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

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.

Study Overview

• Status: Completed
• Conditions: Influenza
• Intervention / Treatment: Drug: MHAA4549A; Drug: Oseltamivir; Drug: Placebo

• Study Type: Interventional
• Enrollment (Actual): 168
• Phase: Phase 2

Contacts and Locations

Study Locations

• Belgium
  • Brussels, Belgium, 1000
    • CHU St Pierre (St Pierre)
  • Bruxelles, Belgium, 1070
    • Hospital Erasme; Neurologie
  • Leuven, Belgium, 3000
    • UZ Leuven Gasthuisberg
  • Mont-godinne, Belgium, 5530
    • CHU UCL Mont-Godinne
• Brazil
  • MG
    • Belo Horizonte, MG, Brazil, 30150-221
      • Santa Casa de Misericordia; de Belo Horizonte
  • RS
    • Passo Fundo, RS, Brazil, 99010-080
      • Hospital São Vicente de Paulo
  • SP
    • Campinas, SP, Brazil, 13060-904
      • PUC Campinas
    • Sao Jose do Rio Preto, SP, Brazil, 15090-000
      • FUNFARME
    • Sao Paulo, SP, Brazil, 01323-020
      • Hospital Alemao Oswaldo Cruz; Oncologia
    • Vila Clementino, SP, Brazil, 04038-905
      • Hospital Edmundo Vasconcelos
• Bulgaria
  • Gabrovo, Bulgaria, 5300
    • MHAT "Dr. Tota Venkova"- Gabrovo
  • Plovdiv, Bulgaria, 4005
    • University Multiprofile Hospital for Active Treatment "St. George"
  • Ruse, Bulgaria, 7002
    • SHATPPD Dr. Dimitar Gramatikov, Ruse Ltd.
  • Sevlievo, Bulgaria, 5400
    • Multiprofile Hospital for Active Treatment AKTA-MEDIKA EOOD
  • Sofia, Bulgaria, 1336
    • MHAT Lyulin EAD, Department of internal diseases
  • Sofia, Bulgaria, 1407
    • MHAT TOKUDA SOFIA/ICU-Intensive Care Unit
  • Sofia, Bulgaria, 1606
    • 5th Multifunctional Hospital for Active treatment
  • Sofia, Bulgaria, 1606
    • Military Medical Academy- MHAT
  • Sofia, Bulgaria, 1606
    • University Multiprofile Hospital for Active Treatment and Emergency Medicine N. I. Pirogov EAD
  • Varna, Bulgaria, 9010
    • MBAL St Marina Dep Pulmonology, ICU
  • Veliko Tarnovo, Bulgaria, 5000
    • Multiprofile District Hospital for Active Treatment Dr. Stefan Cherkezov AD
• Canada
  • Alberta
    • Calgary, Alberta, Canada, T1Y 6J4
      • Peter Lougheed Centre
    • Calgary, Alberta, Canada, T2N 4N2
      • Alberta Health Services
    • Calgary, Alberta, Canada, T2N 4Z6
      • Foothills Medical Centre
    • Calgary, Alberta, Canada, T2V 1P9
      • Rockyview General Hospital
  • British Columbia
    • New Westminster, British Columbia, Canada, V3L 3W7
      • Royal Columbian Hospital
    • Vancouver, British Columbia, Canada, V6Z 1Y6
      • St. Paul's Hospital, Providence Health Care
    • Victora, British Columbia, Canada, V8Z 6R5
      • Victoria General Hospital
    • Victoria, British Columbia, Canada, V8R 1J8
      • Royal Jubilee Hospital Victoria general Hospital
  • New Brunswick
    • Moncton, New Brunswick, Canada, E1C 6Z8
      • Moncton Hospital
  • Ontario
    • London, Ontario, Canada, N6A 5A5
      • LHSC - University Hospital; Research Pharmacy
    • Oshawa, Ontario, Canada, L1G 2B9
      • Lakeridge Health
    • Ottawa, Ontario, Canada, K1Y 4E9
      • Ottawa Hospital Research Institute
    • Ottawa, Ontario, Canada, K1Y 4E9
      • The Ottawa Hospital - Civic Campus
    • Toronto, Ontario, Canada, M5T 2S8
      • Toronto Western Hospital
    • Toronto, Ontario, Canada, M5G 2N2
      • University Health Network
    • Toronto, Ontario, Canada, M4C 3E7
      • Toronto East General
  • Quebec
    • Quebec City, Quebec, Canada, G1V 4G5
      • Centre Hospitalier de la Universite Laval
    • Sainte-foy, Quebec, Canada, G1V 4G2
      • Pavillion Chul-Chuq
    • Trois-Rivieres, Quebec, Canada, G9A1Y1
      • Centre de santé et de services sociaux de Trois-Rivières
• Chile
  • Temuco, Chile, 4781151
    • Hospital Dr. Hernán Henríquez Aravena
  • Vina del Mar, Chile, 2540364
    • Clínica Reñaca
• Czechia
  • Brno, Czechia, 62500
    • The University Hospital Brno
  • Hradec Kralove, Czechia, 500 05
    • Fakultni nemocnice Hradec Kralove
  • Liberec, Czechia, 460 63
    • Anesthesia and Intensive Care Dept., Regional Hospital Liberec
  • Ostrava, Czechia, 708 52
    • University hospital Ostrava, Clinic of infectious medicine
  • Praha 10, Czechia, 100 34
    • Fakultni nemocnice Kralovske Vinohrady, Klinika anesteziologie a resuscitace
• France
  • Argenteuil, France, 95107
    • CH Victor Dupouy
  • Clermont-ferrand, France, 63000
    • Centre Hospitalier Universitaire de Clermont Ferrand
  • Dijon, France, 21079
    • Service de Réanimation médicale - Bocage Central
  • Garches, France, 92380
    • APHP Raymond Poincare
  • La Roche Sur Yon, France, 85025
    • CHD Vendee
  • Lille, France, 59037
    • CHRU Lille
  • Limoges, France, 87043
    • Réanimation Polyvalente, CHU Limoges
  • Nancy, France, 54035
    • Chru Nancy
  • Nice, France, 6202
    • Archet 1 university Hospital
  • Paris, France, 75014
    • HOPITAL COCHIN university hospital
  • Strasbourg, France, 67098
    • Hopital Universitaire Hautepierre
  • Strasbourg, France, 67000
    • Réanimation médicale NHC
  • Tours, France, 37044
    • Service de réanimation médicale, Hôpital Bretonneau
• Germany
  • Frankfurt, Germany, 60590
    • Universitätsklinikum Frankfurt Goethe Universität
  • Heidelberg, Germany, 69120
    • UniversitatsKlinikum Heidelberg
  • Koeln, Germany, 50931
    • Uniklinik Köln, Medizinischen Klinik I
  • Mainz, Germany, 55131
    • Uniklinikum Mainz
  • Tuebingen, Germany, 72076
    • Uniklinik Tübingen
• Hong Kong
  • Hong Kong, Hong Kong
    • University of Hong Kong
• Hungary
  • Kistarcsa, Hungary, 2084
    • Pest Megyei Flor Ferenc Korhaz
  • Veszprém, Hungary, 8200
    • Csolnoky Ferenc Korhaz
  • Vác, Hungary, 2600
    • Javorszky Odon Hospital
  • Zalaegerszeg, Hungary, 8900
    • Zala County Hospital ICU
• Israel
  • Afula, Israel, 18101
    • Haemek Medical Center
  • Beer-Sheva, Israel, 84101
    • Soroka University Medical Centre
  • Holon, Israel, 58100
    • Wolfson Medical Center
  • Jerusalem, Israel, 91999
    • Hadasit Medical Research Services and Development Ltd
  • Nahariya, Israel, 22100
    • Galilee Medical Center
  • Nazareth, Israel, 16100
    • Nazareth EMMS Hospital
  • Petah Tikva, Israel, 4941492
    • Rabin Medical Center
  • Rehovot, Israel, 7661041
    • Kaplan Medical Center
  • Tel Aviv, Israel, 64239
    • Tel-Aviv Sourasky Medical Center
  • Tel Hashomer, Israel, 52661
    • Chaim Sheba Medical Center
  • Zefat, Israel, 1311001
    • Ziv Medical Center
• Italy
  • Basilicata
    • Brescia, Basilicata, Italy
      • University Division of Infective and Tropical Diseases, University of Brescia, Italy
  • Emilia-Romagna
    • Bologna, Emilia-Romagna, Italy, 40127
      • Clinic of Infectious Diseases
    • Modena, Emilia-Romagna, Italy, 41125
      • University Hospital Modena, Intensive Care Unit
  • Lazio
    • Rome, Lazio, Italy, 149
      • National Institute for Infectious Diseases "L. Spallanzani"
  • Lombardia
    • Cremona, Lombardia, Italy, 26100
      • Asst Di Cremona
    • Milano, Lombardia, Italy, 20127
      • Ospedale San Raffaele - Milano
  • Sardegna
    • Salerno, Sardegna, Italy, 84131
      • A.O.U. S. Giovanni di Dio e Ruggi d'Aragona
• Korea, Republic of
  • Busan, Korea, Republic of, 602-739
    • Pusan National University Hospital
  • Incheon, Korea, Republic of
    • Gachon University Gil Hospital
  • Seoul, Korea, Republic of, 02841
    • Korea University Anam Hospital
  • Seoul, Korea, Republic of, 08308
    • Korea University Guro Hospital
  • Seoul, Korea, Republic of, 120-752
    • Yonsei University Health System/Severance Hospital
  • Seoul, Korea, Republic of, 150-950
    • Hallym university Kangnam Sacred Heart Hospital; Infectious devision
  • Wonju, Korea, Republic of, 220-701
    • WonJu Severance Christian Hospital
• Mexico
  • Guadalajara, Mexico, 44280
    • Hospital Civil de Guadalajara Fray Antonio Alcalde
  • Guadalajara, Mexico, 44280
    • Hospital Civil de Guadalajara Dr Juan I Menchaca
  • Mexico, Distrito Federal, Mexico, 14000
    • Instituto Nacional de Ciencias; Medicas y Nutricion; Salvador Zubiran
  • Monterrey, Mexico, 64460
    • CEPREP; Hospital Universitario
  • Tijuana, Mexico, 22320
    • Hospital General de Tijuana
  • Xalapa-enriquez, Mexico, 91020
    • Centro de Especialidades Medicas Del Estado de Veracruz Dr Rafael Lucio
• Netherlands
  • 'S Hertogenbosch, Netherlands, 5223 GZ
    • Jeroen Bosch Ziekenhuis
  • Apeldoorn, Netherlands, 7334 DV
    • Gelre Ziekenhuizen Apeldoorn; Hospitals Pharmacy
  • Leiden, Netherlands, 2300 ZA
    • LUMC
  • Nijmegen, Netherlands, 6500 HB
    • UMC Radboud Nijmegen
  • Rotterdam, Netherlands, 3000 CA
    • Erasmus Medical Centre; Department of Virology L-359
  • Rotterdam, Netherlands, 3083AN
    • Ikazia Hospital
  • Utrecht, Netherlands, 3508 GA
    • UMCU
  • Zwolle, Netherlands, 8025 AB
    • Isala
• New Zealand
  • Auckland, New Zealand, 1124
    • Auckland City Hospital
  • Christchurch, New Zealand, 8011
    • Christchurch Hospital
  • Tauranga, New Zealand, 3143
    • Tauranga Hospital
• Peru
  • Cusco, Peru, 84
    • Hospital Regional del Cusco
  • Cuzco, Peru, 84
    • Hospital Nacional Adolfo Guevara Velasco
  • LIma, Peru, Lima 01
    • Clinica Internacional Sede Lima
  • LIma, Peru, Lima 01
    • Hospital Nacional; Arzobispo Loayza
  • La Victoria, Peru, Lima 13
    • Hospital Guillermo Almenara Irigoyen Hospital Guillermo Almenara Irigoyen Hospital Guillermo Almen
  • Lima, Peru, Lima 41
    • Clinica San Borja
  • Lima, Peru, Lima 29
    • Hospital Maria Auxiliadora
  • Lima, Peru, Lima 10
    • Hospital Nacional Hipolito; Unanue
  • Lima, Peru, Lima 18
    • Hospital Central Fuerza; Aerea del Peru
  • Lima, Peru, Lima 32
    • Clínica San Gabriel
  • Piura, Peru, 20001
    • Hospital de la Amistad Peru Corea II-2 Santa Rosa
  • San Juan de Miraflores, Peru, LIMA 29
    • Clinica Divino Nino Jesus; Orden de Malta
  • Trujillo, Peru, 13011
    • Clinica Peruana Americana
• Poland
  • Lublin, Poland, 20-718
    • Wojewodzki Szpital Specjalistyczny
  • Szczecin, Poland, 70-111
    • Icu Spsk - 2
  • Toruń, Poland, 87-100
    • Oddział Anestezjologii i Intensywnej Terapii;Wojewódzki Szpital Zespolony im. L. Rydygiera
  • Łódź, Poland, 91-347
    • Oddział Anestezjologii i Intensywnej Terapii Wojewódzki Specjalistyczny Szpital im dr Wł Biegańsk
• Russian Federation
  • Chelyabinsk, Russian Federation, 454000
    • Municipal Clinical Hospital #8
  • Engels, Russian Federation, 413124
    • Municipal Healthcare Institution "City Hospital №2"
  • St.Petersburg, Russian Federation, 194044
    • Medical Military Academy n.a S.M.Kirov
  • Vladivostok, Russian Federation, 690002
    • Paciific state medical university
• South Africa
  • Parktown West, South Africa, 2196
    • Milpark Hospital
  • Pretoria, South Africa, 0084
    • Emmed Research
  • Worcester, South Africa, 6850
    • Clinical Projects Research
• Spain
  • Barcelona, Spain, 08003
    • Hospital Del Mar
  • Barcelona, Spain, 08035
    • Hospital Universitari Vall d'Hebron
  • Barcelona, Spain, 08907
    • Bellvitge University Hospital
  • Granada, Spain, 18012
    • Hospital Universitario San Cecilio
  • Madrid, Spain, 28040
    • Hosp. Clinico San Carlos
  • Madrid, Spain, 28905
    • Hospital Univ. de Getafe.Servicio de Neurologia
  • Tarragona, Spain, 43005
    • Joan XXIII University Hospital
  • Valencia, Spain, 46026
    • Servicio de Medicina Intensiva Hospital Universitario la Fe
  • Barcelona
    • Terrassa, Barcelona, Spain, 08221
      • Mútua de Terrassa
  • Cantabria
    • Barcelona, Cantabria, Spain, 08036
      • Hospital Clinic
    • Mataro, Cantabria, Spain, 08304
      • Hospital de Mataró
    • Santander, Cantabria, Spain, 39008
      • Hospital Universitario Marqués de Valdecilla
  • Islas Baleares
    • Palma de Mallorca, Islas Baleares, Spain, 07010
      • Hospital Universitario Son Espases
• Sweden
  • Goteborg, Sweden, 413 45
    • Sahlgrenska Universitetssjukhuset
  • Göteborg, Sweden, 41650
    • Uppsala University Hospital, Department of Infectious Diseases
  • Mamö, Sweden, 205 02
    • Skanes universitetssjukhus
  • Umeå, Sweden, 901 85
    • Norrland Universitetssjukhus
• Taiwan
  • Kaohsiung, Taiwan, 807
    • Kaohsiung Medical University Hospital, Cancer Center
  • New Taipei, Taiwan, 220
    • Far East Memorial Hospital
  • Taipei, Taiwan, 116
    • Wanfang Hospital
  • Taoyuan City, Taiwan, 333
    • Chang Gung Medical Foundation Linkou Branch
• Ukraine
  • Kyiv, Ukraine, 03110
    • Kyiv City Clinical Hospital #4
  • Kyiv, Ukraine, 04060
    • Kyiv City Clinical Hospital #9
  • Odesa, Ukraine, 65023
    • Municipal Institution City Clinical Infectious Diseases Hospital
  • Poltava, Ukraine, 36011
    • Poltava Regional Clinical Infectious Hospital
  • Zhytomyr, Ukraine, 10002
    • Municipal Institution Central City Hospital #1 City of Zhytomyr
• United Kingdom
  • Birmingham, United Kingdom, B15 2TH
    • Queen Elizabeth Hospital
  • Birmingham, United Kingdom, B9 5SS
    • Heart of England NHS Trust
  • Glasgow, United Kingdom, G51 4TF
    • Queen Elizabeth University Hospital
  • Leeds, United Kingdom, LS1 3EX
    • Leeds General Infirmary, Anaesthetic Department, D Floor
  • London, United Kingdom, SE5 9RS
    • King College Hospital NHS Foundation Trust
  • London, United Kingdom, WC1E 6AU
    • University College London Hospitals NHS Foundation Trust - University College Hospital
  • Southampton, United Kingdom, SO16 6YD
    • Southampton University Hospitals NHS Trust
  • Stoke-On-Trent, United Kingdom, ST4 6QG
    • University Hospitals of North Midlands NHS Trust-Royal Stoke University Hospital
  • Taunton, United Kingdom, TA1 5DA
    • Taunton and Somerset NHS Foundation Trust Musgrove Park Hospital

Participation Criteria

Eligibility Criteria

• Ages Eligible for Study: 18 years and older (Adult, Older Adult)
• Accepts Healthy Volunteers: No
• Genders Eligible for Study: All

Description

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

Study Plan

How is the study designed?

Design Details

• Primary Purpose: Treatment
• Allocation: Randomized
• Interventional Model: Parallel Assignment
• Masking: Double

Number of Arms

3

Arms and Interventions

Participant Group / Arm	Intervention / Treatment
Experimental: A: MHAA4549A 3600 mg + Oseltamivir; Participants will receive a single low IV dose of MHAA4549A on Day 1 and standard oseltamivir therapy for minimum of 5 days.	Drug: MHAA4549A; Participants will receive a single dose of MHAA4549A by IV infusion on Day 1; Drug: Oseltamivir; 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.; Other Names: Tamiflu
Experimental: B: MHAA4549A 8400 mg + Oseltamivir; Participants will receive a single high IV dose of MHAA4549A on Day 1 and standard oseltamivir therapy for minimum of 5 days.	Drug: MHAA4549A; Participants will receive a single dose of MHAA4549A by IV infusion on Day 1; Drug: Oseltamivir; 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.; Other Names: Tamiflu
Placebo Comparator: C: Placebo + Oseltamivir; 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.	Drug: Oseltamivir; 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.; Other Names: Tamiflu; Drug: Placebo; Participants will receive a single IV dose of placebo matched to MHAA4549A on Day 1

What is the study measuring?

Primary Outcome Measures

Outcome Measure	Measure Description	Time Frame
Percentage of Participants With Adverse Events	An adverse event is any untoward medical occurrence in a participant administered a pharmaceutical product and which does not necessarily have to have a causal relationship with the treatment. An adverse event can therefore be any unfavorable and unintended sign (including an abnormal laboratory finding, for example), symptom, or disease temporally associated with the use of a pharmaceutical product, whether or not considered related to the pharmaceutical product. Preexisting conditions which worsen during a study are also considered as adverse events.	From randomization up to 60 days
Number of Participants With Anti-Therapeutic Antibodies (ATA) to MHAA4549A During and Following Administration of MHAA4549A	Reported are the number of participants positive for ATAs at baseline, the number of participants with treatment-induced ATAs and the number of participants with treatment-enhanced ATAs.	From randomization up to 60 days
Time to Normalization of Respiratory Function	The time to normalization of respiratory function was defined as the time to removal of the participant from oxygen (O2) supplementation in order to maintain a blood oxygen saturation level (SpO2) equal to or greater than 95% as measured by pulse oximetry.	From randomization up to 60 days

Secondary Outcome Measures

Outcome Measure	Measure Description	Time Frame
Percentage of Participants by Clinical Status Using a Categorical Ordinal Outcome	The clinical status of participants was defined by five mutually exclusive categories: 1. Death; 2. In the Intensive Care Unit (ICU); 3. Non-ICU hospitalization, requiring supplemental oxygen (O2); 4. Non-ICU hospitalization, not requiring supplemental oxygen (O2); 5. Not hospitalized.	Days 1-7, 14 and 30
Percentage of Participants With Clinical Failure	Clinical failure after 24 hours post-infusion of study drug was defined as progression to increased O2 requirement defined by an increase in oxygen supplementation from low flow oxygen (i.e., 2-6 liters per minute [L/min]) to high flow oxygen (i.e., > 6 L/min) or from oxygen supplementation alone to any positive pressure ventilation (PPV) or extracorporeal membrane oxygenation (ECMO), progression to ICU, prolonged ventilation or O2 support defined by > 2 weeks, or death.	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	Description: Clinical resolution of abnormal vital signs was defined as meeting three out of five of the following criteria: 1. SpO2 ≥ 95% without supplemental O2; 2. Respiratory rate < 24 breaths per minute without supplemental O2; 3. Core temperature < 37.2 Celsius (C) immediately prior to receipt of any antipyretic drug, and at least 6-8 hours from the last dose of antipyretic or core temperature > 36 C in participants who are initially hypothermic; 4. Heart rate (HR) < 100 beats/minute; 5. Systolic blood pressure (SBP) >90 mmHg. Reported here is the percentage of participants who had clinical resolution of at least three out of five abnormal vital signs by the end of study.	From randomization up to 60 days
Percentage of Participants Who Died Due to Any Cause		Days 14, 30 and 60
Area Under Viral Load-Time Curve (AUEC ) of Influenza A Virus	Influenza A viral load was measured by quantitative polymerase chain reaction (qPCR) in nasopharyngeal samples at multiple time points during the study. AUEC is the area under the viral load-time curve expressed as log10 (viral particles/milliliter x hour) = log10 (vp/mL x hour).	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)
Peak Influenza A Viral Load	Influenza A viral load was measured by qPCR in nasopharyngeal samples at multiple time points during the study. Reported here is the peak Influenza A viral load expressed as log10 vp/mL.	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 Viral Shedding	Influenza A viral load was measured by qPCR in nasopharyngeal samples at multiple time points during the study. Reported here is the duration of viral shedding.	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 Hospitalization		From randomization up to 60 days
Duration of Intensive Care Unit (ICU) Stay		From randomization up to 60 days
Percentage of Participants Using Antibiotics for Respiratory Infections		From randomization up to 60 days
Percentage of Participants With Secondary Complications of Influenza	The following were considered secondary complications of influenza: pneumonia, including hospital-acquired pneumonia (HAP) and ventilation-acquired pneumonia (VAP), exacerbations of chronic lung disease, myocarditis, acute respiratory distress syndrome (ARDS), otitis media, or other related complications.	From randomization up to 60 days
Percentage of Participants Readmitted to Hospital Due to Any Cause		Days 30 and 60
Duration of Ventilation		From randomization up to 60 days
Area Under Serum Concentration-Time Curve From Time 0 to Infinity (AUC ) of MHAA4549A	AUC0-inf is reported as day*microgram/milliliter (day*mcg/mL).	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		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)
Elimination Half-Life (Terminal t1/2) of MHAA4549A		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 Clearance (CL-obs) of MHAA4549A		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		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)

Collaborators and Investigators

• Sponsor: Genentech, Inc.

Publications and helpful links

General Publications

• Lim JJ, Nilsson AC, Silverman M, Assy N, Kulkarni P, McBride JM, Deng R, Li C, Yang X, Nguyen A, Horn P, Maia M, Castro A, Peck MC, Galanter J, Chu T, Newton EM, Tavel JA. A Phase 2 Randomized, Double-Blind, Placebo-Controlled Trial of MHAA4549A, a Monoclonal Antibody, plus Oseltamivir in Patients Hospitalized with Severe Influenza A Virus Infection. Antimicrob Agents Chemother. 2020 Jun 23;64(7):e00352-20. doi: 10.1128/AAC.00352-20. Print 2020 Jun 23.

Study record dates

Study Major Dates

• Study Start (Actual): January 14, 2015
• Primary Completion (Actual): May 23, 2017
• Study Completion (Actual): May 23, 2017

Study Registration Dates

• First Submitted: November 14, 2014
• First Submitted That Met QC Criteria: November 17, 2014
• First Posted (Estimate): November 18, 2014

Study Record Updates

• Last Update Posted (Actual): June 18, 2018
• Last Update Submitted That Met QC Criteria: May 18, 2018
• Last Verified: May 1, 2018

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Terms related to this study

• Additional Relevant MeSH Terms: RNA Virus Infections; Virus Diseases; Infections; Respiratory Tract Infections; Respiratory Tract Diseases; Orthomyxoviridae Infections; Influenza, Human; Molecular Mechanisms of Pharmacological Action; Anti-Infective Agents; Antiviral Agents; Enzyme Inhibitors; Oseltamivir
• Other Study ID Numbers: GV29216; 2014-000461-43 (EudraCT Number)