A Study of Rilematovir in Infants and Children and Subsequently in Neonates Hospitalized With Acute Respiratory Tract Infection Due to Respiratory Syncytial Virus (RSV)
- Conditions
- Respiratory Tract Infections
- Interventions
- Registration Number
- NCT04583280
- Lead Sponsor
- Janssen Research & Development, LLC
- Brief Summary
The purpose of the study is to evaluate the efficacy of rilematovir compared to placebo treatment with respect to the clinical outcome on the RSV Recovery Scale (RRS).
- Detailed Description
Respiratory syncytial virus (RSV), a negative-stranded ribonucleic acid (RNA) virus belonging to the Pneumoviridae family, is considered the most important cause of acute lower respiratory tract infection (LRTI) in infants and young children. In most patients, RSV results in upper respiratory tract infection (URTI) eliciting "common cold"-like symptoms, which might last up to 2 weeks, and are usually self-limiting. RSV-related LRTI is a major cause of hospital admissions and death in young children worldwide. Rilematovir is an investigational, small molecule, RSV fusion inhibitor. This study aims to evaluate the efficacy and safety of rilematovir in hospitalized infants and children (greater than or equal to \[\>=\] 28 days to less than or equal to \[\<=\] 5 years) and, subsequent to completion of the neonatal substudy, in hospitalized neonates (born at term, less than \[\<\] 28 days of age) with RSV infection. The study will include a Screening Period, a Treatment Period, and a Follow-up Period. The total study duration for each participant will be approximately 36 days (Screening included). The efficacy assessments include evaluation under the RRS and the safety assessments include evaluations of physical examinations, vital signs, electrocardiograms, clinical laboratory tests, and adverse events.
Recruitment & Eligibility
- Status
- TERMINATED
- Sex
- All
- Target Recruitment
- 28
Not provided
Not provided
Study & Design
- Study Type
- INTERVENTIONAL
- Study Design
- PARALLEL
- Arm && Interventions
Group Intervention Description Rilematovir Rilematovir X mg/kg Participants will receive rilematovir orally based on body weight and age group. Placebo Placebo Participants will receive matching placebo of rilematovir based on body weight and age group. Rilematovir Rilematovir Participants will receive rilematovir orally based on body weight and age group.
- Primary Outcome Measures
Name Time Method Percentage of Participants by Respiratory Syncytial Virus (RSV) Recovery Scale (RRS) Category Baseline to Day 8 RRS was an ordinal scale to assess a participant's clinical status. The RRS provided 7 mutually exclusive categories ordered from best (1) to worst (7) where 1 =home without signs/symptoms, 2 =home with sign/symptoms, 3 =ward without supplemental oxygen (O2) or feeding/hydration, 4 =ward with supplemental or feeding/hydration, 5 =intensive care unit (ICU) without mechanical ventilation (included both invasive and non-invasive mechanical ventilation), 6 =required mechanical ventilation and 7=worst (death). Higher category indicates worse condition. With or without signs/symptoms was defined as the key RSV signs/symptoms (breathing problems, retractions, tachypnea, cough, wheezing/breathing sounds, and tachycardia) resolved (absent or mild) or not resolved assessed by parent/caregiver.
- Secondary Outcome Measures
Name Time Method Percentage of Participants Clinically Resolved From RSV Disease Based on the Clinician Reported Outcome (ClinRO) Sign/Symptoms at Day 8 Day 8 Clinically resolved was defined as participant required no oxygen supplementation, no supplemental feeding/hydration, no need for ICU and had Key RSV signs/symptoms resolved to absent or mild as per ClinRO signs/symptoms. Clinically resolved Key RSV signs/symptoms were assessed based on clinician's observations as resolved if participant had no retractions, tachypnea, tachycardia, breathing problems (nasal flaring, head bobbing, grunting); cough (resolved if little or no coughing or occasional strong cough or sometimes productive) and wheezing (resolved if no wheezing or terminal expiratory wheezing or only with stethoscope).
Number of Participants With Abnormalities in Clinical Laboratory Values Up to Day 35 Number of participants with abnormally low (AL) and abnormally high (AH) values of bicarbonate, direct bilirubin, urea nitrogen, basophils, eosinophils, erythrocyte (Ery). mean corpuscular hemoglobin (HGB) concentration (conc), Ery. mean corpuscular hemoglobin, erythrocytes, leukocytes, lymphocytes, monocytes, neutrophils and reticulocytes were reported based on the investigator's discretion.
Number of Participants With Abnormalities in Electrocardiograms (ECGs) Up to Day 35 Number of participants with abnormally low and abnormally high values of ECG parameters (PR interval and RR interval) as assessed based on the investigator's discretion were reported.
Percentage of Participants Requiring Intensive Care Unit (ICU) Stay After First Dose of Rilematovir Up to Day 35 Percentage of participants requiring ICU stay was analyzed and reported.
Percentage of Participants With Acceptability and Palatability of the Rilematovir Formulation as Assessed by Parent(s)/Caregiver(s) Day 8 Acceptability and palatability were assessed by clinician electronic clinical outcome assessment (eCOA) questionnaire which consisted of 7 questions, 1- child took medicine easily, 2- disgusted expressions after tasting medicine, 3- cried after tasting medicine, 4- would not open mouth or turned head away to avoid medicine, 5- spit out or coughed out medicine, 6- gagged, 7- vomited (within 2 minutes of swallowing medicine).
Number of Participants With Post-baseline RSV-related Complications Up to Day 35 RSV related complications included respiratory complications (respiratory failure, apnoeic attacks, bronchiolitis, bronchial obstruction, pneumonia and asthmatic crisis), infectious complications (otitis media, bacterial respiratory tract infections and sepsis), cardiovascular complications (arrhythmia, cardiogenic shock, hemodynamic instability, congestive cardiac failure), acid-base or electrolyte complications (metabolic acidosis, metabolic alkalosis, hyponatremia, hypokalemia, hyperkalemia, hypocalcemia, hypercalcemia, hypoglycemia and hyperglycemia). Participants were counted only once, regardless of the number of complications they actually experienced.
Number of Participants With Abnormalities in Vital Signs Up to Day 35 Number of participants with abnormally low and abnormally high values of vital signs from baseline were assessed based on investigator's discretion. Vital signs included systolic blood pressure (SBP) (millimeter of mercury \[mmHg\]), diastolic blood pressure (DBP) (mmHg), pulse rate (beats per minute), respiratory rate (breaths per minute), temperature (degree Celsius) and oxygen saturation (in percentage).
Duration of Oxygen Supplementation Up to Day 35 Duration (in hours) of oxygen supplementation was defined as total number of hours a participant used supplemental oxygen from either prior to first dose and/or after first dose of drug until study termination, calculated as the sum of all separate records of supplementation.
Number of Participants With Medical Encounters and Treatments Up to Day 35 Medical resource utilization was assessed by medical care encounters and treatments. Medical encounters and treatments included physician or emergency room visits, tests and procedures, and medications, surgeries and other selected procedures, inpatient and outpatient.
Percentage of Participants Requiring Hydration and/or Feeding by Intravenous (IV) Administration or Nasogastric Tube After First Dose of Rilematovir Up to Day 35 Percentage of participants requiring any type of hydration and/or feeding by intravenous (IV) administration or nasogastric tube or percutaneous endoscopic gastrostomy was reported.
Time From First Study Dose to Resolution of Key RSV Signs/Symptoms Based on Observer Reported Outcome (ObsRO) After Free of Supplementation (Oxygen/Feeding/Hydration) for at Least 24 Hours Up to Day 21 Time (in hours) from first dose of study intervention to first resolution of key RSV signs/symptoms was evaluated based on ObsRO assessment after free of supplementation (O2/feeding/hydration) for at least 24 hours. Clinically resolved was defined as participant required no oxygen supplementation, no supplemental feeding/hydration, no need for ICU and had key RSV signs/symptoms resolved to absent or mild as per ObsRO signs/symptoms. Resolution of key signs/symptoms assessment was based on observations of child's parent/caregiver as resolved if no retractions, tachypnea, tachycardia, breathing problems (gasping for air nostrils, flaring when breathing, head bobbed back and forth when breathing), no breathing sound; cough (no coughing, little coughing without problems). Kaplan-Meier method was used for estimation.
Number of Participants With Treatment-emergent Adverse Events (TEAEs) Day 1 up to Day 35 An adverse event (AE) is any untoward medical occurrence in a clinical study participant administered a medicinal (investigational or non-investigational) product and did not necessarily have a causal relationship with the treatment. A TEAE was defined as an AE with an onset after the initiation study drug (Day 1) up to end of study (Day 35). AEs included both serious and non-serious AEs.
Percentage of Participants Requiring Re-hospitalization for Respiratory/Other Reasons Up to Day 35 Percentage of participants requiring re-hospitalization (participants re-hospitalized \[ward or ICU\] after been discharged from hospital) for respiratory/other reasons were reported.
Percentage of Participants Requiring Oxygen Supplementation After First Dose of Rilematovir Up to Day 35 Percentage of participants requiring any type of oxygen supplementation (invasive mechanical ventilation, non-invasive mechanical ventilation and non-invasive non-mechanical ventilation) were reported.
RSV Viral Load at Baseline, Days 2, 3, 5, 8, 14 and 21 Baseline, Days 2, 3, 5, 8, 14 and 21 Antiviral activity was determined based on measurements of RSV viral load which was measured by quantitative reverse transcription polymerase chain reaction (qRT-PCR) in the mid-turbinate (MT) nasal swab specimens.
Change From Baseline in RSV Viral Load at Days 2, 3, 5, 8, 14 and 21 Baseline, Days 2, 3, 5, 8, 14 and 21 Antiviral activity was determined based on measurements of RSV viral load which was measured by qRT-PCR in the MT nasal swab specimens.
Percentage of Participants With Undetectable RSV Viral Load Baseline, Days 2, 3, 5, 8, 14 and 21 Percentage of participants with undetectable RSV viral load was analyzed.
Plasma Concentrations of Rilematovir 1 hour Post-dose (Day 1) and pre-dose (Day 2) Plasma concentrations of rilematovir were assessed. Participant wise data were reported for this outcome measure.
Duration of ICU Stay Up to Day 35 Duration (in hours) of ICU stay was defined as total number of hours a participant experienced an ICU stay from first dose of rilematovir until study termination, calculated as the sum of all separate records of ICU stay.
Duration of Supplemental Feeding/Hydration Up to Day 35 Duration (in hours) of supplemental feeding/hydration was defined as total number of hours a participant was administered feeding/hydration supplementation from either prior to first dose and/or after first dose of drug until study termination, calculated as the sum all separate records of supplementation use per participant.
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Trial Locations
- Locations (142)
Arnold Palmer Hospital For Children
🇺🇸Orlando, Florida, United States
University of Mississippi Medical Center
🇺🇸Jackson, Mississippi, United States
Jacobi Medical Center
🇺🇸Bronx, New York, United States
Le Bonheur Children's Hospital
🇺🇸Memphis, Tennessee, United States
MultiCare Health Systems for Research and Innovation
🇺🇸Tacoma, Washington, United States
Hospital Interzonal General de Agudos Dr. Jose Penna
🇦🇷Bahia Blanca, Argentina
Hospital Italiano Regional Del Sur
🇦🇷Bahía Blanca, Argentina
Hospital General de Niños Pedro de Elizalde
🇦🇷Buenos Aires, Argentina
Hospital Universitario Austral
🇦🇷Pilar, Argentina
Instituto Medico Rio Cuarto
🇦🇷Rio Cuarto, Argentina
Scroll for more (132 remaining)Arnold Palmer Hospital For Children🇺🇸Orlando, Florida, United States