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

• Register: ClinicalTrials.gov
• Last refreshed on: 12 December 2020
• Main ID: NCT02293863
• Date of registration: 14/11/2014
• Prospective Registration: Yes
• Primary sponsor: Genentech, Inc.
• Public title: A Study of MHAA4549A in Combination With Oseltamivir Versus Oseltamivir in Participants With Severe Influenza A Infection
• Date of first enrolment: January 14, 2015
• Target sample size: 168
• Recruitment status: Completed
• URL: https://clinicaltrials.gov/show/NCT02293863
• Study type: Interventional
• Study design: Allocation: Randomized. Intervention model: Parallel Assignment. Primary purpose: Treatment. Masking: Double (Participant, Investigator).
• Phase: Phase 2

Countries of recruitment

Belgium, Brazil, Bulgaria, Canada, Chile, Czech Republic, Czechia, France, Germany, Hong Kong, Hungary, Israel, Italy, Korea, Republic of, Mexico, Netherlands, New Zealand, Peru, Poland, Russian Federation, Singapore, South Africa, Spain, Sweden, Taiwan, Ukraine, United Kingdom

Contacts

• Name: Clinical Trials
• Affiliation: Hoffmann-La Roche

Key inclusion & exclusion 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



Age minimum: 18 Years
Age maximum: N/A
Gender: All

Health Condition(s) or Problem(s) studied

Influenza

Intervention(s)

Drug: MHAA4549A

Drug: Oseltamivir

Drug: Placebo

Primary Outcome(s)

Percentage of Participants With Adverse Events [Time Frame: From randomization up to 60 days]

Number of Participants With Anti-Therapeutic Antibodies (ATA) to MHAA4549A During and Following Administration of MHAA4549A [Time Frame: From randomization up to 60 days]

Time to Normalization of Respiratory Function [Time Frame: From randomization up to 60 days]

Secondary Outcome(s)

Peak Influenza A Viral Load [Time Frame: Immediately prior to MHAA4549A infusion and oseltamivir dosing on Day 1, immediately prior to oseltamivir dosing on Days 2 to 10, Days 14, 20, 25, 30, on day of discharge from hospital (up to Day 60), and at study completion (Day 60)]

Duration of Intensive Care Unit (ICU) Stay [Time Frame: From randomization up to 60 days]

Duration of Ventilation [Time Frame: From randomization up to 60 days]

Observed Clearance (CL-obs) of MHAA4549A [Time Frame: 30 min before & 60 min after end of MHAA4549A infusion (infusion duration = 120 min) on Day 1; immediately prior to oseltamivir dose on Days 2, 3, 5, 7; on Days 14, 30; on day of discharge (up to Day 60); at study completion (Day 60)]

Area Under Serum Concentration-Time Curve From Time 0 to Infinity (AUC ) of MHAA4549A [Time Frame: 30 minutes (min) before & 60 min after end of MHAA4549A infusion (infusion duration = 120 min) on Day 1; immediately prior to oseltamivir dose on Days 2, 3, 5, 7; on Days 14, 30; on day of discharge (up to Day 60); at study completion (Day 60)]

Maximum Serum Concentration (Cmax ) of MHAA4549A [Time Frame: 30 min before & 60 min after end of MHAA4549A infusion (infusion duration = 120 min) on Day 1; immediately prior to oseltamivir dose on Days 2, 3, 5, 7; on Days 14, 30; on day of discharge (up to Day 60); at study completion (Day 60)]

Observed Steady State Volume of Distribution (Vss_obs) of MHAA4549A [Time Frame: 30 min before & 60 min after end of MHAA4549A infusion (infusion duration = 120 min) on Day 1; immediately prior to oseltamivir dose on Days 2, 3, 5, 7; on Days 14, 30; on day of discharge (up to Day 60); at study completion (Day 60)]

Percentage of Participants Readmitted to Hospital Due to Any Cause [Time Frame: Days 30 and 60]

Percentage of Participants With Clinical Failure [Time Frame: 24 hours after end of infusion (infusion duration = approximately 120 minutes) up to Day 60]

Percentage of Participants With Clinical Resolution of Abnormal Vital Signs [Time Frame: From randomization up to 60 days]

Area Under Viral Load-Time Curve (AUEC ) of Influenza A Virus [Time Frame: Immediately prior to MHAA4549A infusion and oseltamivir dosing on Day 1, immediately prior to oseltamivir dosing on Days 2 to 10, Days 14, 20, 25, 30, on day of discharge from hospital (up to Day 60), and at study completion (Day 60)]

Percentage of Participants by Clinical Status Using a Categorical Ordinal Outcome [Time Frame: Days 1-7, 14 and 30]

Percentage of Participants Using Antibiotics for Respiratory Infections [Time Frame: From randomization up to 60 days]

Elimination Half-Life (Terminal t1/2) of MHAA4549A [Time Frame: 30 min before & 60 min after end of MHAA4549A infusion (infusion duration = 120 min) on Day 1; immediately prior to oseltamivir dose on Days 2, 3, 5, 7; on Days 14, 30; on day of discharge (up to Day 60); at study completion (Day 60)]

Duration of Hospitalization [Time Frame: From randomization up to 60 days]

Duration of Viral Shedding [Time Frame: Immediately prior to MHAA4549A infusion and oseltamivir dosing on Day 1, immediately prior to oseltamivir dosing on Days 2 to 10, Days 14, 20, 25, 30, on day of discharge from hospital (up to Day 60), and at study completion (Day 60)]

Percentage of Participants Who Died Due to Any Cause [Time Frame: Days 14, 30 and 60]

Percentage of Participants With Secondary Complications of Influenza [Time Frame: From randomization up to 60 days]

Secondary ID(s)

2014-000461-43

GV29216

Source(s) of Monetary Support

Please refer to primary and secondary sponsors

Results

• Results available: Yes
• Date Posted: 18/06/2018
• URL: https://clinicaltrials.gov/ct2/show/results/NCT02293863