Clinical trial NCT03040141: Study of Efficacy and Safety of IV VIS410 Plus Oseltamivir Versus Oseltamivir in Hospitalized Adults With Influenza A
Official title: Phase 2b, Multicenter, Randomized, Double-blind Study to Evaluate the Efficacy and Safety of IV VIS410 in Addition to Oseltamivir Compared With Oseltamivir Alone in Hospitalized Adults With Influenza A Infection Requiring Oxygen Support
Study type: INTERVENTIONAL
Overall status: COMPLETED
Phase: PHASE2
Conditions: Influenza A
Lead sponsor: Visterra, Inc.
Sponsor class: INDUSTRY
First posted: 2017-02-02
Enrollment: 89
Sex: ALL
Minimum age (years): 18
Standard ages: ADULT
OLDER_ADULT
Accepts healthy volunteers: no
Allocation: RANDOMIZED
Intervention model: PARALLEL
Primary purpose: TREATMENT

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.

Detailed description: 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. Subjects will be followed for 56 days.

Eligibility criteria: 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 (Polymerase chain reaction), FIA (Fluorescent immunoassay), 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.

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

Primary outcomes:
measure: Clinical Status of Participants on Day 7
timeFrame: 7 days
measure: The Number of Participants With Adverse Events and Serious Adverse Events Following Administration of VIS410
timeFrame: 56 days
Secondary outcomes:
measure: Time to Cessation of Oxygen Support Compared to Oseltamivir Alone Among Patients Requiring Supplemental Oxygen Therapy With Baseline Room Air <= 92%
timeFrame: Baseline to Day 56
measure: Time to Cessation of Oxygen Support for Any Patient Requiring Supplemental Oxygen Therapy
timeFrame: Baseline to Day 56
measure: Viral Titer in Upper Respiratory Samples by qRT-PCR
timeFrame: Day 14
measure: Viral Nasopharyngeal AUC
timeFrame: Day 1 Predose, Day 1 End of Infusion, Day 3, Day 5
measure: Area Under the Viral Load-Time Curve (VL AUC) Based on qRT-PCR From Nasopharyngeal Swabs Through Day 7
timeFrame: Day 1 Predose, Day 1 End of Infusion, Day 3, Day 5, Day 7
measure: Area Under the Viral Load-Time Curve (VL AUC) Based on qRT-PCR From Nasopharyngeal Swabs Through Day 14
timeFrame: Day 1 Predose, Day 1 End of Infusion, Day 3, Day 5, Day 7, Day 14
measure: Median Time to Resolution of Viral Load by Treatment Arm by qRT-PCR - From End of Infusion
timeFrame: 14 days
measure: Number of Participants in Whom Peak Viral Load Occurred Post Baseline Measured by qRT-PCR
timeFrame: 14 days
measure: Peak Viral Load by TCID50
timeFrame: Day 7
measure: Number of Participants in Whom Peak Viral Load Occurred Post Baseline Measured by TCID50
timeFrame: 56 days
measure: Viral Nasopharyngeal AUC by TCID50
timeFrame: 5 days
measure: Viral Nasopharyngeal AUC by TCID50
timeFrame: 7 days
measure: Negative Viral Cultures by Study Day
timeFrame: Nominal days 3, 5, 7
measure: Median Time to Resolution of Viral Load by Treatment Arm by TCID50 - From End of Infusion
timeFrame: 7 Days
measure: Median Time to Resolution of Viral Load by Treatment Arm by TCID50 - From Onset of Symptoms
timeFrame: 7 Days
measure: Time to Clinical Response (4 Out of 5 Vital Signs)
timeFrame: Day 56
measure: Time to Complete Clinical Response (Resolution of All Vital Signs)
timeFrame: Day 56
measure: Clinical Status Ordinal Scale Mean Area Under the Curve Through Day 7
timeFrame: Baseline to Day 7
measure: Clinical Status Ordinal Scale Mean Area Under the Curve Through Day 14.
timeFrame: Baseline to Days 14
measure: Comparison of Clinical Status on Seven-level Ordinal Scale Scores
timeFrame: Day 14
measure: Total Number of Days on Ventilation
timeFrame: 56 days
measure: Comparison of Ordinal Scale Parameters - Days on Ventilation
timeFrame: 56 days
measure: Total Number of Days in ICU
timeFrame: 56 days
measure: Comparison of Ordinal Scale Parameters - Days in ICU
timeFrame: 56 days
measure: Number of Days to Resumption of Usual Activities
timeFrame: Day 56
measure: All Cause and Attributable Mortality at Day 14
timeFrame: Day 14
measure: All Cause and Attributable Mortality by Day 28
timeFrame: Day 28
measure: All Cause and Attributable Mortality Day 56
timeFrame: Day 56
measure: Healthcare Resource Utilization. Days in Hospital and/or ICU
timeFrame: Day 56
measure: Comparison of Ordinal Scale Parameters - Days in Hospital/ICU
timeFrame: 56 days
measure: Number of Participants With Rehospitalization Due to Relapse
timeFrame: Day 56
measure: Number of Participants With Influenza-related Complications
timeFrame: Day 56
measure: The Maximum Concentration (Cmax) of VIS410 in Participant's Serum
timeFrame: Baseline, end of infusion, Day 5, Day 14, Day 28, Day 56
measure: The Area Under the Concentration/Time Curve of VIS410 in Participant's Serum
timeFrame: Baseline, end of infusion, Day 5, Day 14, Day 28, Day 56
measure: The Clearance Rate (Cl) of VIS410 in Participant's Serum
timeFrame: PK samples were collected on days 1, 5, 14, 28 and 56.
measure: The Half-life of VIS410 in Participant's Serum
timeFrame: PK samples were collected on days 1, 5, 14, 28 and 56.
measure: Anti-VIS410 Antibody Testing
timeFrame: From anti-VIS410 antibody samples collected on days 28 and 56.
Other outcomes:
Locations:
city: Tucson
country: United States
facility: Visterra
state: Arizona
city: Stanford
country: United States
facility: Visterra
state: California
city: Saint Petersburg
country: United States
facility: Visterra
state: Florida
city: Atlanta
country: United States
facility: Visterra
state: Georgia
city: Decatur
country: United States
facility: Visterra
state: Georgia
city: Blackfoot
country: United States
facility: Visterra
state: Idaho
city: Chicago
country: United States
facility: Visterra
state: Illinois
city: Detroit
country: United States
facility: Visterra
state: Michigan
city: Butte
country: United States
facility: Visterra
state: Montana
city: Albany
country: United States
facility: Visterra
state: New York
city: Syracuse
country: United States
facility: Visterra
state: New York
city: Durham
country: United States
facility: Visterra
state: North Carolina
city: Greensboro
country: United States
facility: Visterra
state: North Carolina
city: Cleveland
country: United States
facility: Visterra
state: Ohio
city: Columbus
country: United States
facility: Visterra
state: Ohio
city: Allentown
country: United States
facility: Visterra
state: Pennsylvania
city: Philadelphia
country: United States
facility: Visterra
state: Pennsylvania
city: York
country: United States
facility: Visterra
state: Pennsylvania
city: Roanoke
country: United States
facility: Visterra
state: Virginia
city: Richland
country: United States
facility: Visterra
state: Washington
city: Tacoma
country: United States
facility: Visterra
state: Washington
city: Adelaide
country: Australia
facility: Visterra
state: South Australia
city: Melbourne
country: Australia
facility: Visterra
city: Parkville
country: Australia
facility: Visterra
city: South Brisbane
country: Australia
facility: Visterra
city: Westmead
country: Australia
facility: Visterra
city: Woolloongabba
country: Australia
facility: Visterra
city: Brest
country: Belarus
facility: Visterra
city: Gomel
country: Belarus
facility: Visterra
city: Gomel
country: Belarus
facility: Visterra
city: Grodno
country: Belarus
facility: Visterra
city: Grodno
country: Belarus
facility: Visterra
city: Lesnoy
country: Belarus
facility: Visterra
city: Minsk
country: Belarus
facility: Visterra
city: Vitebsk
country: Belarus
facility: Visterra
city: Brussels
country: Belgium
facility: Visterra
city: Edegem
country: Belgium
facility: Visterra
city: Kozloduy
country: Bulgaria
facility: Visterra
city: Montana
country: Bulgaria
facility: Visterra
city: Plovdiv
country: Bulgaria
facility: Visterra
city: Sofia
country: Bulgaria
facility: Visterra
city: Sofia
country: Bulgaria
facility: Visterra
city: Sofia
country: Bulgaria
facility: Visterra
city: Veliko Tarnovo
country: Bulgaria
facility: Visterra
city: Moncton
country: Canada
facility: Visterra
state: New Brunswick
city: Pärnu
country: Estonia
facility: Visterra
city: Tallinn
country: Estonia
facility: Visterra
city: Tallinn
country: Estonia
facility: Visterra
city: Tallinn
country: Estonia
facility: Visterra
city: Tartu
country: Estonia
facility: Visterra
city: La Roche-sur-Yon
country: France
facility: Visterra
city: La Tronche
country: France
facility: Visterra
city: Limoges
country: France
facility: Visterra
city: Metz-Tessy
country: France
facility: Visterra
city: Nantes
country: France
facility: Visterra
city: Paris
country: France
facility: Visterra
city: Paris
country: France
facility: Visterra
city: Quimper
country: France
facility: Visterra
city: Tbilisi
country: Georgia
facility: Visterra
city: Tbilisi
country: Georgia
facility: Visterra
city: Tbilisi
country: Georgia
facility: Visterra
city: Daugavpils
country: Latvia
facility: Visterra
city: Liepāja
country: Latvia
facility: Visterra
city: Riga
country: Latvia
facility: Visterra
city: Rēzekne
country: Latvia
facility: Visterra
city: Valmiera
country: Latvia
facility: Visterra
city: Ventspils
country: Latvia
facility: Visterra
city: Alor Setar
country: Malaysia
facility: Visterra
state: Kedah
city: Taiping
country: Malaysia
facility: Visterra
state: Perak
city: Kuala Lumpur
country: Malaysia
facility: Visterra
state: Wilayah Persekutuan
city: Auckland
country: New Zealand
facility: Visterra
city: Auckland
country: New Zealand
facility: Visterra
city: Wellington
country: New Zealand
facility: Visterra
city: Arkhangel'sk
country: Russian Federation
facility: Visterra
city: Kazan
country: Russian Federation
facility: Visterra
city: Novosibirsk
country: Russian Federation
facility: Visterra
city: Smolensk
country: Russian Federation
facility: Visterra
city: Tomsk
country: Russian Federation
facility: Visterra
city: Vladimir
country: Russian Federation
facility: Visterra
city: Kragujevac
country: Serbia
facility: Visterra
city: Niš
country: Serbia
facility: Visterra
city: Novi Sad
country: Serbia
facility: Visterra
city: Singapore
country: Singapore
facility: Visterra
city: Singapore
country: Singapore
facility: Visterra
city: Lyttelton
country: South Africa
facility: Visterra
state: Centurion
city: Auckland Park
country: South Africa
facility: Visterra
state: Gauteng
city: Pretoria
country: South Africa
facility: Visterra
state: Gauteng
city: Thabazimbi
country: South Africa
facility: Visterra
state: Limpopo
city: Benoni
country: South Africa
facility: Visterra
city: Cape Town
country: South Africa
facility: Visterra
city: Durban
country: South Africa
facility: Visterra
city: Worcester
country: South Africa
facility: Visterra
city: Alicante
country: Spain
facility: Visterra
city: Badalona
country: Spain
facility: Visterra
city: Barakaldo
country: Spain
facility: Visterra
city: Barcelona
country: Spain
facility: Visterra
city: Córdoba
country: Spain
facility: Visterra
city: Granada
country: Spain
facility: Visterra
city: Madrid
country: Spain
facility: Visterra
city: Madrid
country: Spain
facility: Visterra
city: Terrassa
country: Spain
facility: Visterra
city: Bangkok
country: Thailand
facility: Visterra
city: Khon Kaen
country: Thailand
facility: Visterra
city: Mueang Nonthaburi
country: Thailand
facility: Visterra
city: Ankara
country: Turkey
facility: Visterra
city: Istanbul
country: Turkey
facility: Visterra
city: Trabzon
country: Turkey
facility: Visterra
city: Ivano-Frankivs'k
country: Ukraine
facility: Visterra
city: Kyiv
country: Ukraine
facility: Visterra
city: Kyiv
country: Ukraine
facility: Visterra
city: Odesa
country: Ukraine
facility: Visterra
city: Poltava
country: Ukraine
facility: Visterra
city: Sumy
country: Ukraine
facility: Visterra
city: Zhytomyr
country: Ukraine
facility: Visterra
Study officials:
affiliation: Visterra, Inc.
name: David Oldach, MD
role: PRINCIPAL_INVESTIGATOR
References: