search
Back to results

A Study to Learn About the Effects of Sisunatovir in Infants With Respiratory Syncytial Virus Lower Respiratory Tract Infection. (REVIRAL 1)

Primary Purpose

Respiratory Syncytial Virus (RSV), Lower Resp Tract Infection

Status
Terminated
Phase
Phase 2
Locations
International
Study Type
Interventional
Intervention
RV521
Placebo
Sponsored by
Pfizer
About
Eligibility
Locations
Arms
Outcomes
Full info

About this trial

This is an interventional treatment trial for Respiratory Syncytial Virus (RSV) focused on measuring RV521, Pediatrics, Children, LRTI, Wheezing, Rhinitis, Cough, sisunatovir

Eligibility Criteria

1 Month - 36 Months (Child)All SexesDoes not accept healthy volunteers

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

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.

Sites / Locations

  • Hospital Interzonal General de Agudos "Dr. José Penna"
  • Hospital Italiano Regional Del Sur
  • Hospital General de Ninos Pedro de Elizalde
  • Hospital de ninos "Ricardo Gutierrez"
  • Hospital de Ninos Dr. Roberto del Rio
  • Hospital Base San Jose Osorno
  • Corporacion Gihema
  • Hospital Clinica Biblica
  • Hospital Metropolitano, Sede San Jose
  • lnstituto de lnvestigacion en Ciencias Medicas(IICIMED)
  • Policlinico San Bosco, Consultorio de Pediatria, Dr. Arturo Solis Moya
  • Semmelweis Egyetem 11.sz. Gyermeklinika
  • Eszak-Kozep-budai Centrum,Uj Szent Janos Korhaz es Szakrendelo,Gyermekosztaly
  • Somogy Megyei Kaposi Mor Oktato Korhaz
  • Soroka University Medical Center
  • Rambam Health Care Campus
  • Schneider Children's Medical Center of Israel
  • Seoul National University Children's Hospital
  • Department of Pediatrics, SoonchunHyang University Seoul Hospital
  • Hospital Raja Perempuan Zainab II
  • Hospital Taiping
  • Hospital Seberang Jaya
  • Sarawak General Hospital
  • Hospital Sibu
  • Hospital Sultanah Nur Zahirah
  • Hospital Seri Manjung
  • Capital and Coast DHB, Wellington Hospital
  • Hospital de Especialidades Pediatricas "Omar Torrijos Herrera"
  • Hospital del Nino Dr. Jose Renan Esquivel
  • Hospital Materno Infantil Jose Domingo de Obaldia
  • Uniwersytecki Szpital Dzieciecy w Krakowie
  • lnstytut Centrum Zdrowia Matki Polki Klinika Pediatrii, Immunologii i Nefrologii
  • Samodzielny Publiczny Dzieciecy Szpital Kliniczny w Warszawie Oddzial Kliniczny Pediatrii
  • Hospital Universitario Sant Joan de Deu
  • Fundacion Hospital de Nens
  • Clinica Universidad de Navarra
  • Hospital Clinico de San carlos
  • Hospital Universitario 12 de Octubre
  • Hospital Universitario de la Paz ,Pediatric Deparment
  • Hospital Universitario La Paz Servicio de Farmacia. Planta baja Edificio Norte
  • Clinica Universidad de Navarra
  • Complejo Hospitalario de Santiago
  • Hsinchu Mackay Memorial Hospital
  • Hualien Tzu Chi Hospital, Buddhist Tzu Chi Medical Foundation
  • Kaohsiung Veterans General Hospital
  • Chi Mei Medical Center
  • Faculty of Medicine Siriraj Hospital, Mahidol University
  • The Pharmacy Unit Ground Floor, OPD Building Faculty of Madicine,
  • Chula Clinical Research Center, Faculty of Medicine
  • King Chulalongkorn Memorial Hospital, Faculty of Medicine, Chulalongkorn University
  • QueenSirikit National Institute of Child Health {QSNICH}
  • Maharaj Nakorn Chiang Mai Hospital,Faculty of Medicine, Chiang Mai University
  • Chiangrai Prachanukroh Hospital
  • Faculty of Medicine, Khon Kaen University
  • Srinagarind Hospital, Faculty of Medicine, Khon Kaen University
  • Naresuan University Hospital ,Faculty of Medicine, Naresuan University
  • Alder Hey Children's NHS Foundation Trust Institute in the Park
  • Guy's and St Thomas' NHS Foundation Trust Evelina London Children's Hospital Westminster
  • Imperial College Healthcare NHS Trust St Mary's Hospital
  • University Hospital Southampton NHS Foundation Trust NIHR Clinical Research Facility ,Mailpoint 218,

Arms of the Study

Arm 1

Arm 2

Arm Type

Experimental

Placebo Comparator

Arm Label

RV521

Placebo

Arm Description

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.

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.

Outcomes

Primary Outcome Measures

To evaluate the safety and tolerability of single (Part A) and multiple (Part B) oral doses of RV521 in infants hospitalised with RSV LRTI by assessing incidence of AEs, TEAEs, SAEs, and withdrawals due to TEAEs.
Summary tables of AEs will be based on TEAEs, defined as events starting, or worsening, after the first dose of IMP.
To evaluate the safety and tolerability of single (Part A) and multiple (Part B) oral doses of RV521 in infants hospitalised with RSV LRTI by assessing changes in physical examinations.
Results at each visit will be summarised using the statistics: n (number of observations), mean, SD, median, minimum and maximum.
To evaluate the safety and tolerability of single (Part A) and multiple (Part B) oral doses of RV521 in infants hospitalised with RSV LRTI by assessing systolic BP (vital sign parameters) and changes from baseline
Baseline characteristics will be summarized descriptively by treatment. Quantitative variables will be summarized used the statistics n, mean, standard deviation, median, minimum and maximum.
To evaluate the safety and tolerability of single (Part A) and multiple (Part B) oral doses of RV521 in infants hospitalised with RSV LRTI by assessing diastolic BP (vital sign parameters) and changes from baseline
Baseline characteristics will be summarized descriptively by treatment. Quantitative variables will be summarized used the statistics n, mean, standard deviation, median, minimum and maximum.
To evaluate the safety and tolerability of single (Part A) and multiple (Part B) oral doses of RV521 in infants hospitalised with RSV LRTI by assessing body temperature (vital sign parameters) and changes from baseline
Baseline characteristics will be summarized descriptively by treatment. Quantitative variables will be summarized used the statistics n, mean, standard deviation, median, minimum and maximum.
To evaluate the safety and tolerability of single (Part A) and multiple (Part B) oral doses of RV521 in infants hospitalised with RSV LRTI by assessing respiration rate (vital sign parameters) and changes from baseline
Baseline characteristics will be summarized descriptively by treatment. Quantitative variables will be summarized used the statistics n, mean, standard deviation, median, minimum and maximum.
To evaluate the safety and tolerability of single (Part A) and multiple (Part B) oral doses of RV521 in infants hospitalised with RSV LRTI by assessing heart rate (vital sign parameters) and changes from baseline
Baseline characteristics will be summarized descriptively by treatment. Quantitative variables will be summarized used the statistics n, mean, standard deviation, median, minimum and maximum.
To evaluate the safety and tolerability of single (Part A) and multiple (Part B) oral doses of RV521 in infants hospitalised with RSV LRTI by assessing pulse oximetry (vital sign parameters) and changes from baseline
Baseline characteristics will be summarized descriptively by treatment. Quantitative variables will be summarized used the statistics n, mean, standard deviation, median, minimum and maximum.
Number of participants with changes in haematology/clinical chemistry/urinalysis laboratory values (laboratory tests read by a central lab) from baseline in Part A and Part B.
Results at each visit will be summarised using the statistics n, mean, standard deviation, median, minimum and maximum. Also, change from baseline will also be summarised by post baseline visits.
Number of participants with changes in ECG measurements from baseline in Part A and Part B
Parameters collected will be: Ventricular Heart Rate (bpm) PR Interval (msec) QRS Interval (msec) QT Interval (msec) QTcB Interval (msec) Results at each visit will be summarised using the statistics: n (number of observations), mean, SD, median, minimum and maximum.
Part C: Evaluate the effect of RV521, compared to placebo, on the clinical course of RSV LRTI using the RSV Clinical Scoring System and the Adapted Version of ReSVinet Scale to show time to resolution of symptoms.
Overall time to resolution of RSV-related signs and symptoms will be calculated from the time of randomization to the time that they are no longer present (absent or severity =0), and will be summarized and analysed as Time to Improvement.
Part C: Evaluate the effect (efficacy) of RV521, compared to placebo, on the clinical course of RSV LRTI using the RSV Clinical Scoring System and the Adapted Version of ReSVinet Scale to assess time to change of symptoms.
Time to change in symptoms will be calculated for RSV-related signs and symptoms that are classified as moderate or severe during the course of the study and will be defined as the time from randomization until no longer present (absent or severity=0) or mild (scores ≤ 5).
Part C: Evaluate the effect (efficacy) of RV521, compared to placebo, on the clinical course of RSV LRTI using the RSV Clinical Scoring System and the Adapted Version of ReSVinet Scale to assess change in severity of symptoms
Change in severity of symptoms by RV521, compared to placebo, will be measured by a composite score over time.
Part C: Evaluate the effect (efficacy) of RV521, compared to placebo, on the clinical course of RSV LRTI using the RSV Clinical Scoring System and the Adapted Version of ReSVinet Scale to assess use of supplemental oxygen.
Duration and maximum level of O2 provided will be assessed.

Secondary Outcome Measures

To characterise the pharmacokinetics (PK) of single (Part A) and multiple (Part B) oral doses of RV521 in infants hospitalised with RSV LRTI by assessing time to maximum plasma concentration (tmax).
Pharmacokinetic analysis will include listings and summaries of PK concentrations by time point, derived PK, parameters and analysis of relationship with dose and body weight.
To characterise the pharmacokinetics (PK) of single (Part A) and multiple (Part B) oral doses of RV521 in infants hospitalised with RSV LRTI by assessing maximum observed plasma concentration (Cmax).
Pharmacokinetic analysis will include listings and summaries of PK concentrations by time point, derived PK, parameters and analysis of relationship with dose and body weight.
To characterise the pharmacokinetics (PK) of single (Part A) and multiple (Part B) oral doses of RV521 in infants hospitalised with RSV LRTI by assessing area under the plasma concentration time curve from time zero to 12 hours (AUC0-12).
Pharmacokinetic analysis will include listings and summaries of PK concentrations by time point, derived PK, parameters and analysis of relationship with dose and body weight.
To characterise the PK of single (Part A) and multiple (Part B) oral doses of RV521 in infants hospitalised with RSV LRTI by assessing the area under the plasma concentration time curve from time zero to last measurable plasma concentration (AUC0 t).
Pharmacokinetic analysis will include listings and summaries of PK concentrations by time point, derived PK, parameters and analysis of relationship with dose and body weight.
To characterise the pharmacokinetics (PK) of single (Part A) and multiple (Part B) oral doses of RV521 in infants hospitalised with RSV LRTI by assessing terminal half-life (t1/2).
Pharmacokinetic analysis will include listings and summaries of PK concentrations by time point, derived PK, parameters and analysis of relationship with dose and body weight.
To characterise the pharmacokinetics (PK) of single (Part A) and multiple (Part B) oral doses of RV521 in infants hospitalised with RSV LRTI by assessing area under the plasma concentration time curve from time zero to infinity (AUC0-∞).
Pharmacokinetic analysis will include listings and summaries of PK concentrations by time point, derived PK, parameters and analysis of relationship with dose and body weight.
To characterise the pharmacokinetics (PK) of single (Part A) and multiple (Part B) oral doses of RV521 in infants hospitalised with RSV LRTI by assessing predicted plasma clearance.
Pharmacokinetic analysis will include listings and summaries of PK concentrations by time point, derived PK, parameters and analysis of relationship with dose and body weight.
To characterise the pharmacokinetics (PK) of single (Part A) and multiple (Part B) oral doses of RV521 in infants hospitalised with RSV LRTI by assessing apparent volume of distribution of the drug after extravascular administration (V/F).
Pharmacokinetic analysis will include listings and summaries of PK concentrations by time point, derived PK, parameters and analysis of relationship with dose and body weight.
To characterise the pharmacokinetics (PK) of single (Part A) and multiple (Part B) oral doses of RV521 in infants hospitalised with RSV LRTI by assessing trough concentration at the end of first dosing interval (C12) (data permitting).
Pharmacokinetic analysis will include listings and summaries of PK concentrations by time point, derived PK, parameters and analysis of relationship with dose and body weight.
To characterise the pharmacokinetics (PK) of multiple (Part B) oral doses of RV521 in infants hospitalised with RSV LRTI by assessing accumulation ratio, percent fluctuation.
Pharmacokinetic analysis will include listings and summaries of PK concentrations by time point, derived PK, parameters and analysis of relationship with dose and body weight.
To characterise the pharmacokinetics (PK) of multiple (Part B) oral doses of RV521 in infants hospitalised with RSV LRTI by assessing the area under the plasma concentration time curve from time zero to the end of last dosing interval (AUC0-tau).
Pharmacokinetic analysis will include listings and summaries of PK concentrations by time point, derived PK, parameters and analysis of relationship with dose and body weight.
To characterise the pharmacokinetics (PK) of multiple (Part B) oral doses of RV521 in infants hospitalised with RSV LRTI by assessing average plasma concentration over dosing interval (Cave).
Pharmacokinetic analysis will include listings and summaries of PK concentrations by time point, derived PK, parameters and analysis of relationship with dose and body weight.
To characterise the pharmacokinetics (PK) of multiple (Part B) oral doses of RV521 in infants hospitalised with RSV LRTI by assessing minimum observed plasma concentration (Cmin).
Pharmacokinetic analysis will include listings and summaries of PK concentrations by time point, derived PK, parameters and analysis of relationship with dose and body weight.
To characterise the pharmacokinetics (PK) of multiple (Part B) oral doses of RV521 in infants hospitalised with RSV LRTI by assessing plasma trough concentration (Ctrough).
Pharmacokinetic analysis will include listings and summaries of PK concentrations by time point, derived PK, parameters and analysis of relationship with dose and body weight.
Part B: To evaluate the antiviral effects of RV521 in infants hospitalised with RSV LRTI by RSV viral load measured in nasopharyngeal swabs by RT qPCR.
Pharmacodynamics analysis will include listing of results of viral load with summary statistics by dose level and time point.
Part B: To evaluate the antiviral effects of RV521 in infants hospitalised with RSV LRTI by RSV viral load measured in nasopharyngeal swabs by CBIA.
Pharmacodynamics analysis will include listing of results of viral load with summary statistics by dose level and time point.
Part B: Evaluate the effect of RV521 compared to placebo on the clinical course of RSV LRTI using the RSV Clinical Scoring System and the Adapted Version of ReSVinet Scale to assess time to resolution of symptoms.
Overall Time to Resolution of RSV-related signs and symptoms will be calculated from the time of randomization to the time that they are no longer present (absent or severity =0), and will be summarized and analysed as for Time to Improvement.
Part B: Evaluate the effect of RV521 compared to placebo on the clinical course of RSV LRTI using the RSV Clinical Scoring System and the Adapted Version of ReSVinet Scale to assess time to improvement evaluated by change in severity of symptoms.
Time to improvement will be calculated for RSV-related signs and symptoms that are classified as moderate or severe during the course of the study and will be defined as the time from randomization until no longer present (absent or severity=0) or mild (scores ≤ 5).
Part B: Evaluate the effect of RV521 compared to placebo on the clinical course of RSV LRTI using the RSV Clinical Scoring System and the Adapted Version of ReSVinet Scale to assess change in severity of symptoms.
Change in severity of symptoms by RV521, compared to placebo, will be measured by a composite score over time.

Full Information

First Posted
December 11, 2019
Last Updated
June 23, 2023
Sponsor
Pfizer
search

1. Study Identification

Unique Protocol Identification Number
NCT04225897
Brief Title
A Study to Learn About the Effects of Sisunatovir in Infants With Respiratory Syncytial Virus Lower Respiratory Tract Infection.
Acronym
REVIRAL 1
Official Title
A Phase 2 Open-Label Study in Infants With REspiratory Syncytial VIRus Lower RespirAtory Tract Infection, Followed by a DoubLe-blind, Placebocontrolled Part, to Evaluate the Safety, Tolerability, Pharmacokinetics and Antiviral Effect of RV521 (REVIRAL 1)
Study Type
Interventional

2. Study Status

Record Verification Date
June 2023
Overall Recruitment Status
Terminated
Why Stopped
Part A and Part B were completed but Pfizer terminated Part C due to strategic consideration. There were no safety concerns in the decision to stop Part C and no changes to the risk-benefit for participants who received RV521 in the study.
Study Start Date
November 13, 2019 (Actual)
Primary Completion Date
December 5, 2022 (Actual)
Study Completion Date
December 5, 2022 (Actual)

3. Sponsor/Collaborators

Responsible Party, by Official Title
Sponsor
Name of the Sponsor
Pfizer

4. Oversight

Studies a U.S. FDA-regulated Drug Product
No
Studies a U.S. FDA-regulated Device Product
No
Data Monitoring Committee
Yes

5. Study Description

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: Age 1 month to 36 months Weight ≥ 3.5 kg Diagnosis of LRTI Diagnosis of RSV 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.

6. Conditions and Keywords

Primary Disease or Condition Being Studied in the Trial, or the Focus of the Study
Respiratory Syncytial Virus (RSV), Lower Resp Tract Infection
Keywords
RV521, Pediatrics, Children, LRTI, Wheezing, Rhinitis, Cough, sisunatovir

7. Study Design

Primary Purpose
Treatment
Study Phase
Phase 2
Interventional Study Model
Sequential Assignment
Model 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. 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
Masking
ParticipantCare ProviderInvestigator
Allocation
Randomized
Enrollment
51 (Actual)

8. Arms, Groups, and Interventions

Arm Title
RV521
Arm Type
Experimental
Arm Description
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.
Arm Title
Placebo
Arm Type
Placebo Comparator
Arm Description
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.
Intervention Type
Drug
Intervention Name(s)
RV521
Other Intervention Name(s)
sisunatovir
Intervention Description
RV521 is an RSV F protein inhibitor administered orally
Intervention Type
Drug
Intervention Name(s)
Placebo
Intervention Description
vehicle administered orally
Primary Outcome Measure Information:
Title
To evaluate the safety and tolerability of single (Part A) and multiple (Part B) oral doses of RV521 in infants hospitalised with RSV LRTI by assessing incidence of AEs, TEAEs, SAEs, and withdrawals due to TEAEs.
Description
Summary tables of AEs will be based on TEAEs, defined as events starting, or worsening, after the first dose of IMP.
Time Frame
48 hours post dose 1 (Part A) and 48 hours post dose 10 (Part B)
Title
To evaluate the safety and tolerability of single (Part A) and multiple (Part B) oral doses of RV521 in infants hospitalised with RSV LRTI by assessing changes in physical examinations.
Description
Results at each visit will be summarised using the statistics: n (number of observations), mean, SD, median, minimum and maximum.
Time Frame
48 hours post dose 1 (Part A) and 48 hours post dose 10 (Part B)
Title
To evaluate the safety and tolerability of single (Part A) and multiple (Part B) oral doses of RV521 in infants hospitalised with RSV LRTI by assessing systolic BP (vital sign parameters) and changes from baseline
Description
Baseline characteristics will be summarized descriptively by treatment. Quantitative variables will be summarized used the statistics n, mean, standard deviation, median, minimum and maximum.
Time Frame
48 hours post dose 1 (Part A) and 48 hours post dose 10 (Part B)
Title
To evaluate the safety and tolerability of single (Part A) and multiple (Part B) oral doses of RV521 in infants hospitalised with RSV LRTI by assessing diastolic BP (vital sign parameters) and changes from baseline
Description
Baseline characteristics will be summarized descriptively by treatment. Quantitative variables will be summarized used the statistics n, mean, standard deviation, median, minimum and maximum.
Time Frame
48 hours post dose 1 (Part A) and 48 hours post dose 10 (Part B)
Title
To evaluate the safety and tolerability of single (Part A) and multiple (Part B) oral doses of RV521 in infants hospitalised with RSV LRTI by assessing body temperature (vital sign parameters) and changes from baseline
Description
Baseline characteristics will be summarized descriptively by treatment. Quantitative variables will be summarized used the statistics n, mean, standard deviation, median, minimum and maximum.
Time Frame
48 hours post dose 1 (Part A) and 48 hours post dose 10 (Part B)
Title
To evaluate the safety and tolerability of single (Part A) and multiple (Part B) oral doses of RV521 in infants hospitalised with RSV LRTI by assessing respiration rate (vital sign parameters) and changes from baseline
Description
Baseline characteristics will be summarized descriptively by treatment. Quantitative variables will be summarized used the statistics n, mean, standard deviation, median, minimum and maximum.
Time Frame
48 hours post dose 1 (Part A) and 48 hours post dose 10 (Part B)
Title
To evaluate the safety and tolerability of single (Part A) and multiple (Part B) oral doses of RV521 in infants hospitalised with RSV LRTI by assessing heart rate (vital sign parameters) and changes from baseline
Description
Baseline characteristics will be summarized descriptively by treatment. Quantitative variables will be summarized used the statistics n, mean, standard deviation, median, minimum and maximum.
Time Frame
48 hours post dose 1 (Part A) and 48 hours post dose 10 (Part B)
Title
To evaluate the safety and tolerability of single (Part A) and multiple (Part B) oral doses of RV521 in infants hospitalised with RSV LRTI by assessing pulse oximetry (vital sign parameters) and changes from baseline
Description
Baseline characteristics will be summarized descriptively by treatment. Quantitative variables will be summarized used the statistics n, mean, standard deviation, median, minimum and maximum.
Time Frame
48 hours post dose 1 (Part A) and 48 hours post dose 10 (Part B)
Title
Number of participants with changes in haematology/clinical chemistry/urinalysis laboratory values (laboratory tests read by a central lab) from baseline in Part A and Part B.
Description
Results at each visit will be summarised using the statistics n, mean, standard deviation, median, minimum and maximum. Also, change from baseline will also be summarised by post baseline visits.
Time Frame
48 hours post dose 1 (Part A) and 48 hours post dose 10 (Part B)
Title
Number of participants with changes in ECG measurements from baseline in Part A and Part B
Description
Parameters collected will be: Ventricular Heart Rate (bpm) PR Interval (msec) QRS Interval (msec) QT Interval (msec) QTcB Interval (msec) Results at each visit will be summarised using the statistics: n (number of observations), mean, SD, median, minimum and maximum.
Time Frame
48 hours post dose 1 (Part A) and 48 hours post dose 10 (Part B)
Title
Part C: Evaluate the effect of RV521, compared to placebo, on the clinical course of RSV LRTI using the RSV Clinical Scoring System and the Adapted Version of ReSVinet Scale to show time to resolution of symptoms.
Description
Overall time to resolution of RSV-related signs and symptoms will be calculated from the time of randomization to the time that they are no longer present (absent or severity =0), and will be summarized and analysed as Time to Improvement.
Time Frame
up to 48 hours post dose 10
Title
Part C: Evaluate the effect (efficacy) of RV521, compared to placebo, on the clinical course of RSV LRTI using the RSV Clinical Scoring System and the Adapted Version of ReSVinet Scale to assess time to change of symptoms.
Description
Time to change in symptoms will be calculated for RSV-related signs and symptoms that are classified as moderate or severe during the course of the study and will be defined as the time from randomization until no longer present (absent or severity=0) or mild (scores ≤ 5).
Time Frame
up to 48 hours post dose 10
Title
Part C: Evaluate the effect (efficacy) of RV521, compared to placebo, on the clinical course of RSV LRTI using the RSV Clinical Scoring System and the Adapted Version of ReSVinet Scale to assess change in severity of symptoms
Description
Change in severity of symptoms by RV521, compared to placebo, will be measured by a composite score over time.
Time Frame
up to 48 hours post dose 10
Title
Part C: Evaluate the effect (efficacy) of RV521, compared to placebo, on the clinical course of RSV LRTI using the RSV Clinical Scoring System and the Adapted Version of ReSVinet Scale to assess use of supplemental oxygen.
Description
Duration and maximum level of O2 provided will be assessed.
Time Frame
up to 48 hours post dose 10
Secondary Outcome Measure Information:
Title
To characterise the pharmacokinetics (PK) of single (Part A) and multiple (Part B) oral doses of RV521 in infants hospitalised with RSV LRTI by assessing time to maximum plasma concentration (tmax).
Description
Pharmacokinetic analysis will include listings and summaries of PK concentrations by time point, derived PK, parameters and analysis of relationship with dose and body weight.
Time Frame
48 hours post dose 1 (Part A)
Title
To characterise the pharmacokinetics (PK) of single (Part A) and multiple (Part B) oral doses of RV521 in infants hospitalised with RSV LRTI by assessing maximum observed plasma concentration (Cmax).
Description
Pharmacokinetic analysis will include listings and summaries of PK concentrations by time point, derived PK, parameters and analysis of relationship with dose and body weight.
Time Frame
48 hours post dose 1 (Part A)
Title
To characterise the pharmacokinetics (PK) of single (Part A) and multiple (Part B) oral doses of RV521 in infants hospitalised with RSV LRTI by assessing area under the plasma concentration time curve from time zero to 12 hours (AUC0-12).
Description
Pharmacokinetic analysis will include listings and summaries of PK concentrations by time point, derived PK, parameters and analysis of relationship with dose and body weight.
Time Frame
48 hours post dose 1 (Part A)
Title
To characterise the PK of single (Part A) and multiple (Part B) oral doses of RV521 in infants hospitalised with RSV LRTI by assessing the area under the plasma concentration time curve from time zero to last measurable plasma concentration (AUC0 t).
Description
Pharmacokinetic analysis will include listings and summaries of PK concentrations by time point, derived PK, parameters and analysis of relationship with dose and body weight.
Time Frame
48 hours post dose 1 (Part A)
Title
To characterise the pharmacokinetics (PK) of single (Part A) and multiple (Part B) oral doses of RV521 in infants hospitalised with RSV LRTI by assessing terminal half-life (t1/2).
Description
Pharmacokinetic analysis will include listings and summaries of PK concentrations by time point, derived PK, parameters and analysis of relationship with dose and body weight.
Time Frame
48 hours post dose 1 (Part A)
Title
To characterise the pharmacokinetics (PK) of single (Part A) and multiple (Part B) oral doses of RV521 in infants hospitalised with RSV LRTI by assessing area under the plasma concentration time curve from time zero to infinity (AUC0-∞).
Description
Pharmacokinetic analysis will include listings and summaries of PK concentrations by time point, derived PK, parameters and analysis of relationship with dose and body weight.
Time Frame
48 hours post dose 1 (Part A)
Title
To characterise the pharmacokinetics (PK) of single (Part A) and multiple (Part B) oral doses of RV521 in infants hospitalised with RSV LRTI by assessing predicted plasma clearance.
Description
Pharmacokinetic analysis will include listings and summaries of PK concentrations by time point, derived PK, parameters and analysis of relationship with dose and body weight.
Time Frame
48 hours post dose 1 (Part A)
Title
To characterise the pharmacokinetics (PK) of single (Part A) and multiple (Part B) oral doses of RV521 in infants hospitalised with RSV LRTI by assessing apparent volume of distribution of the drug after extravascular administration (V/F).
Description
Pharmacokinetic analysis will include listings and summaries of PK concentrations by time point, derived PK, parameters and analysis of relationship with dose and body weight.
Time Frame
48 hours post dose 1 (Part A)
Title
To characterise the pharmacokinetics (PK) of single (Part A) and multiple (Part B) oral doses of RV521 in infants hospitalised with RSV LRTI by assessing trough concentration at the end of first dosing interval (C12) (data permitting).
Description
Pharmacokinetic analysis will include listings and summaries of PK concentrations by time point, derived PK, parameters and analysis of relationship with dose and body weight.
Time Frame
48 hours post dose 1 (Part A)
Title
To characterise the pharmacokinetics (PK) of multiple (Part B) oral doses of RV521 in infants hospitalised with RSV LRTI by assessing accumulation ratio, percent fluctuation.
Description
Pharmacokinetic analysis will include listings and summaries of PK concentrations by time point, derived PK, parameters and analysis of relationship with dose and body weight.
Time Frame
48 hours post dose 10
Title
To characterise the pharmacokinetics (PK) of multiple (Part B) oral doses of RV521 in infants hospitalised with RSV LRTI by assessing the area under the plasma concentration time curve from time zero to the end of last dosing interval (AUC0-tau).
Description
Pharmacokinetic analysis will include listings and summaries of PK concentrations by time point, derived PK, parameters and analysis of relationship with dose and body weight.
Time Frame
48 hours post dose 10
Title
To characterise the pharmacokinetics (PK) of multiple (Part B) oral doses of RV521 in infants hospitalised with RSV LRTI by assessing average plasma concentration over dosing interval (Cave).
Description
Pharmacokinetic analysis will include listings and summaries of PK concentrations by time point, derived PK, parameters and analysis of relationship with dose and body weight.
Time Frame
48 hours post dose 10
Title
To characterise the pharmacokinetics (PK) of multiple (Part B) oral doses of RV521 in infants hospitalised with RSV LRTI by assessing minimum observed plasma concentration (Cmin).
Description
Pharmacokinetic analysis will include listings and summaries of PK concentrations by time point, derived PK, parameters and analysis of relationship with dose and body weight.
Time Frame
48 hours post dose 10
Title
To characterise the pharmacokinetics (PK) of multiple (Part B) oral doses of RV521 in infants hospitalised with RSV LRTI by assessing plasma trough concentration (Ctrough).
Description
Pharmacokinetic analysis will include listings and summaries of PK concentrations by time point, derived PK, parameters and analysis of relationship with dose and body weight.
Time Frame
48 hours post dose 10
Title
Part B: To evaluate the antiviral effects of RV521 in infants hospitalised with RSV LRTI by RSV viral load measured in nasopharyngeal swabs by RT qPCR.
Description
Pharmacodynamics analysis will include listing of results of viral load with summary statistics by dose level and time point.
Time Frame
up to 48 hours post dose 10
Title
Part B: To evaluate the antiviral effects of RV521 in infants hospitalised with RSV LRTI by RSV viral load measured in nasopharyngeal swabs by CBIA.
Description
Pharmacodynamics analysis will include listing of results of viral load with summary statistics by dose level and time point.
Time Frame
up to 48 hours post dose 10
Title
Part B: Evaluate the effect of RV521 compared to placebo on the clinical course of RSV LRTI using the RSV Clinical Scoring System and the Adapted Version of ReSVinet Scale to assess time to resolution of symptoms.
Description
Overall Time to Resolution of RSV-related signs and symptoms will be calculated from the time of randomization to the time that they are no longer present (absent or severity =0), and will be summarized and analysed as for Time to Improvement.
Time Frame
48 hours post dose 10
Title
Part B: Evaluate the effect of RV521 compared to placebo on the clinical course of RSV LRTI using the RSV Clinical Scoring System and the Adapted Version of ReSVinet Scale to assess time to improvement evaluated by change in severity of symptoms.
Description
Time to improvement will be calculated for RSV-related signs and symptoms that are classified as moderate or severe during the course of the study and will be defined as the time from randomization until no longer present (absent or severity=0) or mild (scores ≤ 5).
Time Frame
48 hours post dose 10
Title
Part B: Evaluate the effect of RV521 compared to placebo on the clinical course of RSV LRTI using the RSV Clinical Scoring System and the Adapted Version of ReSVinet Scale to assess change in severity of symptoms.
Description
Change in severity of symptoms by RV521, compared to placebo, will be measured by a composite score over time.
Time Frame
48 hours post dose 10

10. Eligibility

Sex
All
Minimum Age & Unit of Time
1 Month
Maximum Age & Unit of Time
36 Months
Accepts Healthy Volunteers
No
Eligibility Criteria
Inclusion Criteria: 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 Exclusion Criteria: 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.
Overall Study Officials:
First Name & Middle Initial & Last Name & Degree
Pfizer CT.gov Call Center
Organizational Affiliation
Pfizer
Official's Role
Study Director
Facility Information:
Facility Name
Hospital Interzonal General de Agudos "Dr. José Penna"
City
Bahia Blanca
State/Province
Buenos Aires
ZIP/Postal Code
B8001DDU
Country
Argentina
Facility Name
Hospital Italiano Regional Del Sur
City
Bahia Blanca
State/Province
Buenos Aires
ZIP/Postal Code
B8001HXM
Country
Argentina
Facility Name
Hospital General de Ninos Pedro de Elizalde
City
Ciudad Autonoma de Buenos Aires
State/Province
Caba
ZIP/Postal Code
C1270AAN
Country
Argentina
Facility Name
Hospital de ninos "Ricardo Gutierrez"
City
Calgary
State/Province
Alberta
ZIP/Postal Code
T2J 7E1
Country
Canada
Facility Name
Hospital de Ninos Dr. Roberto del Rio
City
Santiago
State/Province
Metropolitana
ZIP/Postal Code
8380418
Country
Chile
Facility Name
Hospital Base San Jose Osorno
City
Osorno
State/Province
Region DE LOS Lagos
ZIP/Postal Code
5311523
Country
Chile
Facility Name
Corporacion Gihema
City
San Jose
Country
Costa Rica
Facility Name
Hospital Clinica Biblica
City
San Jose
Country
Costa Rica
Facility Name
Hospital Metropolitano, Sede San Jose
City
San Jose
Country
Costa Rica
Facility Name
lnstituto de lnvestigacion en Ciencias Medicas(IICIMED)
City
San Jose
Country
Costa Rica
Facility Name
Policlinico San Bosco, Consultorio de Pediatria, Dr. Arturo Solis Moya
City
San Jose
Country
Costa Rica
Facility Name
Semmelweis Egyetem 11.sz. Gyermeklinika
City
Budapest
ZIP/Postal Code
1094
Country
Hungary
Facility Name
Eszak-Kozep-budai Centrum,Uj Szent Janos Korhaz es Szakrendelo,Gyermekosztaly
City
Budapest
ZIP/Postal Code
1125
Country
Hungary
Facility Name
Somogy Megyei Kaposi Mor Oktato Korhaz
City
Kaposvar
ZIP/Postal Code
7400
Country
Hungary
Facility Name
Soroka University Medical Center
City
Beer-Sheva
ZIP/Postal Code
84417
Country
Israel
Facility Name
Rambam Health Care Campus
City
Haifa
ZIP/Postal Code
3109601
Country
Israel
Facility Name
Schneider Children's Medical Center of Israel
City
Petach Tikava
ZIP/Postal Code
49202
Country
Israel
Facility Name
Seoul National University Children's Hospital
City
Seoul
ZIP/Postal Code
03080
Country
Korea, Republic of
Facility Name
Department of Pediatrics, SoonchunHyang University Seoul Hospital
City
Seoul
ZIP/Postal Code
04401
Country
Korea, Republic of
Facility Name
Hospital Raja Perempuan Zainab II
City
Kota Bharu
State/Province
Kelantan
ZIP/Postal Code
15586
Country
Malaysia
Facility Name
Hospital Taiping
City
Taiping
State/Province
Perak
ZIP/Postal Code
34000
Country
Malaysia
Facility Name
Hospital Seberang Jaya
City
Seberang Jaya
State/Province
Pulau Pinang
ZIP/Postal Code
13700
Country
Malaysia
Facility Name
Sarawak General Hospital
City
Kuching
State/Province
Sarawak
ZIP/Postal Code
93586
Country
Malaysia
Facility Name
Hospital Sibu
City
Sibu
State/Province
Sarawak
ZIP/Postal Code
96000
Country
Malaysia
Facility Name
Hospital Sultanah Nur Zahirah
City
Kuala Terengganu
State/Province
Terengganu
ZIP/Postal Code
20400
Country
Malaysia
Facility Name
Hospital Seri Manjung
City
Parek
ZIP/Postal Code
32040
Country
Malaysia
Facility Name
Capital and Coast DHB, Wellington Hospital
City
Riddiford Street
State/Province
Wellington
ZIP/Postal Code
6021
Country
New Zealand
Facility Name
Hospital de Especialidades Pediatricas "Omar Torrijos Herrera"
City
Panama
Country
Panama
Facility Name
Hospital del Nino Dr. Jose Renan Esquivel
City
Panama
Country
Panama
Facility Name
Hospital Materno Infantil Jose Domingo de Obaldia
City
Panama
Country
Panama
Facility Name
Uniwersytecki Szpital Dzieciecy w Krakowie
City
Krakow
ZIP/Postal Code
30-663
Country
Poland
Facility Name
lnstytut Centrum Zdrowia Matki Polki Klinika Pediatrii, Immunologii i Nefrologii
City
Lodz
ZIP/Postal Code
93-338
Country
Poland
Facility Name
Samodzielny Publiczny Dzieciecy Szpital Kliniczny w Warszawie Oddzial Kliniczny Pediatrii
City
Warszawa
ZIP/Postal Code
02-091
Country
Poland
Facility Name
Hospital Universitario Sant Joan de Deu
City
Espluges De Llobregat
State/Province
Barcelona
ZIP/Postal Code
08950
Country
Spain
Facility Name
Fundacion Hospital de Nens
City
Barcelona
ZIP/Postal Code
08009
Country
Spain
Facility Name
Clinica Universidad de Navarra
City
Madrid
ZIP/Postal Code
28027
Country
Spain
Facility Name
Hospital Clinico de San carlos
City
Madrid
ZIP/Postal Code
28040
Country
Spain
Facility Name
Hospital Universitario 12 de Octubre
City
Madrid
ZIP/Postal Code
28041
Country
Spain
Facility Name
Hospital Universitario de la Paz ,Pediatric Deparment
City
Madrid
ZIP/Postal Code
28046
Country
Spain
Facility Name
Hospital Universitario La Paz Servicio de Farmacia. Planta baja Edificio Norte
City
Madrid
ZIP/Postal Code
28046
Country
Spain
Facility Name
Clinica Universidad de Navarra
City
Pamplona
ZIP/Postal Code
31008
Country
Spain
Facility Name
Complejo Hospitalario de Santiago
City
Santiago de Compostela
ZIP/Postal Code
15706
Country
Spain
Facility Name
Hsinchu Mackay Memorial Hospital
City
Hsinchu City
ZIP/Postal Code
30071
Country
Taiwan
Facility Name
Hualien Tzu Chi Hospital, Buddhist Tzu Chi Medical Foundation
City
Hualien
ZIP/Postal Code
970
Country
Taiwan
Facility Name
Kaohsiung Veterans General Hospital
City
Kaohsiung City
ZIP/Postal Code
81362
Country
Taiwan
Facility Name
Chi Mei Medical Center
City
Tainan City
ZIP/Postal Code
710
Country
Taiwan
Facility Name
Faculty of Medicine Siriraj Hospital, Mahidol University
City
Bangkoknoi
State/Province
Bangkok
ZIP/Postal Code
10700
Country
Thailand
Facility Name
The Pharmacy Unit Ground Floor, OPD Building Faculty of Madicine,
City
Bangkoknoi
State/Province
Bangkok
ZIP/Postal Code
10700
Country
Thailand
Facility Name
Chula Clinical Research Center, Faculty of Medicine
City
Patumwan
State/Province
Bangkok
ZIP/Postal Code
10330
Country
Thailand
Facility Name
King Chulalongkorn Memorial Hospital, Faculty of Medicine, Chulalongkorn University
City
Bangkok
ZIP/Postal Code
10330
Country
Thailand
Facility Name
QueenSirikit National Institute of Child Health {QSNICH}
City
Bangkok
ZIP/Postal Code
10400
Country
Thailand
Facility Name
Maharaj Nakorn Chiang Mai Hospital,Faculty of Medicine, Chiang Mai University
City
Chiang Mai
ZIP/Postal Code
50200
Country
Thailand
Facility Name
Chiangrai Prachanukroh Hospital
City
Chiangrai
ZIP/Postal Code
57000
Country
Thailand
Facility Name
Faculty of Medicine, Khon Kaen University
City
khon Kaen
ZIP/Postal Code
40002
Country
Thailand
Facility Name
Srinagarind Hospital, Faculty of Medicine, Khon Kaen University
City
Khon Kaen
ZIP/Postal Code
40002
Country
Thailand
Facility Name
Naresuan University Hospital ,Faculty of Medicine, Naresuan University
City
Phitsanulok
ZIP/Postal Code
65000
Country
Thailand
Facility Name
Alder Hey Children's NHS Foundation Trust Institute in the Park
City
Liverpool
ZIP/Postal Code
L 12 2AP
Country
United Kingdom
Facility Name
Guy's and St Thomas' NHS Foundation Trust Evelina London Children's Hospital Westminster
City
London
ZIP/Postal Code
SE1 7EH
Country
United Kingdom
Facility Name
Imperial College Healthcare NHS Trust St Mary's Hospital
City
London
ZIP/Postal Code
W2 1NY
Country
United Kingdom
Facility Name
University Hospital Southampton NHS Foundation Trust NIHR Clinical Research Facility ,Mailpoint 218,
City
Southampton
ZIP/Postal Code
SO16 6YD
Country
United Kingdom

12. IPD Sharing Statement

Plan to Share IPD
Yes
IPD Sharing Plan Description
Pfizer will provide access to individual de-identified participant data and related study documents (e.g. protocol, Statistical Analysis Plan (SAP), Clinical Study Report (CSR)) upon request from qualified researchers, and subject to certain criteria, conditions, and exceptions. Further details on Pfizer's data sharing criteria and process for requesting access can be found at: https://www.pfizer.com/science/clinical_trials/trial_data_and_results/data_requests.
IPD Sharing URL
https://www.pfizer.com/science/clinical_trials/trial_data_and_results/data_requests
Links:
URL
https://pmiform.com/clinical-trial-info-request?StudyID=REVC003
Description
To obtain contact information for a study center near you, click here.

Learn more about this trial

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

We'll reach out to this number within 24 hrs