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Trial details imported from ClinicalTrials.gov

For full trial details, please see the original record at https://clinicaltrials.gov/show/NCT03040141




Registration number
NCT03040141
Ethics application status
Date submitted
23/01/2017
Date registered
2/02/2017
Date last updated
12/11/2019

Titles & IDs
Public title
Study to Evaluate the Efficacy and Safety of IV VIS410 Plus Oseltamivir Versus Oseltamivir Alone in Hospitalized Adults With Influenza A Infection Requiring Oxygen Support
Scientific title
Phase 2b, Multicenter, Randomized, Double-blind, Controlled Study to Evaluate the Efficacy and Safety of Intravenous VIS410 in Addition to Oseltamivir (Tamiflu®) Compared With Oseltamivir Alone in Hospitalized Adults With Influenza A Infection Requiring Oxygen Support
Secondary ID [1] 0 0
VIS410-203
Universal Trial Number (UTN)
Trial acronym
Linked study record

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

Intervention/exposure
Study type
Interventional
Description of intervention(s) / exposure
Treatment: Drugs - Low dose of VIS410
Treatment: Drugs - High dose of VIS410
Treatment: Drugs - Placebo

Experimental: VIS410 low dose - Single intravenous infusion of fixed low dose of VIS410 in addition to oseltamivir

Experimental: VIS410 high dose - Single intravenous infusion of fixed high dose of VIS410 in addition to oseltamivir

Placebo Comparator: Placebo - Single intravenous infusion of placebo in addition to oseltamivir


Treatment: Drugs: Low dose of VIS410
Single intravenous infusion of fixed low dose of VIS410 in addition to oseltamivir

Treatment: Drugs: High dose of VIS410
Single intravenous infusion of fixed high dose of VIS410 in addition to oseltamivir

Treatment: Drugs: Placebo
Single intravenous infusion of placebo in addition to oseltamivir

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

Outcomes
Primary outcome [1] 0 0
Evaluate the effect of 2 dose levels of VIS410 + oseltamivir on clinical outcome as assessed by comparison of clinical status ordinal Day 7 scores between treatment groups, and between all VIS410 recipients vs placebo. - Clinical status is measured daily for 14 days using a seven-level ordinal scale, subject status will be classified by the worst clinical outcome for which they qualify
Timepoint [1] 0 0
14 days
Primary outcome [2] 0 0
Safety and tolerability of 2 dose levels of a single intravenous (IV) dose of VIS410 when administered in combination with oseltamivir in hospitalized subjects with influenza A infection - The proportion of subjects with AEs and SAEs following administration of VIS410
Timepoint [2] 0 0
56 days
Secondary outcome [1] 0 0
Time to cessation of O2 support compared to oseltamivir alone among patients requiring supplemental oxygen therapy at the time of enrollment with baseline room air oxygen saturation of =92%. - Time to cessation of O2 support resulting in a stable SpO2 by pulse oximetry. Stable SpO2 is defined as two consecutive SpO2 values of >92% on room air that are at least 8 hours apart.
Timepoint [1] 0 0
56 days
Secondary outcome [2] 0 0
Evaluate the effect of 2 dose levels of VIS410 + oseltamivir vs oseltamivir alone on viral titer in upper respiratory samples - The difference between VIS410 + oseltamivir and oseltamivir alone treatment groups in peak viral load from nasopharyngeal swabs
Timepoint [2] 0 0
56 days
Secondary outcome [3] 0 0
Evaluate the effect of 2 dose levels of VIS410 + oseltamivir vs oseltamivir alone on resolution of viral load in upper respiratory samples - The difference between VIS410 + oseltamivir and oseltamivir alone treatment groups in time to resolution of viral load from nasopharyngeal swabs
Timepoint [3] 0 0
56 days
Secondary outcome [4] 0 0
Evaluate the effect of 2 dose levels of VIS410 + oseltamivir vs oseltamivir alone on time to clinical response - The difference between VIS410 + oseltamivir and oseltamivir alone treatment groups in time to clinical response defined as resolution of at least 4 of 5 vital signs
Timepoint [4] 0 0
56 days
Secondary outcome [5] 0 0
Evaluate the effect of 2 dose levels of VIS410 + oseltamivir vs oseltamivir alone on time to cessation of ventilator support - The difference between VIS410 + oseltamivir and oseltamivir alone treatment groups in total number of days on ventilation
Timepoint [5] 0 0
56 days
Secondary outcome [6] 0 0
Evaluate the effect of 2 dose levels of VIS410 + oseltamivir vs oseltamivir alone on time to resumption of normal activities - The difference between VIS410 + oseltamivir and oseltamivir alone treatment groups in the number of days to resumption of normal activities
Timepoint [6] 0 0
56 days
Secondary outcome [7] 0 0
Evaluate the effect of 2 dose levels of VIS410 + oseltamivir vs oseltamivir alone on all-cause and attributable 28- and 56- day mortality - The difference between VIS410 + oseltamivir and oseltamivir alone treatment groups in all-cause and attributable mortality rates at Day 28 and 56
Timepoint [7] 0 0
56 days
Secondary outcome [8] 0 0
Evaluate the effect of 2 dose levels of VIS410 + oseltamivir vs oseltamivir alone on time to alleviation of signs and symptoms of influenza as assessed by the FluPro Questionnaire at baseline and post-dose Kaplan Meier Analysis - The difference between VIS410 + oseltamivir and oseltamivir alone treatment groups in the incidence, severity, and duration of signs and symptoms of influenza-like illness as assessed by the FluPRO Questionnaire
Timepoint [8] 0 0
56 days
Secondary outcome [9] 0 0
Evaluate the effect of 2 dose levels of VIS410 + oseltamivir vs oseltamivir alone on the proportion of subjects with new documented bacterial pneumonia/superinfection - The difference between VIS410 + oseltamivir and oseltamivir alone treatment groups in the percentage of subjects with new bacterial pneumonia/superinfection
Timepoint [9] 0 0
56 days
Secondary outcome [10] 0 0
Evaluate the effect of 2 dose levels of VIS410 + oseltamivir vs oseltamivir alone on the proportion of subjects with influenza-related complications - The difference between VIS410 + oseltamivir and oseltamivir alone treatment groups in the percentage of subjects with influenza-related complications
Timepoint [10] 0 0
56 days
Secondary outcome [11] 0 0
Evaluate the effect of 2 dose levels of VIS410 + oseltamivir vs oseltamivir alone on the immunogenicity of VIS410 - The difference between VIS410 + oseltamivir and oseltamivir alone treatment groups in the titer of anti-VIS410 antibody positive samples
Timepoint [11] 0 0
56 days
Secondary outcome [12] 0 0
Evaluate the effect of 2 dose levels of VIS410 + oseltamivir vs oseltamivir alone on the emergence of resistance to VIS410 and oseltamivir - Genotypic and/or phenotypic assessments to determine the emergence of VIS410 and oseltamivir-resistant viruses
Timepoint [12] 0 0
56 days
Secondary outcome [13] 0 0
Pharmacokinetics of VIS410 in Serum - Assess blood/serum samples to determine concentration of VIS410
Timepoint [13] 0 0
56 days

Eligibility
Key inclusion criteria
- Male and female subjects aged = 18 years.

- Test positive for influenza A by rapid antigen test or with another commercially
available test on an adequate nasopharyngeal specimen in accordance with the
manufacturer's instructions, or an acceptable local test, including PCR, FIA, or ELISA

- Onset of influenza symptoms no more than 5 days before VIS410/placebo infusion;
symptoms may include cough, dyspnea, sore throat, fever, myalgias, headache, nasal
symptoms (rhinorrhea, congestion), fatigue, diarrhea, anorexia, nausea, and vomiting.

- Requirement for oxygen support including any positive pressure ventilation

- Women of childbearing potential must have a negative pregnancy test within 2 days
prior to VIS410/placebo infusion.

- Women should fulfill one of the following criteria:

- Post-menopausal; either amenorrhea = 12 months or follicle stimulating hormone >
40 mIU/mL as documented in their medical history

- Surgically sterile; hysterectomy, bilateral oophorectomy, or tubal ligation

- Women of childbearing potential participating in heterosexual sexual relations
must be willing to use adequate contraception from screening until 60 days post
VIS410/placebo infusion.

- Non-vasectomized (or vasectomized less than 6 months prior to dosing) male subjects
who have a female partner of childbearing potential must use an effective birth
control method from screening until 60 days post VIS410/placebo infusion.

- Subject, or a legally acceptable representative (LAR), is able to understand the
purpose and risks of the study and willing to give voluntary written informed consent.
Minimum age
18 Years
Maximum age
No limit
Gender
Both males and females
Can healthy volunteers participate?
No
Key exclusion criteria
- Known or suspected intolerance or hypersensitivity to VIS410, oseltamivir,
pretreatment medications (diphenhydramine, or to both ibuprofen and acetylsalicylic
acid [ASA]), or closely related compounds (eg, other monoclonal antibodies)

- Subjects who have received VIS410 in the past

- History of receiving monoclonal antibody products (including VIS410) within 3 months
prior to VIS410/placebo dosing or planned administration during the study period

- Subjects who have taken more than 6 doses of an approved antiviral therapy for
influenza within the prior 96 hours (eg, oral oseltamivir, inhaled zanamivir, IV
peramivir, or oral ribavirin) between onset of symptoms and VIS410/placebo dosing

- Subjects with known co-infection with influenza B or other viral respiratory
infections (e.g., respiratory syncytial virus, parainfluenza viruses, respiratory
adenoviruses)

- Subjects with lung transplant or history of severe chronic lung disease, including
cystic fibrosis or any condition requiring home oxygen therapy

- Subjects on extracorporeal membrane oxygenation (ECMO) at time of randomization

- Subjects with end stage renal disease who are not undergoing hemodialysis

- Subjects with active graft-vs-host disease, hematopoietic stem cell transplant within
the previous 90 days, or human immunodeficiency virus infection with a CD4 cell count
of less than 200 per cubic millimeter

- Hospitalization for > 48 hours prior to randomization

- High probability of mortality within 48 hours of randomization as determined by the
Investigator

- Subjects weighing less than 45 kg

- Enrollment in any other investigational drug or device study, any disease or vaccine
study within 30 days prior to Day 1 or within 5 half-lives of the investigational
compound, whichever is longer

- Known or suspected alcohol or drug abuse, that is, abuse of a level that would
compromise the safety or cooperation of the subject in the opinion of the Investigator

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 administering the treatment/s
The people assessing the outcomes
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)
SA
Recruitment hospital [1] 0 0
Visterra - Adelaide
Recruitment hospital [2] 0 0
Visterra - Melbourne
Recruitment hospital [3] 0 0
Visterra - Parkville
Recruitment hospital [4] 0 0
Visterra - South Brisbane
Recruitment hospital [5] 0 0
Visterra - Westmead
Recruitment hospital [6] 0 0
Visterra - Woolloongabba
Recruitment postcode(s) [1] 0 0
5000 - Adelaide
Recruitment postcode(s) [2] 0 0
3168 - Melbourne
Recruitment postcode(s) [3] 0 0
3050 - Parkville
Recruitment postcode(s) [4] 0 0
4101 - South Brisbane
Recruitment postcode(s) [5] 0 0
2145 - Westmead
Recruitment postcode(s) [6] 0 0
4102 - Woolloongabba
Recruitment outside Australia
Country [1] 0 0
United States of America
State/province [1] 0 0
Arizona
Country [2] 0 0
United States of America
State/province [2] 0 0
California
Country [3] 0 0
United States of America
State/province [3] 0 0
Florida
Country [4] 0 0
United States of America
State/province [4] 0 0
Georgia
Country [5] 0 0
United States of America
State/province [5] 0 0
Idaho
Country [6] 0 0
United States of America
State/province [6] 0 0
Illinois
Country [7] 0 0
United States of America
State/province [7] 0 0
Michigan
Country [8] 0 0
United States of America
State/province [8] 0 0
Montana
Country [9] 0 0
United States of America
State/province [9] 0 0
New York
Country [10] 0 0
United States of America
State/province [10] 0 0
North Carolina
Country [11] 0 0
United States of America
State/province [11] 0 0
Ohio
Country [12] 0 0
United States of America
State/province [12] 0 0
Pennsylvania
Country [13] 0 0
United States of America
State/province [13] 0 0
Virginia
Country [14] 0 0
United States of America
State/province [14] 0 0
Washington
Country [15] 0 0
Belarus
State/province [15] 0 0
Brest
Country [16] 0 0
Belarus
State/province [16] 0 0
Gomel
Country [17] 0 0
Belarus
State/province [17] 0 0
Grodno
Country [18] 0 0
Belarus
State/province [18] 0 0
Lesnoy
Country [19] 0 0
Belarus
State/province [19] 0 0
Minsk
Country [20] 0 0
Belarus
State/province [20] 0 0
Vitebsk
Country [21] 0 0
Belgium
State/province [21] 0 0
Brussels
Country [22] 0 0
Belgium
State/province [22] 0 0
Edegem
Country [23] 0 0
Bulgaria
State/province [23] 0 0
Kozloduy
Country [24] 0 0
Bulgaria
State/province [24] 0 0
Montana
Country [25] 0 0
Bulgaria
State/province [25] 0 0
Plovdiv
Country [26] 0 0
Bulgaria
State/province [26] 0 0
Sofia
Country [27] 0 0
Bulgaria
State/province [27] 0 0
Veliko Tarnovo
Country [28] 0 0
Canada
State/province [28] 0 0
New Brunswick
Country [29] 0 0
Estonia
State/province [29] 0 0
Pärnu
Country [30] 0 0
Estonia
State/province [30] 0 0
Tallinn
Country [31] 0 0
Estonia
State/province [31] 0 0
Tartu
Country [32] 0 0
France
State/province [32] 0 0
La Roche-sur-Yon
Country [33] 0 0
France
State/province [33] 0 0
La Tronche
Country [34] 0 0
France
State/province [34] 0 0
Limoges
Country [35] 0 0
France
State/province [35] 0 0
Metz-Tessy
Country [36] 0 0
France
State/province [36] 0 0
Nantes
Country [37] 0 0
France
State/province [37] 0 0
Paris
Country [38] 0 0
France
State/province [38] 0 0
Quimper
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Georgia
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Tbilisi
Country [40] 0 0
Latvia
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Daugavpils
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Latvia
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Liepaja
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Latvia
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Riga
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Latvia
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Rezekne
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Latvia
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Valmiera
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Latvia
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Ventspils
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Malaysia
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Kedah
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Malaysia
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Perak
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Malaysia
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Wilayah Persekutuan
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New Zealand
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Auckland
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New Zealand
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Wellington
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Russian Federation
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Arkhangel'sk
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Russian Federation
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Kazan
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Russian Federation
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Novosibirsk
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Russian Federation
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Smolensk
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Russian Federation
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Tomsk
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Russian Federation
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Vladimir
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Serbia
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Kragujevac
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Serbia
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Niš
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Serbia
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Novi Sad
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Singapore
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Singapore
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South Africa
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Centurion
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South Africa
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Gauteng
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South Africa
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Limpopo
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South Africa
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Benoni
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South Africa
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Cape Town
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South Africa
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Durban
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South Africa
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Worcester
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Spain
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Alicante
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Spain
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Badalona
Country [70] 0 0
Spain
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Barakaldo
Country [71] 0 0
Spain
State/province [71] 0 0
Barcelona
Country [72] 0 0
Spain
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Córdoba
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Spain
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Granada
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Spain
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Madrid
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Spain
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Terrassa
Country [76] 0 0
Thailand
State/province [76] 0 0
Bangkok
Country [77] 0 0
Thailand
State/province [77] 0 0
Khon Kaen
Country [78] 0 0
Thailand
State/province [78] 0 0
Mueang Nonthaburi
Country [79] 0 0
Turkey
State/province [79] 0 0
Ankara
Country [80] 0 0
Turkey
State/province [80] 0 0
Istanbul
Country [81] 0 0
Turkey
State/province [81] 0 0
Trabzon
Country [82] 0 0
Ukraine
State/province [82] 0 0
Ivano-Frankivs'k
Country [83] 0 0
Ukraine
State/province [83] 0 0
Kyiv
Country [84] 0 0
Ukraine
State/province [84] 0 0
Odesa
Country [85] 0 0
Ukraine
State/province [85] 0 0
Poltava
Country [86] 0 0
Ukraine
State/province [86] 0 0
Sumy
Country [87] 0 0
Ukraine
State/province [87] 0 0
Zhytomyr

Funding & Sponsors
Primary sponsor type
Commercial sector/Industry
Name
Visterra, Inc.
Address
Country

Ethics approval
Ethics application status

Summary
Brief summary
This study is to compare the efficacy and safety of VIS410 in combination with oseltamivir vs
oseltamivir alone in severely ill subjects with influenza A infection requiring oxygen
support.
Trial website
https://clinicaltrials.gov/show/NCT03040141
Trial related presentations / publications
Public notes

Contacts
Principal investigator
Name 0 0
David Oldach, MD
Address 0 0
Visterra, Inc.
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

Summary results
Other publications