 1e
Participants (\>= 6 months and \<= 24 months of age) will receive JNJ-53718678 oral solution or placebo \[either in a qd or a bid regimen\] on Day 1 to Day 7. The cohort 1e is optional and may be included at the discretion of the sponsor.
Intervention: Placebo
Part 1: Cohort 2a
Participants (\>= 3 months and less than \[\<\] 6 months of age) will receive total daily dose of 1.5 mg/kg JNJ-53718678 oral solution \[either in a qd or a bid regimen\] on Day 1 to Day 7.
Intervention: JNJ-53718678
Part 1: Cohort 2b
Participants (\>=3 months and \< 6 months of age) will receive total daily dose of 4.5 mg/kg JNJ-53718678 oral solution or placebo \[either in a qd or a bid regimen\] on Day 1 to Day 7.
Intervention: JNJ-53718678
Part 1: Cohort 2b
Participants (\>=3 months and \< 6 months of age) will receive total daily dose of 4.5 mg/kg JNJ-53718678 oral solution or placebo \[either in a qd or a bid regimen\] on Day 1 to Day 7.
Intervention: Placebo
Part 1: Cohort 2c
Participants (\>= 3 months and \< 6 months of age) will receive total daily dose of 13.5 mg/kg JNJ-53718678 oral solution or placebo \[either in a qd or a bid regimen\] on Day 1 to Day 7
Intervention: JNJ-53718678
Part 1: Cohort 2c
Participants (\>= 3 months and \< 6 months of age) will receive total daily dose of 13.5 mg/kg JNJ-53718678 oral solution or placebo \[either in a qd or a bid regimen\] on Day 1 to Day 7
Intervention: Placebo
Part 1: Cohort 2d
Participants (\>= 3 months and \< 6 months of age) will receive JNJ-53718678 oral solution or placebo \[either in a qd or a bid regimen\] on Day 1 to Day 7. The cohort 2d is optional and may be included at the discretion of the sponsor.
Intervention: JNJ-53718678
Part 1: Cohort 2d
Participants (\>= 3 months and \< 6 months of age) will receive JNJ-53718678 oral solution or placebo \[either in a qd or a bid regimen\] on Day 1 to Day 7. The cohort 2d is optional and may be included at the discretion of the sponsor.
Intervention: Placebo
Part 1: Cohort 2e
Participants (\>= 3 months and \< 6 months of age) will receive JNJ-53718678 oral solution or placebo \[either in a qd or a bid regimen\] on Day 1 to Day 7. The cohort 2e is optional and may be included at the discretion of the sponsor.
Intervention: JNJ-53718678
Part 1: Cohort 2e
Participants (\>= 3 months and \< 6 months of age) will receive JNJ-53718678 oral solution or placebo \[either in a qd or a bid regimen\] on Day 1 to Day 7. The cohort 2e is optional and may be included at the discretion of the sponsor.
Intervention: Placebo
Part 1: Cohort 3a
Participants (greater than (\>) 1 month and \< 3 months of age) will receive total daily dose of 1 mg/kg JNJ-53718678 oral solution \[either in a qd or a bid regimen\] on Day 1 to Day 7.
Intervention: JNJ-53718678
Part 1: Cohort 3b
Participants (\> 1 month and \< 3 months of age) will receive total daily dose of 3 mg/kg JNJ-53718678 oral solution or placebo \[either in a qd or a bid regimen\] on Day 1 to Day 7.
Intervention: JNJ-53718678
Part 1: Cohort 3b
Participants (\> 1 month and \< 3 months of age) will receive total daily dose of 3 mg/kg JNJ-53718678 oral solution or placebo \[either in a qd or a bid regimen\] on Day 1 to Day 7.
Intervention: Placebo
Part 1: Cohort 3c
Participants (\> 1 month and \< 3 months of age) will receive total daily dose of 9 mg/kg JNJ-53718678 oral solution or placebo \[either in a qd or a bid regimen\] on Day 1 to Day 7.
Intervention: JNJ-53718678
Part 1: Cohort 3c
Participants (\> 1 month and \< 3 months of age) will receive total daily dose of 9 mg/kg JNJ-53718678 oral solution or placebo \[either in a qd or a bid regimen\] on Day 1 to Day 7.
Intervention: Placebo
Part 1: Cohort 3d
Participants (\> 1 month and \< 3 months of age) will receive JNJ-53718678 oral solution or placebo \[either in a qd or a bid regimen\] on Day 1 to Day 7. The cohort 3d is optional and may be included at the discretion of the sponsor.
Intervention: JNJ-53718678
Part 1: Cohort 3d
Participants (\> 1 month and \< 3 months of age) will receive JNJ-53718678 oral solution or placebo \[either in a qd or a bid regimen\] on Day 1 to Day 7. The cohort 3d is optional and may be included at the discretion of the sponsor.
Intervention: Placebo
Part 1: Cohort 3e
Participants (\> 1 month and \< 3 months of age) will receive JNJ-53718678 oral solution or placebo \[either in a qd or a bid regimen\] on Day 1 to Day 7. The cohort 3e is optional and may be included at the discretion of the sponsor.
Intervention: JNJ-53718678
Part 1: Cohort 3e
Participants (\> 1 month and \< 3 months of age) will receive JNJ-53718678 oral solution or placebo \[either in a qd or a bid regimen\] on Day 1 to Day 7. The cohort 3e is optional and may be included at the discretion of the sponsor.
Intervention: Placebo
Part 2: Cohort f
Participants of all age groups will receive daily dose of JNJ-53718678 oral solution or placebo, either in a qd or a bid regimen on Days 1 to 7.
Intervention: JNJ-53718678
Part 2: Cohort f
Participants of all age groups will receive daily dose of JNJ-53718678 oral solution or placebo, either in a qd or a bid regimen on Days 1 to 7.
Intervention: Placebo
Outcomes
Primary Outcomes
Area Under the Curve From Time Zero to End of Dosing Interval (AUCtau)
Time Frame: Days 1, 2 and 3
The AUCtau is the measure of the plasma drug concentration from time zero to end of dosing interval.
Maximum Observed Plasma Concentration (Cmax) of JNJ-53718678
Time Frame: Days 1, 2 and 3
The Cmax is the maximum observed plasma concentration.
Trough Plasma Concentration (Ctrough) of JNJ-53718678
Time Frame: Days 1, 2 and 3
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.
Number of Participants With Adverse Events
Time Frame: Up to Follow-up (Day 28)
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.
Total Apparent Clearance (CL/F) of JNJ-53718678
Time Frame: Days 1, 2 and 3
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.
Apparent Volume of Distribution (Vd/F) of JNJ-53718678
Time Frame: Days 1, 2 and 3
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.
Secondary Outcomes
- Amount of Viral Load Over Time(Up to Follow-up (Day 28))
- Area Under the Viral Load-time Curve (VL AUC)(Up to Follow-up (Day 28))
- Total RSV Hospitalization Days with Supplemental Oxygen Requirement(Up to Follow-up (Day 28))
- Total Days of Mechanical Ventilation During RSV Hospitalization(Up to Follow-up (Day 28))
- Change from Baseline in Respiratory Rate(Up to Follow-up (Day 28))
- Change from Baseline in Body Temperature(Up to Follow-up (Day 28))
- Clinical Symptom Score(Up to Follow-up (Day 28))
- Number of Participants Reaching Undetectability of virus Between First Administration of Study Drug and Day 28(Day 1 to Day 28)
- Total Number of Respiratory Syncytial Virus (RSV) Hospitalization Days from Admission to Discharge(Up to Follow-up (Day 28))
- The Number of days in Intensive care unit (ICU) due to RSV(Up to Follow-up (Day 28))
- Total Days of non-invasive ventilator support During RSV Hospitalization(Up to Follow-up (Day 28))
- Changes in Peripheral Capillary Oxygen Saturation (SpO2)(Up to Follow-up (Day 28))
- Number of viral particles at Peak Viral Load(Up to Follow-up (Day 28))
- Time To Peak Viral Load(Up to Follow-up (Day 28))