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
试验速览
- 阶段
- 2 期
- 状态
- 终止
- 入组人数
- 3
- 试验地点
- 69
- 主要终点
- Percentage of Participants Who Developed Respiratory Syncytial Virus (RSV) Lower Respiratory Tract Infection (LRTI)
研究概览
简要总结
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.
详细描述
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.
研究设计
- 研究类型
- Interventional
- 分配方式
- Randomized
- 干预模型
- Parallel
- 主要目的
- Treatment
- 盲法
- Double (Participant, Investigator)
入排标准
- 年龄范围
- 13 Years 至 75 Years（Child, Adult, Older Adult）
- 性别
- All
- 接受健康志愿者
- 否
入选标准
- •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
排除标准
- •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
研究组 & 干预措施
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.
干预措施: JNJ-53718678 250 mg (Drug)
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.
干预措施: Placebo (Drug)
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.
干预措施: JNJ-53718678 125 mg (Drug)
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.
干预措施: JNJ-53718678 250 mg (Drug)
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.
干预措施: Placebo (Drug)
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.
干预措施: JNJ-53718678 125 mg (Drug)
结局指标
主要结局
Percentage of Participants Who Developed Respiratory Syncytial Virus (RSV) Lower Respiratory Tract Infection (LRTI)
时间窗: Up to Day 28
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).
次要结局
- Percentage of Participants Who Developed RSV-associated Lower Respiratory Tract Complication (LRTC)(Up to Day 28)
- Number of Participants With Treatment-emergent Adverse Events (TEAEs)(Up to Day 49)
- Percentage of Participants With Treatment-emergent Abnormal (>=Grade 3) Clinical Laboratory Findings(Up to Day 49)
- Percentage of Participants With Clinically Significant Abnormalities in Electrocardiogram (ECG) Findings(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(Up to Day 49)
- Percentage of Participants With Treatment-emergent Abnormal Vital Signs Findings(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)(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(Up to Day 49)
- Percentage of Participants Who Progressed to Death (All-cause Mortality)(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(Up to Day 49)
- Percentage of Participants Who Progressed to Respiratory Failure (of Any Cause) Requiring Mechanical Ventilation (Invasive or Noninvasive)(Up to Day 49)
- Number of Supplemental Oxygen Free Days(Through Day 28)
- Percentage of Participants With Treatment-emergent Oxygen Supplementation(Up to Day 49)
- Respiratory Rate Over Time(Baseline (Day 1), Days 15, 28, and 35)
- Heart Rate Over Time(Baseline (Day 1), Days 15, 28, and 35)
- Peripheral Capillary Oxygen Saturation (SpO2) Over Time(Baseline (Day 1), Days 15, 28, and 35)
- Body Temperature Over Time(Baseline (Day 1), Days 15, 28, and 35)
- Percentage of Participants Hospitalized (of Participants Who Were Not Hospitalized at Baseline)(Up to Day 49)
- Percentage of Participants Who Were Re-hospitalized(Up to Day 49)
- Duration of Hospital Stay(Up to Day 49)
- Duration of Intensive Care Unit (ICU) Stay(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(Up to Day 49)
- Number of Participants With Respiratory Related AEs(Up to Day 49)
- Number of Participants With Thoracic-related AEs(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(Up to Day 49)
- Plasma Concentration of JNJ-53718678(Days 1, 3, 8, 15 and 22)
- RSV Viral Load Over Time(Baseline (Day 1), Days 15, 28, and 35)