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

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)

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

Study Overview

• Status: Terminated
• Conditions: Lower Resp Tract Infection; Respiratory Syncytial Virus (RSV)
• Intervention / Treatment: Drug: RV521; Drug: Placebo

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.

• Study Type: Interventional
• Enrollment (Actual): 51
• Phase: Phase 2

Contacts and Locations

Study Locations

• Argentina
  • Buenos Aires
    • Bahia Blanca, Buenos Aires, Argentina, B8001HXM
      • Hospital Italiano Regional del Sur
    • Bahia Blanca, Buenos Aires, Argentina, B8001DDU
      • Hospital Interzonal General de Agudos "Dr. José Penna"
  • Caba
    • Ciudad Autonoma de Buenos Aires, Caba, Argentina, C1270AAN
      • Hospital General de Niños Pedro de Elizalde
• Canada
  • Alberta
    • Calgary, Alberta, Canada, T2J 7E1
      • Hospital de ninos "Ricardo Gutierrez"
• Chile
  • Metropolitana
    • Santiago, Metropolitana, Chile, 8380418
      • Hospital de Ninos Dr. Roberto del Rio
  • Region DE LOS Lagos
    • Osorno, Region DE LOS Lagos, Chile, 5311523
      • Hospital Base San José Osorno
• Costa Rica
  • San Jose, Costa Rica
    • Hospital Clínica Bíblica
  • San Jose, Costa Rica
    • Corporacion Gihema
  • 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
• Hungary
  • Budapest, Hungary, 1094
    • Semmelweis Egyetem 11.sz. Gyermeklinika
  • Budapest, Hungary, 1125
    • Eszak-Kozep-budai Centrum,Uj Szent Janos Korhaz es Szakrendelo,Gyermekosztaly
  • Kaposvar, Hungary, 7400
    • Somogy Megyei Kaposi Mor Oktato Korhaz
• Israel
  • Beer-Sheva, Israel, 84417
    • Soroka University Medical Center
  • Haifa, Israel, 3109601
    • Rambam Health Care Campus
  • Petach Tikava, Israel, 49202
    • Schneider Children's Medical Center of Israel
• Korea, Republic of
  • Seoul, Korea, Republic of, 03080
    • Seoul National University Children's Hospital
  • Seoul, Korea, Republic of, 04401
    • Department of Pediatrics, SoonchunHyang University Seoul Hospital
• Malaysia
  • Parek, Malaysia, 32040
    • Hospital Seri Manjung
  • Kelantan
    • Kota Bharu, Kelantan, Malaysia, 15586
      • Hospital Raja Perempuan Zainab II
  • Perak
    • Taiping, Perak, Malaysia, 34000
      • Hospital Taiping
  • Pulau Pinang
    • Seberang Jaya, Pulau Pinang, Malaysia, 13700
      • Hospital Seberang Jaya
  • Sarawak
    • Kuching, Sarawak, Malaysia, 93586
      • Sarawak General Hospital
    • Sibu, Sarawak, Malaysia, 96000
      • Hospital Sibu
  • Terengganu
    • Kuala Terengganu, Terengganu, Malaysia, 20400
      • Hospital Sultanah Nur Zahirah
• New Zealand
  • Wellington
    • Riddiford Street, Wellington, New Zealand, 6021
      • Capital and Coast DHB, Wellington Hospital
• Panama
  • Panama, 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
• Poland
  • Krakow, Poland, 30-663
    • Uniwersytecki Szpital Dzieciecy w Krakowie
  • Lodz, Poland, 93-338
    • lnstytut Centrum Zdrowia Matki Polki Klinika Pediatrii, Immunologii i Nefrologii
  • Warszawa, Poland, 02-091
    • Samodzielny Publiczny Dzieciecy Szpital Kliniczny w Warszawie Oddzial Kliniczny Pediatrii
• Spain
  • Barcelona, Spain, 08009
    • Fundacion Hospital de Nens
  • Madrid, Spain, 28041
    • Hospital Universitario 12 de Octubre
  • Madrid, Spain, 28027
    • Clinica Universidad de Navarra
  • Madrid, Spain, 28040
    • Hospital Clinico de San Carlos
  • Madrid, Spain, 28046
    • Hospital Universitario de la Paz ,Pediatric Deparment
  • Madrid, Spain, 28046
    • Hospital Universitario La Paz Servicio de Farmacia. Planta baja Edificio Norte
  • Pamplona, Spain, 31008
    • Clinica Universidad de Navarra
  • Santiago de Compostela, Spain, 15706
    • Complejo Hospitalario de Santiago
  • Barcelona
    • Espluges De Llobregat, Barcelona, Spain, 08950
      • Hospital Universitario Sant Joan de Deu
• Taiwan
  • Hsinchu City, Taiwan, 30071
    • HsinChu MacKay Memorial Hospital
  • Hualien, Taiwan, 970
    • Hualien Tzu Chi Hospital, Buddhist Tzu Chi Medical Foundation
  • Kaohsiung City, Taiwan, 81362
    • Kaohsiung Veterans General Hospital
  • Tainan City, Taiwan, 710
    • Chi Mei Medical Center
• Thailand
  • Bangkok, Thailand, 10330
    • King Chulalongkorn Memorial Hospital, Faculty of Medicine, Chulalongkorn University
  • Bangkok, Thailand, 10400
    • QueenSirikit National Institute of Child Health {QSNICH}
  • Chiang Mai, Thailand, 50200
    • Maharaj Nakorn Chiang Mai Hospital,Faculty of Medicine, Chiang Mai University
  • Chiangrai, Thailand, 57000
    • Chiangrai Prachanukroh Hospital
  • Khon Kaen, Thailand, 40002
    • Srinagarind Hospital, Faculty of Medicine, Khon Kaen University
  • Phitsanulok, Thailand, 65000
    • Naresuan University Hospital ,Faculty of Medicine, Naresuan University
  • khon Kaen, Thailand, 40002
    • Faculty Of Medicine, Khon Kaen University
  • Bangkok
    • Bangkoknoi, Bangkok, Thailand, 10700
      • Faculty of Medicine Siriraj Hospital, Mahidol University
    • Bangkoknoi, Bangkok, Thailand, 10700
      • The Pharmacy Unit Ground Floor, OPD Building Faculty of Madicine,
    • Patumwan, Bangkok, Thailand, 10330
      • Chula Clinical Research Center, Faculty of Medicine
• United Kingdom
  • Liverpool, United Kingdom, L 12 2AP
    • Alder Hey Children's NHS Foundation Trust Institute in the Park
  • London, United Kingdom, W2 1NY
    • Imperial College Healthcare NHS Trust St Mary's Hospital
  • London, United Kingdom, SE1 7EH
    • Guy's and St Thomas' NHS Foundation Trust Evelina London Children's Hospital Westminster
  • Southampton, United Kingdom, SO16 6YD
    • University Hospital Southampton NHS Foundation Trust NIHR Clinical Research Facility ,Mailpoint 218,

Participation Criteria

Eligibility Criteria

• Ages Eligible for Study: 3 years to 5 months (Child)
• Accepts Healthy Volunteers: No

Description

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.

Study Plan

How is the study designed?

Design Details

• Primary Purpose: Treatment
• Allocation: Randomized
• Interventional Model: Sequential Assignment
• Masking: Triple

Number of Arms

2

Arms and Interventions

Participant Group / Arm	Intervention / Treatment
Experimental: RV521; 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; RV521 is an RSV F protein inhibitor administered orally; Other Names: sisunatovir
Placebo Comparator: Placebo; 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; vehicle administered orally

What is the study measuring?

Primary Outcome Measures

Outcome Measure	Measure Description	Time Frame
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 Outcome Measures

Outcome Measure	Measure Description	Time Frame
Part A: Time to Maximum Plasma Concentration (Tmax)	No sampling was done at pre-dose (0 hour) and pre-dose results were imputed for all participants in the Pharmacokinetic (PK) population.	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)	No sampling was done at pre-dose (0 hour) on Day 1 and pre-dose results were imputed for all participants in the PK population.	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)	No sampling was done at pre-dose (0 hour) and pre-dose results were imputed for all participants in the PK population.	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)	No sampling was done at pre-dose (0 hour) on Day 1 and pre-dose results were imputed for all participants in the PK population.	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)	AUC(0 to 12) was calculated using the linear trapezoidal method. No sampling was done at pre-dose (0 hour) and pre-dose results were imputed for all participants in the PK population.	Anytime between 4 to 5 hours, anytime between 6 to 8 hours, 12 hours post-dose on Day 1
Part B: Area Under the Plasma Concentration Time Curve From Time Zero to 12 Hours (AUC0-12)	AUC(0 to 12) was calculated using the linear trapezoidal method. No sampling was done at pre-dose (0 hour) on Day 1 and pre-dose results were imputed for all participants in the PK population.	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 0 to the Last Measurable Concentration (AUC[0 to t])	Area under the plasma concentration-time curve from time 0 to the last measurable concentration was determined using the linear trapezoidal method. No sampling was done at pre-dose (0 hour) and pre-dose results were imputed for all participants in the PK population.	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: Area Under the Plasma Concentration-Time Curve From Time 0 to the Last Measurable Concentration (AUC[0 to t])	Area under the plasma concentration-time curve from time 0 to the last measurable concentration was determined using the linear trapezoidal method. No sampling was done at pre-dose (0 hour) on Day 1 and pre-dose results were imputed for all participants in the PK population.	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: Terminal Half-life (t1/2)	T1/2 was calculated as loge (2) divided by kel, where kel is the terminal phase rate constant calculated by a linear regression of the log-linear concentration-time curve. No sampling was done at pre-dose (0 hour) on Day 1 and pre-dose results were imputed for all participants in the PK population.	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: Terminal Half-life (t1/2)	T1/2 was calculated as loge (2) divided by kel, where kel is the terminal phase rate constant calculated by a linear regression of the log-linear concentration-time curve. No sampling was done at pre-dose (0 hour) on Day 1 and pre-dose results were imputed for all participants in the PK population.	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 Infinity (AUC0 to Inf)	AUCinf was determined as AUC(0 to t) + (Clast/kel), where Clast was the plasma concentration at the last quantifiable timepoint estimated from the log-linear regression analysis and kel was the terminal phase rate. No sampling was done at pre-dose (0 hour) and pre-dose results were imputed for all participants in the PK population.	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: Area Under the Plasma Concentration Time Curve From Time Zero to Infinity (AUC0 to Inf)	AUCinf was determined as AUC(0 to t) + (Clast/kel), where Clast was the plasma concentration at the last quantifiable timepoint estimated from the log-linear regression analysis and kel was the terminal phase rate. No sampling was done at pre-dose (0 hour) on Day 1 and pre-dose results were imputed for all participants in the PK population.	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: Trough Concentration at the End of First Dosing Interval (C12)		At 12 hours post-dose on Day 1
Part B: Trough Concentration at the End of Dose 6 (C12)		At 12 hours post-dose 6
Part A: Predicted Plasma Clearance	Clearance was calculated as Dose divided by AUC(0 to inf). No sampling was done at pre-dose (0 hour) and pre-dose results were imputed for all participants in the PK population.	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: Predicted Plasma Clearance	Clearance was calculated as Dose divided by AUC(0 to inf). No sampling was done at pre-dose (0 hour) on Day 1 and pre-dose results were imputed for all participants in the PK population.	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: Apparent Volume of Distribution of the Drug After Extravascular Administration	Apparent volume of distribution was estimated as Dose/Kel*AUC(0 to inf), where Kel=apparent first-order terminal elimination rate constant. No sampling was done at pre-dose (0 hour) and pre-dose results were imputed for all participants in the PK population.	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: Apparent Volume of Distribution of the Drug After Extravascular Administration	Apparent volume of distribution was estimated as Dose/Kel*AUC(0 to inf), where Kel=apparent first-order terminal elimination rate constant. No sampling was done at pre-dose (0 hour) on Day 1 and pre-dose results were imputed for all participants in the PK population.	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 B: Accumulation Ratio	Accumulation ratio was calculated as ratio of the area under the curve (AUC) during a single dosing interval under steady state conditions to the AUC during a dosing interval after one singe dose. No sampling was done at pre-dose (0 hour) on Day 1 and pre-dose results were imputed for all participants in the PK population.	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 B: Percentage Fluctuation	Percentage fluctuation was calculated as 100*(Cmax-Cmin)/Cavg, where Cmin=minimum plasma concentration and Cmax measured over dosing interval.	Day 3 Dose 6 (pre-dose, anytime between 4 to 5 hours post-dose, 12 hours post-dose)
Part B: Area Under the Plasma Concentration Time Curve From Time Zero to the End of Last Dosing Interval (AUC0-tau)	AUC(0 to tau) was determined using the linear trapezoidal method.	Day 3 Dose 6 (pre-dose, anytime between 4 to 5 hours post-dose, 12 hours post-dose)
Part B: Average Plasma Concentration Over Dosing Interval (Cavg)	Cavg was estimated as AUC(0 to tau)/tau, where tau=dosing interval (12 hours).	Day 3 Dose 6 (pre-dose, anytime between 4 to 5 hours post-dose, 12 hours post-dose)
Part B: Minimum Observed Plasma Concentration		Day 3 Dose 6 (pre-dose)
Part B: Plasma Trough Concentration		Day 3 Dose 6 (pre-dose)
Part B: Percent Change From Baseline in Logarithm to Base10 (Log10) Total RSV Viral Load by Quantitative Reverse Transcription Polymerase Chain Reaction (RT-qPCR)	Percent change from baseline in log10 total RSV viral load was analyzed using a mixed effects analysis of covariance (ANCOVA) model. The model was fitted to the participants treated at the final doses selected for Cohort 5 as pre-planned in statistical analysis plan for age group >=1 month to <6 months.	Baseline (pre-dose on Day 1), 60 hours and 156 hours after first dose on Day 1
Part B: Percent Change From Baseline in Logarithm to Base10 (Log10) Total RSV Viral Load by Cell-Based Infectivity Assay (CBIA)	Percent change from baseline in log10 total RSV viral load was analyzed using a mixed effects ANCOVA model. The model was fitted to the participants treated at the final doses selected for Cohort 5 as pre-planned in statistical analysis plan for age group >=1 month to <6 months.	Baseline (pre-dose on Day 1), 60 hours and 156 hours after first dose on Day 1
Part B: Time to Resolution of RSV-Related Signs and Symptoms	Time to resolution was calculated for RSV-related signs and symptoms that were present at study start and was defined as the time of randomization to the time that RSV-related signs and symptoms were absent.	Up to Day 12
Part B: Time to Improvement in RSV-Related Signs and Symptoms	Time to improvement was calculated for RSV-related signs and symptoms that were classified as moderate or severe during the course of the study and was defined as the time from randomization to the time that RSV-related signs and symptoms were mild or absent.	Up to Day 12
Part B: RSV Clinical Scoring System Scores	RSV clinical score was a composite score for infants with RSV infection >= 1 month of age based on 4 items (respiratory rate, wheezing, retraction of respiratory muscles and general condition). Score for each item ranged from 0 to 3 where 0=none/normal and 3=severe. Total score was calculated as sum of individual items and ranged from 0 to 12, where higher score indicated severe disease. RSV symptoms were graded as mild: score <=5, moderate: score > 5 but < 9 and severe: score >=9.	Baseline (pre-dose 1 on Day 1), pre-dose 3, pre-dose 5, pre-dose 7, pre-dose 9, anytime between 40 to 48 hours post-dose 10 on Day 5

Collaborators and Investigators

• Sponsor: Pfizer
• Investigators: Study Director: Pfizer CT.gov Call Center, Pfizer

Publications and helpful links

Helpful Links

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

Study record dates

Study Major Dates

• Study Start (Actual): November 13, 2019
• Primary Completion (Actual): December 5, 2022
• Study Completion (Actual): December 5, 2022

Study Registration Dates

• First Submitted: December 11, 2019
• First Submitted That Met QC Criteria: January 8, 2020
• First Posted (Actual): January 13, 2020

Study Record Updates

• Last Update Posted (Actual): October 23, 2024
• Last Update Submitted That Met QC Criteria: August 2, 2024
• Last Verified: August 1, 2024

More Information

Terms related to this study

• Keywords: Children; Pediatrics; Cough; Wheezing; LRTI; Rhinitis; RV521; sisunatovir
• Additional Relevant MeSH Terms: Pathologic Processes; Disease Attributes; Respiratory Tract Diseases; Infections; Communicable Diseases; Respiratory Tract Infections
• Other Study ID Numbers: REVC003; C5241003 (Other Identifier: Alias Study Number)

Plan for Individual participant data (IPD)

• Plan to Share Individual Participant Data (IPD)?: YES
• IPD 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.

Drug and device information, study documents

• Studies a U.S. FDA-regulated drug product: No
• Studies a U.S. FDA-regulated device product: No