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

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

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.

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.