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

NCT04225897 | Terminated Phase 2 Results DMC

• 2 other identifiers: REVC003C5241003
• Study Type: interventional
• Target: 51
• Locations: 15 countries
• Sites: 60

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. 1.Age 1 month to 36 months
2. 2.Weight ≥ 3.5 kg
3. 3.Diagnosis of LRTI
4. 4.Diagnosis of RSV
5. 5.Hospitalization due to RSV LRTI

Conditions

Respiratory Syncytial Virus (RSV); Lower Resp Tract Infection

Keywords

RV521; Pediatrics; Children; LRTI; Wheezing; Rhinitis; Cough; sisunatovir

Outcome Measures

Primary Outcomes (49)

• Part A: Number of Participants With Treatment Emergent Adverse Events (TEAEs), Serious Adverse Events (SAEs) and TEAEs Leading to Permanent Discontinuation of IMP

  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.

  From start of IMP on Day 1 up to Day 7

• Part B: Number of Participants With Treatment Emergent Adverse Events (TEAEs), Serious Adverse Events (SAEs) and TEAEs Leading to Permanent Discontinuation of IMP

  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.

  From start of IMP on Day 1 up to Day 12

• Part A: Number of Participants With Abnormal Clinically Significant Physical Examination Results at Baseline

  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.

  Baseline (pre-dose on Day 1)

• Part A: Number of Participants With Abnormal Clinically Significant Physical Examination Results Anytime Between 18 to 24 Hours Post-dose

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

  Anytime between 18 to 24 hours post-dose on Day 1

• Part A: Number of Participants With Abnormal Clinically Significant Physical Examination Results at 48 Hours Post-dose

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

  At 48 hours post-dose on Day 1

• Part B: Number of Participants With Abnormal Clinically Significant Physical Examination Results at Baseline

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

  Baseline (pre-dose on Day 1)

• Part B: Number of Participants With Abnormal Clinically Significant Physical Examination Results Anytime Between 40 to 48 Hours Post-dose 10

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

  Anytime between 40 to 48 hours post-dose 10 on Day 5

• Part A: Number of Participants With Abnormal Clinically Significant Vital Signs Per Investigator's Interpretation at Baseline

  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.

  Baseline (pre-dose on Day 1)

• Part A: Number of Participants With Abnormal Clinically Significant Vital Signs Per Investigator's Interpretation Anytime Between 4 to 5 Hours Post-Dose

  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.

  Anytime between 4 to 5 hours post-dose on Day 1

• Part A: Number of Participants With Abnormal Clinically Significant Vital Signs Per Investigator's Interpretation at 12 Hours Post-Dose

  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.

  At 12 hours post-dose on Day 1

• Part A: Number of Participants With Abnormal Clinically Significant Vital Signs Per Investigator's Interpretation Anytime Between 18 to 24 Hours Post-Dose

  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.

  Anytime between 18 to 24 hours post-dose on Day 1

• Part A: Number of Participants With Abnormal Clinically Significant Vital Signs Per Investigator's Interpretation at 48 Hours Post-Dose

  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.

  48 hours post-dose on Day 1

• Part B: Number of Participants With Abnormal Vital Signs Per Investigator's Interpretation at Baseline

  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.

  Baseline (pre-dose on Day 1)

• Part B: Number of Participants With Abnormal Clinically Significant Vital Signs Per Investigator's Interpretation Anytime Between 4 to 5 Hours Post-Dose 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.

  Anytime between 4 to 5 hours post-dose 1 (Day 1)

• Part B: Number of Participants With Abnormal Clinically Significant Vital Signs Per Investigator's Interpretation At Pre-dose 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 2= assessment prior to receiving dose 2 of IMP on Day 1.

  Pre-dose 2 (Day 1)

• Part B: Number of Participants With Abnormal Clinically Significant Vital Signs Per Investigator's Interpretation at Pre-dose 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 3= assessment prior to receiving dose 3 of IMP on Day 2.

  Pre-dose 3 (Day 2)

• Part B: Number of Participants With Abnormal Clinically Significant Vital Signs Per Investigator's Interpretation at Pre-dose 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 4= assessment prior to receiving dose 4 of IMP on Day 2.

  Pre-dose 4 (Day 2)

• Part B: Number of Participants With Abnormal Clinically Significant Vital Signs Per Investigator's Interpretation at Pre-dose 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 5= assessment prior to receiving dose 5 of IMP on Day 3.

  Pre-dose 5 (Day 3)

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

  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.

  Pre-dose 6 (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 6

  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.

  Anytime between 4 to 5 hours post-dose 6 (Day 3)

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

  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.

  Pre-dose 7 (Day 4)

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

  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.

  Pre-dose 8 (Day 4)

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

  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.

  Pre-dose 9 (Day 5)

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

  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.

  Pre-dose 10 (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 10

  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.

  Anytime between 40 to 48 hours post-dose 10 on Day 5

• Part A: Number of Participants With Abnormal Hematology Results at Baseline

  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.

  Baseline (pre-dose on Day 1)

• Part A: Number of Participants With Abnormal Hematology Results at 48 Hours Post-Dose

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

  At 48 hours post-dose on Day 1

• Part B: Number of Participants With Abnormal Hematology Results at Baseline

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

  Baseline (pre-dose on Day 1)

• Part B: Number of Participants With Abnormal Hematology Results Anytime Between 40 to 48 Hours Post-dose 10

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

  Anytime between 40 to 48 hours post-dose 10 on Day 5

• Part A: Number of Participants With Abnormal Clinical Chemistry Results at Baseline

  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.

  Baseline (pre-dose on Day 1)

• Part A: Number of Participants With Abnormal Clinical Chemistry Results at 48 Hours Post-Dose

  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.

  At 48 hours post-dose on Day 1

• Part B: Number of Participants With Abnormal Clinical Chemistry Results at Baseline

  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.

  Baseline (pre-dose on Day 1)

• Part B: Number of Participants With Abnormal Clinical Chemistry Results Anytime Between 40 to 48 Hours Post-dose 10

  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.

  Anytime between 40 to 48 hours post-dose 10 on Day 5

• Part A: Number of Participants With Abnormal Urinalysis Results at Baseline

  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).

  Baseline (pre-dose on Day 1)

• Part A: Number of Participants With Abnormal Urinalysis Results at 48 Hours Post-dose

  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).

  At 48 hours post-dose on Day 1

• Part B: Number of Participants With Abnormal Urinalysis Results at Baseline

  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).

  Baseline (pre-dose on Day 1)

• Part B: Number of Participants With Abnormal Urinalysis Results Anytime Between 40 to 48 Hours Post-Dose 10

  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).

  Anytime between 40 to 48 hours post-dose 10 on Day 5

• Part A: Number of Participants With Abnormal Clinically Significant Electrocardiogram (ECG) Results Per Investigator's Interpretation at Baseline

  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.

  Baseline (pre-dose on Day 1)

• Part A: Number of Participants With Abnormal Clinically Significant Electrocardiogram (ECG) Results Per Investigator's Interpretation Anytime Between 4 to 5 Hours Post-Dose

  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.

  Anytime between 4 to 5 hours post-dose on Day 1

• Part A: Number of Participants With Abnormal Clinically Significant Electrocardiogram (ECG) Results Per Investigator's Interpretation Anytime Between 18 to 24 Hours Post-dose

  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.

  Anytime between 18 to 24 hours post-dose on Day 1

• Part A: Number of Participants With Abnormal Clinically Significant Electrocardiogram (ECG) Results Per Investigator's Interpretation at 48 Hours Post-dose

  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.

  48 hours post-dose on Day 1

• Part B: Number of Participants With Abnormal Clinically Significant Electrocardiogram (ECG) Results Per Investigator's Interpretation at Baseline

  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.

  Baseline (pre-dose on Day 1)

• Part B: Number of Participants With Abnormal Clinically Significant Electrocardiogram (ECG) Results Per Investigator's Interpretation Anytime Between 4 to 5 Hours Post-Dose 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.

  Anytime between 4 to 5 hours post-dose 1 on Day 1

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

  Pre-dose 3 (Day 2)

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

  Pre-dose 5 (Day 3)

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

  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.

  Anytime between 4 to 5 hours post-dose 6 (Day 3)

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

  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.

  Pre-dose 8 (Day 4)

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

  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.

  Pre-dose 10 (Day 5)

• Part B: Number of Participants With Abnormal Clinically Significant Electrocardiogram (ECG) Results Per Investigator's Interpretation Anytime Between 40 to 48 Hours Post-Dose 10

  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.

  Anytime between 40 to 48 hours post-dose 10 on Day 5

Secondary Outcomes (29)

• 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

• 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)

• 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

• 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)

• 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

Study Arms (2)

RV521

EXPERIMENTAL

sisunatovir 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.

Drug: RV521

Placebo

PLACEBO COMPARATOR

The 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.

Drug: Placebo

Interventions

RV521 DRUG

RV521 is an RSV F protein inhibitor administered orally

Also known as: sisunatovir

RV521

Placebo DRUG

vehicle administered orally

Placebo

Eligibility Criteria

• Age: 1 Month - 36 Months
• Sex: all
• Healthy Volunteers: No
• Age Groups: Child (0-17)

You may qualify if:

• Male or female ≥ 1 month and ≤ 36 months of age
• Weight ≥ 3.5 kg
• Clinical diagnosis of LRTI
• A positive RSV diagnostic test
• Hospitalised because of RSV LRTI
• 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
• Expected to remain in hospital for a minimum of 3 days
• 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

You may not qualify if:

• Premature (gestational age less than 37 weeks) AND \<1 year of post-natal age
• Known to have significant comorbidities that would limit the ability to administer study drug or evaluate the safety or clinical response to study drug.
• Any clinically significant ECG abnormalities.
• Known to be immunocompromised.
• High risk of having developing asthma.
• Suspected of having a clinically significant bacterial infection.
• History of renal failure.
• Clinical evidence of hepatic decompensation
• History of epilepsy or seizures, including febrile seizures
• Allergy to test medication or constituents
• 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.

Sponsors & Collaborators

• Pfizer: lead

Study Sites (60)

Hospital Interzonal General de Agudos "Dr. José Penna"

Bahía Blanca, Buenos Aires, B8001DDU, Argentina

Location

Hospital Italiano Regional Del Sur

Bahía Blanca, Buenos Aires, B8001HXM, Argentina

Location

Hospital General de Ninos Pedro de Elizalde

Buenos Aires, Buenos Aires F.D., C1270AAN, Argentina

Location

Hospital de ninos "Ricardo Gutierrez"

Calgary, Alberta, T2J 7E1, Canada

Location

Hospital Base San Jose Osorno

Osorno, Los Lagos Region, 5311523, Chile

Location

Hospital de Ninos Dr. Roberto del Rio

Santiago, Santiago Metropolitan, 8380418, Chile

Location

Corporacion Gihema

San José, Costa Rica

Location

Hospital Clinica Biblica

San José, Costa Rica

Location

Hospital Metropolitano, Sede San Jose

San José, Costa Rica

Location

lnstituto de lnvestigacion en Ciencias Medicas(IICIMED)

San José, Costa Rica

Location

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

San José, Costa Rica

Location

Semmelweis Egyetem 11.sz. Gyermeklinika

Budapest, 1094, Hungary

Location

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

Budapest, 1125, Hungary

Location

Somogy Megyei Kaposi Mor Oktato Korhaz

Kaposvár, 7400, Hungary

Location

Soroka University Medical Center

Beersheba, 84417, Israel

Location

Rambam Health Care Campus

Haifa, 3109601, Israel

Location

Schneider Children's Medical Center of Israel

Petach Tikava, 49202, Israel

Location

Hospital Raja Perempuan Zainab II

Kota Bharu, Kelantan, 15586, Malaysia

Location

Hospital Taiping

Taiping, Perak, 34000, Malaysia

Location

Hospital Seberang Jaya

Seberang Jaya, Pulau Pinang, 13700, Malaysia

Location

Sarawak General Hospital

Kuching, Sarawak, 93586, Malaysia

Location

Hospital Sibu

Sibu, Sarawak, 96000, Malaysia

Location

Hospital Sultanah Nur Zahirah

Kuala Terengganu, Terengganu, 20400, Malaysia

Location

Hospital Seri Manjung

Parek, 32040, Malaysia

Location

Capital and Coast DHB, Wellington Hospital

Riddiford Street, Wellington Region, 6021, New Zealand

Location

Hospital de Especialidades Pediatricas "Omar Torrijos Herrera"

Panama City, Panama

Location

Hospital del Nino Dr. Jose Renan Esquivel

Panama City, Panama

Location

Hospital Materno Infantil Jose Domingo de Obaldia

Panama City, Panama

Location

Uniwersytecki Szpital Dzieciecy w Krakowie

Krakow, 30-663, Poland

Location

lnstytut Centrum Zdrowia Matki Polki Klinika Pediatrii, Immunologii i Nefrologii

Lodz, 93-338, Poland

Location

Samodzielny Publiczny Dzieciecy Szpital Kliniczny w Warszawie Oddzial Kliniczny Pediatrii

Warsaw, 02-091, Poland

Location

Seoul National University Children's Hospital

Seoul, 03080, South Korea

Location

Department of Pediatrics, SoonchunHyang University Seoul Hospital

Seoul, 04401, South Korea

Location

Hospital Universitario Sant Joan de Deu

Espluges de Llobregat, Barcelona, 08950, Spain

Location

Fundacion Hospital de Nens

Barcelona, 08009, Spain

Location

Clinica Universidad de Navarra

Madrid, 28027, Spain

Location

Hospital Clinico de San carlos

Madrid, 28040, Spain

Location

Hospital Universitario 12 de Octubre

Madrid, 28041, Spain

Location

Hospital Universitario de la Paz ,Pediatric Deparment

Madrid, 28046, Spain

Location

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

Madrid, 28046, Spain

Location

Clinica Universidad de Navarra

Pamplona, 31008, Spain

Location

Complejo Hospitalario de Santiago

Santiago de Compostela, 15706, Spain

Location

Hsinchu Mackay Memorial Hospital

Hsinchu, 30071, Taiwan

Location

Hualien Tzu Chi Hospital, Buddhist Tzu Chi Medical Foundation

Hualien City, 970, Taiwan

Location

Kaohsiung Veterans General Hospital

Kaohsiung City, 81362, Taiwan

Location

Chi Mei Medical Center

Tainan, 710, Taiwan

Location

Faculty of Medicine Siriraj Hospital, Mahidol University

Bangkoknoi, Bangkok, 10700, Thailand

Location

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

Bangkoknoi, Bangkok, 10700, Thailand

Location

Chula Clinical Research Center, Faculty of Medicine

Patumwan, Bangkok, 10330, Thailand

Location

King Chulalongkorn Memorial Hospital, Faculty of Medicine, Chulalongkorn University

Bangkok, 10330, Thailand

Location

QueenSirikit National Institute of Child Health {QSNICH}

Bangkok, 10400, Thailand

Location

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

Chiang Mai, 50200, Thailand

Location

Chiangrai Prachanukroh Hospital

Chiangrai, 57000, Thailand

Location

Faculty of Medicine, Khon Kaen University

Khon Kaen, 40002, Thailand

Location

Srinagarind Hospital, Faculty of Medicine, Khon Kaen University

Khon Kaen, 40002, Thailand

Location

Naresuan University Hospital ,Faculty of Medicine, Naresuan University

Phitsanulok, 65000, Thailand

Location

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

Liverpool, L 12 2AP, United Kingdom

Location

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

London, SE1 7EH, United Kingdom

Location

Imperial College Healthcare NHS Trust St Mary's Hospital

London, W2 1NY, United Kingdom

Location

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

Southampton, SO16 6YD, United Kingdom

Location

Related Links

• To obtain contact information for a study center near you, click here.

MeSH Terms

Conditions

Respiratory Sounds; Rhinitis; Cough

Interventions

sisunatovir

Condition Hierarchy (Ancestors)

Signs and Symptoms, Respiratory; Signs and Symptoms; Pathological Conditions, Signs and Symptoms; Respiratory Tract Infections; Infections; Nose Diseases; Respiratory Tract Diseases; Otorhinolaryngologic Diseases; Respiration Disorders

Results Point of Contact

• Title: Pfizer ClinicalTrials.gov Call Center
• Organization: Pfizer Inc.

ClinicalTrials.gov_Inquiries@pfizer.com

1-800-718-1021

Study Officials

• Pfizer CT.gov Call Center

  Pfizer

  STUDY DIRECTOR

Publication Agreements

• PI is Sponsor Employee: No
• Restriction Type: OTHER
• Restrictive Agreement: Yes

Study Design

• Study Type: interventional
• Phase: phase 2
• Allocation: RANDOMIZED
• Masking: TRIPLE
• Who Masked: PARTICIPANT, CARE PROVIDER, INVESTIGATOR
• Purpose: TREATMENT
• Intervention Model: SEQUENTIAL
• Sponsor Type: INDUSTRY
• Responsible Party: SPONSOR

Model Details: 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. Due to the adaptive study design, the number of enrolled subjects may vary depending on the obtained PK and safety profiles. The clinical study consists of 3 parts: * 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

Study Record Dates

• First Submitted: December 11, 2019
• First Posted: January 13, 2020
• Study Start: November 13, 2019
• Primary Completion: December 5, 2022
• Study Completion: December 5, 2022
• Last Updated: October 23, 2024
• Results First Posted: October 23, 2024

Record last verified: 2024-08

Data Sharing

• IPD Sharing: Will share

Locations

MY (7); ES (9); AR (3); TW (4); CO (5); PA (3); GB (4); KR (2); IL (3); TH (10); PL (3); NZ (1); HU (3); CA (1); CL (2)