The ANZCTR website will be unavailable from 1pm until 3pm (AEDT) on Wednesday the 30th of October for website maintenance. Please be sure to log out of the system in order to avoid any loss of data.

The safety and scientific validity of this study is the responsibility of the study sponsor and investigators. Listing a study does not mean it has been endorsed by the ANZCTR. Before participating in a study, talk to your health care provider and refer to this information for consumers
Trial details imported from ClinicalTrials.gov

For full trial details, please see the original record at https://clinicaltrials.gov/study/NCT02293863




Registration number
NCT02293863
Ethics application status
Date submitted
14/11/2014
Date registered
18/11/2014
Date last updated
18/06/2018

Titles & IDs
Public title
A Study of MHAA4549A in Combination With Oseltamivir Versus Oseltamivir in Participants With Severe Influenza A Infection
Scientific title
Secondary ID [1] 0 0
2014-000461-43
Secondary ID [2] 0 0
GV29216
Universal Trial Number (UTN)
Trial acronym
Linked study record

Health condition
Health condition(s) or problem(s) studied:
Influenza 0 0
Condition category
Condition code

Intervention/exposure
Study type
Interventional
Description of intervention(s) / exposure
Treatment: Drugs - MHAA4549A
Treatment: Drugs - Oseltamivir
Treatment: Drugs - Placebo

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.

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.

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.


Treatment: Drugs: MHAA4549A
Participants will receive a single dose of MHAA4549A by IV infusion on Day 1

Treatment: Drugs: 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.

Treatment: Drugs: Placebo
Participants will receive a single IV dose of placebo matched to MHAA4549A on Day 1

Intervention code [1] 0 0
Treatment: Drugs
Comparator / control treatment
Control group

Outcomes
Primary outcome [1] 0 0
Percentage of Participants With Adverse Events
Timepoint [1] 0 0
From randomization up to 60 days
Primary outcome [2] 0 0
Number of Participants With Anti-Therapeutic Antibodies (ATA) to MHAA4549A During and Following Administration of MHAA4549A
Timepoint [2] 0 0
From randomization up to 60 days
Primary outcome [3] 0 0
Time to Normalization of Respiratory Function
Timepoint [3] 0 0
From randomization up to 60 days
Secondary outcome [1] 0 0
Percentage of Participants by Clinical Status Using a Categorical Ordinal Outcome
Timepoint [1] 0 0
Days 1-7, 14 and 30
Secondary outcome [2] 0 0
Percentage of Participants With Clinical Failure
Timepoint [2] 0 0
24 hours after end of infusion (infusion duration = approximately 120 minutes) up to Day 60
Secondary outcome [3] 0 0
Percentage of Participants With Clinical Resolution of Abnormal Vital Signs
Timepoint [3] 0 0
From randomization up to 60 days
Secondary outcome [4] 0 0
Percentage of Participants Who Died Due to Any Cause
Timepoint [4] 0 0
Days 14, 30 and 60
Secondary outcome [5] 0 0
Area Under Viral Load-Time Curve (AUEC ) of Influenza A Virus
Timepoint [5] 0 0
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)
Secondary outcome [6] 0 0
Peak Influenza A Viral Load
Timepoint [6] 0 0
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)
Secondary outcome [7] 0 0
Duration of Viral Shedding
Timepoint [7] 0 0
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)
Secondary outcome [8] 0 0
Duration of Hospitalization
Timepoint [8] 0 0
From randomization up to 60 days
Secondary outcome [9] 0 0
Duration of Intensive Care Unit (ICU) Stay
Timepoint [9] 0 0
From randomization up to 60 days
Secondary outcome [10] 0 0
Percentage of Participants Using Antibiotics for Respiratory Infections
Timepoint [10] 0 0
From randomization up to 60 days
Secondary outcome [11] 0 0
Percentage of Participants With Secondary Complications of Influenza
Timepoint [11] 0 0
From randomization up to 60 days
Secondary outcome [12] 0 0
Percentage of Participants Readmitted to Hospital Due to Any Cause
Timepoint [12] 0 0
Days 30 and 60
Secondary outcome [13] 0 0
Duration of Ventilation
Timepoint [13] 0 0
From randomization up to 60 days
Secondary outcome [14] 0 0
Area Under Serum Concentration-Time Curve From Time 0 to Infinity (AUC ) of MHAA4549A
Timepoint [14] 0 0
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)
Secondary outcome [15] 0 0
Maximum Serum Concentration (Cmax ) of MHAA4549A
Timepoint [15] 0 0
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)
Secondary outcome [16] 0 0
Elimination Half-Life (Terminal t1/2) of MHAA4549A
Timepoint [16] 0 0
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)
Secondary outcome [17] 0 0
Observed Clearance (CL-obs) of MHAA4549A
Timepoint [17] 0 0
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)
Secondary outcome [18] 0 0
Observed Steady State Volume of Distribution (Vss_obs) of MHAA4549A
Timepoint [18] 0 0
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)

Eligibility
Key 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
Minimum age
18 Years
Maximum age
No limit
Sex
Both males and females
Can healthy volunteers participate?
No
Key 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 design
Purpose of the study
Treatment
Allocation to intervention
Randomised controlled trial
Procedure for enrolling a subject and allocating the treatment (allocation concealment procedures)
Methods used to generate the sequence in which subjects will be randomised (sequence generation)
Masking / blinding
Blinded (masking used)
Who is / are masked / blinded?
The people receiving the treatment/s


The people analysing the results/data
Intervention assignment
Parallel
Other design features
Phase
Phase 2
Type of endpoint/s
Statistical methods / analysis

Recruitment
Recruitment status
Completed
Data analysis
Reason for early stopping/withdrawal
Other reasons
Date of first participant enrolment
Anticipated
Actual
Date of last participant enrolment
Anticipated
Actual
Date of last data collection
Anticipated
Actual
Sample size
Target
Accrual to date
Final
Recruitment in Australia
Recruitment state(s)
Recruitment outside Australia
Country [1] 0 0
Belgium
State/province [1] 0 0
Brussels
Country [2] 0 0
Belgium
State/province [2] 0 0
Bruxelles
Country [3] 0 0
Belgium
State/province [3] 0 0
Leuven
Country [4] 0 0
Belgium
State/province [4] 0 0
Mont-godinne
Country [5] 0 0
Brazil
State/province [5] 0 0
MG
Country [6] 0 0
Brazil
State/province [6] 0 0
RS
Country [7] 0 0
Brazil
State/province [7] 0 0
SP
Country [8] 0 0
Bulgaria
State/province [8] 0 0
Gabrovo
Country [9] 0 0
Bulgaria
State/province [9] 0 0
Plovdiv
Country [10] 0 0
Bulgaria
State/province [10] 0 0
Ruse
Country [11] 0 0
Bulgaria
State/province [11] 0 0
Sevlievo
Country [12] 0 0
Bulgaria
State/province [12] 0 0
Sofia
Country [13] 0 0
Bulgaria
State/province [13] 0 0
Varna
Country [14] 0 0
Bulgaria
State/province [14] 0 0
Veliko Tarnovo
Country [15] 0 0
Canada
State/province [15] 0 0
Alberta
Country [16] 0 0
Canada
State/province [16] 0 0
British Columbia
Country [17] 0 0
Canada
State/province [17] 0 0
New Brunswick
Country [18] 0 0
Canada
State/province [18] 0 0
Ontario
Country [19] 0 0
Canada
State/province [19] 0 0
Quebec
Country [20] 0 0
Chile
State/province [20] 0 0
Temuco
Country [21] 0 0
Chile
State/province [21] 0 0
Vina del Mar
Country [22] 0 0
Czechia
State/province [22] 0 0
Brno
Country [23] 0 0
Czechia
State/province [23] 0 0
Hradec Kralove
Country [24] 0 0
Czechia
State/province [24] 0 0
Liberec
Country [25] 0 0
Czechia
State/province [25] 0 0
Ostrava
Country [26] 0 0
Czechia
State/province [26] 0 0
Praha 10
Country [27] 0 0
France
State/province [27] 0 0
Argenteuil
Country [28] 0 0
France
State/province [28] 0 0
Clermont-ferrand
Country [29] 0 0
France
State/province [29] 0 0
Dijon
Country [30] 0 0
France
State/province [30] 0 0
Garches
Country [31] 0 0
France
State/province [31] 0 0
La Roche Sur Yon
Country [32] 0 0
France
State/province [32] 0 0
Lille
Country [33] 0 0
France
State/province [33] 0 0
Limoges
Country [34] 0 0
France
State/province [34] 0 0
Nancy
Country [35] 0 0
France
State/province [35] 0 0
Nice
Country [36] 0 0
France
State/province [36] 0 0
Paris
Country [37] 0 0
France
State/province [37] 0 0
Strasbourg
Country [38] 0 0
France
State/province [38] 0 0
Tours
Country [39] 0 0
Germany
State/province [39] 0 0
Frankfurt
Country [40] 0 0
Germany
State/province [40] 0 0
Heidelberg
Country [41] 0 0
Germany
State/province [41] 0 0
Koeln
Country [42] 0 0
Germany
State/province [42] 0 0
Mainz
Country [43] 0 0
Germany
State/province [43] 0 0
Tuebingen
Country [44] 0 0
Hong Kong
State/province [44] 0 0
Hong Kong
Country [45] 0 0
Hungary
State/province [45] 0 0
Kistarcsa
Country [46] 0 0
Hungary
State/province [46] 0 0
Veszprém
Country [47] 0 0
Hungary
State/province [47] 0 0
Vác
Country [48] 0 0
Hungary
State/province [48] 0 0
Zalaegerszeg
Country [49] 0 0
Israel
State/province [49] 0 0
Afula
Country [50] 0 0
Israel
State/province [50] 0 0
Beer-Sheva
Country [51] 0 0
Israel
State/province [51] 0 0
Holon
Country [52] 0 0
Israel
State/province [52] 0 0
Jerusalem
Country [53] 0 0
Israel
State/province [53] 0 0
Nahariya
Country [54] 0 0
Israel
State/province [54] 0 0
Nazareth
Country [55] 0 0
Israel
State/province [55] 0 0
Petah Tikva
Country [56] 0 0
Israel
State/province [56] 0 0
Rehovot
Country [57] 0 0
Israel
State/province [57] 0 0
Tel Aviv
Country [58] 0 0
Israel
State/province [58] 0 0
Tel Hashomer
Country [59] 0 0
Israel
State/province [59] 0 0
Zefat
Country [60] 0 0
Italy
State/province [60] 0 0
Basilicata
Country [61] 0 0
Italy
State/province [61] 0 0
Emilia-Romagna
Country [62] 0 0
Italy
State/province [62] 0 0
Lazio
Country [63] 0 0
Italy
State/province [63] 0 0
Lombardia
Country [64] 0 0
Italy
State/province [64] 0 0
Sardegna
Country [65] 0 0
Korea, Republic of
State/province [65] 0 0
Busan
Country [66] 0 0
Korea, Republic of
State/province [66] 0 0
Incheon
Country [67] 0 0
Korea, Republic of
State/province [67] 0 0
Seoul
Country [68] 0 0
Korea, Republic of
State/province [68] 0 0
Wonju
Country [69] 0 0
Mexico
State/province [69] 0 0
Guadalajara
Country [70] 0 0
Mexico
State/province [70] 0 0
Mexico, Distrito Federal
Country [71] 0 0
Mexico
State/province [71] 0 0
Monterrey
Country [72] 0 0
Mexico
State/province [72] 0 0
Tijuana
Country [73] 0 0
Mexico
State/province [73] 0 0
Xalapa-enriquez
Country [74] 0 0
Netherlands
State/province [74] 0 0
'S Hertogenbosch
Country [75] 0 0
Netherlands
State/province [75] 0 0
Apeldoorn
Country [76] 0 0
Netherlands
State/province [76] 0 0
Leiden
Country [77] 0 0
Netherlands
State/province [77] 0 0
Nijmegen
Country [78] 0 0
Netherlands
State/province [78] 0 0
Rotterdam
Country [79] 0 0
Netherlands
State/province [79] 0 0
Utrecht
Country [80] 0 0
Netherlands
State/province [80] 0 0
Zwolle
Country [81] 0 0
New Zealand
State/province [81] 0 0
Auckland
Country [82] 0 0
New Zealand
State/province [82] 0 0
Christchurch
Country [83] 0 0
New Zealand
State/province [83] 0 0
Tauranga
Country [84] 0 0
Peru
State/province [84] 0 0
Cusco
Country [85] 0 0
Peru
State/province [85] 0 0
Cuzco
Country [86] 0 0
Peru
State/province [86] 0 0
La Victoria
Country [87] 0 0
Peru
State/province [87] 0 0
LIma
Country [88] 0 0
Peru
State/province [88] 0 0
Lima
Country [89] 0 0
Peru
State/province [89] 0 0
Piura
Country [90] 0 0
Peru
State/province [90] 0 0
San Juan de Miraflores
Country [91] 0 0
Peru
State/province [91] 0 0
Trujillo
Country [92] 0 0
Poland
State/province [92] 0 0
Lublin
Country [93] 0 0
Poland
State/province [93] 0 0
Szczecin
Country [94] 0 0
Poland
State/province [94] 0 0
Torun
Country [95] 0 0
Poland
State/province [95] 0 0
Lódz
Country [96] 0 0
Russian Federation
State/province [96] 0 0
Chelyabinsk
Country [97] 0 0
Russian Federation
State/province [97] 0 0
Engels
Country [98] 0 0
Russian Federation
State/province [98] 0 0
St.Petersburg
Country [99] 0 0
Russian Federation
State/province [99] 0 0
Vladivostok
Country [100] 0 0
South Africa
State/province [100] 0 0
Parktown West
Country [101] 0 0
South Africa
State/province [101] 0 0
Pretoria
Country [102] 0 0
South Africa
State/province [102] 0 0
Worcester
Country [103] 0 0
Spain
State/province [103] 0 0
Barcelona
Country [104] 0 0
Spain
State/province [104] 0 0
Cantabria
Country [105] 0 0
Spain
State/province [105] 0 0
Islas Baleares
Country [106] 0 0
Spain
State/province [106] 0 0
Granada
Country [107] 0 0
Spain
State/province [107] 0 0
Madrid
Country [108] 0 0
Spain
State/province [108] 0 0
Tarragona
Country [109] 0 0
Spain
State/province [109] 0 0
Valencia
Country [110] 0 0
Sweden
State/province [110] 0 0
Goteborg
Country [111] 0 0
Sweden
State/province [111] 0 0
Göteborg
Country [112] 0 0
Sweden
State/province [112] 0 0
Mamö
Country [113] 0 0
Sweden
State/province [113] 0 0
Umeå
Country [114] 0 0
Taiwan
State/province [114] 0 0
Kaohsiung
Country [115] 0 0
Taiwan
State/province [115] 0 0
New Taipei
Country [116] 0 0
Taiwan
State/province [116] 0 0
Taipei
Country [117] 0 0
Taiwan
State/province [117] 0 0
Taoyuan City
Country [118] 0 0
Ukraine
State/province [118] 0 0
Kyiv
Country [119] 0 0
Ukraine
State/province [119] 0 0
Odesa
Country [120] 0 0
Ukraine
State/province [120] 0 0
Poltava
Country [121] 0 0
Ukraine
State/province [121] 0 0
Zhytomyr
Country [122] 0 0
United Kingdom
State/province [122] 0 0
Birmingham
Country [123] 0 0
United Kingdom
State/province [123] 0 0
Glasgow
Country [124] 0 0
United Kingdom
State/province [124] 0 0
Leeds
Country [125] 0 0
United Kingdom
State/province [125] 0 0
London
Country [126] 0 0
United Kingdom
State/province [126] 0 0
Southampton
Country [127] 0 0
United Kingdom
State/province [127] 0 0
Stoke-On-Trent
Country [128] 0 0
United Kingdom
State/province [128] 0 0
Taunton

Funding & Sponsors
Primary sponsor type
Commercial sector/industry
Name
Genentech, Inc.
Address
Country

Ethics approval
Ethics application status

Summary
Brief summary
Trial website
Trial related presentations / publications
Public notes

Contacts
Principal investigator
Name 0 0
Clinical Trials
Address 0 0
Hoffmann-La Roche
Country 0 0
Phone 0 0
Fax 0 0
Email 0 0
Contact person for public queries
Name 0 0
Address 0 0
Country 0 0
Phone 0 0
Fax 0 0
Email 0 0
Contact person for scientific queries

No information has been provided regarding IPD availability


What supporting documents are/will be available?

Results publications and other study-related documents

No documents have been uploaded by study researchers.