MedPath

A Study to Learn About the Effects of Sisunatovir in Infants With Respiratory Syncytial Virus Lower Respiratory Tract Infection.

Phase 2
Terminated
Conditions
Lower Resp Tract Infection
Respiratory Syncytial Virus (RSV)
Interventions
Drug: RV521
Drug: Placebo
Registration Number
NCT04225897
Lead Sponsor
Pfizer
Brief Summary

The purpose of this clinical trial is to learn about the safety and effects of the study medicine (sisunatovir). Sisunatovir is developed as potential treatment of Respiratory Syncytial Virus (RSV) infections. This study will assess sisunatovir as compared to placebo in infants aged 1 month to 36 months who are hospitalized with RSV lower respiratory tract infection (LRTI). A placebo looks like the study medicine but does not contain any active medicine in it.

This study will be conducted in 3 parts:

In Part A participants aged 6 months to 3 years will be given a single dose of 2.5 mg/kg of sisunatovir in Cohort 1. In Cohort 2, participants age 1 month to 6 months will receive a single dose of 2 mg/kg of sisunatovir only after the completion of Cohort 1. 12-24 participants will be enrolled in Part A In Part B participants age 1 month to 36 months will receive sisunatovir or placebo dosed every 12 hours for 5 days. Doses for part B will be determined after the completion of Part A. 24-40 participants will be enrolled in Part B.

The dose regimen for Part C will be determined after the completion of Part B. Approximately 120 participants age 1 month to 36 months will receive either sisunatovir or placebo.

To participate in this study participants must meet the following criteria:

1. Age 1 month to 36 months

2. Weight ≥ 3.5 kg

3. Diagnosis of LRTI

4. Diagnosis of RSV

5. Hospitalization due to RSV LRTI

Detailed Description

This is a multicentre, 3-part study to evaluate safety, tolerability, PK, PD, and antiviral effect of single and multiple dosing of RV521 in infants hospitalised due to RSV LRTI.

The clinical study consists of 3 parts, the third part (Part C) is optional:

* Part A is an open-label, multicentre, single dose study in infants hospitalised with RSV LRTI (Cohorts 1 \& 2)

* Part B is a randomised, double-blind, placebo-controlled, multicentre multiple dose study in infants hospitalised with RSV LRTI (Cohorts 3, 4 \& 5)

* Part C is a randomised 1:1, double-blind, placebo-controlled, multicentre, multiple-dose study in infants hospitalised with RSV LRTI I The number of subjects enrolled in Parts A and B of the study will depend on the safety and PK data from the group of subjects enrolled in specified age cohorts and the subsequent recommendation of the Data Safety Monitoring Committee (DSMC).

The DSMC may recommend a dose adjustment (either a reduction or an escalation) and/or regimen adjustment (Part B only) for subsequent subjects because of the observation of an unexpected safety/tolerability profile and/or differences between the observed and predicted exposure resulting from a specified dose of RV521.

Recruitment & Eligibility

Status
TERMINATED
Sex
All
Target Recruitment
51
Inclusion Criteria
  1. Male or female ≥ 1 month and ≤ 36 months of age
  2. Weight ≥ 3.5 kg
  3. Clinical diagnosis of LRTI
  4. A positive RSV diagnostic test
  5. Hospitalised because of RSV LRTI
  6. Symptoms of LRTI must be present for no more than 1 week (Part B) and no more than 5 days (Part C) before the Screening Visit
  7. Expected to remain in hospital for a minimum of 3 days
  8. The parent(s)/legal guardian(s) of the subject have provided written informed consent for the subject to participate and are able and willing to comply with the study protocol
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Exclusion Criteria
  1. Premature (gestational age less than 37 weeks) AND <1 year of post-natal age
  2. Known to have significant comorbidities that would limit the ability to administer study drug or evaluate the safety or clinical response to study drug.
  3. Any clinically significant ECG abnormalities.
  4. Known to be immunocompromised.
  5. High risk of having developing asthma.
  6. Suspected of having a clinically significant bacterial infection.
  7. History of renal failure.
  8. Clinical evidence of hepatic decompensation
  9. History of epilepsy or seizures, including febrile seizures
  10. Allergy to test medication or constituents
  11. Has received 1 or more doses of palivizumab at any time before Screening or received treatment with antiviral therapy for RSV (eg, ribavirin or intravenous [IV] immunoglobulin) within 3 months before the Screening Visit.
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Study & Design

Study Type
INTERVENTIONAL
Study Design
SEQUENTIAL
Arm && Interventions
GroupInterventionDescription
RV521RV521sisunatovir is formulated as a dry powder blend of RV521 drug substance with mannitol as excipient. The RV521 dry powder blend will be supplied in capsules containing 10, 20, or 50 mg RV521. The Investigational Medicinal Product (IMP) will be dispersed in a defined volume of suspending diluent prior to oral administration on a mg/kg basis. Instructions for opening the capsule(s) and dispersing the contents in a fixed volume of suspending diluent prior to administration will be provided in the Pharmacy Manual. The proposed dosing regimen for Part A is a single open label dose of RV521. Part B and C is RV521 or placebo administered BID, 12 hours apart, for a period of 5 consecutive days with a total of 10 doses. However, this is subject to the recommendation of the DSMC.
PlaceboPlaceboThe placebo capsules administered in Part B and C will contain mannitol and microcrystalline cellulose (vehicle). The placebo dry powder will be dispersed in suspending diluent and given orally BID. Instructions for opening the capsule(s) and dispersing the contents in a fixed volume of suspending diluent prior to administration will be provided in the Pharmacy Manual.
Primary Outcome Measures
NameTimeMethod
Part A: Number of Participants With Treatment Emergent Adverse Events (TEAEs), Serious Adverse Events (SAEs) and TEAEs Leading to Permanent Discontinuation of IMPFrom start of IMP on Day 1 up to Day 7

An adverse event (AE) was defined as any untoward medical occurrence in a clinical study participant administered a medicinal product which did not necessarily have a causal relationship with the IMP. TEAEs were defined as AEs which started, or worsened, after the first dose of IMP. An SAE was any untoward medical occurrence or effect that, at any dose, resulted in death; was life threatening; required or prolonged inpatient hospitalization; resulted in persistent or significant disability/incapacity or other important medical event.

Part B: Number of Participants With Treatment Emergent Adverse Events (TEAEs), Serious Adverse Events (SAEs) and TEAEs Leading to Permanent Discontinuation of IMPFrom start of IMP on Day 1 up to Day 12

An AE was defined as any untoward medical occurrence in a clinical study participant administered a medicinal product which did not necessarily have a causal relationship with the IMP. TEAEs were defined as AEs which started, or worsened, after the first dose of IMP. An SAE was any untoward medical occurrence or effect that, at any dose, resulted in death; was life threatening; required or prolonged inpatient hospitalization; resulted in persistent or significant disability/incapacity or other important medical event.

Part A: Number of Participants With Abnormal Clinically Significant Physical Examination Results at BaselineBaseline (pre-dose on Day 1)

Physical examination included general appearance; head, eyes, ears, nose and throat (HEENT); dermatologic, cardiovascular, respiratory, gastrointestinal and neurological examination. Clinical significance of results were determined by the investigator.

Part A: Number of Participants With Abnormal Clinically Significant Physical Examination Results Anytime Between 18 to 24 Hours Post-doseAnytime between 18 to 24 hours post-dose on Day 1

Physical examination included general appearance, HEENT, dermatologic, cardiovascular, respiratory, gastrointestinal and neurological examination. Clinical significance of results were determined by the investigator.

Part A: Number of Participants With Abnormal Clinically Significant Physical Examination Results at 48 Hours Post-doseAt 48 hours post-dose on Day 1

Physical examination included general appearance, HEENT, dermatologic, cardiovascular, respiratory, gastrointestinal and neurological examination. Clinical significance of results were determined by the investigator.

Part B: Number of Participants With Abnormal Clinically Significant Physical Examination Results at BaselineBaseline (pre-dose on Day 1)

Physical examination included general appearance, HEENT, dermatologic, cardiovascular, respiratory, gastrointestinal and neurological examination. Clinical significance of results were determined by the investigator.

Part B: Number of Participants With Abnormal Clinically Significant Physical Examination Results Anytime Between 40 to 48 Hours Post-dose 10Anytime between 40 to 48 hours post-dose 10 on Day 5

Physical examination included general appearance, HEENT, dermatologic, cardiovascular, respiratory, gastrointestinal and neurological examination. Clinical significance of results were determined by the investigator.

Part A: Number of Participants With Abnormal Clinically Significant Vital Signs Per Investigator's Interpretation at BaselineBaseline (pre-dose on Day 1)

Vital signs included body temperature, systolic and diastolic blood pressure, respiratory rate, heart rate and pulse oximetry. Number of participants with abnormal clinically significant vital signs per investigator's interpretation are reported in this outcome measure.

Part A: Number of Participants With Abnormal Clinically Significant Vital Signs Per Investigator's Interpretation Anytime Between 4 to 5 Hours Post-DoseAnytime between 4 to 5 hours post-dose on Day 1

Vital signs included body temperature, systolic and diastolic blood pressure, respiratory rate, heart rate and pulse oximetry. Number of participants with abnormal clinically significant vital signs per investigator's interpretation are reported in this outcome measure.

Part A: Number of Participants With Abnormal Clinically Significant Vital Signs Per Investigator's Interpretation at 12 Hours Post-DoseAt 12 hours post-dose on Day 1

Vital signs included body temperature, systolic and diastolic blood pressure, respiratory rate, heart rate and pulse oximetry. Number of participants with abnormal clinically significant vital signs per investigator's interpretation are reported in this outcome measure.

Part A: Number of Participants With Abnormal Clinically Significant Vital Signs Per Investigator's Interpretation Anytime Between 18 to 24 Hours Post-DoseAnytime between 18 to 24 hours post-dose on Day 1

Vital signs included body temperature, systolic and diastolic blood pressure, respiratory rate, heart rate and pulse oximetry. Number of participants with abnormal clinically significant vital signs per investigator's interpretation are reported in this outcome measure.

Part A: Number of Participants With Abnormal Clinically Significant Vital Signs Per Investigator's Interpretation at 48 Hours Post-Dose48 hours post-dose on Day 1

Vital signs included body temperature, systolic and diastolic blood pressure, respiratory rate, heart rate and pulse oximetry. Number of participants with abnormal clinically significant vital signs per investigator's interpretation are reported in this outcome measure.

Part B: Number of Participants With Abnormal Vital Signs Per Investigator's Interpretation at BaselineBaseline (pre-dose on Day 1)

Vital signs included body temperature, systolic and diastolic blood pressure, respiratory rate, heart rate and pulse oximetry. Number of participants with abnormal clinically significant vital signs per investigator's interpretation are reported in this outcome measure.

Part B: Number of Participants With Abnormal Clinically Significant Vital Signs Per Investigator's Interpretation Anytime Between 4 to 5 Hours Post-Dose 1Anytime between 4 to 5 hours post-dose 1 (Day 1)

Vital signs included body temperature, systolic and diastolic blood pressure, respiratory rate, heart rate and pulse oximetry. Number of participants with abnormal clinically significant vital signs per investigator's interpretation are reported in this outcome measure.

Part B: Number of Participants With Abnormal Clinically Significant Vital Signs Per Investigator's Interpretation At Pre-dose 2Pre-dose 2 (Day 1)

Vital signs included body temperature, systolic and diastolic blood pressure, respiratory rate, heart rate and pulse oximetry. Number of participants with abnormal clinically significant vital signs per investigator's interpretation are reported in this outcome measure. Predose 2= assessment prior to receiving dose 2 of IMP on Day 1.

Part B: Number of Participants With Abnormal Clinically Significant Vital Signs Per Investigator's Interpretation at Pre-dose 3Pre-dose 3 (Day 2)

Vital signs included body temperature, systolic and diastolic blood pressure, respiratory rate, heart rate and pulse oximetry. Number of participants with abnormal clinically significant vital signs per investigator's interpretation are reported in this outcome measure. Predose 3= assessment prior to receiving dose 3 of IMP on Day 2.

Part B: Number of Participants With Abnormal Clinically Significant Vital Signs Per Investigator's Interpretation at Pre-dose 4Pre-dose 4 (Day 2)

Vital signs included body temperature, systolic and diastolic blood pressure, respiratory rate, heart rate and pulse oximetry. Number of participants with abnormal clinically significant vital signs per investigator's interpretation are reported in this outcome measure. Predose 4= assessment prior to receiving dose 4 of IMP on Day 2.

Part B: Number of Participants With Abnormal Clinically Significant Vital Signs Per Investigator's Interpretation at Pre-dose 5Pre-dose 5 (Day 3)

Vital signs included body temperature, systolic and diastolic blood pressure, respiratory rate, heart rate and pulse oximetry. Number of participants with abnormal clinically significant vital signs per investigator's interpretation are reported in this outcome measure. Predose 5= assessment prior to receiving dose 5 of IMP on Day 3.

Part B: Number of Participants With Abnormal Clinically Significant Vital Signs Per Investigator's Interpretation at Pre-dose 6Pre-dose 6 (Day 3)

Vital signs included body temperature, systolic and diastolic blood pressure, respiratory rate, heart rate and pulse oximetry. Number of participants with abnormal clinically significant vital signs per investigator's interpretation are reported in this outcome measure. Predose 6= assessment prior to receiving dose 6 of IMP on Day 3.

Part B: Number of Participants With Abnormal Clinically Significant Vital Signs Per Investigator's Interpretation Anytime Between 4 to 5 Hours Post-Dose 6Anytime between 4 to 5 hours post-dose 6 (Day 3)

Vital signs included body temperature, systolic and diastolic blood pressure, respiratory rate, heart rate and pulse oximetry. Number of participants with abnormal clinically significant vital signs per investigator's interpretation are reported in this outcome measure.

Part B: Number of Participants With Abnormal Clinically Significant Vital Signs Per Investigator's Interpretation at Pre-dose 7Pre-dose 7 (Day 4)

Vital signs included body temperature, systolic and diastolic blood pressure, respiratory rate, heart rate and pulse oximetry. Number of participants with abnormal clinically significant vital signs per investigator's interpretation are reported in this outcome measure. Predose 7= assessment prior to receiving dose 7 of IMP on Day 4.

Part B: Number of Participants With Abnormal Clinically Significant Vital Signs Per Investigator's Interpretation at Pre-dose 8Pre-dose 8 (Day 4)

Vital signs included body temperature, systolic and diastolic blood pressure, respiratory rate, heart rate and pulse oximetry. Number of participants with abnormal clinically significant vital signs per investigator's interpretation are reported in this outcome measure. Predose 8= assessment prior to receiving dose 8 of IMP on Day 4.

Part B: Number of Participants With Abnormal Clinically Significant Vital Signs Per Investigator's Interpretation at Pre-dose 9Pre-dose 9 (Day 5)

Vital signs included body temperature, systolic and diastolic blood pressure, respiratory rate, heart rate and pulse oximetry. Number of participants with abnormal clinically significant vital signs per investigator's interpretation are reported in this outcome measure. Predose 9= assessment prior to receiving dose 9 of IMP on Day 5.

Part B: Number of Participants With Abnormal Clinically Significant Vital Signs Per Investigator's Interpretation at Pre-dose 10Pre-dose 10 (Day 5)

Vital signs included body temperature, systolic and diastolic blood pressure, respiratory rate, heart rate and pulse oximetry. Number of participants with abnormal clinically significant vital signs per investigator's interpretation are reported in this outcome measure. Predose 10= assessment prior to receiving dose 10 of IMP on Day 5.

Part B: Number of Participants With Abnormal Clinically Significant Vital Signs Per Investigator's Interpretation Anytime Between 40 to 48 Hours Post-Dose 10Anytime between 40 to 48 hours post-dose 10 on Day 5

Vital signs included body temperature, systolic and diastolic blood pressure, respiratory rate, heart rate and pulse oximetry. Number of participants with abnormal clinically significant vital signs per investigator's interpretation are reported in this outcome measure.

Part A: Number of Participants With Abnormal Hematology Results at BaselineBaseline (pre-dose on Day 1)

Hematology parameters included basophils, eosinophils, mean cell hemoglobin concentration (MCHC), mean cell hemoglobin (MCH), mean cell volume (MCV), red blood cell count (RBC), hematocrit (HCT), hemoglobin (Hb), white blood cell count (WBC), lymphocytes, monocytes, neutrophils and platelet count. Institutional laboratory normal ranges were used.

Part A: Number of Participants With Abnormal Hematology Results at 48 Hours Post-DoseAt 48 hours post-dose on Day 1

Hematology parameters included basophils, eosinophils, MCHC, MCH, MCV, RBC, HCT, Hb, WBC, lymphocytes, monocytes, neutrophils and platelet count. Institutional laboratory normal ranges were used.

Part B: Number of Participants With Abnormal Hematology Results at BaselineBaseline (pre-dose on Day 1)

Hematology parameters included basophils, eosinophils, MCHC, MCH, MCV, RBC, HCT, Hb, WBC, lymphocytes, monocytes, neutrophils and platelet count. Institutional laboratory normal ranges were used.

Part B: Number of Participants With Abnormal Hematology Results Anytime Between 40 to 48 Hours Post-dose 10Anytime between 40 to 48 hours post-dose 10 on Day 5

Hematology parameters included basophils, eosinophils, MCHC, MCH, MCV, RBC, HCT, Hb, WBC, lymphocytes, monocytes, neutrophils and platelet count. Institutional laboratory normal ranges were used.

Part A: Number of Participants With Abnormal Clinical Chemistry Results at BaselineBaseline (pre-dose on Day 1)

Clinical chemistry parameters included alanine aminotransferase (ALT), albumin, alkaline phosphatase (ALP), aspartate aminotransferase (AST), bilirubin, calcium, chloride, creatinine, gamma glutamyltransferase (GGT), glucose, lactate dehydrogenase (LDH), potassium, protein, sodium and urea. Institutional laboratory normal ranges were used.

Part A: Number of Participants With Abnormal Clinical Chemistry Results at 48 Hours Post-DoseAt 48 hours post-dose on Day 1

Clinical chemistry parameters included ALT, albumin, ALP, AST, bilirubin, calcium, chloride, creatinine, GGT, glucose, LDH, potassium, protein, sodium and urea. Institutional laboratory normal ranges were used.

Part B: Number of Participants With Abnormal Clinical Chemistry Results at BaselineBaseline (pre-dose on Day 1)

Clinical chemistry parameters included ALT, albumin, ALP, AST, bilirubin, calcium, chloride, creatinine, GGT, glucose, LDH, potassium, protein, sodium and urea. Institutional laboratory normal ranges were used.

Part B: Number of Participants With Abnormal Clinical Chemistry Results Anytime Between 40 to 48 Hours Post-dose 10Anytime between 40 to 48 hours post-dose 10 on Day 5

Clinical chemistry parameters included ALT, albumin, ALP, AST, bilirubin, calcium, chloride, creatinine, GGT, glucose, LDH, potassium, protein, sodium and urea. Institutional laboratory normal ranges were used.

Part A: Number of Participants With Abnormal Urinalysis Results at BaselineBaseline (pre-dose on Day 1)

Following urine parameters were analyzed: epithelial cells (normal range: 0 to 5 cells per high power field \[hpf\]), erythrocytes (0 to 2 per hpf), granular casts (0 per low power field \[lpf\]), hyaline casts (0 to 1 per lpf), leukocytes (0 to 5 per hpf), RBC casts (0 per lpf), WBC casts (0 per lpf), waxy casts (0 per lpf) and pH (5 to 8).

Part A: Number of Participants With Abnormal Urinalysis Results at 48 Hours Post-doseAt 48 hours post-dose on Day 1

Following urine parameters were analyzed: epithelial cells (normal range: 0 to 5 cells per hpf), erythrocytes (0 to 2 per hpf), granular casts (0 per lpf), hyaline casts (0 to 1 per lpf), leukocytes (0 to 5 per hpf), RBC casts (0 per lpf), WBC casts (0 per lpf), waxy casts (0 per lpf) and potential of hydrogen (pH) (5 to 8).

Part B: Number of Participants With Abnormal Urinalysis Results at BaselineBaseline (pre-dose on Day 1)

Following urine parameters were analyzed: epithelial cells (normal range: 0 to 5 cells per hpf), erythrocytes (0 to 2 per hpf), granular casts (0 per lpf), hyaline casts (0 to 1 per lpf), leukocytes (0 to 5 per hpf), RBC casts (0 per lpf), WBC casts (0 per lpf), waxy casts (0 per lpf) and pH (5 to 8).

Part B: Number of Participants With Abnormal Urinalysis Results Anytime Between 40 to 48 Hours Post-Dose 10Anytime between 40 to 48 hours post-dose 10 on Day 5

Following urine parameters were analysed: epithelial cells (normal range: 0 to 5 cells per hpf), erythrocytes (0 to 2 per hpf), granular casts (0 per lpf), hyaline casts (0 to 1 per lpf), leukocytes (0 to 5 per hpf), RBC casts (0 per lpf), WBC casts (0 per lpf), waxy casts (0 per lpf) and pH (5 to 8).

Part A: Number of Participants With Abnormal Clinically Significant Electrocardiogram (ECG) Results Per Investigator's Interpretation at BaselineBaseline (pre-dose on Day 1)

A 12-lead ECG was performed for assessment of following ECG parameters: ventricular heart rate, PR interval, QRS interval, QT interval and QT interval corrected by Bazzett's formula (QTcB) interval. Number of participants with abnormal clinically significant results for any ECG parameter per investigator's interpretation are reported in this outcome measure.

Part A: Number of Participants With Abnormal Clinically Significant Electrocardiogram (ECG) Results Per Investigator's Interpretation Anytime Between 4 to 5 Hours Post-DoseAnytime between 4 to 5 hours post-dose on Day 1

A 12-lead ECG was performed for assessment of following ECG parameters: ventricular heart rate, PR interval, QRS interval, QT interval and QTcB interval. Number of participants with abnormal clinically significant results for any ECG parameter per investigator's interpretation are reported in this outcome measure.

Part A: Number of Participants With Abnormal Clinically Significant Electrocardiogram (ECG) Results Per Investigator's Interpretation Anytime Between 18 to 24 Hours Post-doseAnytime between 18 to 24 hours post-dose on Day 1

A 12-lead ECG was performed for assessment of following ECG parameters: ventricular heart rate, PR interval, QRS interval, QT interval and QTcB interval. Number of participants with abnormal clinically significant results for any ECG parameter per investigator's interpretation are reported in this outcome measure.

Part A: Number of Participants With Abnormal Clinically Significant Electrocardiogram (ECG) Results Per Investigator's Interpretation at 48 Hours Post-dose48 hours post-dose on Day 1

A 12-lead ECG was performed for assessment of following ECG parameters: ventricular heart rate, PR interval, QRS interval, QT interval and QTcB interval. Number of participants with abnormal clinically significant results for any ECG parameter per investigator's interpretation are reported in this outcome measure.

Part B: Number of Participants With Abnormal Clinically Significant Electrocardiogram (ECG) Results Per Investigator's Interpretation at BaselineBaseline (pre-dose on Day 1)

A 12-lead ECG was performed for assessment of following ECG parameters: ventricular heart rate, PR interval, QRS interval, QT interval and QTcB interval. Number of participants with abnormal clinically significant results for any ECG parameter per investigator's interpretation are reported in this outcome measure.

Part B: Number of Participants With Abnormal Clinically Significant Electrocardiogram (ECG) Results Per Investigator's Interpretation Anytime Between 4 to 5 Hours Post-Dose 1Anytime between 4 to 5 hours post-dose 1 on Day 1

A 12-lead ECG was performed for assessment of following ECG parameters: ventricular heart rate, PR interval, QRS interval, QT interval and QTcB interval. Number of participants with abnormal clinically significant results for any ECG parameter per investigator's interpretation are reported in this outcome measure.

Part B: Number of Participants With Abnormal Clinically Significant Electrocardiogram (ECG) Results Per Investigator's Interpretation at Pre-dose 3Pre-dose 3 (Day 2)

A 12-lead ECG was performed for assessment of following ECG parameters: ventricular heart rate, PR interval, QRS interval, QT interval and QTcB interval. Number of participants with abnormal clinically significant results for any ECG parameter per investigator's interpretation are reported in this outcome measure.

Part B: Number of Participants With Abnormal Clinically Significant Electrocardiogram (ECG) Results Per Investigator's Interpretation at Pre-dose 5Pre-dose 5 (Day 3)

A 12-lead ECG was performed for assessment of following ECG parameters: ventricular heart rate, PR interval, QRS interval, QT interval and QTcB interval. Number of participants with abnormal clinically significant results for any ECG parameter per investigator's interpretation are reported in this outcome measure.

Part B: Number of Participants With Abnormal Clinically Significant Electrocardiogram (ECG) Results Per Investigator's Interpretation Anytime Between 4 to 5 Hours Post-Dose 6Anytime between 4 to 5 hours post-dose 6 (Day 3)

A 12-lead ECG was performed for assessment of following ECG parameters: ventricular heart rate, PR interval, QRS interval, QT interval and QTcB interval. Number of participants with abnormal clinically significant results for any ECG parameter per investigator's interpretation are reported in this outcome measure.

Part B: Number of Participants With Abnormal Clinically Significant Electrocardiogram (ECG) Results Per Investigator's Interpretation at Pre-dose 8Pre-dose 8 (Day 4)

A 12-lead ECG was performed for assessment of following ECG parameters: ventricular heart rate, PR interval, QRS interval, QT interval and QTcB interval. Number of participants with abnormal clinically significant results for any ECG parameter per investigator's interpretation are reported in this outcome measure.

Part B: Number of Participants With Abnormal Clinically Significant Electrocardiogram (ECG) Results Per Investigator's Interpretation at Pre-dose 10Pre-dose 10 (Day 5)

A 12-lead ECG was performed for assessment of following ECG parameters: ventricular heart rate, PR interval, QRS interval, QT interval and QTcB interval. Number of participants with abnormal clinically significant results for any ECG parameter per investigator's interpretation are reported in this outcome measure.

Part B: Number of Participants With Abnormal Clinically Significant Electrocardiogram (ECG) Results Per Investigator's Interpretation Anytime Between 40 to 48 Hours Post-Dose 10Anytime between 40 to 48 hours post-dose 10 on Day 5

A 12-lead ECG was performed for assessment of following ECG parameters: ventricular heart rate, PR interval, QRS interval, QT interval and QTcB interval. Number of participants with abnormal clinically significant results for any ECG parameter per investigator's interpretation are reported in this outcome measure.

Secondary Outcome Measures
NameTimeMethod
Part B: Minimum Observed Plasma ConcentrationDay 3 Dose 6 (pre-dose)
Part B: Plasma Trough ConcentrationDay 3 Dose 6 (pre-dose)
Part A: Predicted Plasma ClearanceAnytime between 4 to 5 hours, anytime between 6 to 8 hours, 12 hours, 18 to 24 hours and 48 hours post-dose on Day 1

Clearance was calculated as Dose divided by AUC(0 to inf). No sampling was done at pre-dose (0 hour) and pre-dose results were imputed for all participants in the PK population.

Part B: Maximum Observed Plasma Concentration (Cmax)Day 1 Dose 1 (anytime between 4 to 5 hours post-dose, 12 hours post-dose), Day 3 Dose 6 (pre-dose, anytime between 4 to 5 hours post-dose, 12 hours post-dose)

No sampling was done at pre-dose (0 hour) on Day 1 and pre-dose results were imputed for all participants in the PK population.

Part A: Area Under the Plasma Concentration Time Curve From Time Zero to 12 Hours (AUC0-12)Anytime between 4 to 5 hours, anytime between 6 to 8 hours, 12 hours post-dose on Day 1

AUC(0 to 12) was calculated using the linear trapezoidal method. No sampling was done at pre-dose (0 hour) and pre-dose results were imputed for all participants in the PK population.

Part A: Time to Maximum Plasma Concentration (Tmax)Anytime between 4 to 5 hours, anytime between 6 to 8 hours, 12 hours, 18 to 24 hours and 48 hours post-dose on Day 1

No sampling was done at pre-dose (0 hour) and pre-dose results were imputed for all participants in the Pharmacokinetic (PK) population.

Part B: Time to Maximum Plasma Concentration (Tmax)Day 1 Dose 1 (anytime between 4 to 5 hours post-dose, 12 hours post-dose), Day 3 Dose 6 (pre-dose, anytime between 4 to 5 hours post-dose, 12 hours post-dose)

No sampling was done at pre-dose (0 hour) on Day 1 and pre-dose results were imputed for all participants in the PK population.

Part A: Maximum Observed Plasma Concentration (Cmax)Anytime between 4 to 5 hours, anytime between 6 to 8 hours, 12 hours, 18 to 24 hours and 48 hours post-dose on Day 1

No sampling was done at pre-dose (0 hour) and pre-dose results were imputed for all participants in the PK population.

Part B: Average Plasma Concentration Over Dosing Interval (Cavg)Day 3 Dose 6 (pre-dose, anytime between 4 to 5 hours post-dose, 12 hours post-dose)

Cavg was estimated as AUC(0 to tau)/tau, where tau=dosing interval (12 hours).

Part B: Area Under the Plasma Concentration Time Curve From Time Zero to 12 Hours (AUC0-12)Day 1 Dose 1 (anytime between 4 to 5 hours post-dose, 12 hours post-dose), Day 3 Dose 6 (pre-dose, anytime between 4 to 5 hours post-dose, 12 hours post-dose)

AUC(0 to 12) was calculated using the linear trapezoidal method. No sampling was done at pre-dose (0 hour) on Day 1 and pre-dose results were imputed for all participants in the PK population.

Part A: Area Under the Plasma Concentration-Time Curve From Time 0 to the Last Measurable Concentration (AUC[0 to t])Anytime between 4 to 5 hours, anytime between 6 to 8 hours, 12 hours, 18 to 24 hours and 48 hours post-dose on Day 1

Area under the plasma concentration-time curve from time 0 to the last measurable concentration was determined using the linear trapezoidal method. No sampling was done at pre-dose (0 hour) and pre-dose results were imputed for all participants in the PK population.

Part B: Area Under the Plasma Concentration-Time Curve From Time 0 to the Last Measurable Concentration (AUC[0 to t])Day 1 Dose 1 (anytime between 4 to 5 hours post-dose, 12 hours post-dose), Day 3 Dose 6 (pre-dose, anytime between 4 to 5 hours post-dose, 12 hours post-dose)

Area under the plasma concentration-time curve from time 0 to the last measurable concentration was determined using the linear trapezoidal method. No sampling was done at pre-dose (0 hour) on Day 1 and pre-dose results were imputed for all participants in the PK population.

Part A: Terminal Half-life (t1/2)Anytime between 4 to 5 hours, anytime between 6 to 8 hours, 12 hours, 18 to 24 hours and 48 hours post-dose on Day 1

T1/2 was calculated as loge (2) divided by kel, where kel is the terminal phase rate constant calculated by a linear regression of the log-linear concentration-time curve. No sampling was done at pre-dose (0 hour) on Day 1 and pre-dose results were imputed for all participants in the PK population.

Part B: Terminal Half-life (t1/2)Day 1 Dose 1 (anytime between 4 to 5 hours post-dose, 12 hours post-dose), Day 3 Dose 6 (pre-dose, anytime between 4 to 5 hours post-dose, 12 hours post-dose)

T1/2 was calculated as loge (2) divided by kel, where kel is the terminal phase rate constant calculated by a linear regression of the log-linear concentration-time curve. No sampling was done at pre-dose (0 hour) on Day 1 and pre-dose results were imputed for all participants in the PK population.

Part A: Area Under the Plasma Concentration Time Curve From Time Zero to Infinity (AUC0 to Inf)Anytime between 4 to 5 hours, anytime between 6 to 8 hours, 12 hours, 18 to 24 hours and 48 hours post-dose on Day 1

AUCinf was determined as AUC(0 to t) + (Clast/kel), where Clast was the plasma concentration at the last quantifiable timepoint estimated from the log-linear regression analysis and kel was the terminal phase rate. No sampling was done at pre-dose (0 hour) and pre-dose results were imputed for all participants in the PK population.

Part B: Area Under the Plasma Concentration Time Curve From Time Zero to Infinity (AUC0 to Inf)Day 1 Dose 1 (anytime between 4 to 5 hours post-dose, 12 hours post-dose), Day 3 Dose 6 (pre-dose, anytime between 4 to 5 hours post-dose, 12 hours post-dose)

AUCinf was determined as AUC(0 to t) + (Clast/kel), where Clast was the plasma concentration at the last quantifiable timepoint estimated from the log-linear regression analysis and kel was the terminal phase rate. No sampling was done at pre-dose (0 hour) on Day 1 and pre-dose results were imputed for all participants in the PK population.

Part A: Trough Concentration at the End of First Dosing Interval (C12)At 12 hours post-dose on Day 1
Part B: Trough Concentration at the End of Dose 6 (C12)At 12 hours post-dose 6
Part B: Predicted Plasma ClearanceDay 1 Dose 1 (anytime between 4 to 5 hours post-dose, 12 hours post-dose), Day 3 Dose 6 (pre-dose, anytime between 4 to 5 hours post-dose, 12 hours post-dose)

Clearance was calculated as Dose divided by AUC(0 to inf). No sampling was done at pre-dose (0 hour) on Day 1 and pre-dose results were imputed for all participants in the PK population.

Part A: Apparent Volume of Distribution of the Drug After Extravascular AdministrationAnytime between 4 to 5 hours, anytime between 6 to 8 hours, 12 hours, 18 to 24 hours and 48 hours post-dose on Day 1

Apparent volume of distribution was estimated as Dose/Kel\*AUC(0 to inf), where Kel=apparent first-order terminal elimination rate constant. No sampling was done at pre-dose (0 hour) and pre-dose results were imputed for all participants in the PK population.

Part B: Apparent Volume of Distribution of the Drug After Extravascular AdministrationDay 1 Dose 1 (anytime between 4 to 5 hours post-dose, 12 hours post-dose), Day 3 Dose 6 (pre-dose, anytime between 4 to 5 hours post-dose, 12 hours post-dose)

Apparent volume of distribution was estimated as Dose/Kel\*AUC(0 to inf), where Kel=apparent first-order terminal elimination rate constant. No sampling was done at pre-dose (0 hour) on Day 1 and pre-dose results were imputed for all participants in the PK population.

Part B: Accumulation RatioDay 1 Dose 1 (anytime between 4 to 5 hours post-dose, 12 hours post-dose), Day 3 Dose 6 (pre-dose, anytime between 4 to 5 hours post-dose, 12 hours post-dose)

Accumulation ratio was calculated as ratio of the area under the curve (AUC) during a single dosing interval under steady state conditions to the AUC during a dosing interval after one singe dose. No sampling was done at pre-dose (0 hour) on Day 1 and pre-dose results were imputed for all participants in the PK population.

Part B: Percentage FluctuationDay 3 Dose 6 (pre-dose, anytime between 4 to 5 hours post-dose, 12 hours post-dose)

Percentage fluctuation was calculated as 100\*(Cmax-Cmin)/Cavg, where Cmin=minimum plasma concentration and Cmax measured over dosing interval.

Part B: Area Under the Plasma Concentration Time Curve From Time Zero to the End of Last Dosing Interval (AUC0-tau)Day 3 Dose 6 (pre-dose, anytime between 4 to 5 hours post-dose, 12 hours post-dose)

AUC(0 to tau) was determined using the linear trapezoidal method.

Part B: Percent Change From Baseline in Logarithm to Base10 (Log10) Total RSV Viral Load by Quantitative Reverse Transcription Polymerase Chain Reaction (RT-qPCR)Baseline (pre-dose on Day 1), 60 hours and 156 hours after first dose on Day 1

Percent change from baseline in log10 total RSV viral load was analyzed using a mixed effects analysis of covariance (ANCOVA) model. The model was fitted to the participants treated at the final doses selected for Cohort 5 as pre-planned in statistical analysis plan for age group \>=1 month to \<6 months.

Part B: Percent Change From Baseline in Logarithm to Base10 (Log10) Total RSV Viral Load by Cell-Based Infectivity Assay (CBIA)Baseline (pre-dose on Day 1), 60 hours and 156 hours after first dose on Day 1

Percent change from baseline in log10 total RSV viral load was analyzed using a mixed effects ANCOVA model. The model was fitted to the participants treated at the final doses selected for Cohort 5 as pre-planned in statistical analysis plan for age group \>=1 month to \<6 months.

Part B: Time to Resolution of RSV-Related Signs and SymptomsUp to Day 12

Time to resolution was calculated for RSV-related signs and symptoms that were present at study start and was defined as the time of randomization to the time that RSV-related signs and symptoms were absent.

Part B: Time to Improvement in RSV-Related Signs and SymptomsUp to Day 12

Time to improvement was calculated for RSV-related signs and symptoms that were classified as moderate or severe during the course of the study and was defined as the time from randomization to the time that RSV-related signs and symptoms were mild or absent.

Part B: RSV Clinical Scoring System ScoresBaseline (pre-dose 1 on Day 1), pre-dose 3, pre-dose 5, pre-dose 7, pre-dose 9, anytime between 40 to 48 hours post-dose 10 on Day 5

RSV clinical score was a composite score for infants with RSV infection \>= 1 month of age based on 4 items (respiratory rate, wheezing, retraction of respiratory muscles and general condition). Score for each item ranged from 0 to 3 where 0=none/normal and 3=severe. Total score was calculated as sum of individual items and ranged from 0 to 12, where higher score indicated severe disease. RSV symptoms were graded as mild: score \<=5, moderate: score \> 5 but \< 9 and severe: score \>=9.

Trial Locations

Locations (59)

Corporacion Gihema

🇨🇷

San Jose, Costa Rica

Hospital Metropolitano, Sede San Jose

🇨🇷

San Jose, Costa Rica

Hospital Seberang Jaya

🇲🇾

Seberang Jaya, Pulau Pinang, Malaysia

Hospital Materno Infantil Jose Domingo de Obaldia

🇵🇦

Panama, Panama

Uniwersytecki Szpital Dzieciecy w Krakowie

🇵🇱

Krakow, Poland

Srinagarind Hospital, Faculty of Medicine, Khon Kaen University

🇹🇭

Khon Kaen, Thailand

Guy's and St Thomas' NHS Foundation Trust Evelina London Children's Hospital Westminster

🇬🇧

London, United Kingdom

Hospital Seri Manjung

🇲🇾

Parek, Malaysia

Hospital Interzonal General de Agudos "Dr. José Penna"

🇦🇷

Bahia Blanca, Buenos Aires, Argentina

Hospital de ninos "Ricardo Gutierrez"

🇨🇦

Calgary, Alberta, Canada

Department of Pediatrics, SoonchunHyang University Seoul Hospital

🇰🇷

Seoul, Korea, Republic of

Seoul National University Children's Hospital

🇰🇷

Seoul, Korea, Republic of

Hospital Sibu

🇲🇾

Sibu, Sarawak, Malaysia

Hospital de Especialidades Pediatricas "Omar Torrijos Herrera"

🇵🇦

Panama, Panama

The Pharmacy Unit Ground Floor, OPD Building Faculty of Madicine,

🇹🇭

Bangkoknoi, Bangkok, Thailand

Hospital Universitario La Paz Servicio de Farmacia. Planta baja Edificio Norte

🇪🇸

Madrid, Spain

Chula Clinical Research Center, Faculty of Medicine

🇹🇭

Patumwan, Bangkok, Thailand

Hualien Tzu Chi Hospital, Buddhist Tzu Chi Medical Foundation

🇨🇳

Hualien, Taiwan

QueenSirikit National Institute of Child Health {QSNICH}

🇹🇭

Bangkok, Thailand

Hospital Universitario 12 de Octubre

🇪🇸

Madrid, Spain

Hospital Universitario Sant Joan de Deu

🇪🇸

Espluges De Llobregat, Barcelona, Spain

University Hospital Southampton NHS Foundation Trust NIHR Clinical Research Facility ,Mailpoint 218,

🇬🇧

Southampton, United Kingdom

Maharaj Nakorn Chiang Mai Hospital,Faculty of Medicine, Chiang Mai University

🇹🇭

Chiang Mai, Thailand

Hsinchu Mackay Memorial Hospital

🇨🇳

Hsinchu City, Taiwan

Faculty of Medicine Siriraj Hospital, Mahidol University

🇹🇭

Bangkoknoi, Bangkok, Thailand

King Chulalongkorn Memorial Hospital, Faculty of Medicine, Chulalongkorn University

🇹🇭

Bangkok, Thailand

Imperial College Healthcare NHS Trust St Mary's Hospital

🇬🇧

London, United Kingdom

Hospital Clinico de San carlos

🇪🇸

Madrid, Spain

Hospital Universitario de la Paz ,Pediatric Deparment

🇪🇸

Madrid, Spain

Complejo Hospitalario de Santiago

🇪🇸

Santiago de Compostela, Spain

Clinica Universidad de Navarra

🇪🇸

Pamplona, Spain

Schneider Children's Medical Center of Israel

🇮🇱

Petach Tikava, Israel

Rambam Health Care Campus

🇮🇱

Haifa, Israel

Eszak-Kozep-budai Centrum,Uj Szent Janos Korhaz es Szakrendelo,Gyermekosztaly

🇭🇺

Budapest, Hungary

Somogy Megyei Kaposi Mor Oktato Korhaz

🇭🇺

Kaposvar, Hungary

Capital and Coast DHB, Wellington Hospital

🇳🇿

Riddiford Street, Wellington, New Zealand

Hospital Italiano Regional Del Sur

🇦🇷

Bahia Blanca, Buenos Aires, Argentina

Hospital Taiping

🇲🇾

Taiping, Perak, Malaysia

Hospital General de Ninos Pedro de Elizalde

🇦🇷

Ciudad Autonoma de Buenos Aires, Caba, Argentina

Hospital Base San Jose Osorno

🇨🇱

Osorno, Region DE LOS Lagos, Chile

Soroka University Medical Center

🇮🇱

Beer-Sheva, Israel

Semmelweis Egyetem 11.sz. Gyermeklinika

🇭🇺

Budapest, Hungary

Sarawak General Hospital

🇲🇾

Kuching, Sarawak, Malaysia

Hospital Raja Perempuan Zainab II

🇲🇾

Kota Bharu, Kelantan, Malaysia

Samodzielny Publiczny Dzieciecy Szpital Kliniczny w Warszawie Oddzial Kliniczny Pediatrii

🇵🇱

Warszawa, Poland

Hospital Sultanah Nur Zahirah

🇲🇾

Kuala Terengganu, Terengganu, Malaysia

lnstytut Centrum Zdrowia Matki Polki Klinika Pediatrii, Immunologii i Nefrologii

🇵🇱

Lodz, Poland

Fundacion Hospital de Nens

🇪🇸

Barcelona, Spain

Kaohsiung Veterans General Hospital

🇨🇳

Kaohsiung City, Taiwan

Faculty of Medicine, Khon Kaen University

🇹🇭

khon Kaen, Thailand

Alder Hey Children's NHS Foundation Trust Institute in the Park

🇬🇧

Liverpool, United Kingdom

Chi Mei Medical Center

🇨🇳

Tainan City, Taiwan

Hospital Clinica Biblica

🇨🇷

San Jose, Costa Rica

Chiangrai Prachanukroh Hospital

🇹🇭

Chiangrai, Thailand

Hospital de Ninos Dr. Roberto del Rio

🇨🇱

Santiago, Metropolitana, Chile

lnstituto de lnvestigacion en Ciencias Medicas(IICIMED)

🇨🇷

San Jose, Costa Rica

Policlinico San Bosco, Consultorio de Pediatria, Dr. Arturo Solis Moya

🇨🇷

San Jose, Costa Rica

Hospital del Nino Dr. Jose Renan Esquivel

🇵🇦

Panama, Panama

Naresuan University Hospital ,Faculty of Medicine, Naresuan University

🇹🇭

Phitsanulok, Thailand

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