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

Respiratory Syncytial Virus (RSV) Clinical Trial

— 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)

Clinical Trial Details — Status: Terminated

Administrative data

• NCT number: NCT04225897
• Other study ID #: REVC003
• Secondary ID: C5241003
• Status: Terminated
• Phase: Phase 2
• Start date: November 13, 2019
• Est. completion date: December 5, 2022

Study information

• Verified date: June 2023
• Source: Pfizer
• Contact: n/a
• Is FDA regulated: No
• Study type: Interventional

Clinical Trial 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

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 information / eligibility

• Status: Terminated
• Enrollment: 51
• Est. completion date: December 5, 2022
• Est. primary completion date: December 5, 2022
• Accepts healthy volunteers: No
• Gender: All
• Age group: 1 Month to 36 Months

Eligibility

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.

Related Conditions & MeSH terms

• Communicable Diseases
• Infections
• Lower Resp Tract Infection
• Respiratory Syncytial Virus (RSV)
• Respiratory Tract Infections

Intervention

Drug:
• RV521
RV521 is an RSV F protein inhibitor administered orally
• Placebo
vehicle administered orally

Locations

Country	Name	City	State
Argentina	Hospital Interzonal General de Agudos "Dr. José Penna"	Bahia Blanca	Buenos Aires
Argentina	Hospital Italiano Regional Del Sur	Bahia Blanca	Buenos Aires
Argentina	Hospital General de Ninos Pedro de Elizalde	Ciudad Autonoma de Buenos Aires	Caba
Canada	Hospital de ninos "Ricardo Gutierrez"	Calgary	Alberta
Chile	Hospital Base San Jose Osorno	Osorno	Region DE LOS Lagos
Chile	Hospital de Ninos Dr. Roberto del Rio	Santiago	Metropolitana
Costa Rica	Corporacion Gihema	San Jose
Costa Rica	Hospital Clinica Biblica	San Jose
Costa Rica	Hospital Metropolitano, Sede San Jose	San Jose
Costa Rica	lnstituto de lnvestigacion en Ciencias Medicas(IICIMED)	San Jose
Costa Rica	Policlinico San Bosco, Consultorio de Pediatria, Dr. Arturo Solis Moya	San Jose
Hungary	Eszak-Kozep-budai Centrum,Uj Szent Janos Korhaz es Szakrendelo,Gyermekosztaly	Budapest
Hungary	Semmelweis Egyetem 11.sz. Gyermeklinika	Budapest
Hungary	Somogy Megyei Kaposi Mor Oktato Korhaz	Kaposvar
Israel	Soroka University Medical Center	Beer-Sheva
Israel	Rambam Health Care Campus	Haifa
Israel	Schneider Children's Medical Center of Israel	Petach Tikava
Korea, Republic of	Department of Pediatrics, SoonchunHyang University Seoul Hospital	Seoul
Korea, Republic of	Seoul National University Children's Hospital	Seoul
Malaysia	Hospital Raja Perempuan Zainab II	Kota Bharu	Kelantan
Malaysia	Hospital Sultanah Nur Zahirah	Kuala Terengganu	Terengganu
Malaysia	Sarawak General Hospital	Kuching	Sarawak
Malaysia	Hospital Seri Manjung	Parek
Malaysia	Hospital Seberang Jaya	Seberang Jaya	Pulau Pinang
Malaysia	Hospital Sibu	Sibu	Sarawak
Malaysia	Hospital Taiping	Taiping	Perak
New Zealand	Capital and Coast DHB, Wellington Hospital	Riddiford Street	Wellington
Panama	Hospital de Especialidades Pediatricas "Omar Torrijos Herrera"	Panama
Panama	Hospital del Nino Dr. Jose Renan Esquivel	Panama
Panama	Hospital Materno Infantil Jose Domingo de Obaldia	Panama
Poland	Uniwersytecki Szpital Dzieciecy w Krakowie	Krakow
Poland	lnstytut Centrum Zdrowia Matki Polki Klinika Pediatrii, Immunologii i Nefrologii	Lodz
Poland	Samodzielny Publiczny Dzieciecy Szpital Kliniczny w Warszawie Oddzial Kliniczny Pediatrii	Warszawa
Spain	Fundacion Hospital de Nens	Barcelona
Spain	Hospital Universitario Sant Joan de Deu	Espluges De Llobregat	Barcelona
Spain	Clinica Universidad de Navarra	Madrid
Spain	Hospital Clinico de San carlos	Madrid
Spain	Hospital Universitario 12 de Octubre	Madrid
Spain	Hospital Universitario de la Paz ,Pediatric Deparment	Madrid
Spain	Hospital Universitario La Paz Servicio de Farmacia. Planta baja Edificio Norte	Madrid
Spain	Clinica Universidad de Navarra	Pamplona
Spain	Complejo Hospitalario de Santiago	Santiago de Compostela
Taiwan	Hsinchu Mackay Memorial Hospital	Hsinchu City
Taiwan	Hualien Tzu Chi Hospital, Buddhist Tzu Chi Medical Foundation	Hualien
Taiwan	Kaohsiung Veterans General Hospital	Kaohsiung City
Taiwan	Chi Mei Medical Center	Tainan City
Thailand	King Chulalongkorn Memorial Hospital, Faculty of Medicine, Chulalongkorn University	Bangkok
Thailand	QueenSirikit National Institute of Child Health {QSNICH}	Bangkok
Thailand	Faculty of Medicine Siriraj Hospital, Mahidol University	Bangkoknoi	Bangkok
Thailand	The Pharmacy Unit Ground Floor, OPD Building Faculty of Madicine,	Bangkoknoi	Bangkok
Thailand	Maharaj Nakorn Chiang Mai Hospital,Faculty of Medicine, Chiang Mai University	Chiang Mai
Thailand	Chiangrai Prachanukroh Hospital	Chiangrai
Thailand	Faculty of Medicine, Khon Kaen University	khon Kaen
Thailand	Srinagarind Hospital, Faculty of Medicine, Khon Kaen University	Khon Kaen
Thailand	Chula Clinical Research Center, Faculty of Medicine	Patumwan	Bangkok
Thailand	Naresuan University Hospital ,Faculty of Medicine, Naresuan University	Phitsanulok
United Kingdom	Alder Hey Children's NHS Foundation Trust Institute in the Park	Liverpool
United Kingdom	Guy's and St Thomas' NHS Foundation Trust Evelina London Children's Hospital Westminster	London
United Kingdom	Imperial College Healthcare NHS Trust St Mary's Hospital	London
United Kingdom	University Hospital Southampton NHS Foundation Trust NIHR Clinical Research Facility ,Mailpoint 218,	Southampton

Sponsors (1)

Lead Sponsor	Collaborator
Pfizer

Countries where clinical trial is conducted

Argentina,  Canada,  Chile,  Costa Rica,  Hungary,  Israel,  Korea, Republic of,  Malaysia,  New Zealand,  Panama,  Poland,  Spain,  Taiwan,  Thailand,  United Kingdom, 

Outcome

Type	Measure	Description	Time frame	Safety issue
Primary	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.	48 hours post dose 1 (Part A) and 48 hours post dose 10 (Part B)
Primary	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.	48 hours post dose 1 (Part A) and 48 hours post dose 10 (Part B)
Primary	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.	48 hours post dose 1 (Part A) and 48 hours post dose 10 (Part B)
Primary	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.	48 hours post dose 1 (Part A) and 48 hours post dose 10 (Part B)
Primary	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.	48 hours post dose 1 (Part A) and 48 hours post dose 10 (Part B)
Primary	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.	48 hours post dose 1 (Part A) and 48 hours post dose 10 (Part B)
Primary	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.	48 hours post dose 1 (Part A) and 48 hours post dose 10 (Part B)
Primary	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.	48 hours post dose 1 (Part A) and 48 hours post dose 10 (Part B)
Primary	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.	48 hours post dose 1 (Part A) and 48 hours post dose 10 (Part B)
Primary	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.	48 hours post dose 1 (Part A) and 48 hours post dose 10 (Part B)
Primary	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.	up to 48 hours post dose 10
Primary	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).	up to 48 hours post dose 10
Primary	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.	up to 48 hours post dose 10
Primary	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.	up to 48 hours post dose 10
Secondary	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.	48 hours post dose 1 (Part A)
Secondary	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.	48 hours post dose 1 (Part A)
Secondary	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.	48 hours post dose 1 (Part A)
Secondary	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.	48 hours post dose 1 (Part A)
Secondary	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.	48 hours post dose 1 (Part A)
Secondary	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 (AUC0-8).	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.	48 hours post dose 1 (Part A)
Secondary	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.	48 hours post dose 1 (Part A)
Secondary	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.	48 hours post dose 1 (Part A)
Secondary	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.	48 hours post dose 1 (Part A)
Secondary	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.	48 hours post dose 10
Secondary	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.	48 hours post dose 10
Secondary	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.	48 hours post dose 10
Secondary	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.	48 hours post dose 10
Secondary	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.	48 hours post dose 10
Secondary	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.	up to 48 hours post dose 10
Secondary	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.	up to 48 hours post dose 10
Secondary	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.	48 hours post dose 10
Secondary	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).	48 hours post dose 10
Secondary	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.	48 hours post dose 10

External Links

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