A Study of MHAA4549A in Combination With Oseltamivir Versus Oseltamivir in Participants With Severe Influenza A Infection

Genentech

Status and phase: Completed; Phase 2

Conditions: Influenza

Treatments: Drug: MHAA4549A; Drug: Oseltamivir; Drug: Placebo

Study type: Interventional

Funder types: Industry

Identifiers

NCT02293863

GV29216

2014-000461-43 (EudraCT Number)

Details and patient eligibility

About

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.

Enrollment: 168 patients

Sex: All

Ages: 18+ years old

Volunteers: No Healthy Volunteers

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

Trial design

Primary purpose: Treatment

Allocation: Randomized

Interventional model: Parallel Assignment

Masking: Double Blind

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168 participants in 3 patient groups, including a placebo group

A: MHAA4549A 3600 mg + Oseltamivir

Experimental group

Description:

Participants will receive a single low IV dose of MHAA4549A on Day 1 and standard oseltamivir therapy for minimum of 5 days.

Treatment:

Drug: Oseltamivir

Drug: MHAA4549A

B: MHAA4549A 8400 mg + Oseltamivir

Experimental group

Description:

Participants will receive a single high IV dose of MHAA4549A on Day 1 and standard oseltamivir therapy for minimum of 5 days.

Treatment:

Drug: Oseltamivir

Drug: MHAA4549A

C: Placebo + Oseltamivir

Placebo Comparator group

Description:

Participants will receive a single IV dose of placebo matched to MHAA4549A on Day 1 and standard oseltamivir therapy (75 or 150 mg BID) for minimum of 5 days.

Treatment:

Drug: Oseltamivir

Drug: Placebo