INFLUENZA MedDRA version: 20.0 Level: LLT Classification code 10016790 Term: Flu System Organ Class: 100000004862 MedDRA version: 20.0 Level: LLT Classification code 10022001 Term: Influenza (epidemic) System Organ Class: 100000004862 MedDRA version: 20.1 Level: LLT Classification code 1
Conditions
Interventions
Product Name: Baloxavir marboxil
Product Code: RO7191686/F04
Pharmaceutical Form: Tablet
INN or Proposed INN: BALOXAVIR MARBOXIL
Current
Sponsors
F. Hoffmann-La Roche Ltd
Eligibility
Sex/Gender
All
Inclusion criteria
Inclusion criteria: - Adult patients: Signed informed consent by any patient capable of giving consent, or, where the patient is not capable of giving consent, by his or her legal/authorized representative - Adolescent patients not able to legally consent: written informed consent for study participation is obtained from patient’s parents or legal guardian, with assent as appropriate by the patient, depending on the patient’s level of understanding and capability to provide assent - Age >= 12 years at the time of signing the Informed Consent Form/Assent Form - Ability to comply with the study protocol, in the investigator’s judgment - Patients who require hospitalization for severe influenza or acquire influenza during hospitalization, the severity of which requires an extension of hospitalization - Diagnosis of influenza A and/or B by a positive Rapid Influenza Diagnostic Test (RIDT) or reverse transcriptase-polymerase chain reaction (RT-PCR) A patient with a negative RIDT may be enrolled if influenza is suspected based on local surveillance data or if the patient reports contact with a known case of influenza within the prior 7 days - The time interval between the onset of symptoms and randomization is within 96 hours - A score of >= 4 based on the NEWS2 - Patients will require objective criteria of seriousness defined by at least one of the following criteria: • Requires ventilation or supplemental oxygen to support respiration • Has a complication related to influenza that requires hospitalization - For women of childbearing potential: Agreement to remain abstinent (refrain from heterosexual intercourse) women must remain abstinent or use contraceptive methods with a failure rate of =65 years) yes F.1.3.1 Number of subjects for this age range 165
Exclusion criteria
Exclusion criteria: - Patients who have received more than 48 hours of antiviral treatment for the current influenza infection prior to screening - Patients who have received baloxavir marboxil for the current influenza infection - Known contraindication to neuraminidase inhibitors - Known hypersensitivity to baloxavir marboxil or the drug product excipients - Patients hospitalized for exclusively social reasons (e.g., lack of caregivers at home) - Patients expected to die or be discharged within 48 hours, according to the investigator’s judgement - Patients weighing 5 times the upper limit of normal (ULN) OR • ALT or AST >3 times the ULN and total bilirubin level >2 times the ULN - Pregnant or breastfeeding, or positive pregnancy test in a predose examination, or intending to become pregnant during the study or within 28 days after the last dose of study treatment - Exposure to an investigational drug within 5 half-lives or 30 days (whichever is longer) of randomization - Any serious medical condition or abnormality in clinical laboratory tests that, in the investigator’s judgment, precludes the patient’s safe participation in and completion of the study - Known hypersensitivity to baloxavir marboxil or the drug product excipients
Design outcomes
Primary
| Measure | Time frame |
|---|---|
| Main Objective: To evaluate the clinical efficacy of baloxavir marboxil plus a standard-of-care (SOC) neuraminidase inhibitor (NAI) compared with matching placebo plus a SOC NAI based on time to clinical improvement; Secondary Objective: To evaluate • the clinical efficacy of baloxavir marboxil plus a SOC NAI compared with matching placebo plus a SOC NAI based on response rates of the 6-point ordinal scale at Day 7, time to clinical response, incidence and duration of mechanical ventilation, intensive care unit stay, incidence of post-treatment influenza-related complications, time to clinical failure, hospital discharge, National Early Warning Score (NEWS) 2 of <= 2 maintained for 24 hours, mortality rate at Day 7 and 28 • the antiviral activity of baloxavir marboxil plus a SOC NAI compared with matching placebo plus a SOC NAI • the polymorphic and treatment-emergent amino acid substitutions in the PA, PB1, PB2, and NA genes and drug susceptibility in patients with evaluable virus • the safety of baloxavir marboxil plus a SOC NAI compared with matching placebo plus a SOC NAI in hospitalized patients with influenza • the single- and multiple dose pharmacokinetics of baloxavir ;Primary end point(s): 1. Time to clinical improvement (defined as time to hospital discharge OR time to NEWS2 of less than or equal to 2 maintained for 24 hours);Timepoint(s) of evaluation of this end point: 1. Up to Day 35 | — |
Secondary
| Measure | Time frame |
|---|---|
| Secondary end point(s): Key secondary efficacy: 1. Response rates of the 6-point ordinal scale at Day 7 2. Time to clinical response based on temperature ranges, oxygen saturation, respiratory status, heart rate, and hospitalization Status Secondary efficacy: 3. Incidence of mechanical ventilation 4. Duration of mechanical ventilation 5. Incidence of Intensive Care Unit stay 6. Duration of Intensive Care Unit stay 7. Time to clinical failure 8. Time to hospital discharge 9. Incidence of post-treatment influenza-related complications 10. Mortality rate at Day 7 11. Mortality rate at Day 28 12. Time to NEWS2 of 3 × ULN, >5 × ULN, >10 × ULN PK 23. Plasma concentrations of baloxavir (active metabolite) at specified timepoints 24. Baloxavir concentration at pre-dose and at 24 hour after each dose of baloxavir marboxil (C24) (all patients) 25. Total drug exposure area under the curve (AUC), maximum plasma concentration (Cmax) and Half-life (t1/2) area under the concentration–time curve from time 0 to infinity (AUCinf) and clearance at steady state (CL) of baloxavir (only for patients undergoing sequential PK sampling) ; Timepoint(s) of evaluation of this end point: 1. At Day 7 2-9. Up to Day 35 10. At Day 7 11. At Day 28 12-22. Up to Day 35 23-25. Up to Day 35 | — |
Countries
Argentina, Australia, Belgium, Brazil, Bulgaria, Canada, Czech Republic, Estonia, Finland, France, Germany, Hong Kong, Hungary, Israel, Japan, Korea, Republic of, Mexico, Netherlands, New Zealand, Peru, Romania, Serbia, Singapore, Spain, Sweden, Turkey, Ukraine, United States
Contacts
Public ContactTrial Information Support Line-TISL
F. Hoffmann-La Roche Ltd
Outcome results
None listed