Study to Assess Efficacy and Safety of Baloxavir Marboxil In Combination With Standard-of-Care Neuraminidase Inhibitor In Hospitalized Participants With Severe Influenza
Condition: Influenza
MeSH terms: Influenza, Human
Intervention: Baloxavir Marboxil; Placebo
Intervention description: Baloxavir marboxil will be administered as a weight-based dose on Days 1 and 4. A third dose will be given on Day 7 for participants who have not improved according to protocol defined criteria on Day 5.; Participants will receive matching placebo on Days 1, 4 and 7.
Intervention MeSH terms: Baloxavir
Phase: Phase 3
Study type: Interventional
Primary purpose: Treatment
Allocation: Randomized
Intervention model: Parallel Assignment
Masking: Double (Participant, Investigator)
Enrollment: 363.0
Sex: All
Minimum age: 12 Years
Healthy volunteers: No

Summary:

      This study will evaluate the efficacy, safety, and pharmacokinetics of baloxavir marboxil in
      combination with a standard-of-care (SOC) neuraminidase inhibitor (NAI) (i.e., oseltamivir,
      zanamivir, or peramivir) compared with a matching placebo in combination with a SOC NAI in
      hospitalized patients with influenza.
    

Eligibility criteria:

        Inclusion Criteria:

          -  Adult participants: Signed informed consent by any participant capable of giving
             consent, or, where the participant is not capable of giving consent, by his or her
             legal/authorized representative

          -  Adolescent participants not able to legally consent: written informed consent for
             study participation is obtained from participant's parents or legal guardian, with
             assent as appropriate by the participant, depending on the participant's level of
             understanding and capability to provide assent

          -  Participants 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)

          -  The time interval between the onset of symptoms and randomization is within 96 hours

          -  A score of ≥4 based on the National Early Warning Score 2 (NEWS2)

          -  Participants 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 (e.g.,
             pneumonia, central nervous system involvement, myositis, rhabdomyolysis, acute
             exacerbation of chronic kidney disease, asthma or chronic obstructive pulmonary
             disease (COPD), severe dehydration, myocarditis, pericarditis, exacerbation of
             ischemic heart disease)

          -  For women of childbearing potential: Agreement to remain abstinent or use
             contraceptive methods with a failure rate of < 1% per year during the treatment period
             and for 28 days after the last dose of study treatment. Hormonal contraceptive methods
             must be supplemented by a barrier method.

        Exclusion Criteria:

          -  Participants who have received more than 48 hours of antiviral treatment for the
             current influenza infection prior to screening

          -  Participants who have received baloxavir marboxil for the current influenza infection

          -  Known contraindication to neuraminidase inhibitors

          -  Participants hospitalized for exclusively social reasons (e.g., lack of caregivers at
             home)

          -  Participants expected to die or be discharged within 48 hours, according to the
             investigator's judgement

          -  Participants weighing < 40 kg

          -  Participants with known severe renal impairment (estimated glomerular filtration rate
             < 30 mL/min/1.73 m2) or receiving continuous renal replacement therapy, hemodialysis,
             peritoneal dialysis

          -  Participants with any of the following laboratory abnormalities detected within 24
             hours prior to or during screening (according to local laboratory reference ranges:

          -  Alanine Transaminase (ALT) or Aspartate Transaminase (AST) level > 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 participant's safe participation in and
             completion of the study

          -  Known hypersensitivity to baloxavir marboxil or the drug product excipients