InfluenzaPhase 2NCT02293863
A Study of MHAA4549A in Combination With Oseltamivir Versus Oseltamivir in Participants With Severe Influenza A Infection
A Phase 2 study testing MHAA4549A and Oseltamivir in people with Influenza, run by Genentech, Inc. at 171 sites in 25 countries.
Trial 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. Read more about this study
- Who is it for?
- Ages 18 years and older
- Conditions the study is for
- Influenza
- What is being tested?
- MHAA4549A and Oseltamivir
- Type of treatment
- Pill or oral medicine, Injection or infusion
- Could I receive a placebo?
- Yes, some participants may receive a placebo
- How many people
- 168 participants
- Where
- 171 sitesin 25 countries
- Study dates
- 14 Jan 2015to 23 May 2017
- Phase
- Phase 2
- Are there results?
- Yes, posted in the registrySummary in the doctors' view
Key requirements
Who can take part, as listed by the sponsor. Only the study team can confirm whether you are eligible, so take this list to your doctor.
- Ages 18 years and older
- All sexes
- No healthy volunteers
- Adult, Older adult
Who may be able to join
- 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
Who cannot join
- 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
Show all 17Show fewer
- 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 locations and contacts
171 sites in 25 countries.
171 sites in 25 countries
Canada19 sites
Peter Lougheed Centre
Calgary, Alberta, T1Y 6J4
Alberta Health Services
Calgary, Alberta, T2N 4N2
Foothills Medical Centre
Calgary, Alberta, T2N 4Z6
Rockyview General Hospital
Calgary, Alberta, T2V 1P9
LHSC - University Hospital; Research Pharmacy
London, Ontario, N6A 5A5
Moncton Hospital
Moncton, New Brunswick, E1C 6Z8
Royal Columbian Hospital
New Westminster, British Columbia, V3L 3W7
Lakeridge Health
Oshawa, Ontario, L1G 2B9
Ottawa Hospital Research Institute
Ottawa, Ontario, K1Y 4E9
The Ottawa Hospital - Civic Campus
Ottawa, Ontario, K1Y 4E9
Centre Hospitalier de la Universite Laval
Québec, Quebec, G1V 4G5
Pavillion Chul-Chuq
Sainte-Foy, Quebec, G1V 4G2
Toronto East General
Toronto, Ontario, M4C 3E7
University Health Network
Toronto, Ontario, M5G 2N2
Toronto Western Hospital
Toronto, Ontario, M5T 2S8
Centre de santé et de services sociaux de Trois-Rivières
Trois-Rivières, Quebec, G9A1Y1
St. Paul's Hospital, Providence Health Care
Vancouver, British Columbia, V6Z 1Y6
Victoria General Hospital
Victora, British Columbia, V8Z 6R5
Royal Jubilee Hospital Victoria general Hospital
Victoria, British Columbia, V8R 1J8
France13 sites
CH Victor Dupouy
Argenteuil, 95107
Centre Hospitalier Universitaire de Clermont Ferrand
Clermont-Ferrand, 63000
Service de Réanimation médicale - Bocage Central
Dijon, 21079
APHP Raymond Poincare
Garches, 92380
CHD Vendée
La Roche-sur-Yon, 85025
CHRU Lille
Lille, 59037
Réanimation Polyvalente, CHU Limoges
Limoges, 87043
CHRU Nancy
Nancy, 54035
Archet 1 university Hospital
Nice, 6202
HOPITAL COCHIN university hospital
Paris, 75014
Réanimation médicale NHC
Strasbourg, 67000
Hopital Universitaire Hautepierre
Strasbourg, 67098
Service de réanimation médicale, Hôpital Bretonneau
Tours, 37044
Peru13 sites
Hospital Regional del Cusco
Cusco, 84
Hospital Nacional Adolfo Guevara Velasco
Cuzco, 84
Hospital Guillermo Almenara Irigoyen Hospital Guillermo Almenara Irigoyen Hospital Guillermo Almen
La Victoria, Lima 13
Clinica Internacional Sede Lima
Lima, Lima 01
Hospital Nacional; Arzobispo Loayza
Lima, Lima 01
Hospital Nacional Hipolito; Unanue
Lima, Lima 10
Hospital Central Fuerza; Aerea del Peru
Lima, Lima 18
Hospital Maria Auxiliadora
Lima, Lima 29
Clínica San Gabriel
Lima, Lima 32
Clinica San Borja
Lima, Lima 41
Hospital de la Amistad Peru Corea II-2 Santa Rosa
Piura, 20001
Clinica Divino Nino Jesus; Orden de Malta
San Juán de Miraflores, LIMA 29
Clinica Peruana Americana
Trujillo, 13011
Spain13 sites
Hospital Clinic
Barcelona, Cantabria, 08036
Hospital del Mar
Barcelona, 08003
Hospital Universitari Vall d'Hebron
Barcelona, 08035
Bellvitge University Hospital
Barcelona, 08907
Hospital Universitario San Cecilio
Granada, 18012
Hosp. Clinico San Carlos
Madrid, 28040
Hospital Univ. de Getafe.Servicio de Neurologia
Madrid, 28905
Hospital de Mataro
Mataro, Cantabria, 08304
Hospital Universitario Son Espases
Palma de Mallorca, Balearic Islands, 07010
Hospital Universitario Marques de Valdecilla
Santander, Cantabria, 39008
Joan XXIII University Hospital
Tarragona, 43005
Mutua de Terrassa
Terrassa, Barcelona, 08221
Servicio de Medicina Intensiva Hospital Universitario la Fe
Valencia, 46026
Bulgaria11 sites
MHAT "Dr. Tota Venkova"- Gabrovo
Gabrovo, 5300
University Multiprofile Hospital for Active Treatment "St. George"
Plovdiv, 4005
SHATPPD Dr. Dimitar Gramatikov, Ruse Ltd.
Rousse, 7002
Multiprofile Hospital for Active Treatment AKTA-MEDIKA EOOD
Sevlievo, 5400
MHAT Lyulin EAD, Department of internal diseases
Sofia, 1336
MHAT TOKUDA SOFIA/ICU-Intensive Care Unit
Sofia, 1407
5th Multifunctional Hospital for Active treatment
Sofia, 1606
Military Medical Academy- MHAT
Sofia, 1606
University Multiprofile Hospital for Active Treatment and Emergency Medicine N. I. Pirogov EAD
Sofia, 1606
MBAL St Marina Dep Pulmonology, ICU
Varna, 9010
Multiprofile District Hospital for Active Treatment Dr. Stefan Cherkezov AD
Veliko Tarnovo, 5000
Israel11 sites
Haemek Medical Center
Afula, 18101
Soroka University Medical Centre
Beersheba, 84101
Wolfson Medical Center
Holon, 58100
Hadasit Medical Research Services and Development Ltd
Jerusalem, 91999
Galilee Medical Center
Nahariya, 22100
Nazareth EMMS Hospital
Nazareth, 16100
Rabin Medical Center
Petah Tikva, 4941492
Kaplan Medical Center
Rehovot, 7661041
Ziv Medical Center
Safed, 1311001
Tel-Aviv Sourasky Medical Center
Tel Aviv, 64239
Chaim Sheba Medical Center
Tel HaShomer, 52661
United Kingdom9 sites
Queen Elizabeth Hospital
Birmingham, B15 2TH
Heart of England NHS Trust
Birmingham, B9 5SS
Queen Elizabeth University Hospital
Glasgow, G51 4TF
Leeds General Infirmary, Anaesthetic Department, D Floor
Leeds, LS1 3EX
King College Hospital NHS Foundation Trust
London, SE5 9RS
University College London Hospitals NHS Foundation Trust - University College Hospital
London, WC1E 6AU
Southampton University Hospitals NHS Trust
Southampton, SO16 6YD
University Hospitals of North Midlands NHS Trust-Royal Stoke University Hospital
Stoke-on-Trent, ST4 6QG
Taunton and Somerset NHS Foundation Trust Musgrove Park Hospital
Taunton, TA1 5DA
Netherlands8 sites
Jeroen Bosch Ziekenhuis
's-Hertogenbosch, 5223 GZ
Gelre Ziekenhuizen Apeldoorn; Hospitals Pharmacy
Apeldoorn, 7334 DV
LUMC
Leiden, 2300 ZA
UMC Radboud Nijmegen
Nijmegen, 6500 HB
Erasmus Medical Centre; Department of Virology L-359
Rotterdam, 3000 CA
Ikazia Hospital
Rotterdam, 3083AN
UMCU
Utrecht, 3508 GA
Isala
Zwolle, 8025 AB
Italy7 sites
Clinic of Infectious Diseases
Bologna, Emilia-Romagna, 40127
University Division of Infective and Tropical Diseases, University of Brescia, Italy
Brescia, Basilicate
Asst Di Cremona
Cremona, Lombardy, 26100
Ospedale San Raffaele - Milano
Milan, Lombardy, 20127
University Hospital Modena, Intensive Care Unit
Modena, Emilia-Romagna, 41125
National Institute for Infectious Diseases "L. Spallanzani"
Rome, Lazio, 149
A.O.U. S. Giovanni di Dio e Ruggi d'Aragona
Salerno, Sardinia, 84131
South Korea7 sites
Pusan National University Hospital
Busan, 602-739
Gachon University Gil Hospital
Incheon
Korea University Anam Hospital
Seoul, 02841
Korea University Guro Hospital
Seoul, 08308
Yonsei University Health System/Severance Hospital
Seoul, 120-752
Hallym university Kangnam Sacred Heart Hospital; Infectious devision
Seoul, 150-950
Wonju Severance Christian Hospital
Wŏnju, 220-701
Brazil6 sites
Santa Casa de Misericordia; de Belo Horizonte
Belo Horizonte, Minas Gerais, 30150-221
PUC Campinas
Campinas, São Paulo, 13060-904
Hospital Sao Vicente de Paulo
Passo Fundo, Rio Grande do Sul, 99010-080
FUNFARME
São José do Rio Preto, São Paulo, 15090-000
Hospital Alemao Oswaldo Cruz; Oncologia
São Paulo, São Paulo, 01323-020
Hospital Edmundo Vasconcelos
Vila Clementino, São Paulo, 04038-905
Mexico6 sites
Hospital Civil de Guadalajara Dr Juan I Menchaca
Guadalajara, 44280
Hospital Civil de Guadalajara Fray Antonio Alcalde
Guadalajara, 44280
Instituto Nacional de Ciencias; Medicas y Nutricion; Salvador Zubiran
Mexico City, 14000
CEPREP; Hospital Universitario
Monterrey, 64460
Hospital General de Tijuana
Tijuana, 22320
Centro de Especialidades Medicas Del Estado de Veracruz Dr Rafael Lucio
Xalapa, 91020
Czechia5 sites
The University Hospital Brno
Brno, 62500
Fakultni nemocnice Hradec Kralove
Hradec Králové, 500 05
Anesthesia and Intensive Care Dept., Regional Hospital Liberec
Liberec, 460 63
University hospital Ostrava, Clinic of infectious medicine
Ostrava, 708 52
Fakultni nemocnice Kralovske Vinohrady, Klinika anesteziologie a resuscitace
Prague, 100 34
Germany5 sites
Uniklinik Köln, Medizinischen Klinik I
Cologne, 50931
Universitätsklinikum Frankfurt Goethe Universität
Frankfurt, 60590
Universitätsklinikum Heidelberg
Heidelberg, 69120
Uniklinikum Mainz
Mainz, 55131
Uniklinik Tübingen
Tübingen, 72076
Ukraine5 sites
Kyiv City Clinical Hospital #4
Kyiv, 03110
Kyiv City Clinical Hospital #9
Kyiv, 04060
Municipal Institution City Clinical Infectious Diseases Hospital
Odesa, 65023
Poltava Regional Clinical Infectious Hospital
Poltava, 36011
Municipal Institution Central City Hospital #1 City of Zhytomyr
Zhytomyr, 10002
Belgium4 sites
CHU St Pierre (St Pierre)
Brussels, 1000
Hospital Erasme; Neurologie
Brussels, 1070
UZ Leuven Gasthuisberg
Leuven, 3000
CHU UCL Mont-Godinne
Mont-godinne, 5530
Hungary4 sites
Pest Megyei Flor Ferenc Korhaz
Kistarcsa, 2084
Jávorszky Ödön Hospital
Vác, 2600
Csolnoky Ferenc Kórház
Veszprém, 8200
Zala County Hospital ICU
Zalaegerszeg, 8900
Poland4 sites
Oddział Anestezjologii i Intensywnej Terapii Wojewódzki Specjalistyczny Szpital im dr Wł Biegańsk
Lodz, 91-347
Wojewodzki Szpital Specjalistyczny
Lublin, 20-718
Icu Spsk - 2
Szczecin, 70-111
Oddział Anestezjologii i Intensywnej Terapii;Wojewódzki Szpital Zespolony im. L. Rydygiera
Torun, 87-100
Russia4 sites
Municipal Clinical Hospital #8
Chelyabinsk, 454000
Municipal Healthcare Institution "City Hospital №2"
Engel's, 413124
Medical Military Academy n.a S.M.Kirov
Saint Petersburg, 194044
Paciific state medical university
Vladivostok, 690002
Sweden4 sites
Sahlgrenska Universitetssjukhuset
Gothenburg, 413 45
Uppsala University Hospital, Department of Infectious Diseases
Gothenburg, 41650
Skånes Universitetssjukhus
Mamö, 205 02
Norrland Universitetssjukhus
Umeå, 901 85
Taiwan4 sites
Kaohsiung Medical University Hospital, Cancer Center
Kaohsiung City, 807
Far East Memorial Hospital
New Taipei City, 220
Wanfang Hospital
Taipei, 116
Chang Gung Medical Foundation Linkou Branch
Taoyuan City, 333
New Zealand3 sites
Auckland City Hospital
Auckland, 1124
Christchurch Hospital
Christchurch, 8011
Tauranga Hospital
Tauranga, 3143
South Africa3 sites
Milpark Hospital
Parktown West, 2196
Emmed Research
Pretoria, 0084
Clinical Projects Research
Worcester, 6850
Chile2 sites
Hospital Dr. Hernan Henriquez Aravena
Temuco, 4781151
Clinica Renaca
Viña del Mar, 2540364
About this study
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.
- Conditions
- Influenza
- Being tested
- MHAA4549A, Oseltamivir, Placebo
- Medical subject headings
- Influenza, Human
What participants receive
What participants receive. In a randomised study each person is assigned to one group by chance.
MHAA4549ADrug
Participants will receive a single dose of MHAA4549A by IV infusion on Day 1
OseltamivirDrug
Also called Tamiflu
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.
PlaceboDrug
Participants will receive a single IV dose of placebo matched to MHAA4549A on Day 1
| Study group | Role | What they receive |
|---|---|---|
| A: MHAA4549A 3600 mg + Oseltamivir | Experimental | Participants will receive a single low IV dose of MHAA4549A on Day 1 and standard oseltamivir therapy for minimum of 5 days. Receives: Drug: MHAA4549A; Drug: Oseltamivir |
| B: MHAA4549A 8400 mg + Oseltamivir | Experimental | Participants will receive a single high IV dose of MHAA4549A on Day 1 and standard oseltamivir therapy for minimum of 5 days. Receives: Drug: MHAA4549A; Drug: Oseltamivir |
| C: Placebo + Oseltamivir | Placebo comparator | 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. Receives: Drug: Oseltamivir; Drug: Placebo |
What is being measured
The primary outcome is the main question the study is designed to answer.
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.
Measured: 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.
Measured: 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.
Measured: From randomization up to 60 days
Secondary outcomes (18)
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.
Measured: 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.
Measured: 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.
Measured: From randomization up to 60 days
Percentage of Participants Who Died Due to Any Cause
Measured: 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).
Measured: 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.
Measured: 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.
Measured: 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
Measured: From randomization up to 60 days
Duration of Intensive Care Unit (ICU) Stay
Measured: From randomization up to 60 days
Percentage of Participants Using Antibiotics for Respiratory Infections
Measured: 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.
Measured: From randomization up to 60 days
Percentage of Participants Readmitted to Hospital Due to Any Cause
Measured: Days 30 and 60
Duration of Ventilation
Measured: 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).
Measured: 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
Measured: 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
Measured: 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
Measured: 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
Measured: 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)
Timeline
From the start of the study to its completion; the mark is today. Estimated dates are the sponsor’s plan.
- First posted18 Nov 2014 (estimated)
- Study start14 Jan 2015
- Primary completion23 May 2017
- Study completion23 May 2017
Resources
- Official record on ClinicalTrials.govThe registry entry this page is built from, with its full change history.
- Posted resultsParticipant flow, outcome measures and adverse events reported by the sponsor.
- Publications (1)Papers the sponsor has linked to this study.
- Other trials for InfluenzaStudies of the same condition, open and under way.
- More trials run by Genentech, Inc.The sponsor's other registered studies.
- What the trial phases meanHow a treatment moves from first tests in people to approval.
More details
For doctors and researchers: how the study is designed, who runs it, and its registry IDs.
Study design
- Study type
- Interventional
- Phase
- Phase 2
- Primary purpose
- Treatment
- Allocation
- Randomised
- Intervention model
- Parallel groups
- Masking
- Double blind
- Who is masked
- Participant, Investigator
- Enrolment
- 168 participants (actual)
Sponsor and investigators
- Lead sponsor
- Genentech, Inc.
- Sponsor type
- Industry (pharma, biotech, devices)
- Responsible party
- Sponsor
- Investigators
- Clinical Trials, Study director, Hoffmann-La Roche
IDs, dates and publications
- ClinicalTrials.gov ID
- NCT02293863
- Sponsor's protocol ID
- GV29216
- Other IDs
- 2014-000461-43, 2014
- Status last verified
- May 2018
- First submitted
- 14 Nov 2014
- Last updated
- 18 Jun 2018
- Results posted
- Yes, on ClinicalTrials.gov
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.
PubMed 32393496
Study at a glance
From the registry record, last updated by the sponsor on 18 Jun 2018. Recruitment status is as the sponsor reported it: confirm with the study team.
- Official title
- A Study of MHAA4549A in Combination With Oseltamivir Versus Oseltamivir in Participants With Severe Influenza A Infection
- ClinicalTrials.gov ID
- NCT02293863
- Acronym / sponsor ID
- GV29216
- Conditions
- Influenza
- Phase
- Phase 2
- Study type
- Interventional
- Recruitment status
- Completed
- Enrolment
- 168 participants (actual)
- Lead sponsor
- Genentech, Inc.Industry (pharma, biotech, devices)
- Study start
- 14 Jan 2015 (actual)
- Primary completion
- 23 May 2017 (actual)
- Study completion
- 23 May 2017 (actual)
- First posted
- 18 Nov 2014 (estimated)
- Results
- Posted 18 Jun 2018
Clinical summary
The research question as the sponsor registered it. This describes what the study plans to test, not what it found.
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 design
- Primary purpose
- Treatment
- Allocation
- Randomised
- Intervention model
- Parallel groups
- Masking
- Double blind (participant, investigator)
- Number of arms
- 3
| Arm | Type | Receives |
|---|---|---|
| A: MHAA4549A 3600 mg + Oseltamivir | Experimental | Drug: MHAA4549A, Drug: OseltamivirParticipants 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 | Experimental | Drug: MHAA4549A, Drug: OseltamivirParticipants 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 comparator | Drug: Oseltamivir, Drug: PlaceboParticipants 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. |
Who may qualify
- Ages
- 18 years and older
- Sex
- All
- Healthy volunteers
- Not accepted
- Age groups
- Adult, Older adult
Key inclusion criteria (4 listed)
- 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
Key exclusion criteria (17 listed)
- 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
Eligibility is decided by the study team after screening; this overview does not establish that a patient qualifies. Full inclusion and exclusion criteria.
Interventions
| Intervention | Type | Arms |
|---|---|---|
| MHAA4549AParticipants will receive a single dose of MHAA4549A by IV infusion on Day 1 | Drug | A: MHAA4549A 3600 mg + Oseltamivir, B: MHAA4549A 8400 mg + Oseltamivir |
| OseltamivirAlso: TamifluParticipants 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. | Drug | A: MHAA4549A 3600 mg + Oseltamivir, B: MHAA4549A 8400 mg + Oseltamivir, C: Placebo + Oseltamivir |
| PlaceboParticipants will receive a single IV dose of placebo matched to MHAA4549A on Day 1 | Drug | C: Placebo + Oseltamivir |
Primary outcome
Percentage of Participants With Adverse Events
Time frame: From randomization up to 60 days
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.
Number of Participants With Anti-Therapeutic Antibodies (ATA) to MHAA4549A During and Following Administration of MHAA4549A
Time frame: From randomization up to 60 days
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.
Time to Normalization of Respiratory Function
Time frame: From randomization up to 60 days
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.
18 secondary outcomes
Percentage of Participants by Clinical Status Using a Categorical Ordinal Outcome
Time frame: Days 1-7, 14 and 30
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
Percentage of Participants Who Died Due to Any Cause
Time frame: Days 14, 30 and 60
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)
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 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)
Duration of Hospitalization
Time frame: From randomization up to 60 days
Duration of Intensive Care Unit (ICU) Stay
Time frame: From randomization up to 60 days
Percentage of Participants Using Antibiotics for Respiratory Infections
Time frame: From randomization up to 60 days
Percentage of Participants With Secondary Complications of Influenza
Time frame: From randomization up to 60 days
Percentage of Participants Readmitted to Hospital Due to Any Cause
Time frame: Days 30 and 60
Duration of Ventilation
Time frame: From randomization up to 60 days
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)
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)
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)
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)
Results and safety
Loading the posted results from ClinicalTrials.gov…
Research links
- Official record on ClinicalTrials.govLast updated by the sponsor 18 Jun 2018.
- Posted resultsParticipant flow, baseline, all outcome measures and adverse events.
- Derived from this study: PubMed 32393496Lim 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.
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Referral and contact
AzTrials does not enrol participants or take referrals. Contact the study team or a site listed below; they decide who can take part. This study is not recruiting at the moment.
Clinical Trials study director
Hoffmann-La Roche
171 sites in 25 countries: see every site and its status.
Questions about this trial
What is this clinical trial studying?
A Phase 2 study testing MHAA4549A and Oseltamivir in people with Influenza, run by Genentech, Inc. at 171 sites in 25 countries.
The full registered description is in the About this study section and the official record.
Who may be eligible to take part?
The sponsor lists 4 inclusion and 17 exclusion criteria. Eligibility is decided by the study team after screening, so read the full criteria and contact a listed site.
Is this clinical trial currently recruiting?
The record says: finished, as of the sponsor's last update on 18 Jun 2018. Status can change between updates, so confirm with the study contact before making plans.
Where is the study taking place?
The record lists 171 sites in Canada, France, Peru, Spain, Bulgaria and 20 more countries. Whether a site is taking part right now should be confirmed with that site. See every site.
What are the possible benefits and risks?
They depend on the study and the treatment, and no study can promise a benefit. Some participants in this study may receive a placebo. The study team explains the known risks during informed consent, before anyone joins; the record itself does not list them.
What does this phase mean?
Phase 2 studies give the treatment to a larger group to see whether it has the intended effect and to keep checking safety.
Not every study follows the same path, and some studies (observational studies, device studies) have no phase.
Are results available for this study?
Yes. Results are posted in the registry (first posted 18 Jun 2018). A summary is in the For doctors view, and the full results are on ClinicalTrials.gov.
How can a doctor refer a patient or contact the research team?
The record lists no contact. The official record names the sponsor, who can be asked directly. AzTrials does not enrol participants or take referrals.
What does the primary outcome measure?
Percentage of Participants With Adverse Events (time frame: From randomization up to 60 days). The study lists 3 primary outcomes in all. It is what the study was designed to measure, not a finding.
Where can I read the original study information?
On the ClinicalTrials.gov record for NCT02293863, which also lists 1 linked publication.
Does a listing mean the treatment is approved or proven to work?
No. A listing means the study is registered. It does not show that the treatment is safe, works, or is approved by a regulator.
How often is this information updated?
AzTrials copies changed records from ClinicalTrials.gov every night and reloads the whole registry every week. The sponsor last updated this record on 18 Jun 2018.