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)

Phase 2TerminatedNCT04056611

Janssen Sciences Ireland UC3 enrolled

Overview

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.

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.

Study Type

INTERVENTIONAL

Allocation

RANDOMIZED

Purpose

TREATMENT

Masking

DOUBLE

Enrollment

Conditions

Respiratory Syncytial Virus Infections

Interventions

JNJ-53718678 250 mgDRUG

JNJ-53718678 250 mg will be administered orally.

PlaceboDRUG

Matching placebo will be administered orally.

JNJ-53718678 125 mgDRUG

JNJ-53718678 125 mg will be administered orally.

Eligibility

Sex: ALLMin age: 13 YearsMax age: 75 Years

Medical Language ↔ Plain English

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

Locations (69)

Outcomes

Primary Outcomes

Percentage of Participants Who Developed Respiratory Syncytial Virus (RSV) Lower Respiratory Tract Infection (LRTI)

Percentage of participants who developed RSV LRTI was assessed. RSV LRTI was defined as the development of a lower respiratory sign or symptom (including decrease in oxygen saturation or increase in supplemental oxygen to maintain oxygen saturation, wheezing, rhonchi, rales, dyspnea, tachypnea, worsening cough) and positive RSV test from lower respiratory tract sample (example \[eg\], sputum, induced sputum, bronchoalveolar lavage (BAL), lung biopsy, or autopsy specimen) within +-4 days of a new chest image finding, compared to baseline, consistent with a LRTI; OR positive RSV test from lower respiratory tract sample (eg, sputum, induced sputum, BAL, lung biopsy, or autopsy specimen) only; OR positive RSV test from upper respiratory tract sample within ±4 days of a new chest image finding, compared to baseline, consistent with a RSV LRTI as determined by the Endpoint Adjudication Committee (EAC).

Time frame: Up to Day 28

Secondary Outcomes

Percentage of Participants Who Developed RSV-associated Lower Respiratory Tract Complication (LRTC)

Percentage of participants who developed RSV-associated LRTC was assessed. RSV-associated LRTC defined as development of lower respiratory sign/symptom (includes decrease in oxygen saturation/increase in supplemental oxygen to maintain oxygen saturation, wheezing, rhonchi, rales, dyspnea, tachypnea, and worsening cough) and met 1 of following subcategories determined by EAC: a) RSV LRTI, b) secondary bacterial LRTI (positive specimen for clinically significant bacterium within 4 days of new chest image finding, compared to baseline, consistent with LRTI), c) secondary LRTI due to unusual pathogens (positive specimen for clinically significant unusual organism within 4 days of new chest image finding, compared to baseline, consistent with LRTI), d) secondary LRTC of unknown etiology (new chest image finding than baseline, consistent with LRTI, inflammatory process/ some other clinically significant pulmonary process which were absent within 4 days of new chest image finding).

Time frame: Up to Day 28

Number of Participants With Treatment-emergent Adverse Events (TEAEs)

Data from ClinicalTrials.gov

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Ronald Reagan UCLA Medical Center

Los Angeles, California, United States

Henry Ford Hospital - Hematology/oncology

Detroit, Michigan, United States

University Of Minnesota

Minneapolis, Minnesota, United States

Northwell Health Cancer Institute

Lake Success, New York, United States

Weill Cornell Medical College

New York, New York, United States

University Hospitals Cleveland Medical Center

Cleveland, Ohio, United States

Fox Chase Cancer Center

Philadelphia, Pennsylvania, United States

Baylor Scott and White Research Institute

Dallas, Texas, United States

MD Anderson Cancer Center - University of Texas

Houston, Texas, United States

Hospital Espanol De Bahia Blanca

Bahía Blanca, Argentina

...and 59 more locations

An AE is any untoward medical occurrence in a clinical study participant administered a medicinal (investigational or non investigational) product. An AE did not necessarily have a causal relationship with the intervention. Any AE which occurred post first dose administration of study drug up to the end of study (EOS) (that is, Day 49) was considered as treatment-emergent.

Time frame: Up to Day 49

Percentage of Participants With Treatment-emergent Abnormal (>=Grade 3) Clinical Laboratory Findings

Percentage of participants with greater than or equal to (\>=) Grade 3 treatment-emergent laboratory abnormalities (platelet count decreased, glucose increase) was assessed in this outcome measure. Treatment-emergent: any abnormality occurred post first dose of study drug up to end of study (that is, Day 49).

Time frame: Up to Day 49

Percentage of Participants With Clinically Significant Abnormalities in Electrocardiogram (ECG) Findings

Percentage of participants with clinically significant abnormalities in ECG findings was assessed in this outcome measure. Various ECG variables assessed were heart rate: abnormally low (\<= 45 beats per minute \[bpm\]), abnormally high (\>= 120 bpm); PR interval: abnormally high (\>=210 milliseconds \[msec\]); QRS interval: abnormally high (\>=120 msec), QT interval and corrected QT (QTcF; according to Fridericia's formula) interval (\>450 msec, \>480 msec, or \>500 msec, increases from baseline \>30 msec or \>60 msec.)

Time frame: Up to Day 49

Percentage of Participants With Treatment-emergent Abnormal Vital Signs Findings

Percentage of participants with abnormal vital signs findings was assessed. Abnormal vital parameters included pulse rate: abnormally low \<=45 bpm, abnormally high \>=120 bpm; Systolic Blood Pressure (SBP): abnormally low \<=90 Millimeter of mercury (mmHg), Grade 1 (mild): \> 90 mmHg - \< 100 mmHg, Grade 2 (moderate): \>= 100 mmHg to \<110 mmHg, Grade 3 (severe): \>=110 mmHg; Diastolic BP: abnormally low \<=50 mmHg, Grade 1: \>90 mmHg to \<100 mmHg, Grade 2: \>=100 mmHg to \<110 mmHg, Grade 3: \>=110 mmHg; Respiratory rate- Grade 1 (mild): 17-20 breaths per minute, Grade 2 (moderate): 21-25 breaths per minute, Grade 3 (severe): \>25 breaths per minute, Grade 4 (potentially life threatening): intubation; Temperature: abnormally high \>38.0 degree celsius. Vital signs abnormalities reported for at least 1 participant were reported in this outcome measure. Treatment-emergent: any abnormality occurred post first dose of study drug up to EOS (that is, Day 49).

Time frame: Up to Day 49

Percentage of Participants Who Progressed to Respiratory Failure (of Any Cause) Requiring Mechanical Ventilation (Invasive or Noninvasive) and/or Death Among Those Who Developed RSV LRTI or RSV-associated LRTC Per the EAC's Assessment

Percentage of participants who progressed to respiratory failure (of any cause) requiring mechanical ventilation (invasive or noninvasive) and/or death among those who developed RSV LRTI or RSV-associated LRTC per the EAC's assessment was assessed. Here, '0' in the 'number of participants analyzed' field (N=0) signifies that no participants were available for the analysis because none of the participants developed RSV LRTI or RSV-associated LRTC per the EAC's Assessment.

Time frame: Up to Day 49

Percentage of Participants Who Progressed to Respiratory Failure (of Any Cause) Requiring Mechanical Ventilation (Invasive or Noninvasive) and/or Death (All-cause Mortality)

Percentage of participants who progressed to respiratory failure (of any cause) requiring mechanical ventilation (invasive or noninvasive) and/or death (all-cause mortality) was assessed.

Time frame: Up to Day 49

Percentage of Participants Who Progressed to Death (All-cause Mortality) Among Those Who Developed RSV LRTI or RSV-associated LRTC Per the EAC's Assessment

Percentage of participants who progressed to death (all-cause mortality) among those who developed RSV LRTI or RSV-associated LRTC per the EAC's assessment was assessed. Here, '0' in the 'number of participants analyzed' field (N=0) signifies that no participants were available for the analysis because none of the participants developed RSV LRTI or RSV-associated LRTC per the EAC's Assessment.

Time frame: Up to Day 49

Percentage of Participants Who Progressed to Death (All-cause Mortality)

Percentage of participants who progressed to death (all-cause mortality) was assessed.

Time frame: Up to Day 49

Percentage of Participants Who Progressed to Respiratory Failure (of Any Cause) Requiring Mechanical Ventilation (Invasive or Noninvasive) Among Those Who Developed RSV LRTI or RSV-associated LRTC Per the EAC's Assessment

Percentage of participants who progressed to respiratory failure (of any cause) requiring mechanical ventilation (invasive or noninvasive) among those who developed RSV LRTI or RSV-associated LRTC per the EAC's assessment was assessed. Here, '0' in the 'number of participants analyzed' field (N=0) signifies that no participants were available for the analysis because none of the participants developed RSV LRTI or RSV-associated LRTC per the EAC's Assessment.

Time frame: Up to Day 49

Percentage of Participants Who Progressed to Respiratory Failure (of Any Cause) Requiring Mechanical Ventilation (Invasive or Noninvasive)

Percentage of participants who progressed to respiratory failure (of any cause) requiring mechanical ventilation (invasive or noninvasive) was assessed.

Time frame: Up to Day 49

Number of Supplemental Oxygen Free Days

Number of supplemental oxygen free days was assessed. The number of supplemental oxygen free days was the number of days the participants did not receive/require supplemental oxygen during the first 28 days post treatment.

Time frame: Through Day 28

Percentage of Participants With Treatment-emergent Oxygen Supplementation

Percentage of participants who required treatment-emergent oxygen supplementation (e.g., supplemental oxygen, noninvasive pressure ventilation, invasive mechanical ventilation \[tracheal tube, laryngeal mask or tracheostomy\]). Any AE which occurred post first dose administration of study drug up to the end of study (that is, Day 49) were considered as treatment-emergent.

Time frame: Up to Day 49

Respiratory Rate Over Time

Respiratory rate over time was reported by investigator. In this outcome measure, only those timepoints in which individual participant had data were reported.

Time frame: Baseline (Day 1), Days 15, 28, and 35

Heart Rate Over Time

Heart rate over time was reported by investigator. In this outcome measure, only those timepoints in which individual participant had data were reported.

Time frame: Baseline (Day 1), Days 15, 28, and 35

Peripheral Capillary Oxygen Saturation (SpO2) Over Time

Peripheral capillary oxygen saturation (SpO2) over time was reported by investigator. In this outcome measure, only those timepoints in which individual participant had data were reported.

Time frame: Baseline (Day 1), Days 15, 28, and 35

Body Temperature Over Time

Body temperature (in Degrees Celsius) over time was reported. In this outcome measure, only those timepoints in which individual participant had data were reported.

Time frame: Baseline (Day 1), Days 15, 28, and 35

Percentage of Participants Hospitalized (of Participants Who Were Not Hospitalized at Baseline)

Percentage of participants who were not hospitalized at baseline and required hospitalization during the study was assessed.

Time frame: Up to Day 49

Percentage of Participants Who Were Re-hospitalized

Percentage of participants who were re-hospitalized (of participants who were hospitalized at baseline and discharged during the study and of participants who were not hospitalized at baseline and required hospitalization and were discharged during the study) was assessed in this outcome measure.

Time frame: Up to Day 49

Duration of Hospital Stay

Duration (in days) of hospital stay was assessed.

Time frame: Up to Day 49

Duration of Intensive Care Unit (ICU) Stay

Duration of ICU stay was assessed. Duration (in hours) was defined as total number of hours a participant was in ICU from first dose of study drug until study termination.

Time frame: Up to Day 49

Number of Participants With Grade 3 and Grade 4 Treatment-emergent Adverse Events (TEAEs) in the Infections and Infestations System Organ Class

An AE is any untoward medical occurrence in a clinical study participant administered a medicinal (investigational or non investigational) product. An AE did not necessarily had a causal relationship with the intervention. Participants with Grade 3 or Grade 4 TEAE were assessed in this outcome measure. Any AE which occurred post first dose administration of study drug up to the end of study (that is, Day 49) were considered as treatment-emergent.

Time frame: Up to Day 49

Number of Participants With Respiratory Related AEs

Number of participants with respiratory related AEs (respiratory infections) was assessed.

Time frame: Up to Day 49

Number of Participants With Thoracic-related AEs

Number of participants with thoracic-related AEs was assessed.

Time frame: Up to Day 49

Number of Participants With Antibiotic Use Among Those Who Developed RSV LRTI or RSV-Associated LRTC Per the EAC's Assessment

Number of participants with antibiotic use among those who developed RSV LRTI or RSV-associated LRTC per the EAC's assessment was assessed. Here, '0' in the 'number of participants analyzed' field (N=0) signifies that no participants were available for the analysis because none of the participants developed RSV LRTI or RSV-associated LRTC per the EAC's Assessment.

Time frame: Up to Day 49

Plasma Concentration of JNJ-53718678

Plasma Concentration of JNJ-53718678 was reported. In this outcome measure, only those timepoints in which individual participant had data were reported.

Time frame: Days 1, 3, 8, 15 and 22

RSV Viral Load Over Time

RSV viral load (RSV B) was measured over time by quantitative reverse transcription polymerase chain reaction (qRT-PCR) in the nasal swab specimens collected at the clinic visits and at home. In this outcome measure, only those timepoints in which individual participant had data were reported.

Time frame: Baseline (Day 1), Days 15, 28, and 35