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)

Respiratory Syncytial Virus Infections Clinical Trial

— FREESIA  

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

Clinical Trial Details — Status: Terminated

Administrative data

• NCT number: NCT04056611
• Other study ID #: CR108662
• Secondary ID: 53718678RSV20052
• Status: Terminated
• Phase: Phase 2
• Start date: December 26, 2019
• Est. completion date: February 4, 2022

Study information

• Verified date: March 2023
• Source: Janssen Sciences Ireland UC
• Contact: n/a
• Is FDA regulated: No
• Study type: Interventional

Clinical Trial 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.

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.

Recruitment information / eligibility

• Status: Terminated
• Enrollment: 3
• Est. completion date: February 4, 2022
• Est. primary completion date: February 4, 2022
• Accepts healthy volunteers: No
• Gender: All
• Age group: 13 Years to 75 Years

Eligibility

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

Related Conditions & MeSH terms

• Infections
• Respiratory Syncytial Virus Infections
• Virus Diseases

Intervention

Drug:
• JNJ-53718678 250 mg
JNJ-53718678 250 mg will be administered orally.
• Placebo
Matching placebo will be administered orally.
• JNJ-53718678 125 mg
JNJ-53718678 125 mg will be administered orally.

Locations

Country	Name	City	State
Argentina	Hospital Español De Bahia Blanca	Bahia Blanca
Argentina	Hospital Italiano de La Plata	Ciudad De La Plata
Argentina	Hospital Privado-Universitario de Cordoba	Cordoba
Argentina	Sanatorio Allende	Cordoba
Argentina	Clinica Mayo de UMCB	San Miguel de Tucuman
Australia	Peter MacCallum Cancer Centre	Melbourne
Australia	Royal Melbourne Hospital	Melbourne
Australia	Westmead Hospital	Westmead
Belgium	AZ Sint-Jan	Brugge
Belgium	Jules Bordet Institute	Brussels
Belgium	UZ Brussel	Brussels
Belgium	UZ Gent	Gent
Belgium	UZ Leuven	Leuven
Belgium	CHU de Liège	Liege
Belgium	Jessa Ziekenhuis	Limburg
Brazil	Fundacao Pio XII	Barretos
Brazil	Universidade Federal De Minas Gerais - Hospital das Clínicas	Belo Horizonte
Brazil	Centro de Pesquisa e Ensino em Oncologia de Santa Catarina - CEPEN	Florianopolis
Brazil	Universidade Federal do Ceara - Hospital Universitario Walter Cantidio	Fortaleza
Brazil	Fundacao Doutor Amaral Carvalho	Jau
Brazil	Hospital das Clinicas de Porto Alegre	Porto Alegre
Brazil	Fundação Faculdade Regional de Medicina de São José do Rio Preto - Hospital de Base	Sao Jose do Rio Preto
Brazil	Real e Benemérita Associação Portuguesa de Beneficência	Sao Paulo
Brazil	Fundação Antônio Prudente - A.C. Camargo Cancer Center	São Paulo
Brazil	Sociedade Beneficente de Senhoras - Hospital Sírio Libanês	São Paulo
Bulgaria	UMHAT 'Sveti Georgi'-Plovdiv	Plovdiv
Bulgaria	Specialized Hospital for Active Treatment of Haematologic Diseases	Sofia
Bulgaria	Multiprofile Hospital for Active Treatment 'Sveta Marina' EAD	Varna
France	Hôpital d'Instruction des Armées Percy	Clamart
France	Institut Universitaire du Cancer Toulouse - Oncopole	Toulouse
Israel	Rambam Medical Center	Haifa
Israel	Hadassah Medical Center	Jerusalem
Israel	Sheba Medical Center	Ramat Gan
Israel	Sourasky (Ichilov) Medical Center	Tel Aviv
Italy	Ospedale San Raffaele HSR Istituto Scientifico Universitario San Raffaele	Milano
Italy	Ematologia Fondazione Univ. Policlinico Gemelli Università Cattolica del Sacro Cuore	Roma
Japan	Akita University Hospital	Akita
Japan	Chiba University Hospital	Chiba
Japan	Tokai University Hospital	Isehara
Japan	Japanese Red Cross Society Nagano Hospital	Nagano
Japan	Okayama University Hospital	Okayama
Korea, Republic of	The Catholic University of Korea, Seoul St. Mary's Hospital	Seoul
Malaysia	Hospital Ampang	Ampang Jaya
Malaysia	Penang General Hospital	Georgetown
Malaysia	University Malaya Medical Centre	Kuala Lumpur
Malaysia	Sunway Medical Centre	Petaling Jaya, Selangor
Netherlands	Leiden University Medical Center	Leiden
Spain	Hosp. de la Santa Creu i Sant Pau	Barcelona
Spain	Hosp. Univ. Vall D Hebron	Barcelona
Spain	Hosp. Gral. Univ. Gregorio Marañon	Madrid
Spain	Hosp. Univ. 12 De Octubre	Madrid
Spain	Hosp. Clinico Univ. de Salamanca	Salamanca
Spain	Hosp. Univ. Marques De Valdecilla	Santander
Spain	Hosp. Virgen Del Rocio	Sevilla
Sweden	Skanes universitetssjukhus	Malmö
Taiwan	Kaohsiung Medical University Hospital	Kaohsiung
Taiwan	China Medical University Hospital	Taichung
Taiwan	National Cheng Kung University Hospital	Tainan
Taiwan	National Taiwan University Hospital	Taipei
United Kingdom	Kings College Hospital NHS Trust	London
United States	University Hospitals Cleveland Medical Center	Cleveland	Ohio
United States	Baylor Scott & White Research Institute	Dallas	Texas
United States	Henry Ford Hospital - Hematology/oncology	Detroit	Michigan
United States	MD Anderson Cancer Center - University of Texas	Houston	Texas
United States	Northwell Health Cancer Institute	Lake Success	New York
United States	Ronald Reagan UCLA Medical Center	Los Angeles	California
United States	University Of Minnesota	Minneapolis	Minnesota
United States	Weill Cornell Medical College	New York	New York
United States	Fox Chase Cancer Center	Philadelphia	Pennsylvania

Sponsors (1)

Lead Sponsor	Collaborator
Janssen Sciences Ireland UC

Countries where clinical trial is conducted

United States,  Argentina,  Australia,  Belgium,  Brazil,  Bulgaria,  France,  Israel,  Italy,  Japan,  Korea, Republic of,  Malaysia,  Netherlands,  Spain,  Sweden,  Taiwan,  United Kingdom, 

Outcome

Type	Measure	Description	Time frame	Safety issue
Primary	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).	Up to Day 28
Secondary	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).	Up to Day 28
Secondary	Number of Participants With Treatment-emergent Adverse Events (TEAEs)	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.	Up to Day 49
Secondary	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).	Up to Day 49
Secondary	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.)	Up to Day 49
Secondary	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).	Up to Day 49
Secondary	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.	Up to Day 49
Secondary	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.	Up to Day 49
Secondary	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.	Up to Day 49
Secondary	Percentage of Participants Who Progressed to Death (All-cause Mortality)	Percentage of participants who progressed to death (all-cause mortality) was assessed.	Up to Day 49
Secondary	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.	Up to Day 49
Secondary	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.	Up to Day 49
Secondary	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.	Through Day 28
Secondary	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.	Up to Day 49
Secondary	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.	Baseline (Day 1), Days 15, 28, and 35
Secondary	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.	Baseline (Day 1), Days 15, 28, and 35
Secondary	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.	Baseline (Day 1), Days 15, 28, and 35
Secondary	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.	Baseline (Day 1), Days 15, 28, and 35
Secondary	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.	Up to Day 49
Secondary	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.	Up to Day 49
Secondary	Duration of Hospital Stay	Duration (in days) of hospital stay was assessed.	Up to Day 49
Secondary	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.	Up to Day 49
Secondary	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.	Up to Day 49
Secondary	Number of Participants With Respiratory Related AEs	Number of participants with respiratory related AEs (respiratory infections) was assessed.	Up to Day 49
Secondary	Number of Participants With Thoracic-related AEs	Number of participants with thoracic-related AEs was assessed.	Up to Day 49
Secondary	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.	Up to Day 49
Secondary	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.	Days 1, 3, 8, 15 and 22
Secondary	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.	Baseline (Day 1), Days 15, 28, and 35