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Effects of JNJ-53718678 in Adult and Adolescent Participants Who Had a Hematopoietic Stem Cell Transplantation and Who Are Infected With Respiratory Syncytial Virus (RSV) (FREESIA)

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. Know the risks and potential benefits of clinical studies and talk to your health care provider before participating. Read our disclaimer for details.
 
ClinicalTrials.gov Identifier: NCT04056611
Recruitment Status : Recruiting
First Posted : August 14, 2019
Last Update Posted : November 25, 2020
Sponsor:
Information provided by (Responsible Party):
Janssen Sciences Ireland UC

Brief Summary:
The purpose of this study is to evaluate the effect of JNJ-53718678 on the development of respiratory syncytial virus (RSV) lower respiratory tract infection (LRTIs) in adult hematopoietic stem cell transplant (HSCT) recipients with RSV upper RTI.

Condition or disease Intervention/treatment Phase
Respiratory Syncytial Virus Infections Drug: JNJ-53718678 250 mg Drug: Placebo Drug: JNJ-53718678 125 mg Phase 2

Expanded Access : An investigational treatment associated with this study is available outside the clinical trial.   More info ...

Detailed Description:
RSV is recognized as major respiratory pathogen in infants and young children and causes upper and lower respiratory illness among all age groups, often going undiagnosed. Immunocompromised (IC) participants have a reduced ability to combat infection due to an impaired or weakened immune system. Within the IC population, HSCT recipients are generally regarded as having a particularly high risk for more severe disease caused by RSV, representing a substantial unmet need for antiviral treatment of RSV infections in this participant population. JNJ-53718678 is an investigational, potent, small molecule, respiratory syncytial virus (RSV)-specific fusion inhibitor. The study will include a Screening Period (Day -2 to Day 1), a Treatment Period (Day 1 to Day 21), and a Follow-up Period (1 year). Assessments like chest X-ray, pulse/heart rate, respiratory rate, electrocardiogram (ECG), etc will be performed. Safety and efficacy will be assessed through the study. The total study duration for each participant will be approximately 49 days.

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Study Type : Interventional  (Clinical Trial)
Estimated Enrollment : 375 participants
Allocation: Randomized
Intervention Model: Parallel Assignment
Masking: Double (Participant, Investigator)
Primary Purpose: Treatment
Official Title: A Randomized, Double-blind, Placebo-controlled Study to Evaluate the Clinical Outcomes, Antiviral Activity, Safety, Tolerability, Pharmacokinetics, and Pharmacokinetics/Pharmacodynamics of JNJ-53718678 in Adult and Adolescent Hematopoietic Stem Cell Transplant Recipients With Respiratory Syncytial Virus Infection of the Upper Respiratory Tract
Actual Study Start Date : December 26, 2019
Estimated Primary Completion Date : August 15, 2022
Estimated Study Completion Date : March 30, 2024

Resource links provided by the National Library of Medicine


Arm Intervention/treatment
Experimental: Adult cohort: JNJ-53718678 or Placebo
Participants greater than or equal to (>=) 18 to less than or equal to (<=) 75 years of age will receive 250 milligram (mg) JNJ-53718678 twice daily (bid) for 21 days (without coadministration with moderate or strong CYP3A4 inhibitors), or 125 mg JNJ-53718678 bid for 21 days (coadministered with moderate or strong CYP3A4 inhibitors with the exception of posaconazole), or 125 mg once daily (qd) for 21 days (when coadministered with posaconazole), or matching placebo for 21 days.
Drug: JNJ-53718678 250 mg
JNJ-53718678 250 mg will be administered orally.

Drug: Placebo
Matching placebo will be administered orally.

Drug: JNJ-53718678 125 mg
JNJ-53718678 125 mg will be administered orally.

Experimental: Adolescent cohort: JNJ-53718678 or Placebo
Participants >=13 to <18 years of age will receive 250 mg JNJ-53718678 bid for 21 days (without coadministration with moderate or strong CYP3A4 inhibitors), or 125 mg JNJ-53718678 bid for 21 days (coadministered with moderate or strong CYP3A4 inhibitors with the exception of posaconazole), or 125 mg qd for 21 days (when coadministered with posaconazole), or matching placebo for 21 days.
Drug: JNJ-53718678 250 mg
JNJ-53718678 250 mg will be administered orally.

Drug: Placebo
Matching placebo will be administered orally.

Drug: JNJ-53718678 125 mg
JNJ-53718678 125 mg will be administered orally.




Primary Outcome Measures :
  1. Proportion of Participants who Develop Respiratory Syncytial Virus (RSV) Lower Respiratory Tract Infection (LRTI) [ Time Frame: Up to Day 28 ]
    The proportion of participants who develop RSV LRTI through Visit Day 28 per the Endpoint Adjudication Committee (EAC) assessment will be reported.


Secondary Outcome Measures :
  1. Proportion of Participants who Develop RSV-associated Lower Respiratory Tract Complication (LRTC) [ Time Frame: Up to Day 28 ]
    The proportion of participants who develop RSV-associated LRTC through Visit Day 28 per the EAC's assessment will be reported.

  2. Number of Participants with Adverse Events (AEs) [ Time Frame: Up to 49 days ]
    An AE is any untoward medical occurrence in a participant who received study drug without regard to possibility of causal relationship.

  3. Percentage of Participants with Abnormal Clinical Laboratory Findings [ Time Frame: Up to 49 days ]
    Percentage of participants with abnormal clinical laboratory findings will be reported.

  4. Percentage of Participants with Abnormal Electrocardiograms (ECGs) Findings [ Time Frame: Up to 49 days ]
    Percentage of participants with abnormal ECGs findings will be reported.

  5. Percentage of Participants with Abnormal Vital Signs Findings [ Time Frame: Up to 49 days ]
    Percentage of participants with abnormal vital signs findings will be reported.

  6. Proportion of Participants Progressing to Respiratory Failure (of any Cause) Requiring Mechanical Ventilation (Invasive or Noninvasive) and/or Death, in Participants who Develop RSV LRTI or RSV-associated LRTC per the EAC's Assessment [ Time Frame: Up to 49 days ]
    The proportion of participants progressing to respiratory failure (of any cause) requiring mechanical ventilation (invasive or noninvasive) and/or death, in participants who develop RSV LRTI or RSV-associated LRTC per the EAC's assessment will be reported.

  7. Proportion of Participants Progressing to Respiratory Failure (of any Cause) Requiring Mechanical Ventilation (Invasive or Noninvasive) and/or Death, (all-cause Mortality) [ Time Frame: Up to 49 days ]
    Proportion of participants progressing to respiratory failure (of any cause) requiring mechanical ventilation (invasive or noninvasive) and/or death, (all-cause mortality) will be reported.

  8. Proportion of Participants Progressing to Death (All-cause Mortality), in Participants who Develop RSV LRTI or RSV-associated LRTC per the EAC's Assessment [ Time Frame: Up to 49 days ]
    Proportion of participants progressing to death (all-cause mortality), in participants who develop RSV LRTI or RSV-associated LRTC per the EAC's assessment will be reported.

  9. Proportion of Participants Progressing to Death (All-cause Mortality) [ Time Frame: Up to 1 year ]
    Proportion of participants progressing to death (all-cause mortality) will be reported.

  10. Proportion of Participants Progressing to Respiratory Failure (of any Cause) Requiring Mechanical Ventilation (Invasive or Noninvasive), in Participants who Develop RSV LRTI or RSV-associated LRTC per the EAC's Assessment [ Time Frame: Up to 49 days ]
    Proportion of participants progressing to respiratory failure (of any cause) requiring mechanical ventilation (invasive or noninvasive), in participants who develop RSV LRTI or RSV-associated LRTC per the EAC's assessment will be reported.

  11. Proportion of Participants Progressing to Respiratory Failure (of any Cause) Requiring Mechanical Ventilation (Invasive or Noninvasive) [ Time Frame: Up to 49 days ]
    Proportion of participants progressing to respiratory failure (of any cause) requiring mechanical ventilation (invasive or noninvasive) will be reported.

  12. Number of Supplemental Oxygen (O2) Free Days Through Day 28 [ Time Frame: Through Day 28 ]
    Number of supplemental O2 free days will be reported.

  13. Incidence of Supplemental Oxygen Requirement [ Time Frame: Up to 28 days ]
    Incidence of supplemental oxygen requirement in participants will be reported.

  14. Duration of Supplemental Oxygen [ Time Frame: Up to 28 days ]
    Duration of supplemental oxygen requirement in participants will be reported.

  15. Change from Baseline in Respiratory Rate [ Time Frame: Baseline up to 49 days ]
    Change from baseline in respiratory rate as measured by the investigator during scheduled visits will be reported.

  16. Change from Baseline in Heart Rate [ Time Frame: Baseline up to 49 days ]
    Change from baseline in heart rate as measured by the investigator during scheduled visits will be reported.

  17. Change from Baseline in Peripheral Capillary Oxygen Saturation (SpO2) [ Time Frame: Baseline up to 49 days ]
    Change from baseline in SpO2 as measured by the investigator during scheduled visits will be reported.

  18. Change from Baseline in Body Temperature [ Time Frame: Baseline up to 49 days ]
    Change from baseline in body temperature as measured by the investigator during scheduled visits will be reported.

  19. Proportion of Participants Hospitalized (of Participants who Were not Hospitalized at Baseline) [ Time Frame: Up to 1 year ]
    Proportion of participants hospitalized (of participants who were not hospitalized at baseline) will be reported.

  20. Proportion of Participants Re-hospitalized [ Time Frame: Up to 1 year ]
    Proportion of participants re-hospitalized (of participants who were hospitalized at baseline and discharged during the study and of participants who were not hospitalized at baseline, required hospitalization, and were discharged during the study) will be reported.

  21. Total Length of Hospital Stay [ Time Frame: Up to 49 days ]
    Total length of hospital stay (time in hospital from first dosing) will be reported.

  22. Total Time in the Intensive Care Unit (ICU) [ Time Frame: Up to 49 days ]
    Total time in the ICU (time in ICU from first dosing) will be reported.

  23. Incidence of Grade 3 and Grade 4 Adverse Events (AEs) [ Time Frame: Up to 49 days ]
    Incidence of Grade 3 and Grade 4 AEs will be assessed by system organ class where Grade 3: Severe and Grade 4: Life-threatening.

  24. Incidence of Respiratory AEs [ Time Frame: Up to 49 days ]
    Incidence of respiratory AEs will be reported.

  25. Incidence of Thoracic-related AEs [ Time Frame: Up to 49 days ]
    Incidence of thoracic-related AEs will be reported.

  26. Incidence of Antibiotic use in Participants who Develop and in Those who do not Develop RSV LRTI or RSV-Associated LRTC per the EAC's Assessment [ Time Frame: Up to 49 days ]
    Incidence of antibiotic use in participants who develop and in those who do not develop RSV LRTI or RSV-associated LRTC per the EAC's assessment will be reported.

  27. Time to Resolution of Symptoms as Assessed by Respiratory Infection Intensity and Impact Questionnaire (RiiQ) Symptom Scale [ Time Frame: Up to 49 days ]
    Time to resolution of symptoms, assessed through an instrument for participant-reported symptoms (RiiQ Symptom Scale) will be reported.

  28. Change from Baseline in Severity of Symptoms Reported by Participants in the RiiQ Symptom Scale Through Day 28 [ Time Frame: Baseline up to Day 28 ]
    Change from baseline in severity of symptoms reported by participants in the RiiQ symptom scale through Day 28 will be reported.

  29. Time to Resolution of Respiratory Illness as Assessed by Patient Global Impression of Severity (PGI-S) Scale [ Time Frame: Up to 49 days ]
    Time to resolution of respiratory illness, through the PGI-S Scale, will be reported.

  30. Change from Baseline in Patient Global Impression of Health (PGI-H) Scale Through Day 28 [ Time Frame: Baseline up to Day 28 ]
    Change from baseline in PGI-H scale through Day 28 will be reported.

  31. Change from Baseline in Patient Global Impression of Change (PGI-C) Scale Through Day 28 [ Time Frame: Baseline up to Day 28 ]
    Change from baseline in PGI-C scale through Day 28 will be reported.

  32. Area Under the Plasma Concentration-time Curve from Time Zero to 24 Hours Postdose (AUC [0-24]) of JNJ-53718678 [ Time Frame: Up to 24 hours postdose (on Days 1 and 8) ]
    AUC (0-24h) is defined as area under the plasma concentration-time curve from time 0 to 24 hours postdose.

  33. Trough Plasma Concentration (Ctrough) of JNJ-53718678 [ Time Frame: Predose on Days 1 and 8 ]
    Ctrough is defined as the observed plasma concentration before dosing or at the end of the dosing interval.

  34. Maximum Observed Plasma Concentration (Cmax) of JNJ-53718678 [ Time Frame: Day 1 ]
    Cmax is defined as the maximum observed plasma concentration of JNJ-53718678 in the dosing interval.

  35. Association of Plasma Concentration-time Data of JNJ-53718678 and Antiviral Activity [ Time Frame: Up to 49 days ]
    The potential association of plasma concentration-time data of JNJ-53718678 with antiviral activity (RSV viral kinetics) will be analyzed. Association will be analyzed using (non)-linear mixed-effects models in a tabular and/or graphical display.

  36. Association of Plasma Concentration-time Data of JNJ-53718678 and Safety Parameters [ Time Frame: Up to 49 days ]
    The potential association of plasma concentration-time data of JNJ-53718678 with selected safety (including AEs and laboratory abnormalities) parameters will be analyzed. Association will be analyzed using (non)-linear mixed-effects models in a tabular and/or graphical display.

  37. Association of Plasma Concentration-time Data of JNJ-53718678 and Clinical Outcomes [ Time Frame: Up to 49 days ]
    The potential association of plasma concentration-time data of JNJ-53718678 with clinical outcomes (proportion of participants developing LRTI) will be analyzed. Association will be analyzed using (non)-linear mixed-effects models in a tabular and/or graphical display.

  38. RSV Viral Load and Change from Baseline Over Time [ Time Frame: Baseline up to Day 28 ]
    RSV viral load and change from baseline over time will be measured by quantitative reverse transcription polymerase chain reaction (qRT-PCR) assay in the mid-turbinate nasal swab specimens.

  39. RSV Viral Load AUC from Immediately Prior to First Dose of Study Drug (Baseline) Through Days 8, 11, 15, 22 and 28 [ Time Frame: Baseline up to Days 8, 11, 15, 22 and 28 ]
    RSV viral load AUC will be determined by quantitative qRT-PCR assay of nasal swabs.

  40. Time to Undetectable RSV Viral Load [ Time Frame: Up to 49 days ]
    Time to undetectable RSV viral load (per the detection limit of the assay used in the study) will be reported.

  41. Proportion of Participants with Undetectable RSV Viral Load at Each Timepoint [ Time Frame: Up to 49 days ]
    Proportion of participants with undetectable RSV viral load at each time point throughout the study will be reported.

  42. Change from Baseline for the Health-related Quality of Life (HRQOL) as Assessed by 5-level EuroQol 5-Dimension (EQ-5D-5L) Through Day 28 [ Time Frame: Baseline up to Day 28 ]
    Change from baseline for the HRQOL assessment as assessed through the EQ-5D-5L through Day 28 will be reported.

  43. Change from Baseline for the HRQOL as Assessed by RiiQ Impact Scales Through Day 28 [ Time Frame: Baseline up to Day 28 ]
    Change from baseline for the HRQOL assessment as assessed through RiiQ impact scales through Day 28 will be reported.

  44. Change from Baseline in the RSV F Gene Sequence [ Time Frame: Baseline up to 49 days ]
    Change from baseline in the RSV F gene sequence will be reported.



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:   13 Years to 75 Years   (Child, Adult, Older Adult)
Sexes Eligible for Study:   All
Accepts Healthy Volunteers:   No
Criteria

Inclusion Criteria:

  • Received an autologous or allogeneic hematopoietic stem cell transplant (HSCT) using any conditioning regimen
  • Absolute lymphocyte count (ALC) less than (<) 1,000 cells/microliter (mL)
  • Participant has laboratory confirmed RSV diagnosis within 48 hours of randomization
  • New onset of at least 1 of the following respiratory symptoms within 4 days prior to the anticipated start of dosing nasal congestion, rhinorrhea, cough or pharyngitis (sore throat), and/or worsening of one of these chronic (associated with previously existing diagnosis, example, chronic rhinorrhea, seasonal allergies, chronic lung disease) respiratory symptoms within 4 days prior to the anticipated start of dosing
  • Peripheral capillary oxygen saturation (SpO2) greater than or equal to (>=) 92 percent (%) on room air

Exclusion Criteria:

  • Admitted to the hospital primarily for a lower respiratory tract disease of any cause as determined by the investigator
  • Requires supplemental oxygen at Screening or any time between Screening and randomization
  • Documented to be positive for other respiratory viruses (limited to influenza, parainfluenza, human rhinovirus, adenovirus, human metapneumovirus, or coronavirus) within 7 days prior to or at the Screening visit, if determined by local SOC testing (additional testing is not required)
  • Clinically significant bacteremia or fungemia within 7 days prior to or at Screening that has not been adequately treated, as determined by the investigator

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): NCT04056611


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

Locations
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Sponsors and Collaborators
Janssen Sciences Ireland UC
Investigators
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Study Director: Janssen Sciences Ireland UC Clinical Trial Janssen Sciences Ireland UC
Additional Information:
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Responsible Party: Janssen Sciences Ireland UC
ClinicalTrials.gov Identifier: NCT04056611    
Other Study ID Numbers: CR108662
53718678RSV2005 ( Other Identifier: Janssen Sciences Ireland UC )
2019-001551-39 ( EudraCT Number )
First Posted: August 14, 2019    Key Record Dates
Last Update Posted: November 25, 2020
Last Verified: November 2020
Individual Participant Data (IPD) Sharing Statement:
Plan to Share IPD: Yes
Plan Description: The data sharing policy of the Janssen Pharmaceutical Companies of Johnson & Johnson is available at www.janssen.com/clinical trials/transparency. As noted on this site, requests for access to the study data can be submitted through Yale open Data Access (YODA) Project site at yoda.yale.edu
URL: https://www.janssen.com/clinical-trials/transparency

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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
Virus Diseases
Respiratory Syncytial Virus Infections
Pneumovirus Infections
Paramyxoviridae Infections
Mononegavirales Infections
RNA Virus Infections