Study of Efficacy and Safety of IV VIS410 Plus Oseltamivir Versus Oseltamivir in Hospitalized Adults With Influenza A
Condition: Influenza A
MeSH terms: Influenza, Human
Intervention: Low dose of VIS410; High dose of VIS410; Placebo
Intervention description: Single intravenous infusion of fixed low dose of VIS410 in addition to oseltamivir; Single intravenous infusion of fixed high dose of VIS410 in addition to oseltamivir; Single intravenous infusion of placebo in addition to oseltamivir
Intervention MeSH terms: Oseltamivir
Phase: Phase 2
Study type: Interventional
Primary purpose: Treatment
Allocation: Randomized
Intervention model: Parallel Assignment
Masking: Quadruple (Participant, Care Provider, Investigator, Outcomes Assessor)
Masking description: Double-blind
Enrollment: 89.0
Sex: All
Minimum age: 18 Years
Healthy volunteers: No

Summary:

      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.
    

Eligibility criteria:

        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 (Polymerase
             chain reaction), FIA (Fluorescent immunoassay), 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