NCT03040141
Completed
Phase 2
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
ConditionsInfluenza A
Overview
- Phase
- Phase 2
- Status
- Completed
- Sponsor
- Visterra, Inc.
- Enrollment
- 89
- Locations
- 1
- Primary Endpoint
- The Number of Participants With Adverse Events and Serious Adverse Events Following Administration of VIS410
Overview
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.
Study Design
- Study Type
- Interventional
- Allocation
- Randomized
- Intervention Model
- Parallel
- Primary Purpose
- Treatment
- Masking
- Quadruple (Participant, Care Provider, Investigator, Outcomes Assessor)
Masking Description
Double-blind
Eligibility Criteria
- Ages
- 18 Years to — (Adult, Older Adult)
- Sex
- All
- Accepts Healthy Volunteers
- No
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.
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
Arms & Interventions
VIS410 low dose
Experimental
Single intravenous infusion of fixed low dose of VIS410 in addition to oseltamivir
Intervention: Low dose of VIS410 (Drug)
VIS410 high dose
Experimental
Single intravenous infusion of fixed high dose of VIS410 in addition to oseltamivir
Intervention: High dose of VIS410 (Drug)
Placebo
Placebo Comparator
Single intravenous infusion of placebo in addition to oseltamivir
Intervention: Placebo (Drug)
Outcomes
Primary Outcomes
The Number of Participants With Adverse Events and Serious Adverse Events Following Administration of VIS410
Time Frame: 56 days
Safety and tolerability of 2 dose levels of a single intravenous (IV) dose of VIS410 when administered in combination with oseltamivir in hospitalized participants with influenza A infection. Data presents the count of participants who experienced an adverse event (AE) or serious treatment emergent adverse events (TEAE).
Clinical Status of Participants on Day 7
Time Frame: 7 days
Evaluate the effect of 2 dose levels of VIS410 + oseltamivir on clinical status using a seven-level ordinal scale. Comparison between treatment groups and between all VIS410 recipients versus placebo were assessed.
Secondary Outcomes
- Number of Participants in Whom Peak Viral Load Occurred Post Baseline Measured by qRT-PCR(14 days)
- Peak Viral Load by TCID50(Day 7)
- Time to Cessation of Oxygen Support Compared to Oseltamivir Alone Among Patients Requiring Supplemental Oxygen Therapy With Baseline Room Air <= 92%(Baseline to Day 56)
- Time to Cessation of Oxygen Support for Any Patient Requiring Supplemental Oxygen Therapy(Baseline to Day 56)
- Number of Participants in Whom Peak Viral Load Occurred Post Baseline Measured by TCID50(56 days)
- Viral Titer in Upper Respiratory Samples by qRT-PCR(Day 14)
- Viral Nasopharyngeal AUC(Day 1 Predose, Day 1 End of Infusion, Day 3, Day 5)
- Area Under the Viral Load-Time Curve (VL AUC) Based on qRT-PCR From Nasopharyngeal Swabs Through Day 7(Day 1 Predose, Day 1 End of Infusion, Day 3, Day 5, Day 7)
- Area Under the Viral Load-Time Curve (VL AUC) Based on qRT-PCR From Nasopharyngeal Swabs Through Day 14(Day 1 Predose, Day 1 End of Infusion, Day 3, Day 5, Day 7, Day 14)
- Viral Nasopharyngeal AUC by TCID50(7 days)
- Comparison of Clinical Status on Seven-level Ordinal Scale Scores(Day 14)
- All Cause and Attributable Mortality at Day 14(Day 14)
- Median Time to Resolution of Viral Load by Treatment Arm by qRT-PCR - From End of Infusion(14 days)
- Negative Viral Cultures by Study Day(Nominal days 3, 5, 7)
- Time to Complete Clinical Response (Resolution of All Vital Signs)(Day 56)
- Total Number of Days on Ventilation(56 days)
- Comparison of Ordinal Scale Parameters - Days in ICU(56 days)
- Median Time to Resolution of Viral Load by Treatment Arm by TCID50 - From End of Infusion(7 Days)
- Time to Clinical Response (4 Out of 5 Vital Signs)(Day 56)
- Comparison of Ordinal Scale Parameters - Days on Ventilation(56 days)
- Number of Participants With Influenza-related Complications(Day 56)
- The Maximum Concentration (Cmax) of VIS410 in Participant's Serum(Baseline, end of infusion, Day 5, Day 14, Day 28, Day 56)
- The Clearance Rate (Cl) of VIS410 in Participant's Serum(PK samples were collected on days 1, 5, 14, 28 and 56.)
- Anti-VIS410 Antibody Testing(From anti-VIS410 antibody samples collected on days 28 and 56.)
- Median Time to Resolution of Viral Load by Treatment Arm by TCID50 - From Onset of Symptoms(7 Days)
- Clinical Status Ordinal Scale Mean Area Under the Curve Through Day 7(Baseline to Day 7)
- Total Number of Days in ICU(56 days)
- Number of Days to Resumption of Usual Activities(Day 56)
- Healthcare Resource Utilization. Days in Hospital and/or ICU(Day 56)
- Number of Participants With Rehospitalization Due to Relapse(Day 56)
- The Half-life of VIS410 in Participant's Serum(PK samples were collected on days 1, 5, 14, 28 and 56.)
- Clinical Status Ordinal Scale Mean Area Under the Curve Through Day 14.(Baseline to Days 14)
- All Cause and Attributable Mortality by Day 28(Day 28)
- All Cause and Attributable Mortality Day 56(Day 56)
- Comparison of Ordinal Scale Parameters - Days in Hospital/ICU(56 days)
- The Area Under the Concentration/Time Curve of VIS410 in Participant's Serum(Baseline, end of infusion, Day 5, Day 14, Day 28, Day 56)
Investigators
Study Sites (1)
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