Study to Evaluate the Efficacy and Safety of Intravenous VIS410 in Addition to Oseltamivir (Tamiflu®) Compared With Oseltamivir Alone in Hospitalized Adults With Influenza A Infection Requiring Oxygen Support

This study is to compare the efficacy and safety of VIS410 in combination with oseltamivir vs
oseltamivir alone in severely ill subjects with influenza A infection requiring oxygen
support. Subjects will be followed for 56 days.

Inclusion Criteria:

- Male and female subjects aged ≥ 18 years.

- Test positive for influenza A by rapid antigen test or with another commercially
available test on an adequate nasopharyngeal specimen in accordance with the
manufacturer's instructions, or an acceptable local test, including PCR, FIA, or ELISA

- Onset of influenza symptoms no more than 5 days before VIS410/placebo infusion;
symptoms may include cough, dyspnea, sore throat, fever, myalgias, headache, nasal
symptoms (rhinorrhea, congestion), fatigue, diarrhea, anorexia, nausea, and vomiting.

- Requirement for oxygen support including any positive pressure ventilation

- Women of childbearing potential must have a negative pregnancy test within 2 days
prior to VIS410/placebo infusion.

- Women should fulfill one of the following criteria:

- Post-menopausal; either amenorrhea ≥ 12 months or follicle stimulating hormone >
40 mIU/mL as documented in their medical history

- Surgically sterile; hysterectomy, bilateral oophorectomy, or tubal ligation

- Women of childbearing potential participating in heterosexual sexual relations
must be willing to use adequate contraception from screening until 60 days post
VIS410/placebo infusion.

- Non-vasectomized (or vasectomized less than 6 months prior to dosing) male subjects
who have a female partner of childbearing potential must use an effective birth
control method from screening until 60 days post VIS410/placebo infusion.

- Subject, or a legally acceptable representative (LAR), is able to understand the
purpose and risks of the study and willing to give voluntary written informed consent.

Exclusion Criteria:

- Known or suspected intolerance or hypersensitivity to VIS410, oseltamivir,
pretreatment medications (diphenhydramine, or to both ibuprofen and acetylsalicylic
acid [ASA]), or closely related compounds (eg, other monoclonal antibodies)

- Subjects who have received VIS410 in the past

- History of receiving monoclonal antibody products (including VIS410) within 3 months
prior to VIS410/placebo dosing or planned administration during the study period

- Subjects who have taken more than 6 doses of an approved antiviral therapy for
influenza within the prior 96 hours (eg, oral oseltamivir, inhaled zanamivir, IV
peramivir, or oral ribavirin) between onset of symptoms and VIS410/placebo dosing

- Subjects with known co-infection with influenza B or other viral respiratory
infections (e.g., respiratory syncytial virus, parainfluenza viruses, respiratory
adenoviruses)

- Subjects with lung transplant or history of severe chronic lung disease, including
cystic fibrosis or any condition requiring home oxygen therapy

- Subjects on extracorporeal membrane oxygenation (ECMO) at time of randomization

- Subjects with end stage renal disease who are not undergoing hemodialysis

- Subjects with active graft-vs-host disease, hematopoietic stem cell transplant within
the previous 90 days, or human immunodeficiency virus infection with a CD4 cell count
of less than 200 per cubic millimeter

- Hospitalization for > 48 hours prior to randomization

- High probability of mortality within 48 hours of randomization as determined by the
Investigator

- Subjects weighing less than 45 kg

- Enrollment in any other investigational drug or device study, any disease or vaccine
study within 30 days prior to Day 1 or within 5 half-lives of the investigational
compound, whichever is longer

- Known or suspected alcohol or drug abuse, that is, abuse of a level that would
compromise the safety or cooperation of the subject in the opinion of the Investigator