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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

The safety and scientific validity of this study is the responsibility of the study sponsor and investigators. Listing a study does not mean it has been evaluated by the U.S. Federal Government. Read our disclaimer for details.
 
ClinicalTrials.gov Identifier: NCT02593851
Recruitment Status : Terminated (Trial was cancelled due to availability of clinical supplies.)
First Posted : November 1, 2015
Last Update Posted : December 6, 2019
Sponsor:
Information provided by (Responsible Party):
Janssen Sciences Ireland UC

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.

Condition or disease Intervention/treatment Phase
Respiratory Syncytial Virus Infections Virus Diseases Drug: JNJ-53718678 Drug: Placebo Phase 1

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.

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Study Type : Interventional  (Clinical Trial)
Actual Enrollment : 45 participants
Allocation: Randomized
Intervention Model: Parallel Assignment
Masking: Double (Participant, Investigator)
Primary Purpose: Treatment
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
Actual Study Start Date : December 4, 2015
Actual Primary Completion Date : March 21, 2017
Actual Study Completion Date : November 10, 2017

Resource links provided by the National Library of Medicine


Arm Intervention/treatment
Experimental: 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.
Drug: JNJ-53718678
JNJ-53718678 oral solution will be administered once or twice daily for 7 days.

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

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

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

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

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

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

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

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

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

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

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

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

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

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

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

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

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

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

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

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

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

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

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

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

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

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

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

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




Primary Outcome Measures :
  1. Maximum Observed Plasma Concentration (Cmax) of JNJ-53718678 [ Time Frame: Days 1, 2 and 3 ]
    The Cmax is the maximum observed plasma concentration.

  2. 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.

  3. 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.

  4. 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.

  5. 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.

  6. 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.


Secondary Outcome Measures :
  1. Area Under the Viral Load-time Curve (VL AUC) [ Time Frame: Up to Follow-up (Day 28) ]
    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.

  2. Amount of Viral Load Over Time [ Time Frame: Up to Follow-up (Day 28) ]
    VL (copies/ml) at each assessment timepoint where a nasal sample is obtained.

  3. Number of viral particles at Peak Viral Load [ Time Frame: Up to Follow-up (Day 28) ]
    Peak viral load (copies/ml) is a measure of the maximum number of viral particles present in nasal swabs.

  4. Time To Peak Viral Load [ Time Frame: Up to Follow-up (Day 28) ]
    Time (hours) to peak viral load will be reported.

  5. Number of Participants Reaching Undetectability of virus Between First Administration of Study Drug and Day 28 [ Time Frame: Day 1 to Day 28 ]
    Non-detectability of virus in nasal swabs between first administration of study drug and Day 28 will be reported.

  6. Total Number of Respiratory Syncytial Virus (RSV) Hospitalization Days from Admission to Discharge [ Time Frame: Up to Follow-up (Day 28) ]
    The total number of Respiratory Syncytial Virus (RSV) hospitalization days from admission to discharge will be reported.

  7. Total RSV Hospitalization Days with Supplemental Oxygen Requirement [ Time Frame: Up to Follow-up (Day 28) ]
    The total number of RSV Hospitalization Days with Supplemental Oxygen Requirement will be reported.

  8. The Number of days in Intensive care unit (ICU) due to RSV [ Time Frame: Up to Follow-up (Day 28) ]
    The number of days stayed in ICU due to RSV will be reported.

  9. Total Days of non-invasive ventilator support During RSV Hospitalization [ Time Frame: Up to Follow-up (Day 28) ]
    The total number of days with non-invasive ventilator support during RSV hospitalization will be reported.

  10. Total Days of Mechanical Ventilation During RSV Hospitalization [ Time Frame: Up to Follow-up (Day 28) ]
    The total number of days with Mechanical Ventilation during RSV hospitalization will be reported.

  11. Changes in Peripheral Capillary Oxygen Saturation (SpO2) [ Time Frame: Up to Follow-up (Day 28) ]
    The Percentage of Peripheral Capillary Oxygen Saturation (SpO2) will be assessed by the investigator during hospitalisation.

  12. Change from Baseline in Respiratory Rate [ Time Frame: Up to Follow-up (Day 28) ]
    The Respiratory rate (number of breaths per minute) will be assessed by the investigator and caregiver during hospitalisation.

  13. Change from Baseline in Body Temperature [ Time Frame: Up to Follow-up (Day 28) ]
    The body temperature (degrees Celcius) will be assessed by the investigator and caregiver during hospitalisation.

  14. Clinical Symptom Score [ Time Frame: Up to Follow-up (Day 28) ]
    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).



Information from the National Library of Medicine

Choosing to participate in a study is an important personal decision. Talk with your doctor and family members or friends about deciding to join a study. To learn more about this study, you or your doctor may contact the study research staff using the contacts provided below. For general information, Learn About Clinical Studies.


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Ages Eligible for Study:   1 Month to 24 Months   (Child)
Sexes Eligible for Study:   All
Accepts Healthy Volunteers:   No
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

Information from the National Library of Medicine

To learn more about this study, you or your doctor may contact the study research staff using the contact information provided by the sponsor.

Please refer to this study by its ClinicalTrials.gov identifier (NCT number): NCT02593851


Locations
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United States, Missouri
Kirksville, Missouri, United States
Argentina
Bahía Blanca, Argentina
City of Buenos Aires, Argentina
Córdoba, Argentina
Australia
Geelong, Australia
Hobart, Australia
Westmead, Australia
Belgium
Anderlecht, Belgium
Bruxelles, Belgium
Charleroi, Belgium
Edegem, Belgium
Leuven, Belgium
Lier, Belgium
Brazil
Curitiba, Brazil
Porto Alegre, Brazil
Ribeirao Preto, Brazil
Rio de Janeiro, Brazil
São Paulo, Brazil
Germany
Freiburg, Germany
Hamm, Germany
Heidelberg, Germany
München, Germany
Netherlands
Hoofddorp, Netherlands
Utrecht, Netherlands
Philippines
Cebu City, Philippines
Manila City, Philippines
Spain
Almeria, Spain
Barcelona, Spain
Esplugues de Llobregat, Spain
Getafe, Spain
Madrid, Spain
Malaga, Spain
Santiago de Compostela, Spain
Sevilla, Spain
Valencia, Spain
Sweden
Göteborg, Sweden
Linköping, Sweden
Lund, Sweden
Malmö, Sweden
Sponsors and Collaborators
Janssen Sciences Ireland UC
Investigators
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Study Director: Janssen Sciences Ireland UC Clinical Trial Janssen Sciences Ireland UC
Publications automatically indexed to this study by ClinicalTrials.gov Identifier (NCT Number):
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Responsible Party: Janssen Sciences Ireland UC
ClinicalTrials.gov Identifier: NCT02593851    
Other Study ID Numbers: CR107945
2015-002003-28 ( EudraCT Number )
53718678RSV1005 ( Other Identifier: Janssen Sciences Ireland UC )
First Posted: November 1, 2015    Key Record Dates
Last Update Posted: December 6, 2019
Last Verified: December 2019

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Studies a U.S. FDA-regulated Drug Product: Yes
Keywords provided by Janssen Sciences Ireland UC:
Respiratory Syncytial Virus Infections
JNJ-53718678
Placebo
Infants
Additional relevant MeSH terms:
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Infection
Communicable Diseases
Virus Diseases
Respiratory Syncytial Virus Infections
Pneumovirus Infections
Paramyxoviridae Infections
Mononegavirales Infections
RNA Virus Infections