Respiratory Syncytial Virus Infection MedDRA version: 21.1 Level: PT Classification code 10061603 Term: Respiratory syncytial virus infection System Organ Class: 10021881 - Infections and infestations
Conditions
Interventions
Product Name: Sisunatovir
Product Code: RV521
Pharmaceutical Form: Powder for oral solution
INN or Proposed INN: Sisunatovir
CAS Number: 1903763-83-6
Current Sponsor code: RV521
Other descriptive name
Sponsors
ReViral Ltd.
Eligibility
Sex/Gender
All
Inclusion criteria
Inclusion criteria: 1. Male or female = 1 month and = 36 months of age 2. Weight = 3.5 kg 3. Clinical diagnosis of LRTI defined by a. Evidence of respiratory infection by one or both of the following with or without fever: i. Rhinitis/coryza ii. Cough AND b. Evidence of LRTI by the presence of one or more of the following: i. Increased respiratory rate PLUS other evidence of lower respiratory tract disease (eg, laboratory or radiographic evidence). ii. Increased respiratory effort as evidenced by one or more of the following: 1. Grunting with expiration 2. Nasal flaring 3. Retraction: intercostal or subcostal iii. Wheezing: audible or on chest auscultation 4. A positive RSV diagnostic test (RSV infection confirmed either according to routine site practice [polymerase chain reaction or diagnostic quick test], or using a [Sponsor-provided] commercial kit. 5. Hospitalised because of RSV LRTI (bronchiolitis or bronchopneumonia) 6. For Part B, symptoms of LRTI must be present for no more than 1 week before the Screening Visit, with the first day of symptoms counting as Day 1. 7. For Part C, symptoms of LRTI must be present for no more than 5 days prior to the Screening Visit, with the first day of symptoms counting as Day 1. 8. Expected to remain in hospital for a minimum of 3 days (administration of 6 doses for both Parts B and C) 9. The parent(s)/legal guardian(s) of the subject have provided written informed consent for the subject to participate 10. The parent(s)/legal guardian(s) are able and willing to comply with the study protocol Are the trial subjects under 18? yes Number of subjects for this age range: 184 F.1.2 Adults (18-64 years) no F.1.2.1 Number of subjects for this age range F.1.3 Elderly (>=65 years) no F.1.3.1 Number of subjects for this age range
Exclusion criteria
Exclusion criteria: 1. Premature (gestational age less than 37 weeks) AND 10 days during upper respiratory infections b. > 3 wheezing episodes per year (during the previous 12 months) or severe episodes and/or night wheezing c. Between episodes, child has cough, wheeze, or heavy breathing during play or when laughing d. Atopy or family history of asthma in a first degree relative 7. Suspected of having a clinically significant bacterial infection as indicated by symptoms or laboratory findings consistent with a bacterial infection including but not limited to: elevated white blood cell count, elevated C-reactive protein, chest X-ray consistent with bacterial pneumonia, unstable vital signs, hypotension, or evidence of shock or poor perfusion. 8. Has significant oral and/or maxillofacial malformations that would limit the ability to administer IMP. 9. History of renal failure including renal anomalies likely to be associated with renal insufficiency (eg, clinical conditions of renal dysplasia, polycystic renal disease, renal agenesis) 10. Clinical evidence of hepatic decompensation (eg, hepatic disorder with associated coagulopathy or associated encephalopathy) or significantly elevated liver enzymes (aspartate aminotransferase [AST] and/or alanine aminotransferase [ALT] >3 × the upper limit of normal) 11. History of epilepsy or seizures, including febrile seizures 12. Allergy to test medication or constituents 13. Requires any prohibited medication/therapy as listed in the body of the protocol. a. Receiving treatment with inhaled, oral, or IV corticosteroids and requires continued corticosteroid therapy b. Has taken within 21 days before dosing, any drug that could impact by any mechanism of action on the PK of the investigational product including any substrates, inducers, inhibitors of CYP3A4 and/or Pglycoprotein (P-gp); or the use of prescription medications, over-thecounter (OTC) medications, herbal remedies or dietary supplements containing St. John's Wort, or the consumption of drugs or other substances (eg, grapefruit, Seville oranges, or cranberry juice-containing products) known to be potent inhibitors or inducers of CYP P450s. c. Requires the use of Heliox, Leukotriene receptor antagonist (eg, Montelukast, exogenous surfactant, mucolytics or Hypertonic saline [allowed in the Part A of the study]). 14. Has received 1 or more doses of palivizumab at any time before Screening
Design outcomes
Primary
| Measure | Time frame |
|---|---|
| Main Objective: To evaluate the safety and tolerability of single (Part A) and multiple (Part B) oral doses of RV521 in infants hospitalised with Respiratory Syncytial Virus (RSV) lower respiratory tract infection (LRTI) Part C: Evaluate the effect of RV521, compared to placebo, on the clinical course of RSV LRTI;Secondary Objective: To characterise the pharmacokinetics (PK) of single (Part A) and multiple (Part B) oral doses of RV521 in infants hospitalised with RSV LRTI. To evaluate the antiviral effects of RV521 in infants hospitalised with RSV LRTI. Part B: To evaluate the antiviral effects of RV521 in infants hospitalised with RSV LRTI Part B: Evaluate the effect of RV521 compared to placebo on the clinical course of RSV infection Part C: Evaluate the safety of RV521 given as a multiple dose regimen Part C: Effect of RV521, compared to placebo, on nasopharyngeal shedding of RSV Part C: To evaluate the PK and PK-PD relationship through correlation of RV521 plasma levels with changes in viral load after repeated oral dosing Part C: Comparison between RV521 and placebo on the development of viral mutations associated with in vitro resistance;Primary end point(s): Safety and tolerability parameters to be assessed will include, but are not limited to: ? Adverse events (AEs), treatment-emergent AEs (TEAEs), serious AEs (SAEs), and withdrawals due to TEAEs ? Physical examinations ? Vital sign parameters (ie, systolic and diastolic blood pressure [BP], temperature, respiration rate [RR], heart rate [HR], and pulse oximetry), and changes from baseline in these parameters at predefined time points ? Laboratory tests (haematology, chemistry, and urinalysis test results) and changes from baseline in these parameters, at predefined time points ? Electrocardiogram (ECG) measurements and changes from baseline in these parameters at predefined time points Part C: Time to resolution of symptoms Time to improvement of symptoms Reduction in severity of symptoms by RV521, compar | — |
Secondary
| Measure | Time frame |
|---|---|
| Secondary end point(s): Secondary endpoints related to PK will include but are not limited to: ? Time to maximum plasma concentration (tmax) ? Maximum observed plasma concentration(Cmax) ? Area under the plasma concentration time curve from time zero to 12 hours (AUC0-12) ? Area under the plasma concentration time curve from time zero to last measurable plasma concentration (AUC0-t) ? Terminal half-life (t1/2) ? Area under the plasma concentration time curve from time zero to infinity (AUC0-8) ? Predicted plasma clearance ? Apparent volume of distribution of the drug after extravascular administration (V/F) ? Trough concentration at the end of first dosing interval (C12) (data permitting) In addition for Part B: ? Accumulation ratio, percent fluctuation ? Area under the plasma concentration time curve from time zero to the end of last dosing interval (AUC0-tau) ? Average plasma concentration over dosing interval (Cave) ? Minimum observed plasma concentration (Cmin) ? Plasma trough concentration (Ctrough) ? Any other relevant parameters Secondary endpoints related to assessment of antiviral activity and efficacy in Part B include but are not limited to: ? RSV viral load measured in nasopharyngeal swabs by quantitative reverse transcription polymerase chain reaction (RT-qPCR) ? RSV viral load measured in nasopharyngeal swabs by cell-based infectivity assay (CBIA) Secondary endpoints related to assessment of the effect of RV521 compared to placebo on the clinical course of RSV infection: Time to resolution of symptoms Time to improvement evaluated by reduction in severity of symptoms Reduction in severity of symptoms by RV521, compared to placebo, measured by a composite score over time Secondary endpoints of Part C: Safety of RV521 compared to placebo assessed by incidences of AEs, discontinuations due to AEs, SAEs, and clinically significant changes in clinical laboratory tests Comparison between RV521 and placebo for changes in viral load over time as for Part B C | — |
Countries
Argentina, Chile, Costa Rica, Hungary, Malaysia, New Zealand, Panama, Poland, Spain, Taiwan, Thailand, United States
Contacts
Public ContactMary Luz Aparicio
Syneos Health
Outcome results
None listed