Clinical Trial Results:
A Phase 3, Randomized, Double-blind, Placebo-controlled Study to Evaluate the Efficacy and Safety of Rilematovir in Infants and Children (>=28 Days to <=5 Years of Age) and Subsequently in Neonates (<28 Days of Age), Hospitalized With Acute Respiratory Tract Infection Due to Respiratory Syncytial Virus (RSV)
|
Summary
|
|
EudraCT number |
2020-002023-11 |
Trial protocol |
BG DE SE CZ HU BE PL Outside EU/EEA EE LV SK IT |
Global end of trial date |
18 Mar 2022
|
|
Results information
|
|
Results version number |
v1(current) |
This version publication date |
04 Oct 2022
|
First version publication date |
04 Oct 2022
|
Other versions |
|
Trial Information
Subject Disposition
Baseline Characteristics
End Points
Adverse Events
More Information
Subject Disposition
Baseline Characteristics
End Points
Adverse Events
More Information
|
|||
|
Trial identification
|
|||
Sponsor protocol code |
53718678RSV3001
|
||
|
Additional study identifiers
|
|||
ISRCTN number |
- | ||
US NCT number |
NCT04583280 | ||
WHO universal trial number (UTN) |
- | ||
|
Sponsors
|
|||
Sponsor organisation name |
Janssen Research & Development LLC
|
||
Sponsor organisation address |
920 Route 202, South Raritan New Jersey, United States, 08869
|
||
Public contact |
Clinical Registry Group, Janssen Research & Development LLC, ClinicalTrialsEU@its.jnj.com
|
||
Scientific contact |
Clinical Registry Group, Janssen Research & Development LLC, ClinicalTrialsEU@its.jnj.com
|
||
|
Paediatric regulatory details
|
|||
Is trial part of an agreed paediatric investigation plan (PIP) |
Yes
|
||
EMA paediatric investigation plan number(s) |
EMEA-001838-PIP01-15 | ||
Does article 45 of REGULATION (EC) No 1901/2006 apply to this trial? |
No
|
||
Does article 46 of REGULATION (EC) No 1901/2006 apply to this trial? |
No
|
||
|
Results analysis stage
|
|||
Analysis stage |
Final
|
||
Date of interim/final analysis |
01 Jun 2022
|
||
Is this the analysis of the primary completion data? |
No
|
||
Global end of trial reached? |
Yes
|
||
Global end of trial date |
18 Mar 2022
|
||
Was the trial ended prematurely? |
Yes
|
||
|
General information about the trial
|
|||
Main objective of the trial |
Main objective of the trial was to evaluate the superiority of rilematovir compared to placebo treatment with respect to the clinical outcome on the respiratory syncytial virus (RSV) Recovery Scale (RRS).
|
||
Protection of trial subjects |
This study was conducted in accordance with the ethical principles that have their origin in the Declaration of Helsinki and that are consistent with Good Clinical Practice (GCP) and applicable regulatory requirements.
|
||
Background therapy |
- | ||
Evidence for comparator |
- | ||
Actual start date of recruitment |
06 Sep 2021
|
||
Long term follow-up planned |
No
|
||
Independent data monitoring committee (IDMC) involvement? |
Yes
|
||
|
Population of trial subjects
|
|||
Number of subjects enrolled per country |
|||
Country: Number of subjects enrolled |
Argentina: 7
|
||
Country: Number of subjects enrolled |
Brazil: 2
|
||
Country: Number of subjects enrolled |
Czechia: 1
|
||
Country: Number of subjects enrolled |
Spain: 5
|
||
Country: Number of subjects enrolled |
Hungary: 1
|
||
Country: Number of subjects enrolled |
Japan: 2
|
||
Country: Number of subjects enrolled |
Malaysia: 1
|
||
Country: Number of subjects enrolled |
Ukraine: 9
|
||
Worldwide total number of subjects |
28
|
||
EEA total number of subjects |
7
|
||
Number of subjects enrolled per age group |
|||
In utero |
0
|
||
Preterm newborn - gestational age < 37 wk |
0
|
||
Newborns (0-27 days) |
0
|
||
Infants and toddlers (28 days-23 months) |
20
|
||
Children (2-11 years) |
8
|
||
Adolescents (12-17 years) |
0
|
||
Adults (18-64 years) |
0
|
||
From 65 to 84 years |
0
|
||
85 years and over |
0
|
||
|
||||||||||||||||
|
Recruitment
|
||||||||||||||||
Recruitment details |
- | |||||||||||||||
|
Pre-assignment
|
||||||||||||||||
Screening details |
A total of 28 subjects with acute respiratory tract infection due to RSV were randomised and treated (8 subjects in Placebo arm and 20 subjects in rilematovir arm). Of these, 27 subjects completed the study. | |||||||||||||||
|
Period 1
|
||||||||||||||||
Period 1 title |
Overall Study (overall period)
|
|||||||||||||||
Is this the baseline period? |
Yes | |||||||||||||||
Allocation method |
Randomised - controlled
|
|||||||||||||||
Blinding used |
Double blind | |||||||||||||||
Roles blinded |
Investigator, Subject | |||||||||||||||
|
Arms
|
||||||||||||||||
Are arms mutually exclusive |
Yes
|
|||||||||||||||
|
Arm title
|
Placebo | |||||||||||||||
Arm description |
Subjects 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). | |||||||||||||||
Arm type |
Placebo | |||||||||||||||
Investigational medicinal product name |
Placebo
|
|||||||||||||||
Investigational medicinal product code |
||||||||||||||||
Other name |
||||||||||||||||
Pharmaceutical forms |
Oral suspension
|
|||||||||||||||
Routes of administration |
Oral use
|
|||||||||||||||
Dosage and administration details |
Subjects received placebo matching to rilematovir BID from Days 1 to 7.
|
|||||||||||||||
|
Arm title
|
Rilematovir | |||||||||||||||
Arm description |
Subjects aged >=28 days to <3 months, >=3 to <6 months, and >=6 months to <=5 years received rilematovir 2.5 milligram 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). | |||||||||||||||
Arm type |
Experimental | |||||||||||||||
Investigational medicinal product name |
Rilematovir 2.5 mg/kg
|
|||||||||||||||
Investigational medicinal product code |
JNJ-53718678
|
|||||||||||||||
Other name |
||||||||||||||||
Pharmaceutical forms |
Oral suspension
|
|||||||||||||||
Routes of administration |
Oral use
|
|||||||||||||||
Dosage and administration details |
Subjects aged >=28 days to <3 months received rilematovir 2.5 mg/kg orally as 20 mg/mL suspension BID from Days 1 to 7.
|
|||||||||||||||
Investigational medicinal product name |
Rilematovir 4.5 mg/kg
|
|||||||||||||||
Investigational medicinal product code |
JNJ-53718678
|
|||||||||||||||
Other name |
||||||||||||||||
Pharmaceutical forms |
Oral suspension
|
|||||||||||||||
Routes of administration |
Oral use
|
|||||||||||||||
Dosage and administration details |
Subjects aged >=6 months to <=5 years received rilematovir 4.5 mg/kg orally as 20 mg/mL suspension BID from Days 1 to 7.
|
|||||||||||||||
Investigational medicinal product name |
Rilematovir 3 mg/kg
|
|||||||||||||||
Investigational medicinal product code |
JNJ-53718678
|
|||||||||||||||
Other name |
||||||||||||||||
Pharmaceutical forms |
Oral suspension
|
|||||||||||||||
Routes of administration |
Oral use
|
|||||||||||||||
Dosage and administration details |
Subjects aged >=3 to <6 months received rilematovir 3 mg/kg orally as 20 mg/mL suspension BID from Days 1 to 7.
|
|||||||||||||||
|
||||||||||||||||
|
|||||||||||||||||||||||||||||||||||||||||||||||||||||
|
Baseline characteristics reporting groups
|
|||||||||||||||||||||||||||||||||||||||||||||||||||||
Reporting group title |
Placebo
|
||||||||||||||||||||||||||||||||||||||||||||||||||||
Reporting group description |
Subjects 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). | ||||||||||||||||||||||||||||||||||||||||||||||||||||
Reporting group title |
Rilematovir
|
||||||||||||||||||||||||||||||||||||||||||||||||||||
Reporting group description |
Subjects aged >=28 days to <3 months, >=3 to <6 months, and >=6 months to <=5 years received rilematovir 2.5 milligram 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). | ||||||||||||||||||||||||||||||||||||||||||||||||||||
|
|||||||||||||||||||||||||||||||||||||||||||||||||||||
|
|||
|
End points reporting groups
|
|||
Reporting group title |
Placebo
|
||
Reporting group description |
Subjects 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). | ||
Reporting group title |
Rilematovir
|
||
Reporting group description |
Subjects aged >=28 days to <3 months, >=3 to <6 months, and >=6 months to <=5 years received rilematovir 2.5 milligram 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). | ||
|
||||||||||||||||||||||||||||||||||
End point title |
Percentage of Subjects by Respiratory Syncytial Virus (RSV) Recovery Scale (RRS) Category [1] | |||||||||||||||||||||||||||||||||
End point description |
RRS was an ordinal scale to assess a subject's clinical status. The RRS provided 7 mutually exclusive categories ordered from best to worst where 1 =home without signs/symptoms, 2 =home with sign/symptoms, 3 =ward without supplemental oxygen (O2) or feeding/hydration, 4 =ward with supplemental O2 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 indicated worst condition. With or without signs/symptoms was defined as the key RSV signs/symptoms resolved (absent or mild) or not resolved assessed by parent/caregiver. Intent-to-Treat-infected (ITT-i) analysis set was analysed. 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% subjects would have been discharged.
|
|||||||||||||||||||||||||||||||||
End point type |
Primary
|
|||||||||||||||||||||||||||||||||
End point timeframe |
Baseline to Day 8
|
|||||||||||||||||||||||||||||||||
| Notes [1] - No statistical analyses have been specified for this primary end point. It is expected there is at least one statistical analysis for each primary end point. Justification: Descriptive statistics was done, no inferential statistical analysis was performed. |
||||||||||||||||||||||||||||||||||
|
||||||||||||||||||||||||||||||||||
| No statistical analyses for this end point | ||||||||||||||||||||||||||||||||||
|
|||||||||||||
End point title |
Percentage of Subjects Clinically Resolved From RSV Disease Based on the Clinician Reported Outcome (ClinRO) Sign/Symptoms Questionnaire at Day 8 | ||||||||||||
End point description |
Clinically resolved was defined as subject 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 questionnaire. Clinically resolved Key RSV signs/symptoms were assessed based on clinician's observations as resolved if subject 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). ITT-i analysis set included all randomised subjects who received at least 1 dose of study intervention and had an RSV infection confirmed by central laboratory analysis.
|
||||||||||||
End point type |
Secondary
|
||||||||||||
End point timeframe |
Day 8
|
||||||||||||
|
|||||||||||||
| No statistical analyses for this end point | |||||||||||||
|
|||||||||||||
End point title |
Time From First Study Dose to Resolution of key RSV Signs/Symptoms Based on Observer Reported Outcome (ObsRO) Questionnaire After Free of Supplementation (Oxygen/Feeding/Hydration) for at Least 24 Hours | ||||||||||||
End point description |
Time 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 subject 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 questionnaire. 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. ITT-i analysis set was analysed. 99999 indicated upper limit of 95% confidence interval (CI) in placebo arm could not be estimated due to low number of subjects with events.
|
||||||||||||
End point type |
Secondary
|
||||||||||||
End point timeframe |
up to Day 21
|
||||||||||||
|
|||||||||||||
| No statistical analyses for this end point | |||||||||||||
|
|||||||||||||
End point title |
Time From Discharge to Resolution of key RSV Signs/Symptoms Based on ObsRO Sign/Symptoms Questionnaire | ||||||||||||
End point description |
Time (hours) from discharge from the hospital to resolution of key RSV Signs/Symptoms (breathing problems, retractions, tachypnea, cough, wheezing/breathing sounds, and tachycardia) was planned to be reported. ObsRO Signs/Symptoms questionnaire was based on observations by child’s parent/caregiver to assess resolution of key Signs/symptoms of RSV disease 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, a little coughing without problems caused by coughing). Data for this endpoint was not analysed as the study was terminated early.
|
||||||||||||
End point type |
Secondary
|
||||||||||||
End point timeframe |
Up to 21 Days
|
||||||||||||
|
|||||||||||||
| Notes [2] - Data for this endpoint was not analysed as the study was terminated early. [3] - Data for this endpoint was not analysed as the study was terminated early. |
|||||||||||||
| No statistical analyses for this end point | |||||||||||||
|
|||||||||||||
End point title |
Time From First Dosing to end of Oxygen Supplementation | ||||||||||||
End point description |
Time from first dosing to end of oxygen supplementation was planned to be analysed. Data for this endpoint was not analysed as the study was terminated early.
|
||||||||||||
End point type |
Secondary
|
||||||||||||
End point timeframe |
Up to Day 35
|
||||||||||||
|
|||||||||||||
| Notes [4] - Data for this endpoint was not analysed as the study was terminated early. [5] - Data for this endpoint was not analysed as the study was terminated early. |
|||||||||||||
| No statistical analyses for this end point | |||||||||||||
|
||||||||||
End point title |
Number of Subjects with Post-baseline RSV-Related Complications | |||||||||
End point description |
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). Subjects were counted only once for any given event, regardless of the number of times they actually experienced the event. ITT-i analysis set included all randomised subjects who received at least 1 dose of study intervention and had an RSV infection confirmed by central laboratory analysis. Subjects were counted only once for any given event, regardless of the number of times they actually experienced the event.
|
|||||||||
End point type |
Secondary
|
|||||||||
End point timeframe |
Up to Day 35
|
|||||||||
|
||||||||||
| No statistical analyses for this end point | ||||||||||
|
||||||||||
End point title |
Number of Subjects with Treatment-emergent Adverse Events (TEAEs) | |||||||||
End point description |
An adverse event (AE) is any untoward medical occurrence in a clinical study subject 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). Safety analysis set included all subjects who received at least 1 dose of study intervention.
|
|||||||||
End point type |
Secondary
|
|||||||||
End point timeframe |
Up to Day 35
|
|||||||||
|
||||||||||
| No statistical analyses for this end point | ||||||||||
|
||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||
End point title |
Number of Subjects with Abnormalities in Clinical Laboratory Values | |||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||
End point description |
Number of subjects 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 compared to baseline as assessed based on the investigator's discretion were reported. Safety analysis set included all subjects who received at least 1 dose of study intervention. Here, N (number of subjects analysed) signifies subjects evaluated for this endpoint and 'n' (number analysed) signifies number of subjects with available data at each specified category.
|
|||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||
End point type |
Secondary
|
|||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||
End point timeframe |
Up to Day 35
|
|||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||
|
||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||
| No statistical analyses for this end point | ||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||
|
||||||||||||||||||||||
End point title |
Number of Subjects with Abnormalities in Electrocardiograms (ECG) | |||||||||||||||||||||
End point description |
Number of subjects with abnormally low and abnormally high values of ECG Abnormalities (PR Interval and RR Interval) as assessed based on the investigator's discretion were reported. Safety analysis set included all subjects who received at least 1 dose of study intervention.
|
|||||||||||||||||||||
End point type |
Secondary
|
|||||||||||||||||||||
End point timeframe |
Up to Day 35
|
|||||||||||||||||||||
|
||||||||||||||||||||||
| No statistical analyses for this end point | ||||||||||||||||||||||
|
||||||||||||||||||||||||||||||||||||||||||||||
End point title |
Number of Subjects with Abnormalities in Vital Signs | |||||||||||||||||||||||||||||||||||||||||||||
End point description |
Number of subjects with abnormally low and abnormally high vital signs as assessed based on the investigator's discretion were reported. Abnormal 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 (Celsius) and oxygen saturation (%). Safety analysis set included all subjects who received at least 1 dose of study intervention. Here, 'n' (number analysed) signifies number of subjects with available data at specified categories.
|
|||||||||||||||||||||||||||||||||||||||||||||
End point type |
Secondary
|
|||||||||||||||||||||||||||||||||||||||||||||
End point timeframe |
Up to Day 35
|
|||||||||||||||||||||||||||||||||||||||||||||
|
||||||||||||||||||||||||||||||||||||||||||||||
| No statistical analyses for this end point | ||||||||||||||||||||||||||||||||||||||||||||||
|
|||||||||||||
End point title |
Time to Resolution of Signs/symptoms of RSV Disease as Assessed by ObsRO Signs/Symptoms Questionnaire | ||||||||||||
End point description |
Time to resolution of signs/symptoms of RSV disease symptoms was planned to be reported. Resolution of signs/symptoms assessment was based on observations of child’s parent/caregiver as per ObsRO signs/symptoms questionnaire as resolved if general illness behavior appeared well, less active, less interested in playing/toys, tired more easily; sleep disturbance(as usual, little more restless, disturbed); crying: resolved if subject cried(as usual/cried more than usual but calmed if held/soothed);feeding problems: as usual/little less than usual; no dehydration(dark yellow urine/less urine/soft spot on top of head sunk in/sunken eyes/dry skin or lips);retractions (belly sucked in when breathing in/ribs more visible than usual when breathing in/skin at base of throat sucked in when breathing in),no tachypnea/tachycardia; no nasal signs; no breathing problems. Data for this endpoint was not analysed as study was terminated early.
|
||||||||||||
End point type |
Secondary
|
||||||||||||
End point timeframe |
Up to Day 21
|
||||||||||||
|
|||||||||||||
| Notes [6] - Data for this endpoint was not analysed as the study was terminated early. [7] - Data for this endpoint was not analysed as the study was terminated early. |
|||||||||||||
| No statistical analyses for this end point | |||||||||||||
|
|||||||||||||
End point title |
ObsRO Signs/Symptoms Questionnaire Scores | ||||||||||||
End point description |
ObsRO Signs/Symptoms questionnaire was used to monitor specific signs/symptoms of RSV disease based on observations by child’s parent/caregiver. It consisted of 9 items, each item was scored as follows: sleep disturbance =0,1,2,3; crying =0,1,2,3; illness behavior =0,1,2,3; nasal signs =0,1,2; breathing problems [tachypnea, tachycardia, retractions] =0,2,3; breathing sounds =0,3; cough =0,1,2,3; feeding problems =0,1,2,3; and dehydration =0,1,2,3. In each item score of 0 and 1 indicated signs/symptoms resolved and score of 2 and 3 indicated signs/symptoms not resolved. A summary score was derived (mean of the item scores) and rated on a 4-point scale, with scores ranging from 0 to 3, higher score indicated, worse/higher severity of sign/symptom. Data for this endpoint was not analysed as the study was terminated early.
|
||||||||||||
End point type |
Secondary
|
||||||||||||
End point timeframe |
Up to Day 21
|
||||||||||||
|
|||||||||||||
| Notes [8] - Data for this endpoint was not analysed as the study was terminated early. [9] - Data for this endpoint was not analysed as the study was terminated early. |
|||||||||||||
| No statistical analyses for this end point | |||||||||||||
|
|||||||||||||
End point title |
Change From Baseline in ObsRO Signs/Symptoms Questionnaire Scores Over Time | ||||||||||||
End point description |
ObsRO Signs/Symptoms questionnaire was used to monitor specific signs/symptoms of RSV disease based on observations by child’s parent/caregiver. It consisted of 9 items, each item was scored as follows: sleep disturbance =0,1,2,3; crying =0,1,2,3; illness behavior =0,1,2,3; nasal signs =0,1,2; breathing problems [tachypnea, tachycardia, retractions] =0,2,3; breathing sounds =0,3; cough =0,1,2,3; feeding problems =0,1,2,3; and dehydration =0,1,2,3. In each item score of 0 and 1 indicated signs/symptoms resolved and score of 2 and 3 indicated signs/symptoms not resolved. A summary score was derived (mean of the item scores) and rated on a 4-point scale, with scores ranging from 0 to 3, higher score indicated, worse/higher severity of sign/symptom. Data for this endpoint was not analysed as the study was terminated early.
|
||||||||||||
End point type |
Secondary
|
||||||||||||
End point timeframe |
Up to Day 21
|
||||||||||||
|
|||||||||||||
| Notes [10] - Data for this endpoint was not analysed as the study was terminated early. [11] - Data for this endpoint was not analysed as the study was terminated early. |
|||||||||||||
| No statistical analyses for this end point | |||||||||||||
|
|||||||||||||
End point title |
Time to Improvement in RSV disease Based on ObsRO General Health Questions (GHQ) | ||||||||||||
End point description |
ObsRO GHQ was a 5-item questionnaire to evaluate parent/caregiver's general impression of child’s RSV disease severity, change in RSV disease, and overall health status. Subject had to choose one answer from multiple options for each question i.e. how would you rate child’s RSV now: recovered, very mild, mild, moderate, severe, very severe); would you say child’s RSV had improved is about same or is worse than when child entered study: very much improved, much improved, a little improved, about the same, a little worse, much worse, very much worse); overall, how is the child’s health now: excellent, very good, good, fair, poor, very poor; has the child’s health returned to normal how the child was before RSV: Yes, No); which of these did you use to decide your answers: what I saw myself, what I saw and what another caregiver told me, what another caregiver told me. Data for this endpoint was not analysed as the study was terminated early.
|
||||||||||||
End point type |
Secondary
|
||||||||||||
End point timeframe |
Up to Day 21
|
||||||||||||
|
|||||||||||||
| Notes [12] - Data for this endpoint was not analysed as the study was terminated early. [13] - Data for this endpoint was not analysed as the study was terminated early. |
|||||||||||||
| No statistical analyses for this end point | |||||||||||||
|
|||||||||||||
End point title |
Time to Resolution of Signs/Symptoms of RSV Disease as Assessed by ClinRO Signs/Symptoms Questionnaire | ||||||||||||
End point description |
Time to resolution from first dose of study drug until first time of resolution of all RSV Symptoms was planned to be reported. Clinically resolved RSV signs/symptoms were assessed based on clinician's observations by ClinRO signs/symptoms questionnaire as activity level (resolved if subject was alert and active or irritable), sleep disturbance (resolved if subject was normal or occasional restlessness/disturbed), feeding problems (resolved if subject took >75% of normal amount of feeds via usual route), resolved if subject had no dehydration, retractions, tachypnea and tachycardia, nasal secretions (resolved if subjects had none or minimal/moderate nasal secretions), had no breathing problems, cough (resolved if little or no coughing/occasional strong cough/sometimes productive) and wheezing (resolved if no wheezing/terminal expiratory wheezing/only with stethoscope). Data for this endpoint was not analysed as the study was terminated early.
|
||||||||||||
End point type |
Secondary
|
||||||||||||
End point timeframe |
Up to Day 21
|
||||||||||||
|
|||||||||||||
| Notes [14] - Data for this endpoint was not analysed as the study was terminated early. [15] - Data for this endpoint was not analysed as the study was terminated early. |
|||||||||||||
| No statistical analyses for this end point | |||||||||||||
|
|||||||||||||
End point title |
ClinRO Signs/Symptoms Questionnaire Scores | ||||||||||||
End point description |
ClinRO Signs/Symptoms questionnaire was based on observations by clinician and it consisted of 12 items, each item was scored as follows: activity level =0,1,2,3; sleep disturbance =0,1,2,3; retractions =2,3; tachypnea =2; breathing problems =0,2,3; tachycardia =0,2; feeding problems =0,2,3; cough =0,1,3; nasal secretions =0,1,2; wheezing =0,1,2,3; and dehydration =0,3. In each item score of 0 and 1 indicated signs/symptoms were resolved and score of 2 and 3 indicated signs/symptoms were not resolved. A summary score was derived =mean of the item scores) and rated on a 4-point scale, with scores ranging from 0 to 3, higher score indicated, worse/higher severity of sign/symptom. Data for this endpoint was not analysed as the study was terminated early.
|
||||||||||||
End point type |
Secondary
|
||||||||||||
End point timeframe |
Up to Day 21
|
||||||||||||
|
|||||||||||||
| Notes [16] - Data for this endpoint was not analysed as the study was terminated early. [17] - Data for this endpoint was not analysed as the study was terminated early. |
|||||||||||||
| No statistical analyses for this end point | |||||||||||||
|
|||||||||||||
End point title |
Change From Baseline in ClinRO Signs/Symptoms Questionnaire Scores | ||||||||||||
End point description |
ClinRO Signs/Symptoms questionnaire was based on observations by clinician and it consisted of 12 items, each item was scored as follows: activity level =0,1,2,3; sleep disturbance =0,1,2,3; retractions =2,3; tachypnea =2; breathing problems =0,2,3; tachycardia =0,2; feeding problems =0,2,3; cough =0,1,3; nasal secretions =0,1,2; wheezing =0,1,2,3; and dehydration =0,3. In each item score of 0 and 1 indicated signs/symptoms were resolved and score of 2 and 3 indicated signs/symptoms were not resolved. A summary score was derived =mean of the item scores) and rated on a 4-point scale, with scores ranging from 0 to 3, higher score indicated, worse/higher severity of sign/symptom. Data for this endpoint was not analysed as the study was terminated early.
|
||||||||||||
End point type |
Secondary
|
||||||||||||
End point timeframe |
Up to Day 21
|
||||||||||||
|
|||||||||||||
| Notes [18] - Data for this endpoint was not analysed as the study was terminated early. [19] - Data for this endpoint was not analysed as the study was terminated early. |
|||||||||||||
| No statistical analyses for this end point | |||||||||||||
|
|||||||||||||
End point title |
Change From Baseline in ClinRO GHQ Over Time | ||||||||||||
End point description |
ClinRO GHQ was a 3 items questionnaire to evaluate the clinician’s general impression of the child’s RSV severity, change in RSV disease, and overall health status. Subject had to choose one answer from multiple options for each question i.e. do you have any concerns relating to the subject’s overall condition (no concerns [condition is stable or improving], some concerns [may become unstable/requires close observation], extremely concerned [unstable, requires immediate medical review]; overall, how would you rate the subject’s current health status (excellent, good, fair, poor); with respect to the child’s RSV infection, how would you describe the child’s health now compared to the baseline assessment (very much worse, much worse, a little worse, unchanged a little improved, much very improved, much improved. Data for this endpoint was not analysed as the study was terminated early.
|
||||||||||||
End point type |
Secondary
|
||||||||||||
End point timeframe |
Up to Day 21
|
||||||||||||
|
|||||||||||||
| Notes [20] - Data for this endpoint was not analysed as the study was terminated early. [21] - Data for this endpoint was not analysed as the study was terminated early. |
|||||||||||||
| No statistical analyses for this end point | |||||||||||||
|
|||||||||||||
End point title |
Time to Hospital Discharge From Start of Dosing | ||||||||||||
End point description |
Time (in hours) from first dose of study intervention to first hospital discharge was planned to be analysed. Data for this endpoint was not analysed as the study was terminated early.
|
||||||||||||
End point type |
Secondary
|
||||||||||||
End point timeframe |
Up to Day 35
|
||||||||||||
|
|||||||||||||
| Notes [22] - Data for this endpoint was not analysed as the study was terminated early. [23] - Data for this endpoint was not analysed as the study was terminated early. |
|||||||||||||
| No statistical analyses for this end point | |||||||||||||
|
|||||||||||||
End point title |
Time to Readiness for Hospital Discharge | ||||||||||||
End point description |
Hospital discharge readiness referred to a subject having improved respiratory effort (example: improved retractions, stable respiratory rate), improved O2 saturation to greater than or equal to (>=) 92 percent (%) without need for supplemental oxygen, fever control, adequate hydration/feeding without supplementation, stable and/or baseline mental status. Data for this endpoint was not analysed as the study was terminated early.
|
||||||||||||
End point type |
Secondary
|
||||||||||||
End point timeframe |
Up to Day 35
|
||||||||||||
|
|||||||||||||
| Notes [24] - Data for this endpoint was not analysed as the study was terminated early. [25] - Data for this endpoint was not analysed as the study was terminated early. |
|||||||||||||
| No statistical analyses for this end point | |||||||||||||
|
|||||||||||||
End point title |
Percentage of Subjects Required Intensive Care Unit (ICU) Stay After First Dose of Rilematovir | ||||||||||||
End point description |
Percentage of subjects required ICU stay were analysed and reported. ITT-i analysis set included all randomized subjects who received at least 1 dose of study intervention and had an RSV infection confirmed by central laboratory analysis. Here, N (number of subjects analysed) signifies subjects with no ICU stay before first dose of rilematovir.
|
||||||||||||
End point type |
Secondary
|
||||||||||||
End point timeframe |
Up to Day 35
|
||||||||||||
|
|||||||||||||
| No statistical analyses for this end point | |||||||||||||
|
|||||||||||||
End point title |
Duration of Requiring ICU Stay | ||||||||||||
End point description |
Duration (in hours) of requiring ICU stay was defined as total number of hours a subject experienced an ICU stay from first dose of rilematovir until study termination, calculated as the sum of all separate records of ICU stay. ITT-i analysis set included all randomized subjects who received at least 1 dose of study intervention and had an RSV infection confirmed by central laboratory analysis. Here, N (number of subjects analysed) signifies subjects who required ICU stay before first dose of rilematovir and continued after first dose plus subjects who required ICU stay after first dose of drug without prior ICU stay.
|
||||||||||||
End point type |
Secondary
|
||||||||||||
End point timeframe |
Up to Day 35
|
||||||||||||
|
|||||||||||||
| No statistical analyses for this end point | |||||||||||||
|
|||||||||||||
End point title |
Percentage of Subjects Requiring Re-hospitalization for Respiratory/other Reasons | ||||||||||||
End point description |
Percentage of subjects requiring re-hospitalization (subjects re-hospitalized [ward or ICU] after been discharged from hospital) for respiratory/other reasons were reported. ITT-i analysis set included all randomised subjects who received at least 1 dose of study intervention and had an RSV infection confirmed by central laboratory analysis.
|
||||||||||||
End point type |
Secondary
|
||||||||||||
End point timeframe |
Up to Day 35
|
||||||||||||
|
|||||||||||||
| No statistical analyses for this end point | |||||||||||||
|
|||||||||||||
End point title |
Percentage of Subjects Requiring Oxygen Supplementation After First Dose of Rilematovir | ||||||||||||
End point description |
Percentage of subjects requiring any type of oxygen supplementation (invasive mechanical ventilation, non-invasive mechanical ventilation and non-invasive non-mechanical ventilation) were reported. ITT-i analysis set included all randomised subjects who received at least 1 dose of study intervention and had an RSV infection confirmed by central laboratory analysis. Here, N (number of subjects analysed) signifies subjects with no use of oxygen supplementation before first dose of rilematovir.
|
||||||||||||
End point type |
Secondary
|
||||||||||||
End point timeframe |
Up to Day 35
|
||||||||||||
|
|||||||||||||
| No statistical analyses for this end point | |||||||||||||
|
|||||||||||||
End point title |
Duration of Oxygen Supplementation | ||||||||||||
End point description |
Duration (in hours) of oxygen supplementation was defined as total number of hours a subject used supplemental oxygen from first dose of rilematovir until study termination, calculated as the sum of all separate records of supplementation. ITT-i analysis set included all randomised subjects who received at least 1 dose of study intervention and had an RSV infection confirmed by central laboratory analysis. Here, N (number of subjects analysed) signifies subjects required oxygen supplementation before first dose of rilematovir and continued after first dose plus subjects who required oxygen supplementation after first dose of rilematovir without prior oxygen supplementation.
|
||||||||||||
End point type |
Secondary
|
||||||||||||
End point timeframe |
Up to Day 35
|
||||||||||||
|
|||||||||||||
| No statistical analyses for this end point | |||||||||||||
|
|||||||||||||
End point title |
Time to end of Supplemental Feeding/hydration | ||||||||||||
End point description |
Time (in hours) to end of supplemental feeding/hydration was planned to be reported. Data for this endpoint was not analysed as the study was terminated early.
|
||||||||||||
End point type |
Secondary
|
||||||||||||
End point timeframe |
Up to Day 35
|
||||||||||||
|
|||||||||||||
| Notes [26] - Data for this endpoint was not analysed as the study was terminated early. [27] - Data for this endpoint was not analysed as the study was terminated early. |
|||||||||||||
| No statistical analyses for this end point | |||||||||||||
|
|||||||||||||
End point title |
Percentage of Subjects Requiring Hydration and/or Feeding by Intravenous (IV) Administration or Nasogastric Tube After First Dose of Rilematovir | ||||||||||||
End point description |
Percentage of subjects requiring any type of hydration and/or feeding by intravenous (IV) administration or nasogastric tube or percutaneous endoscopic gastrostomy were reported. ITT-i analysis set included all randomized subjects who received at least 1 dose of study intervention and had an RSV infection confirmed by central laboratory analysis. Here, N (number of subjects analysed) signifies subjects with no use of feeding/hydration supplementation before 1st dose of study drug.
|
||||||||||||
End point type |
Secondary
|
||||||||||||
End point timeframe |
Up to Day 35
|
||||||||||||
|
|||||||||||||
| No statistical analyses for this end point | |||||||||||||
|
|||||||||||||
End point title |
Duration of Supplemental Feeding/hydration | ||||||||||||
End point description |
Duration (in hours) of supplemental feeding/hydration was defined as total number of hours a subject was administered feeding/hydration supplementation from first dose of rilematovir until study termination, calculated as the sum all separate records of supplementation use per subject. ITT-i analysis set included all randomized subjects who received at least 1 dose of study intervention and had an RSV infection confirmed by central laboratory analysis. Here, N (number of subjects analysed) signifies subjects required supplemental feeding/hydration before first dose of rilematovir and continued after first dose plus subjects required supplemental feeding/hydration after first dose of rilematovir without prior supplemental feeding/hydration.
|
||||||||||||
End point type |
Secondary
|
||||||||||||
End point timeframe |
Up to Day 35
|
||||||||||||
|
|||||||||||||
| No statistical analyses for this end point | |||||||||||||
|
|||||||||||||
End point title |
Time to end of Supplemental Oxygen and/or Feeding/hydration | ||||||||||||
End point description |
Time to end of supplemental oxygen and/or feeding/hydration was planned to be analysed. Data for this endpoint was not analysed as the study was terminated early.
|
||||||||||||
End point type |
Secondary
|
||||||||||||
End point timeframe |
Up to Day 35
|
||||||||||||
|
|||||||||||||
| Notes [28] - Data for this endpoint was not analysed as the study was terminated early. [29] - Data for this endpoint was not analysed as the study was terminated early. |
|||||||||||||
| No statistical analyses for this end point | |||||||||||||
|
||||||||||
End point title |
Number of Subjects with Medical Encounters and Treatments | |||||||||
End point description |
Medical resource utilization was assessed by number of medical care encounters. Medical encounters referred as physician or emergency room visits, tests and procedures, and medications, surgeries and other selected procedures, inpatient and outpatient. ITT-i analysis set included all randomised subjects who received at least 1 dose of study intervention and had an RSV infection confirmed by central laboratory analysis.
|
|||||||||
End point type |
Secondary
|
|||||||||
End point timeframe |
Up to Day 35
|
|||||||||
|
||||||||||
| No statistical analyses for this end point | ||||||||||
|
||||||||||
End point title |
Number of Subjects with Antibiotic Treatment Episodes | |||||||||
End point description |
Number of subjects with antibiotic treatment episodes were planned to be reported. Data for this endpoint was not analysed as the study was terminated early.
|
|||||||||
End point type |
Secondary
|
|||||||||
End point timeframe |
Up to Day 35
|
|||||||||
|
||||||||||
| Notes [30] - Data for this endpoint was not analysed as the study was terminated early. [31] - Data for this endpoint was not analysed as the study was terminated early. |
||||||||||
| No statistical analyses for this end point | ||||||||||
|
||||||||||
End point title |
Number of Subjects with Systemic or Inhaled Corticosteroids and Bronchodilators use | |||||||||
End point description |
Number of subjects with systemic or inhaled corticosteroids and bronchodilators use were planned to be reported. Data for this endpoint was not analysed as the study was terminated early.
|
|||||||||
End point type |
Secondary
|
|||||||||
End point timeframe |
Up to Day 35
|
|||||||||
|
||||||||||
| Notes [32] - Data for this endpoint was not analysed as the study was terminated early. [33] - Data for this endpoint was not analysed as the study was terminated early. |
||||||||||
| No statistical analyses for this end point | ||||||||||
|
|||||||||||||
End point title |
Area Under the RSV Viral Load-time Curve [AUC]) From Immediately Prior to First Dose of Study Intervention (Baseline) Through Day 8 | ||||||||||||
End point description |
Area under the RSV viral load-time curve was planned to be analysed. RSV viral load was planned to be measured by quantitative reverse transcription (qRT)- polymerase chain reaction (PCR) in the mid-turbinate (MT) nasal swab specimens. Data for this endpoint was not analysed as the study was terminated early.
|
||||||||||||
End point type |
Secondary
|
||||||||||||
End point timeframe |
Baseline up to Day 8
|
||||||||||||
|
|||||||||||||
| Notes [34] - Data for this endpoint was not analysed as the study was terminated early. [35] - Data for this endpoint was not analysed as the study was terminated early. |
|||||||||||||
| No statistical analyses for this end point | |||||||||||||
|
||||||||||||||||||||||||||||||||||
End point title |
RSV Viral Load at Baseline, Days 2, 3, 5, 8, 14 and 21 | |||||||||||||||||||||||||||||||||
End point description |
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. ITT-i analysis set included all randomized subjects who received at least 1 dose of study intervention and had an RSV infection confirmed by central laboratory analysis. Here, 'n' (number analysed) signifies number of subjects with data evaluable at each specified time points.
|
|||||||||||||||||||||||||||||||||
End point type |
Secondary
|
|||||||||||||||||||||||||||||||||
End point timeframe |
Baseline, Days 2, 3, 5, 8, 14 and 21
|
|||||||||||||||||||||||||||||||||
|
||||||||||||||||||||||||||||||||||
| No statistical analyses for this end point | ||||||||||||||||||||||||||||||||||
|
|||||||||||||||||||||||||||||||
End point title |
Change From Baseline in RSV Viral Load at Days 2, 3, 5, 8, 14 and 21 | ||||||||||||||||||||||||||||||
End point description |
Antiviral activity was determined based on measurements of RSV viral load which was measured by qRT-PCR, in the MT nasal swab specimens. ITT-i analysis set included all randomized subjects who received at least 1 dose of study intervention and had an RSV infection confirmed by central laboratory analysis. Here, N (number of subjects analysed) signifies subjects evaluated for this endpoint and 'n' (number analysed) signifies number of subjects evaluable at specified time points.
|
||||||||||||||||||||||||||||||
End point type |
Secondary
|
||||||||||||||||||||||||||||||
End point timeframe |
Baseline, Days 2, 3, 5, 8, 14 and 21
|
||||||||||||||||||||||||||||||
|
|||||||||||||||||||||||||||||||
| No statistical analyses for this end point | |||||||||||||||||||||||||||||||
|
||||||||||||||||||||||||||||||||||
End point title |
Percentage of Subjects with Undetectable RSV Viral Load | |||||||||||||||||||||||||||||||||
End point description |
Percentage of subjects with undetectable RSV viral load was analysed. ITT-i analysis set included all randomized subjects who received at least 1 dose of study intervention and had an RSV infection confirmed by central laboratory analysis. Here, 'n' (number analysed) signifies number of subjects evaluable at specified time points.
|
|||||||||||||||||||||||||||||||||
End point type |
Secondary
|
|||||||||||||||||||||||||||||||||
End point timeframe |
Baseline, Days 2, 3, 5, 8, 14 and 21
|
|||||||||||||||||||||||||||||||||
|
||||||||||||||||||||||||||||||||||
| No statistical analyses for this end point | ||||||||||||||||||||||||||||||||||
|
||||||||||
End point title |
Number of Subjects with Post-baseline Changes in the RSV F-gene Compared with Baseline Sequences | |||||||||
End point description |
Number of subjects with post-baseline changes in the RSV F-gene compared with baseline sequences was planned to be reported. Data for this endpoint was not analysed as the study was terminated early.
|
|||||||||
End point type |
Secondary
|
|||||||||
End point timeframe |
Baseline up to Day 21
|
|||||||||
|
||||||||||
| Notes [36] - Data for this endpoint was not analysed as the study was terminated early. [37] - Data for this endpoint was not analysed as the study was terminated early. |
||||||||||
| No statistical analyses for this end point | ||||||||||
|
|||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||
End point title |
Plasma Concentrations of Rilematovir [38] | ||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||
End point description |
Plasma concentrations of rilematovir was analysed. Subject wise data were reported for this endpoint. Pharmacokinetics analysis set (PKAS) included subjects 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 subject wise data were reported. Here, "n" signifies specific subject with data available at specified timepoint.
|
||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||
End point type |
Secondary
|
||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||
End point timeframe |
1 hour Post-dose (Day 1) and pre-dose (Day 2)
|
||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||
| Notes [38] - The end point is not reporting statistics for all the arms in the baseline period. It is expected all the baseline period arms will be reported on when providing values for an end point on the baseline period. Justification: Endpoint was planned to be analysed for specified arms only. |
|||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||
|
|||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||
| No statistical analyses for this end point | |||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||
|
||||||||||||||||||||||||||||
End point title |
Percentage of Subjects With Acceptability and Palatability of the Rilematovir Formulation as Assessed by Parent(s)/Caregiver(s) | |||||||||||||||||||||||||||
End point description |
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). ITT-i analysis set included all randomized subjects who received at least 1 dose of study intervention and had an RSV infection confirmed by central laboratory analysis. Here, N (number of subjects analysed) signifies subjects evaluated for this endpoint. Reported only those categories which had data for at least one reporting arm.
|
|||||||||||||||||||||||||||
End point type |
Secondary
|
|||||||||||||||||||||||||||
End point timeframe |
Day 8
|
|||||||||||||||||||||||||||
|
||||||||||||||||||||||||||||
| No statistical analyses for this end point | ||||||||||||||||||||||||||||
|
|||||||||
End point title |
Maximum Observed Plasma Concentration (Cmax) of Rilematovir [39] | ||||||||
End point description |
Cmax of rilematovir was planned to be analysed. Data for this endpoint was not analysed as the study was terminated early.
|
||||||||
End point type |
Secondary
|
||||||||
End point timeframe |
Up to Day 35
|
||||||||
| Notes [39] - The end point is not reporting statistics for all the arms in the baseline period. It is expected all the baseline period arms will be reported on when providing values for an end point on the baseline period. Justification: Endpoint was planned to be analysed for specified arms only. |
|||||||||
|
|||||||||
| Notes [40] - Data for this endpoint was not analysed as the study was terminated early. |
|||||||||
| No statistical analyses for this end point | |||||||||
|
|||||||||
End point title |
Pre dose Plasma Concentration (Ctrough) of Rilematovir [41] | ||||||||
End point description |
Ctrough of rilematovir was planned to be analysed. Data for this endpoint was not analysed as the study was terminated early.
|
||||||||
End point type |
Secondary
|
||||||||
End point timeframe |
Pre-dose on Day 1
|
||||||||
| Notes [41] - The end point is not reporting statistics for all the arms in the baseline period. It is expected all the baseline period arms will be reported on when providing values for an end point on the baseline period. Justification: Endpoint was planned to be analysed for specified arms only. |
|||||||||
|
|||||||||
| Notes [42] - Data for this endpoint was not analysed as the study was terminated early. |
|||||||||
| No statistical analyses for this end point | |||||||||
|
||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||
|
Adverse events information
|
||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||
Timeframe for reporting adverse events |
Up to Day 35
|
|||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||
Assessment type |
Non-systematic | |||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||
|
Dictionary used for adverse event reporting
|
||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||
Dictionary name |
MedDRA | |||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||
Dictionary version |
24.1
|
|||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||
|
Reporting groups
|
||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||
Reporting group title |
Placebo
|
|||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||
Reporting group description |
Subjects aged >=28 days to <3 months, >=3 to <6 months and >=6 months to <=5 years received placebo matching to rilematovir BID from Days 1 to 7 (14 consecutive doses). | |||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||
Reporting group title |
Rilematovir
|
|||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||
Reporting group description |
Subjects aged >=28 days to <3 months, >=3 to <6 months and >=6 months to <=5 years received 2.5, 3 and 4.5 mg/kg rilematovir respectively as 20 mg/mL suspension BID from Days 1 to 7 (14 consecutive doses). | |||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||
|
||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||
| Frequency threshold for reporting non-serious adverse events: 0% | ||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||
|
||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||
|
|||
Substantial protocol amendments (globally) |
|||
| Were there any global substantial amendments to the protocol? Yes | |||
Date |
Amendment |
||
04 May 2021 |
Amendment 1 included the following changes: addition of estimand language for the primary endpoint, revised assessments for follow-up of subjects who prematurely discontinued the study intervention/the study, inclusion criterion was updated to clarify correction of gestational age applied only to subjects born preterm, inclusion criterion 5 was updated to ensure enrollment of subjects with at least moderate RSV disease severity who were more likely to benefit from RSV treatment, protocol-defined RRS categories were further specified, additional laboratory assessments were added to further evaluate hepatobiliary effects, values for vital sign abnormalities for age group 3 to less than or equal to (<=) 5 years of age were updated, and PRESORS timing and instructions were clarified and minor changes were incorporated. |
||
Interruptions (globally) |
|||
| Were there any global interruptions to the trial? No | |||
Limitations and caveats |
|||
| Limitations of the trial such as small numbers of subjects analysed or technical problems leading to unreliable data. | |||
| Data collection and analysis was not performed for few secondary endpoints. | |||
