Respiratory Tract Infections
Conditions
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.
Interventions
DRUGRilematovir
Participants of age group greater than or equal to (\>=) 28 days to less than (\<) 3 months (age group 1) or \>= 3 months to \< 6 months (age group 2) or \>= 6 months to less than or equal to (\<=) 5 years (age group 3) will receive rilematovir orally twice a day (BID) from Days 1 to Day 7 or Day 8.
DRUGRilematovir X mg/kg
Participants of age group birth at term (after at least 37 weeks of gestation) to \< 28 days (age group 4) will receive rilematovir orally BID from Days 1 to Day 7 or Day 8. The dose is dependent on outcome of the substudy in neonates and following independent data monitoring (IDMC) review and recommendation.
DRUGPlacebo
Participant of age group 1, 2, 3 and 4 will receive matching placebo of rilematovir BID from Days 1 to Day 7 or Day 8 as per assigned age group.
Sponsors
Janssen Research & Development, LLC
Study design
Allocation
RANDOMIZED
Intervention model
PARALLEL
Primary purpose
TREATMENT
Masking
DOUBLE (Subject, Investigator)
Eligibility
Sex/Gender
ALL
Age
1 Days to 5 Years
Healthy volunteers
No
Inclusion criteria
* The participant weighs within greater than or equal to (\>=) 2.4 kilograms (kg) and less than or equal to (\<=) 24.6 kg * Each participant's parent(s) (preferably both if available or as per local requirements) or their legally acceptable representative(s) has/have signed an informed consent form (ICF) indicating that (s)he understands the purpose of, and procedures required for, the study; is willing for their child to participate in the study; with regards to the concomitant medication, the lifestyle consideration and study procedures and assessments to be performed by the parent(s)/caregiver(s) as well as those by the investigator/study site personnel * The participant has an acute respiratory illness with at least 1 of the signs/symptoms within 24 hours prior to start of screening and at screening, as evaluated by the investigator in Upper respiratory tract infection: nasal congestion or rhinorrhea; and Lower respiratory tract infection: increased respiratory effort (as evidenced by subcostal, intercostal or tracheosternal retractions, grunting, head bobbing, nasal flaring, or tachypnea), wheezing, cough, cyanosis, or apnea; and systemic/general: feeding difficulties (defined as \<75 percent \[%\] intake of normal food amounts); dehydration; fever; disturbed sleep, or disturbed activity level (irritable/restless/agitated/less responsive). Cough or wheezing cannot be the only LRTI sign/symptom present, that is, at least one other LRTI sign/symptom needs to be present for eligibility * The time of onset of RSV signs/symptoms to the anticipated time of randomization must be less than or equal to (\<=) 3 days. Onset of signs/symptoms is defined as the time of the day (or part of the day if time of the day cannot be specified) the parent(s)/caregiver(s) became aware of the first sign and/or symptom consistent with respiratory or systemic/general manifestation of signs/symptoms of RSV infection. The time of sign/symptom onset has to be assessed as accurately as possible * Participants are otherwise healthy or have (a) risk factor(s) for severe RSV disease
Exclusion criteria
* The participant has had either confirmed severe acute respiratory syndrome coronavirus-2 (SARS-CoV-2) infection (test positive) during the four weeks prior to randomization, or close contact with a person with COVID-19 (test confirmed or suspected SARS CoV-2 infection) within 14 days prior to randomization * Confirmed QT interval corrected for heart rate according to Fridericia's formula (QTcF) interval greater than (\>) 450 milliseconds (msec) per the machine read parameter result at screening. Presence of an abnormal QTcF interval should be confirmed by repeat electrocardiogram (ECG) recording during screening * Known personal or family history of Long QT Syndrome or sudden cardiac death * Presence of repetitive ventricular premature contractions (\>10/minutes \[min\]), second- or third-degree heart block, or complete or incomplete left bundle branch block, or complete right bundle branch block per the machine read ECG result at screening. Presence of any of the above abnormalities should be confirmed by repeat ECG recording during screening
Design outcomes
Primary
| Measure | Time frame | Description |
|---|---|---|
| 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
| Measure | Time frame | Description |
|---|---|---|
| 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. |
| 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 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 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. |
| 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. |
| 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). |
| 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 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). |
| 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. |
| 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. |
| 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. |
| 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. |
| 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. |
| 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 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). |
| 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. |
Countries
Argentina, Belgium, Brazil, Bulgaria, China, Czechia, Estonia, Germany, Hungary, Israel, Italy, Japan, Latvia, Malaysia, Mexico, Panama, Poland, Slovakia, South Korea, Spain, Sweden, Taiwan, Thailand, Turkey (Türkiye), Ukraine, United States
Participant flow
Pre-assignment details
A total of 28 participants with acute respiratory tract infection due to respiratory syncytial virus (RSV) were randomized and treated (8 participants in placebo arm and 20 participants in rilematovir arm). Of these, 27 participants completed the study.
Participants by arm
| Arm | Count |
|---|---|
| Placebo Participants aged greater than or equal to (\>=) 28 days to less than (\<) 3 months, \>=3 to \<6 months, and \>=6 months to less than or equal to (\<=) 5 years received placebo matching to rilematovir as oral suspension twice daily (BID) from Days 1 to 7 (14 consecutive doses). | 8 |
| Rilematovir Participants aged \>=28 days to \<3 months, \>=3 to \<6 months, and \>=6 months to \<=5 years received rilematovir 2.5 milligrams per kilogram (mg/kg), 3 mg/kg and 4.5 mg/kg respectively, as oral suspension BID from Days 1 to 7 (14 consecutive doses). | 20 |
| Total | 28 |
Withdrawals & dropouts
| Period | Reason | FG000 | FG001 |
|---|---|---|---|
| Overall Study | Consent withdrawn by parent/caregiver | 0 | 1 |
Baseline characteristics
| Characteristic | Placebo | Rilematovir | Total |
|---|---|---|---|
| Age, Continuous | 15.3 months STANDARD_DEVIATION 19.4 | 16.2 months STANDARD_DEVIATION 13.67 | 15.9 months STANDARD_DEVIATION 15.14 |
| Age, Customized Children (2-11 years) | 2 Participants | 6 Participants | 8 Participants |
| Age, Customized Infants and toddlers(28 days-23 months) | 6 Participants | 14 Participants | 20 Participants |
| Ethnicity (NIH/OMB) Hispanic or Latino | 3 Participants | 8 Participants | 11 Participants |
| Ethnicity (NIH/OMB) Not Hispanic or Latino | 5 Participants | 8 Participants | 13 Participants |
| Ethnicity (NIH/OMB) Unknown or Not Reported | 0 Participants | 4 Participants | 4 Participants |
| Race/Ethnicity, Customized American Indian or Alaska Native | 0 Participants | 1 Participants | 1 Participants |
| Race/Ethnicity, Customized Asian | 2 Participants | 1 Participants | 3 Participants |
| Race/Ethnicity, Customized Black or African American | 0 Participants | 0 Participants | 0 Participants |
| Race/Ethnicity, Customized Missing | 0 Participants | 1 Participants | 1 Participants |
| Race/Ethnicity, Customized More than one race | 0 Participants | 0 Participants | 0 Participants |
| Race/Ethnicity, Customized Native Hawaiian or Other Pacific Islander | 0 Participants | 0 Participants | 0 Participants |
| Race/Ethnicity, Customized Other | 0 Participants | 0 Participants | 0 Participants |
| Race/Ethnicity, Customized Unknown or Not Reported | 0 Participants | 3 Participants | 3 Participants |
| Race/Ethnicity, Customized White | 6 Participants | 14 Participants | 20 Participants |
| Sex: Female, Male Female | 6 Participants | 12 Participants | 18 Participants |
| Sex: Female, Male Male | 2 Participants | 8 Participants | 10 Participants |
Adverse events
| Event type | EG000 affected / at risk | EG001 affected / at risk |
|---|---|---|
| deaths Total, all-cause mortality | 0 / 8 | 0 / 20 |
| other Total, other adverse events | 5 / 8 | 10 / 20 |
| serious Total, serious adverse events | 0 / 8 | 1 / 20 |
Outcome results
Primary
Percentage of Participants by Respiratory Syncytial Virus (RSV) Recovery Scale (RRS) Category
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.
Time frame: Baseline to Day 8
Population: Intent to treat - infected (ITT-i) analysis set included all randomized participants who received at least 1 dose of study intervention and had an RSV infection confirmed by central laboratory analysis. Due to the early termination of study, last day of RRS treatment (Day 8) was considered instead of the original planned day defined as when 50% participants would have been discharged.
| Arm | Measure | Group | Value (NUMBER) |
|---|---|---|---|
| Placebo | Percentage of Participants by Respiratory Syncytial Virus (RSV) Recovery Scale (RRS) Category | Home without symptoms | 25.0 Percentage of participants |
| Placebo | Percentage of Participants by Respiratory Syncytial Virus (RSV) Recovery Scale (RRS) Category | ICU without mechanical ventilation | 0 Percentage of participants |
| Placebo | Percentage of Participants by Respiratory Syncytial Virus (RSV) Recovery Scale (RRS) Category | Ward without supplemental oxygen/feeding/hydration | 25.0 Percentage of participants |
| Placebo | Percentage of Participants by Respiratory Syncytial Virus (RSV) Recovery Scale (RRS) Category | Requiring mechanical ventilation | 0 Percentage of participants |
| Placebo | Percentage of Participants by Respiratory Syncytial Virus (RSV) Recovery Scale (RRS) Category | Home with symptoms | 50.0 Percentage of participants |
| Placebo | Percentage of Participants by Respiratory Syncytial Virus (RSV) Recovery Scale (RRS) Category | Death | 0 Percentage of participants |
| Placebo | Percentage of Participants by Respiratory Syncytial Virus (RSV) Recovery Scale (RRS) Category | Ward with supplemental or feeding/hydration | 0 Percentage of participants |
| Rilematovir | Percentage of Participants by Respiratory Syncytial Virus (RSV) Recovery Scale (RRS) Category | Death | 0 Percentage of participants |
| Rilematovir | Percentage of Participants by Respiratory Syncytial Virus (RSV) Recovery Scale (RRS) Category | Home with symptoms | 26.3 Percentage of participants |
| Rilematovir | Percentage of Participants by Respiratory Syncytial Virus (RSV) Recovery Scale (RRS) Category | Ward without supplemental oxygen/feeding/hydration | 36.8 Percentage of participants |
| Rilematovir | Percentage of Participants by Respiratory Syncytial Virus (RSV) Recovery Scale (RRS) Category | Ward with supplemental or feeding/hydration | 5.3 Percentage of participants |
| Rilematovir | Percentage of Participants by Respiratory Syncytial Virus (RSV) Recovery Scale (RRS) Category | ICU without mechanical ventilation | 0 Percentage of participants |
| Rilematovir | Percentage of Participants by Respiratory Syncytial Virus (RSV) Recovery Scale (RRS) Category | Requiring mechanical ventilation | 0 Percentage of participants |
| Rilematovir | Percentage of Participants by Respiratory Syncytial Virus (RSV) Recovery Scale (RRS) Category | Home without symptoms | 31.6 Percentage of participants |
Secondary
Change From Baseline in RSV Viral Load at 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.
Time frame: Baseline, Days 2, 3, 5, 8, 14 and 21
Population: ITT-i analysis set included all randomized participants who received at least 1 dose of study intervention and had an RSV infection confirmed by central laboratory analysis. Here, N (Overall number of participants analyzed) signifies participants evaluable for this outcome measure and 'n' (number analyzed) signifies number of participants with data evaluable at each specified time point.
| Arm | Measure | Group | Value (MEAN) | Dispersion |
|---|---|---|---|---|
| Placebo | Change From Baseline in RSV Viral Load at Days 2, 3, 5, 8, 14 and 21 | Day 2 | -1.031 log10 copies per milliter | Standard Deviation 0.6091 |
| Placebo | Change From Baseline in RSV Viral Load at Days 2, 3, 5, 8, 14 and 21 | Day 3 | -1.566 log10 copies per milliter | Standard Deviation 2.2167 |
| Placebo | Change From Baseline in RSV Viral Load at Days 2, 3, 5, 8, 14 and 21 | Day 5 | -2.965 log10 copies per milliter | Standard Deviation 1.9154 |
| Placebo | Change From Baseline in RSV Viral Load at Days 2, 3, 5, 8, 14 and 21 | Day 8 | -5.658 log10 copies per milliter | Standard Deviation 1.9872 |
| Placebo | Change From Baseline in RSV Viral Load at Days 2, 3, 5, 8, 14 and 21 | Day 14 | -5.693 log10 copies per milliter | Standard Deviation 2.2654 |
| Placebo | Change From Baseline in RSV Viral Load at Days 2, 3, 5, 8, 14 and 21 | Day 21 | -7.207 log10 copies per milliter | Standard Deviation 1.3201 |
| Rilematovir | Change From Baseline in RSV Viral Load at Days 2, 3, 5, 8, 14 and 21 | Day 14 | -5.640 log10 copies per milliter | Standard Deviation 2.0261 |
| Rilematovir | Change From Baseline in RSV Viral Load at Days 2, 3, 5, 8, 14 and 21 | Day 2 | -0.825 log10 copies per milliter | Standard Deviation 1.2906 |
| Rilematovir | Change From Baseline in RSV Viral Load at Days 2, 3, 5, 8, 14 and 21 | Day 8 | -4.126 log10 copies per milliter | Standard Deviation 1.8461 |
| Rilematovir | Change From Baseline in RSV Viral Load at Days 2, 3, 5, 8, 14 and 21 | Day 3 | -1.436 log10 copies per milliter | Standard Deviation 1.5185 |
| Rilematovir | Change From Baseline in RSV Viral Load at Days 2, 3, 5, 8, 14 and 21 | Day 21 | -5.789 log10 copies per milliter | Standard Deviation 1.956 |
| Rilematovir | Change From Baseline in RSV Viral Load at Days 2, 3, 5, 8, 14 and 21 | Day 5 | -2.241 log10 copies per milliter | Standard Deviation 1.3393 |
Secondary
Duration of ICU Stay
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.
Time frame: Up to Day 35
Population: ITT-i analysis set included all randomized participants who received at least 1 dose of study intervention and had an RSV infection confirmed by central laboratory analysis. Here, N (Overall number of participants analyzed) signifies participants who required ICU stay before first dose of rilematovir and continued after first dose plus participants who required ICU stay after first dose of drug without prior ICU stay.
| Arm | Measure | Value (MEAN) | Dispersion |
|---|---|---|---|
| Placebo | Duration of ICU Stay | 66.46 hours | Standard Deviation 24.145 |
| Rilematovir | Duration of ICU Stay | 40.83 hours | Standard Deviation 22.822 |
Secondary
Duration of Oxygen Supplementation
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.
Time frame: Up to Day 35
Population: ITT-i analysis set included all randomized participants who received at least 1 dose of study intervention and had an RSV infection confirmed by central laboratory analysis. Here, N (Overall number of participants analyzed) signifies participants who required oxygen supplementation before first dose of rilematovir and continued after first dose plus participants who required oxygen supplementation after first dose of rilematovir without prior oxygen supplementation.
| Arm | Measure | Value (MEAN) | Dispersion |
|---|---|---|---|
| Placebo | Duration of Oxygen Supplementation | 39.91 Hours | Standard Deviation 26.146 |
| Rilematovir | Duration of Oxygen Supplementation | 66.59 Hours | Standard Deviation 51.956 |
Secondary
Duration of Supplemental Feeding/Hydration
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.
Time frame: Up to Day 35
Population: ITT-i analysis set included all randomized participants who received at least 1 dose of study intervention and had an RSV infection confirmed by central laboratory analysis. Here, N (Overall number of participants analyzed) signifies participants who required supplemental feeding/hydration before first dose of rilematovir and continued after first dose plus participants who required supplemental feeding/hydration after first dose of rilematovir without prior supplemental feeding/hydration.
| Arm | Measure | Value (MEAN) | Dispersion |
|---|---|---|---|
| Placebo | Duration of Supplemental Feeding/Hydration | 43.13 Hours | Standard Deviation 41.526 |
| Rilematovir | Duration of Supplemental Feeding/Hydration | 31.96 Hours | Standard Deviation 21.311 |
Secondary
Number of Participants With Abnormalities in Clinical Laboratory Values
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.
Time frame: Up to Day 35
Population: Safety analysis set included all participants who received at least 1 dose of study intervention. Here, N (Overall number of participants analyzed) signifies participants evaluable for this outcome measure and 'n' (number analyzed) signifies number of participants with available data at each specified category.
| Arm | Measure | Group | Value (COUNT_OF_PARTICIPANTS) |
|---|---|---|---|
| Placebo | Number of Participants With Abnormalities in Clinical Laboratory Values | Bicarbonate- Abnormally high | 0 Participants |
| Placebo | Number of Participants With Abnormalities in Clinical Laboratory Values | Ery. mean corpuscular hemoglobin-AH | 0 Participants |
| Placebo | Number of Participants With Abnormalities in Clinical Laboratory Values | Urea nitrogen- Abnormally high | 0 Participants |
| Placebo | Number of Participants With Abnormalities in Clinical Laboratory Values | Erythrocytes- Abnormally low | 0 Participants |
| Placebo | Number of Participants With Abnormalities in Clinical Laboratory Values | Monocytes- Abnormally high | 0 Participants |
| Placebo | Number of Participants With Abnormalities in Clinical Laboratory Values | Erythrocytes- Abnormally high | 0 Participants |
| Placebo | Number of Participants With Abnormalities in Clinical Laboratory Values | Basophils- Abnormally low | 0 Participants |
| Placebo | Number of Participants With Abnormalities in Clinical Laboratory Values | Leukocytes- Abnormally low | 1 Participants |
| Placebo | Number of Participants With Abnormalities in Clinical Laboratory Values | Direct bilirubin- Abnormally low | 2 Participants |
| Placebo | Number of Participants With Abnormalities in Clinical Laboratory Values | Leukocytes- Abnormally high | 0 Participants |
| Placebo | Number of Participants With Abnormalities in Clinical Laboratory Values | Basophils- Abnormally high | 0 Participants |
| Placebo | Number of Participants With Abnormalities in Clinical Laboratory Values | Lymphocytes- Abnormally low | 0 Participants |
| Placebo | Number of Participants With Abnormalities in Clinical Laboratory Values | Bicarbonate- Abnormally low | 1 Participants |
| Placebo | Number of Participants With Abnormalities in Clinical Laboratory Values | Lymphocytes- Abnormally high | 0 Participants |
| Placebo | Number of Participants With Abnormalities in Clinical Laboratory Values | Eosinophils- Abnormally low | 0 Participants |
| Placebo | Number of Participants With Abnormalities in Clinical Laboratory Values | Monocytes- Abnormally low | 1 Participants |
| Placebo | Number of Participants With Abnormalities in Clinical Laboratory Values | Direct bilirubin- Abnormally high | 0 Participants |
| Placebo | Number of Participants With Abnormalities in Clinical Laboratory Values | Eosinophils- Abnormally high | 5 Participants |
| Placebo | Number of Participants With Abnormalities in Clinical Laboratory Values | Neutrophils- Abnormally low | 4 Participants |
| Placebo | Number of Participants With Abnormalities in Clinical Laboratory Values | Ery. mean corpuscular HGB conc.-AH | 0 Participants |
| Placebo | Number of Participants With Abnormalities in Clinical Laboratory Values | Neutrophils- Abnormally high | 0 Participants |
| Placebo | Number of Participants With Abnormalities in Clinical Laboratory Values | Ery. mean corpuscular HGB conc.-AL | 1 Participants |
| Placebo | Number of Participants With Abnormalities in Clinical Laboratory Values | Reticulocytes- Abnormally low | 0 Participants |
| Placebo | Number of Participants With Abnormalities in Clinical Laboratory Values | Urea nitrogen- Abnormally low | 1 Participants |
| Placebo | Number of Participants With Abnormalities in Clinical Laboratory Values | Reticulocytes- Abnormally high | 1 Participants |
| Placebo | Number of Participants With Abnormalities in Clinical Laboratory Values | Ery. mean corpuscular hemoglobin-AL | 0 Participants |
| Rilematovir | Number of Participants With Abnormalities in Clinical Laboratory Values | Reticulocytes- Abnormally high | 1 Participants |
| Rilematovir | Number of Participants With Abnormalities in Clinical Laboratory Values | Bicarbonate- Abnormally low | 3 Participants |
| Rilematovir | Number of Participants With Abnormalities in Clinical Laboratory Values | Bicarbonate- Abnormally high | 0 Participants |
| Rilematovir | Number of Participants With Abnormalities in Clinical Laboratory Values | Direct bilirubin- Abnormally low | 9 Participants |
| Rilematovir | Number of Participants With Abnormalities in Clinical Laboratory Values | Direct bilirubin- Abnormally high | 0 Participants |
| Rilematovir | Number of Participants With Abnormalities in Clinical Laboratory Values | Urea nitrogen- Abnormally low | 3 Participants |
| Rilematovir | Number of Participants With Abnormalities in Clinical Laboratory Values | Urea nitrogen- Abnormally high | 0 Participants |
| Rilematovir | Number of Participants With Abnormalities in Clinical Laboratory Values | Basophils- Abnormally low | 0 Participants |
| Rilematovir | Number of Participants With Abnormalities in Clinical Laboratory Values | Basophils- Abnormally high | 1 Participants |
| Rilematovir | Number of Participants With Abnormalities in Clinical Laboratory Values | Eosinophils- Abnormally low | 0 Participants |
| Rilematovir | Number of Participants With Abnormalities in Clinical Laboratory Values | Eosinophils- Abnormally high | 12 Participants |
| Rilematovir | Number of Participants With Abnormalities in Clinical Laboratory Values | Ery. mean corpuscular HGB conc.-AH | 0 Participants |
| Rilematovir | Number of Participants With Abnormalities in Clinical Laboratory Values | Ery. mean corpuscular hemoglobin-AL | 3 Participants |
| Rilematovir | Number of Participants With Abnormalities in Clinical Laboratory Values | Ery. mean corpuscular hemoglobin-AH | 0 Participants |
| Rilematovir | Number of Participants With Abnormalities in Clinical Laboratory Values | Erythrocytes- Abnormally low | 0 Participants |
| Rilematovir | Number of Participants With Abnormalities in Clinical Laboratory Values | Erythrocytes- Abnormally high | 2 Participants |
| Rilematovir | Number of Participants With Abnormalities in Clinical Laboratory Values | Leukocytes- Abnormally low | 1 Participants |
| Rilematovir | Number of Participants With Abnormalities in Clinical Laboratory Values | Leukocytes- Abnormally high | 5 Participants |
| Rilematovir | Number of Participants With Abnormalities in Clinical Laboratory Values | Lymphocytes- Abnormally low | 0 Participants |
| Rilematovir | Number of Participants With Abnormalities in Clinical Laboratory Values | Lymphocytes- Abnormally high | 3 Participants |
| Rilematovir | Number of Participants With Abnormalities in Clinical Laboratory Values | Monocytes- Abnormally low | 4 Participants |
| Rilematovir | Number of Participants With Abnormalities in Clinical Laboratory Values | Monocytes- Abnormally high | 0 Participants |
| Rilematovir | Number of Participants With Abnormalities in Clinical Laboratory Values | Neutrophils- Abnormally low | 10 Participants |
| Rilematovir | Number of Participants With Abnormalities in Clinical Laboratory Values | Neutrophils- Abnormally high | 0 Participants |
| Rilematovir | Number of Participants With Abnormalities in Clinical Laboratory Values | Reticulocytes- Abnormally low | 0 Participants |
| Rilematovir | Number of Participants With Abnormalities in Clinical Laboratory Values | Ery. mean corpuscular HGB conc.-AL | 3 Participants |
Secondary
Number of Participants With Abnormalities in Electrocardiograms (ECGs)
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.
Time frame: Up to Day 35
Population: Safety analysis set included all participants who received at least 1 dose of study intervention.
| Arm | Measure | Group | Value (COUNT_OF_PARTICIPANTS) |
|---|---|---|---|
| Placebo | Number of Participants With Abnormalities in Electrocardiograms (ECGs) | PR Interval- Abnormally low | 0 Participants |
| Placebo | Number of Participants With Abnormalities in Electrocardiograms (ECGs) | RR Interval- Abnormally low | 1 Participants |
| Placebo | Number of Participants With Abnormalities in Electrocardiograms (ECGs) | PR Interval- Abnormally high | 0 Participants |
| Placebo | Number of Participants With Abnormalities in Electrocardiograms (ECGs) | RR Interval- Abnormally high | 0 Participants |
| Rilematovir | Number of Participants With Abnormalities in Electrocardiograms (ECGs) | RR Interval- Abnormally high | 0 Participants |
| Rilematovir | Number of Participants With Abnormalities in Electrocardiograms (ECGs) | PR Interval- Abnormally low | 0 Participants |
| Rilematovir | Number of Participants With Abnormalities in Electrocardiograms (ECGs) | PR Interval- Abnormally high | 1 Participants |
| Rilematovir | Number of Participants With Abnormalities in Electrocardiograms (ECGs) | RR Interval- Abnormally low | 7 Participants |
Secondary
Number of Participants With Abnormalities in Vital Signs
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).
Time frame: Up to Day 35
Population: Safety analysis set included all participants who received at least 1 dose of study intervention. Here, 'n' (number analyzed) signifies number of participants with available data at each specified category.
| Arm | Measure | Group | Value (COUNT_OF_PARTICIPANTS) |
|---|---|---|---|
| Placebo | Number of Participants With Abnormalities in Vital Signs | SBP- Abnormally high | 0 Participants |
| Placebo | Number of Participants With Abnormalities in Vital Signs | Respiratory Rate- Abnormally low | 0 Participants |
| Placebo | Number of Participants With Abnormalities in Vital Signs | DBP- Abnormally high | 1 Participants |
| Placebo | Number of Participants With Abnormalities in Vital Signs | Respiratory Rate- Abnormally high | 0 Participants |
| Placebo | Number of Participants With Abnormalities in Vital Signs | SBP- Abnormally low | 0 Participants |
| Placebo | Number of Participants With Abnormalities in Vital Signs | Temperature - Abnormally low | 0 Participants |
| Placebo | Number of Participants With Abnormalities in Vital Signs | Pulse Rate- Abnormally low | 0 Participants |
| Placebo | Number of Participants With Abnormalities in Vital Signs | Temperature - Abnormally high | 1 Participants |
| Placebo | Number of Participants With Abnormalities in Vital Signs | DBP- Abnormally low | 0 Participants |
| Placebo | Number of Participants With Abnormalities in Vital Signs | Pulse Rate- Abnormally high | 1 Participants |
| Placebo | Number of Participants With Abnormalities in Vital Signs | Oxygen Saturation- Abnormally high | 0 Participants |
| Placebo | Number of Participants With Abnormalities in Vital Signs | Oxygen Saturation- Abnormally low | 0 Participants |
| Rilematovir | Number of Participants With Abnormalities in Vital Signs | Oxygen Saturation- Abnormally high | 0 Participants |
| Rilematovir | Number of Participants With Abnormalities in Vital Signs | SBP- Abnormally low | 0 Participants |
| Rilematovir | Number of Participants With Abnormalities in Vital Signs | SBP- Abnormally high | 4 Participants |
| Rilematovir | Number of Participants With Abnormalities in Vital Signs | DBP- Abnormally low | 0 Participants |
| Rilematovir | Number of Participants With Abnormalities in Vital Signs | DBP- Abnormally high | 3 Participants |
| Rilematovir | Number of Participants With Abnormalities in Vital Signs | Pulse Rate- Abnormally low | 0 Participants |
| Rilematovir | Number of Participants With Abnormalities in Vital Signs | Pulse Rate- Abnormally high | 2 Participants |
| Rilematovir | Number of Participants With Abnormalities in Vital Signs | Respiratory Rate- Abnormally low | 0 Participants |
| Rilematovir | Number of Participants With Abnormalities in Vital Signs | Respiratory Rate- Abnormally high | 3 Participants |
| Rilematovir | Number of Participants With Abnormalities in Vital Signs | Temperature - Abnormally low | 0 Participants |
| Rilematovir | Number of Participants With Abnormalities in Vital Signs | Temperature - Abnormally high | 0 Participants |
| Rilematovir | Number of Participants With Abnormalities in Vital Signs | Oxygen Saturation- Abnormally low | 1 Participants |
Secondary
Number of Participants With Medical Encounters and Treatments
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.
Time frame: Up to Day 35
Population: ITT-i analysis set included all randomized participants who received at least 1 dose of study intervention and had an RSV infection confirmed by central laboratory analysis.
| Arm | Measure | Value (COUNT_OF_PARTICIPANTS) |
|---|---|---|
| Placebo | Number of Participants With Medical Encounters and Treatments | 1 Participants |
| Rilematovir | Number of Participants With Medical Encounters and Treatments | 3 Participants |
Secondary
Number of Participants With Post-baseline RSV-related Complications
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.
Time frame: Up to Day 35
Population: ITT-i analysis set included all randomized participants who received at least 1 dose of study intervention and had an RSV infection confirmed by central laboratory analysis.
| Arm | Measure | Value (COUNT_OF_PARTICIPANTS) |
|---|---|---|
| Placebo | Number of Participants With Post-baseline RSV-related Complications | 1 Participants |
| Rilematovir | Number of Participants With Post-baseline RSV-related Complications | 3 Participants |
Secondary
Number of Participants With Treatment-emergent Adverse Events (TEAEs)
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.
Time frame: Day 1 up to Day 35
Population: Safety analysis set included all participants who received at least 1 dose of study intervention.
| Arm | Measure | Value (COUNT_OF_PARTICIPANTS) |
|---|---|---|
| Placebo | Number of Participants With Treatment-emergent Adverse Events (TEAEs) | 5 Participants |
| Rilematovir | Number of Participants With Treatment-emergent Adverse Events (TEAEs) | 11 Participants |
Secondary
Percentage of Participants Clinically Resolved From RSV Disease Based on the Clinician Reported Outcome (ClinRO) Sign/Symptoms at 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).
Time frame: Day 8
Population: ITT-i analysis set included all randomized participants who received at least 1 dose of study intervention and had an RSV infection confirmed by central laboratory analysis.
| Arm | Measure | Value (NUMBER) |
|---|---|---|
| Placebo | Percentage of Participants Clinically Resolved From RSV Disease Based on the Clinician Reported Outcome (ClinRO) Sign/Symptoms at Day 8 | 37.5 Percentage of participants |
| Rilematovir | Percentage of Participants Clinically Resolved From RSV Disease Based on the Clinician Reported Outcome (ClinRO) Sign/Symptoms at Day 8 | 31.6 Percentage of participants |
Secondary
Percentage of Participants Requiring Hydration and/or Feeding by Intravenous (IV) Administration or Nasogastric Tube After First Dose of Rilematovir
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 frame: Up to Day 35
Population: ITT-i analysis set included all randomized participants who received at least 1 dose of study intervention and had an RSV infection confirmed by central laboratory analysis. Here, N (Overall number of participants analyzed) signifies participants with no use of feeding/hydration supplementation before 1st dose of study drug.
| Arm | Measure | Value (NUMBER) |
|---|---|---|
| Placebo | Percentage of Participants Requiring Hydration and/or Feeding by Intravenous (IV) Administration or Nasogastric Tube After First Dose of Rilematovir | 33.3 Percentage of participants |
| Rilematovir | Percentage of Participants Requiring Hydration and/or Feeding by Intravenous (IV) Administration or Nasogastric Tube After First Dose of Rilematovir | 0 Percentage of participants |
Secondary
Percentage of Participants Requiring Intensive Care Unit (ICU) Stay After First Dose of Rilematovir
Percentage of participants requiring ICU stay was analyzed and reported.
Time frame: Up to Day 35
Population: ITT-i analysis set included all randomized participants who received at least 1 dose of study intervention and had an RSV infection confirmed by central laboratory analysis. Here, N (Overall number of participants analyzed) signifies participants with no ICU stay before first dose of rilematovir.
| Arm | Measure | Value (NUMBER) |
|---|---|---|
| Placebo | Percentage of Participants Requiring Intensive Care Unit (ICU) Stay After First Dose of Rilematovir | 0 Percentage of Participants |
| Rilematovir | Percentage of Participants Requiring Intensive Care Unit (ICU) Stay After First Dose of Rilematovir | 0 Percentage of Participants |
Secondary
Percentage of Participants Requiring Oxygen Supplementation After First Dose of Rilematovir
Percentage of participants requiring any type of oxygen supplementation (invasive mechanical ventilation, non-invasive mechanical ventilation and non-invasive non-mechanical ventilation) were reported.
Time frame: Up to Day 35
Population: ITT-i analysis set included all randomized participants who received at least 1 dose of study intervention and had an RSV infection confirmed by central laboratory analysis. Here, N (overall number of participants analyzed) signifies participants with no use of oxygen supplementation before first dose of rilematovir.
| Arm | Measure | Value (NUMBER) |
|---|---|---|
| Placebo | Percentage of Participants Requiring Oxygen Supplementation After First Dose of Rilematovir | 16.7 Percentage of participants |
| Rilematovir | Percentage of Participants Requiring Oxygen Supplementation After First Dose of Rilematovir | 30.8 Percentage of participants |
Secondary
Percentage of Participants Requiring Re-hospitalization for Respiratory/Other Reasons
Percentage of participants requiring re-hospitalization (participants re-hospitalized \[ward or ICU\] after been discharged from hospital) for respiratory/other reasons were reported.
Time frame: Up to Day 35
Population: ITT-i analysis set included all randomized participants who received at least 1 dose of study intervention and had an RSV infection confirmed by central laboratory analysis.
| Arm | Measure | Value (NUMBER) |
|---|---|---|
| Placebo | Percentage of Participants Requiring Re-hospitalization for Respiratory/Other Reasons | 0 Percentage of participants |
| Rilematovir | Percentage of Participants Requiring Re-hospitalization for Respiratory/Other Reasons | 0 Percentage of participants |
Secondary
Percentage of Participants With Acceptability and Palatability of the Rilematovir Formulation as Assessed by Parent(s)/Caregiver(s)
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).
Time frame: Day 8
Population: ITT-i analysis set included all randomized participants who received at least 1 dose of study intervention and had an RSV infection confirmed by central laboratory analysis. Here, N (Overall number of participants analyzed) signifies participants evaluable for this outcome measure.
| Arm | Measure | Group | Value (NUMBER) |
|---|---|---|---|
| Placebo | Percentage of Participants With Acceptability and Palatability of the Rilematovir Formulation as Assessed by Parent(s)/Caregiver(s) | Disgusted expressions after tasting medicine | 0 Percentage of participants |
| Placebo | Percentage of Participants With Acceptability and Palatability of the Rilematovir Formulation as Assessed by Parent(s)/Caregiver(s) | Spit out or coughed out medicine | 14.3 Percentage of participants |
| Placebo | Percentage of Participants With Acceptability and Palatability of the Rilematovir Formulation as Assessed by Parent(s)/Caregiver(s) | Gagged | 0 Percentage of participants |
| Placebo | Percentage of Participants With Acceptability and Palatability of the Rilematovir Formulation as Assessed by Parent(s)/Caregiver(s) | Child took medicine easily | 85.7 Percentage of participants |
| Placebo | Percentage of Participants With Acceptability and Palatability of the Rilematovir Formulation as Assessed by Parent(s)/Caregiver(s) | Vomited (within 2 minutes of swallowing medicine) | 0 Percentage of participants |
| Placebo | Percentage of Participants With Acceptability and Palatability of the Rilematovir Formulation as Assessed by Parent(s)/Caregiver(s) | Did not open mouth or turned head away | 14.3 Percentage of participants |
| Rilematovir | Percentage of Participants With Acceptability and Palatability of the Rilematovir Formulation as Assessed by Parent(s)/Caregiver(s) | Vomited (within 2 minutes of swallowing medicine) | 0 Percentage of participants |
| Rilematovir | Percentage of Participants With Acceptability and Palatability of the Rilematovir Formulation as Assessed by Parent(s)/Caregiver(s) | Child took medicine easily | 86.7 Percentage of participants |
| Rilematovir | Percentage of Participants With Acceptability and Palatability of the Rilematovir Formulation as Assessed by Parent(s)/Caregiver(s) | Disgusted expressions after tasting medicine | 13.3 Percentage of participants |
| Rilematovir | Percentage of Participants With Acceptability and Palatability of the Rilematovir Formulation as Assessed by Parent(s)/Caregiver(s) | Did not open mouth or turned head away | 6.7 Percentage of participants |
| Rilematovir | Percentage of Participants With Acceptability and Palatability of the Rilematovir Formulation as Assessed by Parent(s)/Caregiver(s) | Gagged | 6.7 Percentage of participants |
| Rilematovir | Percentage of Participants With Acceptability and Palatability of the Rilematovir Formulation as Assessed by Parent(s)/Caregiver(s) | Spit out or coughed out medicine | 0 Percentage of participants |
Secondary
Percentage of Participants With Undetectable RSV Viral Load
Percentage of participants with undetectable RSV viral load was analyzed.
Time frame: Baseline, Days 2, 3, 5, 8, 14 and 21
Population: ITT-i analysis set included all randomized participants who received at least 1 dose of study intervention and had an RSV infection confirmed by central laboratory analysis. Here, 'n' (number analyzed) signifies number of participants with data evaluable at each specified time point.
| Arm | Measure | Group | Value (NUMBER) |
|---|---|---|---|
| Placebo | Percentage of Participants With Undetectable RSV Viral Load | Day 3 | 0 Percentage of Participants |
| Placebo | Percentage of Participants With Undetectable RSV Viral Load | Day 8 | 62.5 Percentage of Participants |
| Placebo | Percentage of Participants With Undetectable RSV Viral Load | Day 2 | 0 Percentage of Participants |
| Placebo | Percentage of Participants With Undetectable RSV Viral Load | Day 14 | 71.4 Percentage of Participants |
| Placebo | Percentage of Participants With Undetectable RSV Viral Load | Day 5 | 0 Percentage of Participants |
| Placebo | Percentage of Participants With Undetectable RSV Viral Load | Day 21 | 85.7 Percentage of Participants |
| Placebo | Percentage of Participants With Undetectable RSV Viral Load | Baseline | 0 Percentage of Participants |
| Rilematovir | Percentage of Participants With Undetectable RSV Viral Load | Day 21 | 88.2 Percentage of Participants |
| Rilematovir | Percentage of Participants With Undetectable RSV Viral Load | Baseline | 0 Percentage of Participants |
| Rilematovir | Percentage of Participants With Undetectable RSV Viral Load | Day 2 | 0 Percentage of Participants |
| Rilematovir | Percentage of Participants With Undetectable RSV Viral Load | Day 3 | 5.3 Percentage of Participants |
| Rilematovir | Percentage of Participants With Undetectable RSV Viral Load | Day 5 | 0 Percentage of Participants |
| Rilematovir | Percentage of Participants With Undetectable RSV Viral Load | Day 8 | 44.4 Percentage of Participants |
| Rilematovir | Percentage of Participants With Undetectable RSV Viral Load | Day 14 | 76.5 Percentage of Participants |
Secondary
Plasma Concentrations of Rilematovir
Plasma concentrations of rilematovir were assessed. Participant wise data were reported for this outcome measure.
Time frame: 1 hour Post-dose (Day 1) and pre-dose (Day 2)
Population: Pharmacokinetics analysis set (PKAS) included participants who had received at least 1 dose of rilematovir and had at least 1 valid blood sample drawn for pharmacokinetics analysis. No summary analysis was done as study was terminated early and participant wise data were reported. Here, n (Number analyzed) signifies specific participant with data evaluable at each specified timepoint.
| Arm | Measure | Group | Value (NUMBER) |
|---|---|---|---|
| Placebo | Plasma Concentrations of Rilematovir | Participant 2 Day 2 | 281 nanogram per milliliter |
| Placebo | Plasma Concentrations of Rilematovir | Participant 3 Day 2 | 5.74 nanogram per milliliter |
| Placebo | Plasma Concentrations of Rilematovir | Participant 5 Day 2 | 417 nanogram per milliliter |
| Placebo | Plasma Concentrations of Rilematovir | Participant 1 Day 1 | 1450 nanogram per milliliter |
| Placebo | Plasma Concentrations of Rilematovir | Participant 2 Day 1 | 1750 nanogram per milliliter |
| Placebo | Plasma Concentrations of Rilematovir | Participant 3 Day 1 | 72.5 nanogram per milliliter |
| Placebo | Plasma Concentrations of Rilematovir | Participant 4 Day 1 | 656 nanogram per milliliter |
| Placebo | Plasma Concentrations of Rilematovir | Participant 5 Day 1 | 918 nanogram per milliliter |
| Placebo | Plasma Concentrations of Rilematovir | Participant 6 Day 1 | 1050 nanogram per milliliter |
| Placebo | Plasma Concentrations of Rilematovir | Participant 7 Day 1 | 135 nanogram per milliliter |
| Placebo | Plasma Concentrations of Rilematovir | Participant 8 Day 1 | 1730 nanogram per milliliter |
| Placebo | Plasma Concentrations of Rilematovir | Participant 9 Day 1 | 602 nanogram per milliliter |
| Placebo | Plasma Concentrations of Rilematovir | Participant 10 Day 1 | 1810 nanogram per milliliter |
| Placebo | Plasma Concentrations of Rilematovir | Participant 11 Day 1 | 1640 nanogram per milliliter |
| Placebo | Plasma Concentrations of Rilematovir | Participant 12 Day 1 | 3760 nanogram per milliliter |
| Placebo | Plasma Concentrations of Rilematovir | Participant 13 Day 1 | 561 nanogram per milliliter |
| Placebo | Plasma Concentrations of Rilematovir | Participant 14 Day 1 | 127 nanogram per milliliter |
| Placebo | Plasma Concentrations of Rilematovir | Participant 15 Day 1 | 787 nanogram per milliliter |
| Placebo | Plasma Concentrations of Rilematovir | Participant 16 Day 1 | 2020 nanogram per milliliter |
| Placebo | Plasma Concentrations of Rilematovir | Participant 17 Day 1 | 157 nanogram per milliliter |
| Placebo | Plasma Concentrations of Rilematovir | Participant 18 Day 1 | 1260 nanogram per milliliter |
| Placebo | Plasma Concentrations of Rilematovir | Participant 1 Day 2 | 134 nanogram per milliliter |
| Placebo | Plasma Concentrations of Rilematovir | Participant 6 Day 2 | 828 nanogram per milliliter |
| Placebo | Plasma Concentrations of Rilematovir | Participant 7 Day 2 | 1030 nanogram per milliliter |
| Placebo | Plasma Concentrations of Rilematovir | Participant 8 Day 2 | 339 nanogram per milliliter |
| Placebo | Plasma Concentrations of Rilematovir | Participant 9 Day 2 | 186 nanogram per milliliter |
| Placebo | Plasma Concentrations of Rilematovir | Participant 10 Day 2 | 687 nanogram per milliliter |
| Placebo | Plasma Concentrations of Rilematovir | Participant 11 Day 2 | 1750 nanogram per milliliter |
| Placebo | Plasma Concentrations of Rilematovir | Participant 12 Day 2 | 4650 nanogram per milliliter |
| Placebo | Plasma Concentrations of Rilematovir | Participant 13 Day 2 | 311 nanogram per milliliter |
| Placebo | Plasma Concentrations of Rilematovir | Participant 14 Day 2 | 77.3 nanogram per milliliter |
| Placebo | Plasma Concentrations of Rilematovir | Participant 15 Day 2 | 749 nanogram per milliliter |
| Placebo | Plasma Concentrations of Rilematovir | Participant 16 Day 2 | 457 nanogram per milliliter |
| Placebo | Plasma Concentrations of Rilematovir | Participant 17 Day 2 | 493 nanogram per milliliter |
| Placebo | Plasma Concentrations of Rilematovir | Participant 18 Day 2 | 2930 nanogram per milliliter |
Secondary
RSV Viral Load at 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.
Time frame: Baseline, Days 2, 3, 5, 8, 14 and 21
Population: ITT-i analysis set included all randomized participants who received at least 1 dose of study intervention and had an RSV infection confirmed by central laboratory analysis. Here, 'n' (number analyzed) signifies number of participants with data evaluable at each specified time point.
| Arm | Measure | Group | Value (MEAN) | Dispersion |
|---|---|---|---|---|
| Placebo | RSV Viral Load at Baseline, Days 2, 3, 5, 8, 14 and 21 | Day 3 | 5.465 log10 copies per milliliter | Standard Deviation 1.7454 |
| Placebo | RSV Viral Load at Baseline, Days 2, 3, 5, 8, 14 and 21 | Day 8 | 1.373 log10 copies per milliliter | Standard Deviation 2.0865 |
| Placebo | RSV Viral Load at Baseline, Days 2, 3, 5, 8, 14 and 21 | Day 2 | 6.000 log10 copies per milliliter | Standard Deviation 1.5678 |
| Placebo | RSV Viral Load at Baseline, Days 2, 3, 5, 8, 14 and 21 | Day 14 | 1.217 log10 copies per milliliter | Standard Deviation 2.1478 |
| Placebo | RSV Viral Load at Baseline, Days 2, 3, 5, 8, 14 and 21 | Day 5 | 4.066 log10 copies per milliliter | Standard Deviation 1.5565 |
| Placebo | RSV Viral Load at Baseline, Days 2, 3, 5, 8, 14 and 21 | Day 21 | 0.414 log10 copies per milliliter | Standard Deviation 1.0961 |
| Placebo | RSV Viral Load at Baseline, Days 2, 3, 5, 8, 14 and 21 | Baseline | 7.031 log10 copies per milliliter | Standard Deviation 1.9995 |
| Rilematovir | RSV Viral Load at Baseline, Days 2, 3, 5, 8, 14 and 21 | Day 21 | 0.464 log10 copies per milliliter | Standard Deviation 1.4547 |
| Rilematovir | RSV Viral Load at Baseline, Days 2, 3, 5, 8, 14 and 21 | Baseline | 6.286 log10 copies per milliliter | Standard Deviation 1.3671 |
| Rilematovir | RSV Viral Load at Baseline, Days 2, 3, 5, 8, 14 and 21 | Day 2 | 5.579 log10 copies per milliliter | Standard Deviation 1.5668 |
| Rilematovir | RSV Viral Load at Baseline, Days 2, 3, 5, 8, 14 and 21 | Day 3 | 4.981 log10 copies per milliliter | Standard Deviation 1.953 |
| Rilematovir | RSV Viral Load at Baseline, Days 2, 3, 5, 8, 14 and 21 | Day 5 | 4.132 log10 copies per milliliter | Standard Deviation 1.5199 |
| Rilematovir | RSV Viral Load at Baseline, Days 2, 3, 5, 8, 14 and 21 | Day 8 | 2.156 log10 copies per milliliter | Standard Deviation 2.1681 |
| Rilematovir | RSV Viral Load at Baseline, Days 2, 3, 5, 8, 14 and 21 | Day 14 | 0.709 log10 copies per milliliter | Standard Deviation 1.3389 |
Secondary
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
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.
Time frame: Up to Day 21
Population: ITT-i analysis set included all randomized participants who received at least 1 dose of study intervention and had RSV infection confirmed by central laboratory analysis.
| Arm | Measure | Value (MEDIAN) |
|---|---|---|
| Placebo | 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 | 237.0 Hours |
| Rilematovir | 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 | 144.8 Hours |