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Study to Evaluate Safety and Antiviral Activity of Doses of JNJ-53718678 in Children (>=28 Days to <=3 Years) With Respiratory Syncytial Virus Infection

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ClinicalTrials.gov Identifier: NCT03656510
Recruitment Status : Recruiting
First Posted : September 3, 2018
Last Update Posted : September 4, 2019
Sponsor:
Information provided by (Responsible Party):
Janssen Research & Development, LLC

Brief Summary:
The purpose of this study is to evaluate the antiviral activity, clinical outcomes, safety, tolerability, and pharmacokinetic/pharmacodynamic relationships of different oral dose levels of JNJ-53718678 in children greater than or equal to 28 days and less than or equal to 3 years of age with respiratory syncytial virus (RSV) disease (hospitalized participants [Cohort 1] or outpatients [Cohort 2]).

Condition or disease Intervention/treatment Phase
Respiratory Syncytial Virus Infections Drug: JNJ-53718678 Drug: Placebo Phase 2

Detailed Description:
JNJ-53718678 is an investigational respiratory syncytial virus (RSV) specific fusion inhibitor and is under development for the treatment of RSV infection, which results in an upper and/or lower respiratory tract illness. The primary hypothesis of this study is that JNJ-53718678 has antiviral activity against RSV (that is, results in a decrease in RSV nasal viral load from immediately prior to first dose of study drug until Day 5). This will be assessed by a positive dose-response relationship of JNJ-53718678 compared to placebo. Besides the RSV nasal viral load through day 5, other timepoints will also be evaluated as well as other nasal viral load related parameters. In addition, the evolution of signs and symptoms of RSV disease will be evaluated. Participants' safety will be monitored throughout the study by evaluating the occurrence and severity of adverse events and by laboratory and electrocardiogram measurements. Study participants will be identified when they are hospitalized or expected to be hospitalized within 24 hours after presentation to the hospital (Cohort 1) or present for medical care as outpatients (Cohort 2) with symptoms of an acute respiratory illness supporting a diagnosis of RSV infection. Eligible participants will be randomized 1:1:1 to receive either a low or a high dose of JNJ 53718678 or placebo and will be receiving study treatment for 7 days. They will be followed up for 3 weeks after the last dose. The total study duration for each participant will be approximately 29 days.

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Study Type : Interventional  (Clinical Trial)
Estimated Enrollment : 294 participants
Allocation: Randomized
Intervention Model: Parallel Assignment
Masking: Double (Participant, Investigator)
Primary Purpose: Treatment
Official Title: A Phase 2, Double-blind, Placebo-controlled Study to Evaluate the Antiviral Activity, Clinical Outcomes, Safety, Tolerability, and Pharmacokinetic/Pharmacodynamic Relationships of Different Doses of JNJ-53718678 in Children >=28 Days and <=3 Years of Age With Acute Respiratory Tract Infection Due to Respiratory Syncytial Virus Infection
Actual Study Start Date : November 29, 2018
Estimated Primary Completion Date : November 27, 2020
Estimated Study Completion Date : November 30, 2020

Resource links provided by the National Library of Medicine


Arm Intervention/treatment
Experimental: High Dose: JNJ-53718678
Participants will be randomized to receive JNJ-53718678 5 milligram per kilogram (mg/kg) (Age Group 1: greater than or equal to [>=] 28 days and less than [<] 3 months of age), 6 mg/kg (Age Group 2: >=3 months and <6 months of age) and 9 mg/kg (Age Group 3: >=6 months and less than or equal to [<=3] years of age) orally once daily on Day 1 to Day 7.
Drug: JNJ-53718678
Participants will receive of JNJ-53718678 (high dose or low dose) orally once daily for 7 days.

Experimental: Low Dose: JNJ-53718678
Participants will be randomized to receive JNJ-53718678 1.7 mg/kg (Age Group 1: >=28 days and <3 months of age), 2 mg/kg (Age Group 2: >=3 months and <6 months of age) and 3 mg/kg (Age Group 3: >=6 months and 3 years of age) orally once daily on Day 1 to Day 7.
Drug: JNJ-53718678
Participants will receive of JNJ-53718678 (high dose or low dose) orally once daily for 7 days.

Placebo Comparator: Placebo
Participants will be randomized to receive matching placebo (i.e. high volume placebo or low volume placebo to match the calculated volume of the JNJ-53718678 for the high dose or low dose) orally once daily on Day 1 to Day 7.
Drug: Placebo
Participants will receive of matching placebo (high volume or low volume) orally once daily for 7 days.




Primary Outcome Measures :
  1. Respiratory Syncytial Virus (RSV) Viral Load Area Under Curve (AUC) from Immediately Prior to First Dose of Study Drug Through Day 5 [ Time Frame: Baseline through Day 5 ]
    RSV viral load AUC will be determined from immediately prior to first dose of study drug through Day 5. The RSV viral load is measured by the RSV viral load as measured by quantitative real-time reverse transcription-polymerase chain reaction (qRT-PCR) assay of nasal swabs.


Secondary Outcome Measures :
  1. RSV Viral Load and Change from Baseline Over Time [ Time Frame: Baseline through Day 21 ]
    RSV viral load and change from baseline over time will be measured by qRT-PCR assay in the mid-turbinate nasal swab specimens.

  2. RSV Viral Load AUC from Immediately Prior to First Dose of Study Drug (Baseline) Through Days 3, 8, and 14 [ Time Frame: Baseline through Days 3, 8 and 14 ]
    RSV viral load AUC will be determined by quantitative qRT-PCR assay of nasal swabs.

  3. Time to Undetectable RSV Viral Load [ Time Frame: Up to 21 days ]
    Time to undetectable RSV viral load (per the detection limit of the assay used in the study) will be reported.

  4. Proportion of Participants with Undetectable RSV Viral Load at each timepoint [ Time Frame: Up to 21 days ]
    Proportion of participants with undetectable RSV viral load will be reported.

  5. Duration of Signs and Symptoms of RSV Disease Assessed by the Pediatric RSV Electronic Severity and Outcome Rating Scale (PRESORS) [ Time Frame: Up to 21 days ]
    Duration of signs and symptoms of RSV disease will be assessed by PRESORS. PRESORS is a questionnaire recording presence and severity of signs and symptoms of RSV disease (fever, cough, sputum, wheezing, difficulty breathing, nasal congestion, and feeding issues).

  6. Severity of RSV Disease Assessed by PRESORS [ Time Frame: Up to 21 days ]
    Severity of RSV disease will be assessed by PRESORS. PRESORS is a questionnaire recording presence and severity of signs and symptoms of RSV disease (fever, cough, sputum, wheezing, difficulty breathing, nasal congestion, and feeding issues).

  7. Change from Baseline in Parent(s)/Caregiver(s) PRESORS Scores [ Time Frame: Baseline up to 21 days ]
    Change from baseline in parent(s)/caregiver(s) PRESORS scores (worsening or improvement) will be reported. PRESORS is a questionnaire recording presence and severity of signs and symptoms of RSV disease (fever, cough, sputum, wheezing, difficulty breathing, nasal congestion, and feeding issues) daily by parent/caregiver.

  8. Change from Baseline in Clinician PRESORS Scores [ Time Frame: Baseline up to 21 days ]
    Change from baseline in clinician PRESORS scores (worsening or improvement) will be reported. PRESORS is a questionnaire recording presence and severity of signs and symptoms of RSV disease (fever, cough, sputum, wheezing, difficulty breathing, nasal congestion, and feeding issues) by clinician.

  9. Time to Resolution of RSV Symptoms [ Time Frame: Up to 21 days ]
    Time to resolution (that is, to none or mild) of RSV symptoms will be recorded.

  10. Time to Improvement on Overall Health [ Time Frame: Up to 21 days ]
    Time to improvement based on general questions on overall health will be reported.

  11. Proportion of Participants with Improvement or Worsening of RSV Disease [ Time Frame: Up to 21 days ]
    Proportion of participants with improvement or worsening of RSV disease based on general questions on overall health will be reported.

  12. Time to Return to Pre-RSV Health as Rated by the Parent(s)/Caregiver(s) [ Time Frame: Up to 21 days ]
    Time to return to pre-RSV health as rated by the parent(s)/caregiver(s) will be recorded.

  13. Proportion of Participants with Vital Sign Abnormalities [ Time Frame: Up to 28 days ]
    Proportion of participants with vital signs (heart rate, respiratory rate, body temperature and peripheral capillary oxygen saturation [SpO2]) abnormalities will be reported.

  14. Proportion of Participants with Abnormal Body Temperature as Measured by the Parent(s)/Caregiver(s) [ Time Frame: Up to 28 days ]
    Proportion of participants with abnormal body temperature will be reported.

  15. Proportion of Participants who Require (re)Hospitalization During Treatment and Follow-up [ Time Frame: Up to 21 days ]
    Proportion of participants who require (re)hospitalization during treatment and follow-up will be reported.

  16. Time Return to Age-Adjusted Normal Values for vital signs (Heart Rate, Respiratory Rate, and/or Blood Oxygen) for Participants with Risk Factors for Severe RSV Disease [ Time Frame: Up to 21 days ]
    Time return to age-adjusted normal values for vital signs (heart rate, respiratory rate, and/or blood oxygen) for participants with risk factors for severe RSV Disease will be recorded.

  17. Cohort 1: Time to Discharge [ Time Frame: Up to 21 days ]
    Time to discharge (from initial admission and from initiation of treatment) will be recorded for Cohort 1 only.

  18. Cohort 1: Proportion of Participants who Require to be Admitted to Intensive Care Unit (ICU) [ Time Frame: Up to 21 days ]
    Proportion of participants who require to be admitted to the ICU will be reported for Cohort 1 only.

  19. Cohort 1: Duration of ICU Stay [ Time Frame: Up to 21 days ]
    In the event that a participant requires ICU, admission, the duration of need for ICU stay will be reported for Cohort 1 only.

  20. Cohort 1: Proportion Participants who Require Supplemental Oxygen [ Time Frame: Up to 21 days ]
    Proportion of participants who require supplemental oxygen will be reported for Cohort 1 only.

  21. Cohort 1: Duration of Supplemental Oxygen [ Time Frame: Up to 21 days ]
    Duration of the oxygen supplementation in participants requiring will be reported for Cohort 1 only.

  22. Cohort 1: Proportion of Participants who Require Non-invasive Ventilator Support [ Time Frame: Up to 21 days ]
    Proportion of participants who require non-invasive ventilator support (for example [e.g], continuous positive airway pressure) status will be reported for Cohort 1 only.

  23. Cohort 1: Proportion of Participants who Require Invasive Mechanical Ventilation Support [ Time Frame: Up to 21 days ]
    Proportion of participants who require invasive ventilator support (e.g, endotracheal-mechanical ventilation) will be reported for Cohort 1 only.

  24. Cohort 1: Duration of Non-invasive Ventilator Support [ Time Frame: Up to 21 days ]
    Duration of non-invasive ventilator support (e.g, continuous positive airway pressure) to deliver oxygen will be measured for Cohort 1 only.

  25. Cohort 1: Duration of Invasive Ventilator Support [ Time Frame: Up to 21 days ]
    Duration of invasive ventilator support (e.g, endotracheal-mechanical ventilation) to deliver oxygen will be measured for Cohort 1 only.

  26. Cohort 1: Proportion of Participants who Need Hydration and/or Feeding by Intravenously (IV) Administration or Nasogastric Tube [ Time Frame: Up to 21 days ]
    Proportion of participants who need (defined by <50% of normal oral intake) hydration and/or feeding by IV administration or nasogastric tube will be reported for Cohort 1 only.

  27. Cohort 1: Time to Clinical Stability with Clinical Stability Evaluated by the Investigator [ Time Frame: Up to 21 days ]
    Time to clinical stability is defined as the time from initiation of study treatment until the time at which the following criteria are met: Time to return to age-adjusted normal values for otherwise healthy and pre-RSV infection status for participants with risk factor for severe RSV disease (heart rate, respiratory rate, blood oxygen level), no more oxygen supplementation or otherwise healthy participants and with risk factor(s) for severe RSV disease and no more intravenously (IV)/nasogastric tube feeding/hydration) in otherwise healthy participants or return to pre-RSV status of IV/nasogastric tube feeding/hydration in participants with risk factor for severe RSV disease for Cohort 1 only.

  28. Cohort 1: Time From Initiation of Study Treatment Until Peripheral Capillary Oxygen Saturation (SpO2) >= 92% and SpO2 >= 95% on Room Air Among Participants who Were not on Supplemental Oxygen Prior to Onset of Respiratory Symptoms [ Time Frame: Up to 21 days ]
    Time from initiation of study treatment until SpO2 >=92 percentage (%) and SpO2 >= 95% on room air among participants who were not on supplemental oxygen prior to the onset of respiratory symptoms will be reported for Cohort 1 only.

  29. Percentage of Participants with Adverse Events [ Time Frame: Up to 28 days ]
    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.

  30. Percentage of Participants with Abnormal Laboratory Findings [ Time Frame: Up to 28 days ]
    Percentage of participants with abnormal laboratory (serum chemistry, hematology and urinalysis) findings will be reported.

  31. Percentage of Participants with Abnormal Electrocardiograms (ECGs) Findings [ Time Frame: Up to 21 days ]
    Percentage of participants with abnormal ECGs findings will be reported.

  32. Plasma Concentrations of JNJ-53718678 [ Time Frame: Days 1 and 2 ]
    Plasma Concentrations of JNJ-53718678 will be evaluated and determined by population pharmacokinetics (popPK) modelling.

  33. Medical Resource Utilization [ Time Frame: Up to 28 days ]
    Number of medical care encounters and treatments (including physician or emergency room visits, tests and procedures, and medications, surgeries and other procedures) will be reported.

  34. Acceptability and Palatability of the JNJ-53718678 Formulation as Assessed by Parent(s)/Caregiver(s) [ Time Frame: Day 8 ]
    Acceptability and palatability of the JNJ-53718678 formulation will be assessed through a questionnaire asking about the child's reaction when given the medicine, completed by parent(s)/caregiver(s) after last dosing.

  35. Number of Participants with Post-baseline Changes in the RSV F-gene Compared with Baseline Sequences [ Time Frame: Up to 21 days ]
    Number of participants with changes in the RSV F-gene compared with baseline sequences will be assessed by sequencing of the viral genome.



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:   up to 3 Years   (Child)
Sexes Eligible for Study:   All
Accepts Healthy Volunteers:   No
Criteria

Inclusion Criteria:

  • Informed consent form (ICF) must be given
  • Laboratory diagnosis of respiratory syncytial virus (RSV) infection
  • The participant has an acute respiratory illness
  • The time of onset of RSV symptoms to the anticipated time of randomization must be less than or equal to (<=) 5 days
  • Except for the RSV-related illness, the Participant must be medically stable in case of allowed co-morbid conditions

Exclusion Criteria:

  • The participant is less than (<) 3 months postnatal age at screening and was born prematurely (i.e, <37 weeks and 0 days of gestation) OR if the participant weighs <2.4 kilogram (kg) or greater than (>) 16.8 kg
  • Participant is considered by the investigator to be immunocompromised within the past 12 months
  • Participant unwilling or unable to undergo mid-turbinate nasal swab procedures
  • Participant is receiving chronic home oxygen therapy at screening
  • Participant with clinically significant abnormal electrocardiogram findings or prolonged Corrected QT by Fridericia Formula (QTcF)-interval at screening

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): NCT03656510


Contacts
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Contact: Study Contact 844-434-4210 JNJ.CT@sylogent.com

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Sponsors and Collaborators
Janssen Research & Development, LLC
Investigators
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Study Director: Janssen Research & Development, LLC Clinical Trial Janssen Research & Development, LLC

Additional Information:
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Responsible Party: Janssen Research & Development, LLC
ClinicalTrials.gov Identifier: NCT03656510     History of Changes
Other Study ID Numbers: CR108520
2016-003642-93 ( EudraCT Number )
53718678RSV2002 ( Other Identifier: Janssen Research & Development, LLC )
First Posted: September 3, 2018    Key Record Dates
Last Update Posted: September 4, 2019
Last Verified: September 2019

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Studies a U.S. FDA-regulated Drug Product: Yes
Studies a U.S. FDA-regulated Device Product: No
Additional relevant MeSH terms:
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Infection
Communicable Diseases
Respiratory Syncytial Virus Infections
Virus Diseases
Pneumovirus Infections
Paramyxoviridae Infections
Mononegavirales Infections
RNA Virus Infections
Antiviral Agents
Anti-Infective Agents