A Study of MHAA4549A in Combination With Oseltamivir Versus Oseltamivir in Participants With Severe Influenza A Infection
Condition: Influenza
MeSH terms: Influenza, Human
Intervention: MHAA4549A; Oseltamivir; Placebo
Intervention description: Participants will receive a single dose of MHAA4549A by IV infusion on Day 1; Participants will receive oseltamivir capsule either 75 mg or 150 mg BID orally for minimum of 5 days. Dosage and administration should follow local prescribing information for oseltamivir.; Participants will receive a single IV dose of placebo matched to MHAA4549A on Day 1
Intervention MeSH terms: Oseltamivir
Phase: Phase 2
Study type: Interventional
Primary purpose: Treatment
Allocation: Randomized
Intervention model: Parallel Assignment
Masking: Double (Participant, Investigator)
Enrollment: 168.0
Sex: All
Minimum age: 18 Years
Healthy volunteers: No

Summary:

      This is a randomized, double-blind, placebo-controlled study that will investigate the safety
      and clinical activity of a single intravenous (IV) dose of MHAA4549A in adult participants
      hospitalized with severe influenza A in combination with oseltamivir versus a comparator arm
      of placebo with oseltamivir.
    

Eligibility criteria:

        Inclusion Criteria:

          -  Diagnosis of influenza A where a Sponsor-approved influenza test is used as an aid in
             diagnosis. A Sponsor-approved influenza test includes: Influenza antigen test or
             Influenza polymerase chain reaction (PCR) test

          -  One of the following markers of severity within 24 hours of admission: requirement for
             O2 supplementation to maintain SpO2 greater than (>) 92 %; or requirement for Positive
             Pressure Ventilation (PPV)

          -  A negative urine or serum pregnancy test for women of childbearing potential within 2
             days prior to study treatment

          -  Participants of reproductive potential must agree to use acceptable contraceptive
             measures as per the protocol as a minimum, and local guidelines, if more stringent

        Exclusion Criteria:

          -  Pregnant or lactating women, or women who intend to become pregnant during the study

          -  Hypersensitivity to monoclonal antibodies or any constituents (sodium succinate,
             sucrose, polysorbate 20) of study drug

          -  Hypersensitivity to the active substance or to any excipients of oseltamivir

          -  Investigational therapy within the 30 days prior to study treatment

          -  Received prior therapy with any anti-influenza monoclonal antibody therapy (including
             MHAA4549A) within 8 months prior to study treatment

          -  Current treatment (within 7 days of dosing) with probenecid, amantadine or rimantidine

          -  Participants who have taken more than a total of 6 doses (3 doses for peramivir) of
             anti-influenza therapy (e.g., oseltamivir, zanamivir, laninamivir, peramivir) in the
             period from onset of symptoms and prior to study treatment

          -  Admission >48 hours prior to study treatment

          -  Onset of influenza symptoms (including fever, chills, malaise, dry cough, loss of
             appetite, myalgias, coryza, or nausea) >5 days prior to study treatment

          -  Positive influenza B or influenza A + B infection within 2 weeks prior to study
             treatment

          -  High probability of mortality in the next 48 hours as determined by the investigator

          -  Participants requiring home or baseline oxygenation therapy

          -  Participants with history of chronic lung disease with a documented SpO2 less than (<)
             95% off oxygen

          -  Participants on chronic dose of corticosteroids exceeding 10 milligrams per day
             (mg/day) of prednisone or equivalent steroid dose for duration of greater than 14 days
             within 30 days of entry into study

          -  Participants with the following significant immune suppression: bone marrow or solid
             organ transplant in the previous 12 months; cancer chemotherapy in the previous 12
             months, HIV infection with most recent Cluster of Differentiation 4 (CD4) <200 cells
             per milliliter (cells/mL), or other significant immune suppression as determined by
             the investigator in discussion with the Sponsor Medical Monitor

          -  Participants on extracorporeal membrane oxygenation (ECMO) at time of randomization

          -  Any disease or condition that would, in the opinion of the site investigator or
             Sponsor, place the participant at an unacceptable risk of injury or render the
             participant unable to meet the requirements of the protocol