A Study of MHAA4549A in Combination With Oseltamivir Versus Oseltamivir in Participants With Severe Influenza A Infection
2 other identifiers
interventional
168
25 countries
171
Brief Summary
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.
Trial Health
Trial Health Score
Automated assessment based on enrollment pace, timeline, and geographic reach
participants targeted
Target at P75+ for phase_2
Started Jan 2015
171 active sites
Health score is calculated from publicly available data and should be used for screening purposes only.
Trial Relationships
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Study Timeline
Key milestones and dates
First Submitted
Initial submission to the registry
November 14, 2014
CompletedFirst Posted
Study publicly available on registry
November 18, 2014
CompletedStudy Start
First participant enrolled
January 14, 2015
CompletedPrimary Completion
Last participant's last visit for primary outcome
May 23, 2017
CompletedStudy Completion
Last participant's last visit for all outcomes
May 23, 2017
CompletedResults Posted
Study results publicly available
June 18, 2018
CompletedJune 18, 2018
May 1, 2018
2.4 years
November 14, 2014
May 18, 2018
May 18, 2018
Conditions
Outcome Measures
Primary Outcomes (3)
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 Outcomes (18)
Percentage of Participants by Clinical Status Using a Categorical Ordinal Outcome
Days 1-7, 14 and 30
Percentage of Participants With Clinical Failure
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
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
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)
- +13 more secondary outcomes
Study Arms (3)
A: MHAA4549A 3600 mg + Oseltamivir
EXPERIMENTALParticipants will receive a single low IV dose of MHAA4549A on Day 1 and standard oseltamivir therapy for minimum of 5 days.
B: MHAA4549A 8400 mg + Oseltamivir
EXPERIMENTALParticipants will receive a single high IV dose of MHAA4549A on Day 1 and standard oseltamivir therapy for minimum of 5 days.
C: Placebo + Oseltamivir
PLACEBO COMPARATORParticipants 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.
Interventions
Participants will receive a single dose of MHAA4549A by IV infusion on Day 1
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.
Participants will receive a single IV dose of placebo matched to MHAA4549A on Day 1
Eligibility Criteria
You may qualify if:
- 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
You may not qualify if:
- 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
- +2 more criteria
Contact the study team to confirm eligibility.
Sponsors & Collaborators
- Genentech, Inc.lead
Study Sites (171)
CHU St Pierre (St Pierre)
Brussels, 1000, Belgium
Hospital Erasme; Neurologie
Brussels, 1070, Belgium
UZ Leuven Gasthuisberg
Leuven, 3000, Belgium
CHU UCL Mont-Godinne
Mont-godinne, 5530, Belgium
Santa Casa de Misericordia; de Belo Horizonte
Belo Horizonte, Minas Gerais, 30150-221, Brazil
Hospital Sao Vicente de Paulo
Passo Fundo, Rio Grande do Sul, 99010-080, Brazil
PUC Campinas
Campinas, São Paulo, 13060-904, Brazil
FUNFARME
São José do Rio Preto, São Paulo, 15090-000, Brazil
Hospital Alemao Oswaldo Cruz; Oncologia
São Paulo, São Paulo, 01323-020, Brazil
Hospital Edmundo Vasconcelos
Vila Clementino, São Paulo, 04038-905, Brazil
MHAT "Dr. Tota Venkova"- Gabrovo
Gabrovo, 5300, Bulgaria
University Multiprofile Hospital for Active Treatment "St. George"
Plovdiv, 4005, Bulgaria
SHATPPD Dr. Dimitar Gramatikov, Ruse Ltd.
Rousse, 7002, Bulgaria
Multiprofile Hospital for Active Treatment AKTA-MEDIKA EOOD
Sevlievo, 5400, Bulgaria
MHAT Lyulin EAD, Department of internal diseases
Sofia, 1336, Bulgaria
MHAT TOKUDA SOFIA/ICU-Intensive Care Unit
Sofia, 1407, Bulgaria
5th Multifunctional Hospital for Active treatment
Sofia, 1606, Bulgaria
Military Medical Academy- MHAT
Sofia, 1606, Bulgaria
University Multiprofile Hospital for Active Treatment and Emergency Medicine N. I. Pirogov EAD
Sofia, 1606, Bulgaria
MBAL St Marina Dep Pulmonology, ICU
Varna, 9010, Bulgaria
Multiprofile District Hospital for Active Treatment Dr. Stefan Cherkezov AD
Veliko Tarnovo, 5000, Bulgaria
Peter Lougheed Centre
Calgary, Alberta, T1Y 6J4, Canada
Alberta Health Services
Calgary, Alberta, T2N 4N2, Canada
Foothills Medical Centre
Calgary, Alberta, T2N 4Z6, Canada
Rockyview General Hospital
Calgary, Alberta, T2V 1P9, Canada
Royal Columbian Hospital
New Westminster, British Columbia, V3L 3W7, Canada
St. Paul's Hospital, Providence Health Care
Vancouver, British Columbia, V6Z 1Y6, Canada
Victoria General Hospital
Victora, British Columbia, V8Z 6R5, Canada
Royal Jubilee Hospital Victoria general Hospital
Victoria, British Columbia, V8R 1J8, Canada
Moncton Hospital
Moncton, New Brunswick, E1C 6Z8, Canada
LHSC - University Hospital; Research Pharmacy
London, Ontario, N6A 5A5, Canada
Lakeridge Health
Oshawa, Ontario, L1G 2B9, Canada
Ottawa Hospital Research Institute
Ottawa, Ontario, K1Y 4E9, Canada
The Ottawa Hospital - Civic Campus
Ottawa, Ontario, K1Y 4E9, Canada
Toronto East General
Toronto, Ontario, M4C 3E7, Canada
University Health Network
Toronto, Ontario, M5G 2N2, Canada
Toronto Western Hospital
Toronto, Ontario, M5T 2S8, Canada
Centre Hospitalier de la Universite Laval
Québec, Quebec, G1V 4G5, Canada
Pavillion Chul-Chuq
Sainte-Foy, Quebec, G1V 4G2, Canada
Centre de santé et de services sociaux de Trois-Rivières
Trois-Rivières, Quebec, G9A1Y1, Canada
Hospital Dr. Hernan Henriquez Aravena
Temuco, 4781151, Chile
Clinica Renaca
Viña del Mar, 2540364, Chile
The University Hospital Brno
Brno, 62500, Czechia
Fakultni nemocnice Hradec Kralove
Hradec Králové, 500 05, Czechia
Anesthesia and Intensive Care Dept., Regional Hospital Liberec
Liberec, 460 63, Czechia
University hospital Ostrava, Clinic of infectious medicine
Ostrava, 708 52, Czechia
Fakultni nemocnice Kralovske Vinohrady, Klinika anesteziologie a resuscitace
Prague, 100 34, Czechia
CH Victor Dupouy
Argenteuil, 95107, France
Centre Hospitalier Universitaire de Clermont Ferrand
Clermont-Ferrand, 63000, France
Service de Réanimation médicale - Bocage Central
Dijon, 21079, France
APHP Raymond Poincare
Garches, 92380, France
CHD Vendée
La Roche-sur-Yon, 85025, France
CHRU Lille
Lille, 59037, France
Réanimation Polyvalente, CHU Limoges
Limoges, 87043, France
CHRU Nancy
Nancy, 54035, France
Archet 1 university Hospital
Nice, 6202, France
HOPITAL COCHIN university hospital
Paris, 75014, France
Réanimation médicale NHC
Strasbourg, 67000, France
Hopital Universitaire Hautepierre
Strasbourg, 67098, France
Service de réanimation médicale, Hôpital Bretonneau
Tours, 37044, France
Uniklinik Köln, Medizinischen Klinik I
Cologne, 50931, Germany
Universitätsklinikum Frankfurt Goethe Universität
Frankfurt, 60590, Germany
Universitätsklinikum Heidelberg
Heidelberg, 69120, Germany
Uniklinikum Mainz
Mainz, 55131, Germany
Uniklinik Tübingen
Tübingen, 72076, Germany
University of Hong Kong
Hong Kong, Hong Kong
Pest Megyei Flor Ferenc Korhaz
Kistarcsa, 2084, Hungary
Jávorszky Ödön Hospital
Vác, 2600, Hungary
Csolnoky Ferenc Kórház
Veszprém, 8200, Hungary
Zala County Hospital ICU
Zalaegerszeg, 8900, Hungary
Haemek Medical Center
Afula, 18101, Israel
Soroka University Medical Centre
Beersheba, 84101, Israel
Wolfson Medical Center
Holon, 58100, Israel
Hadasit Medical Research Services and Development Ltd
Jerusalem, 91999, Israel
Galilee Medical Center
Nahariya, 22100, Israel
Nazareth EMMS Hospital
Nazareth, 16100, Israel
Rabin Medical Center
Petah Tikva, 4941492, Israel
Kaplan Medical Center
Rehovot, 7661041, Israel
Ziv Medical Center
Safed, 1311001, Israel
Tel-Aviv Sourasky Medical Center
Tel Aviv, 64239, Israel
Chaim Sheba Medical Center
Tel Litwinsky, 52661, Israel
University Division of Infective and Tropical Diseases, University of Brescia, Italy
Brescia, Basilicate, Italy
Clinic of Infectious Diseases
Bologna, Emilia-Romagna, 40127, Italy
University Hospital Modena, Intensive Care Unit
Modena, Emilia-Romagna, 41125, Italy
National Institute for Infectious Diseases "L. Spallanzani"
Rome, Lazio, 149, Italy
Asst Di Cremona
Cremona, Lombardy, 26100, Italy
Ospedale San Raffaele - Milano
Milan, Lombardy, 20127, Italy
A.O.U. S. Giovanni di Dio e Ruggi d'Aragona
Salerno, Sardinia, 84131, Italy
Hospital Civil de Guadalajara Dr Juan I Menchaca
Guadalajara, 44280, Mexico
Hospital Civil de Guadalajara Fray Antonio Alcalde
Guadalajara, 44280, Mexico
Instituto Nacional de Ciencias; Medicas y Nutricion; Salvador Zubiran
Mexico City, 14000, Mexico
CEPREP; Hospital Universitario
Monterrey, 64460, Mexico
Hospital General de Tijuana
Tijuana, 22320, Mexico
Centro de Especialidades Medicas Del Estado de Veracruz Dr Rafael Lucio
Xalapa, 91020, Mexico
Jeroen Bosch Ziekenhuis
's-Hertogenbosch, 5223 GZ, Netherlands
Gelre Ziekenhuizen Apeldoorn; Hospitals Pharmacy
Apeldoorn, 7334 DV, Netherlands
LUMC
Leiden, 2300 ZA, Netherlands
UMC Radboud Nijmegen
Nijmegen, 6500 HB, Netherlands
Erasmus Medical Centre; Department of Virology L-359
Rotterdam, 3000 CA, Netherlands
Ikazia Hospital
Rotterdam, 3083AN, Netherlands
UMCU
Utrecht, 3508 GA, Netherlands
Isala
Zwolle, 8025 AB, Netherlands
Auckland City Hospital
Auckland, 1124, New Zealand
Christchurch Hospital
Christchurch, 8011, New Zealand
Tauranga Hospital
Tauranga, 3143, New Zealand
Hospital Regional del Cusco
Cusco, 84, Peru
Hospital Nacional Adolfo Guevara Velasco
Cuzco, 84, Peru
Hospital Guillermo Almenara Irigoyen Hospital Guillermo Almenara Irigoyen Hospital Guillermo Almen
La Victoria, Lima 13, Peru
Clinica Internacional Sede Lima
Lima, Lima 01, Peru
Hospital Nacional; Arzobispo Loayza
Lima, Lima 01, Peru
Hospital Nacional Hipolito; Unanue
Lima, Lima 10, Peru
Hospital Central Fuerza; Aerea del Peru
Lima, Lima 18, Peru
Hospital Maria Auxiliadora
Lima, Lima 29, Peru
Clínica San Gabriel
Lima, Lima 32, Peru
Clinica San Borja
Lima, Lima 41, Peru
Hospital de la Amistad Peru Corea II-2 Santa Rosa
Piura, 20001, Peru
Clinica Divino Nino Jesus; Orden de Malta
San Juán de Miraflores, LIMA 29, Peru
Clinica Peruana Americana
Trujillo, 13011, Peru
Oddział Anestezjologii i Intensywnej Terapii Wojewódzki Specjalistyczny Szpital im dr Wł Biegańsk
Lodz, 91-347, Poland
Wojewodzki Szpital Specjalistyczny
Lublin, 20-718, Poland
Icu Spsk - 2
Szczecin, 70-111, Poland
Oddział Anestezjologii i Intensywnej Terapii;Wojewódzki Szpital Zespolony im. L. Rydygiera
Torun, 87-100, Poland
Municipal Clinical Hospital #8
Chelyabinsk, 454000, Russia
Municipal Healthcare Institution "City Hospital №2"
Engel's, 413124, Russia
Medical Military Academy n.a S.M.Kirov
Saint Petersburg, 194044, Russia
Paciific state medical university
Vladivostok, 690002, Russia
Milpark Hospital
Parktown West, 2196, South Africa
Emmed Research
Pretoria, 0084, South Africa
Clinical Projects Research
Worcester, 6850, South Africa
Pusan National University Hospital
Busan, 602-739, South Korea
Gachon University Gil Hospital
Incheon, South Korea
Korea University Anam Hospital
Seoul, 02841, South Korea
Korea University Guro Hospital
Seoul, 08308, South Korea
Yonsei University Health System/Severance Hospital
Seoul, 120-752, South Korea
Hallym university Kangnam Sacred Heart Hospital; Infectious devision
Seoul, 150-950, South Korea
Wonju Severance Christian Hospital
Wŏnju, 220-701, South Korea
Hospital Universitario Son Espases
Palma de Mallorca, Balearic Islands, 07010, Spain
Mutua de Terrassa
Terrassa, Barcelona, 08221, Spain
Hospital Clinic
Barcelona, Cantabria, 08036, Spain
Hospital de Mataro
Mataro, Cantabria, 08304, Spain
Hospital Universitario Marques de Valdecilla
Santander, Cantabria, 39008, Spain
Hospital del Mar
Barcelona, 08003, Spain
Hospital Universitari Vall d'Hebron
Barcelona, 08035, Spain
Bellvitge University Hospital
Barcelona, 08907, Spain
Hospital Universitario San Cecilio
Granada, 18012, Spain
Hosp. Clinico San Carlos
Madrid, 28040, Spain
Hospital Univ. de Getafe.Servicio de Neurologia
Madrid, 28905, Spain
Joan XXIII University Hospital
Tarragona, 43005, Spain
Servicio de Medicina Intensiva Hospital Universitario la Fe
Valencia, 46026, Spain
Sahlgrenska Universitetssjukhuset
Gothenburg, 413 45, Sweden
Uppsala University Hospital, Department of Infectious Diseases
Gothenburg, 41650, Sweden
Skånes Universitetssjukhus
Mamö, 205 02, Sweden
Norrland Universitetssjukhus
Umeå, 901 85, Sweden
Kaohsiung Medical University Hospital, Cancer Center
Kaohsiung City, 807, Taiwan
Far East Memorial Hospital
New Taipei City, 220, Taiwan
Wanfang Hospital
Taipei, 116, Taiwan
Chang Gung Medical Foundation Linkou Branch
Taoyuan, 333, Taiwan
Kyiv City Clinical Hospital #4
Kyiv, 03110, Ukraine
Kyiv City Clinical Hospital #9
Kyiv, 04060, Ukraine
Municipal Institution City Clinical Infectious Diseases Hospital
Odesa, 65023, Ukraine
Poltava Regional Clinical Infectious Hospital
Poltava, 36011, Ukraine
Municipal Institution Central City Hospital #1 City of Zhytomyr
Zhytomyr, 10002, Ukraine
Queen Elizabeth Hospital
Birmingham, B15 2TH, United Kingdom
Heart of England NHS Trust
Birmingham, B9 5SS, United Kingdom
Queen Elizabeth University Hospital
Glasgow, G51 4TF, United Kingdom
Leeds General Infirmary, Anaesthetic Department, D Floor
Leeds, LS1 3EX, United Kingdom
King College Hospital NHS Foundation Trust
London, SE5 9RS, United Kingdom
University College London Hospitals NHS Foundation Trust - University College Hospital
London, WC1E 6AU, United Kingdom
Southampton University Hospitals NHS Trust
Southampton, SO16 6YD, United Kingdom
University Hospitals of North Midlands NHS Trust-Royal Stoke University Hospital
Stoke-on-Trent, ST4 6QG, United Kingdom
Taunton and Somerset NHS Foundation Trust Musgrove Park Hospital
Taunton, TA1 5DA, United Kingdom
Related Publications (1)
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.
PMID: 32393496DERIVED
MeSH Terms
Conditions
Interventions
Condition Hierarchy (Ancestors)
Intervention Hierarchy (Ancestors)
Results Point of Contact
- Title
- Medical Communications
- Organization
- Hoffmann-La Roche
Study Officials
- STUDY DIRECTOR
Clinical Trials
Hoffmann-La Roche
Publication Agreements
- PI is Sponsor Employee
- No
- Restriction Type
- OTHER
- Restrictive Agreement
- Yes
Study Design
- Study Type
- interventional
- Phase
- phase 2
- Allocation
- RANDOMIZED
- Masking
- DOUBLE
- Who Masked
- PARTICIPANT, INVESTIGATOR
- Purpose
- TREATMENT
- Intervention Model
- PARALLEL
- Sponsor Type
- INDUSTRY
- Responsible Party
- SPONSOR
Study Record Dates
First Submitted
November 14, 2014
First Posted
November 18, 2014
Study Start
January 14, 2015
Primary Completion
May 23, 2017
Study Completion
May 23, 2017
Last Updated
June 18, 2018
Results First Posted
June 18, 2018
Record last verified: 2018-05