Influenza A
Conditions
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.
Interventions
DRUGLow dose of VIS410
Single intravenous infusion of fixed low dose of VIS410 in addition to oseltamivir
DRUGHigh dose of VIS410
Single intravenous infusion of fixed high dose of VIS410 in addition to oseltamivir
DRUGPlacebo
Single intravenous infusion of placebo in addition to oseltamivir
Sponsors
Visterra, Inc.
Study design
Allocation
RANDOMIZED
Intervention model
PARALLEL
Primary purpose
TREATMENT
Masking
QUADRUPLE (Subject, Caregiver, Investigator, Outcomes Assessor)
Masking description
Double-blind
Eligibility
Sex/Gender
ALL
Age
18 Years to No maximum
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. * 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
Design outcomes
Primary
| Measure | Time frame | Description |
|---|---|---|
| Clinical Status of Participants on Day 7 | 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. |
| The Number of Participants With Adverse Events and Serious Adverse Events Following Administration of VIS410 | 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). |
Secondary
| Measure | Time frame | Description |
|---|---|---|
| Viral Titer in Upper Respiratory Samples by qRT-PCR | Day 14 | The difference between VIS410 + oseltamivir and oseltamivir alone treatment groups in peak viral load by qRT-PCR from nasopharyngeal swabs through Day 14 |
| Viral Nasopharyngeal AUC | Day 1 Predose, Day 1 End of Infusion, Day 3, Day 5 | The difference between VIS410 + oseltamivir and oseltamivir alone treatment groups in nasopharyngeal qRT-PCR area under the viral load-time curve (AUC) from baseline to 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 | The difference between VIS410 + oseltamivir and oseltamivir alone treatment groups in nasopharyngeal qRT-PCR area under the viral load-time curve (AUC) from baseline to 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 | The difference between VIS410 + oseltamivir and oseltamivir alone treatment groups in nasopharyngeal qRT-PCR area under the viral load-time curve (AUC) from baseline to Day 14. |
| Median Time to Resolution of Viral Load by Treatment Arm by qRT-PCR - From End of Infusion | 14 days | Number of days from the end of infusion until virus is no longer detectable (at or below the limit of detection) with no samples following that are greater than the BLQ through the Day 14 (quantitative reverse-transcription polymerase chain reaction - qRT-PCR) |
| Number of Participants in Whom Peak Viral Load Occurred Post Baseline Measured by qRT-PCR | 14 days | Number of participants in whom peak viral load is observed post-baseline based on quantitative reverse-transcription polymerase chain reaction (qRT-PCR). Post-baseline was considered the day 3 sample or later. |
| Peak Viral Load by TCID50 | Day 7 | Peak viral load based on TCID50 from nasopharyngeal swabs |
| Number of Participants in Whom Peak Viral Load Occurred Post Baseline Measured by TCID50 | 56 days | Number of participants in whom peak viral load occurred post-baseline measured by TCID50. Post-baseline was considered the day 3 sample or later. |
| Viral Nasopharyngeal AUC by TCID50 | 5 days | The area under the viral load-time curve (AUC) for VIS410 + oseltamivir and oseltamivir alone treatment groups from baseline to Day 5 measured by TCID50 from nasopharyngeal swabs. |
| Negative Viral Cultures by Study Day | Nominal days 3, 5, 7 | Number of participants negative for viral titer by study day determined by TCID50 on nominal days 3, 5, 7 |
| Median Time to Resolution of Viral Load by Treatment Arm by TCID50 - From End of Infusion | 7 Days | Number of days from the end of infusion until virus is no longer detectable (at or below the limit of detection) with no samples following that are greater than the BLQ through the Day 7 (TCID50) |
| Median Time to Resolution of Viral Load by Treatment Arm by TCID50 - From Onset of Symptoms | 7 Days | Number of days from the onset of symptoms until virus is no longer detectable (at or below the limit of detection) with no samples following that are greater than the BLQ through the Day 7 (TCID50) |
| Time to Clinical Response (4 Out of 5 Vital Signs) | Day 56 | Median time to clinical response defined by resolution of at least 4 of 5 vital signs: * Afebrile with core temperature ≤ 37.8°C, without use of antipyretics (oral ≤ 37.2°C) * Oxygen saturation ≥ 95% on room air without support or a return to preinfection status, if pre-infection status was \< 95% * Pulse rate ≤ 100/min * Systolic blood pressure ≥ 90 mm/Hg, without vasopressor use * Respiratory rate ≤ 24 beats per minute |
| Time to Complete Clinical Response (Resolution of All Vital Signs) | Day 56 | Median time to clinical response defined by resolution of at all 5 vital signs: * Afebrile with core temperature ≤ 37.8°C, without use of antipyretics (oral ≤ 37.2°C) * Oxygen saturation ≥ 95% on room air without support or a return to pre-infection status, if pre-infection status was \< 95% * Pulse rate ≤ 100/min * Systolic blood pressure ≥ 90 mm/Hg, without vasopressor use * Respiratory rate ≤ 24 beats per minute |
| Clinical Status Ordinal Scale Mean Area Under the Curve Through Day 7 | Baseline to Day 7 | Summary of area under the curve (AUC) over time for seven-level ordinal scale. Area under the curve (AUC) is calculated using the linear trapezoidal rule. Seven-Level Ordinal Scale is a hierarchical scale with the classifications presented from the worst clinical outcome to the best clinical outcome in descending order with 7=death, 6=Intensive care unit (ICU) stay with mechanical ventilation , 5=ICU stay without mechanical ventilation, 4=Non-ICU hospitalization with supplemental oxygen, 3=Non-ICU hospitalization without supplemental oxygen, 2=Discharge with partial resumption of normal activities, 1=Discharge with full resumption of normal activities. Time frame is from baseline to day 7. Therefore, maximum and minimum values possible for the AUC Clinical Status Ordinal Scale scores range from 7 to 49. |
| Clinical Status Ordinal Scale Mean Area Under the Curve Through Day 14. | Baseline to Days 14 | Summary of area under the curve (AUC) over time for seven-level ordinal scale. Area under the curve (AUC) is calculated using the linear trapezoidal rule. Seven-Level Ordinal Scale is a hierarchical scale with the classifications presented from the worst clinical outcome to the best clinical outcome in descending order with 7=death, 6=Intensive care unit (ICU) stay with mechanical ventilation , 5=ICU stay without mechanical ventilation, 4=Non-ICU hospitalization with supplemental oxygen, 3=Non-ICU hospitalization without supplemental oxygen, 2=Discharge with partial resumption of normal activities, 1=Discharge with full resumption of normal activities. Time frame is from baseline to day 14. Therefore, maximum and minimum values possible for the AUC Clinical Status Ordinal Scale scores range from 14 to 98. |
| Comparison of Clinical Status on Seven-level Ordinal Scale Scores | Day 14 | Summary of Clinical Outcome on Seven-Level Ordinal Scale through Day 14. Worst post-baseline assessment observed. Seven-Level Ordinal Scale is a hierarchical scale with the classifications presented from the worst clinical outcome to the best clinical outcome in descending order with 7=death, 6=Intensive care unit (ICU) stay with mechanical ventilation , 5=ICU stay without mechanical ventilation, 4=Non-ICU hospitalization with supplemental oxygen, 3=Non-ICU hospitalization without supplemental oxygen, 2=Discharge with partial resumption of normal activities, 1=Discharge with full resumption of normal activities. |
| 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 O2 support in patients with supplemental oxygen with baseline room air \<= 92%. Patients with treatment 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. |
| Comparison of Ordinal Scale Parameters - Days on Ventilation | 56 days | Total number of days on ventilation for participations who used ventilation, including participants on ventilation at baseline. Better and worse outcome groups defined based on the Seven-Level Ordinal Scale scores, \<= 4 Seven-Level Ordinal Scale Score is better; \> 4 Seven-Level Ordinal Scale Score is worse group. Seven-Level Ordinal Scale is a hierarchical scale with the classifications presented from the worst clinical outcome to the best clinical outcome in descending order with 7=death, 6=Intensive care unit (ICU) stay with mechanical ventilation , 5=ICU stay without mechanical ventilation, 4=Non-ICU hospitalization with supplemental oxygen, 3=Non-ICU hospitalization without supplemental oxygen, 2=Discharge with partial resumption of normal activities, 1=Discharge with full resumption of normal activities. |
| Total Number of Days in ICU | 56 days | Total number of days in intensive care (ICU) for participants who admitted to the ICU, including participants in ICU at baseline |
| Comparison of Ordinal Scale Parameters - Days in ICU | 56 days | Total number of days in intensive care for participants who admitted to ICU, including participants in ICU at baseline. Better and worse outcome groups defined based on the Seven-Level Ordinal Scale scores, \<= 4 Seven-Level Ordinal Scale Score is better; \> 4 Seven-Level Ordinal Scale Score is worse group. Seven-Level Ordinal Scale is a hierarchical scale with the classifications presented from the worst clinical outcome to the best clinical outcome in descending order with 7=death, 6=Intensive care unit (ICU) stay with mechanical ventilation , 5=ICU stay without mechanical ventilation, 4=Non-ICU hospitalization with supplemental oxygen, 3=Non-ICU hospitalization without supplemental oxygen, 2=Discharge with partial resumption of normal activities, 1=Discharge with full resumption of normal activities. |
| Number of Days to Resumption of Usual Activities | Day 56 | Number of days until resumption of usual activities by treatment group |
| All Cause and Attributable Mortality at Day 14 | Day 14 | Number of patients experiencing all-cause and attributable mortality rates at Day 14. Attributable mortality was derived from the Complication of Influenza eCRF; all-cause mortality was derived from Complication of Influenza, Seven-Level Ordinal Scale, AE and Study Completion eCRFs |
| All Cause and Attributable Mortality by Day 28 | Day 28 | Number of patients experiencing all-cause and attributable mortality by Day 28. Attributable mortality was derived from the Complication of Influenza eCRF; all-cause mortality was derived from Complication of Influenza, Seven-Level Ordinal Scale, AE and Study Completion eCRFs |
| All Cause and Attributable Mortality Day 56 | Day 56 | Number of patients experiencing all-cause and attributable mortality by Day 56. Attributable mortality was derived from the Complication of Influenza eCRF; all-cause mortality was derived from Complication of Influenza, Seven-Level Ordinal Scale, AE and Study Completion eCRFs |
| Healthcare Resource Utilization. Days in Hospital and/or ICU | Day 56 | Total number of days in hospital and/or ICU from admission to discharge |
| Comparison of Ordinal Scale Parameters - Days in Hospital/ICU | 56 days | Total number of days in hospital or intensive care for participations who were admitted to Hospital/ICU, including participants in Hospital/ICU at baseline. Better and worse outcome groups defined based on the Seven-Level Ordinal Scale scores, \<= 4 Seven-Level Ordinal Scale Score is better; \> 4 Seven-Level Ordinal Scale Score is worse group. Seven-Level Ordinal Scale is a hierarchical scale with the classifications presented from the worst clinical outcome to the best clinical outcome in descending order with 7=death, 6=Intensive care unit (ICU) stay with mechanical ventilation , 5=ICU stay without mechanical ventilation, 4=Non-ICU hospitalization with supplemental oxygen, 3=Non-ICU hospitalization without supplemental oxygen, 2=Discharge with partial resumption of normal activities, 1=Discharge with full resumption of normal activities. |
| Number of Participants With Rehospitalization Due to Relapse | Day 56 | Number of participants with rehospitalization due to influenza A relapse |
| Number of Participants With Influenza-related Complications | Day 56 | Summary of influenza symptom complications, including baseline and incident complications |
| The Maximum Concentration (Cmax) of VIS410 in Participant's Serum | Baseline, end of infusion, Day 5, Day 14, Day 28, Day 56 | Summary of Serum VIS410 Pharmacokinetic Parameters in PK Population by maximum concentration (Cmax) of VIS410 in participant's serum. |
| 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 | Summary of Serum VIS410 Pharmacokinetic Parameters in PK Population by the area under the concentration/time curve from 0 to infinity (AUC0-inf) of VIS410 in participant's serum. |
| The Clearance Rate (Cl) of VIS410 in Participant's Serum | PK samples were collected on days 1, 5, 14, 28 and 56. | Summary of Serum VIS410 Pharmacokinetic Parameters in PK Population by the clearance rate (Cl) of VIS410 in participant's serum. |
| The Half-life of VIS410 in Participant's Serum | PK samples were collected on days 1, 5, 14, 28 and 56. | Summary of Serum VIS410 Pharmacokinetic Parameters in PK Population by the half-life (t1/2) of VIS410 in participant's serum. |
| Anti-VIS410 Antibody Testing | From anti-VIS410 antibody samples collected on days 28 and 56. | Summary of the maximum fold increase for anti-VIS410 antibody testing for VIS410 groups and placebo. |
| Total Number of Days on Ventilation | 56 days | Total number of days on ventilation for participants who used ventilation, including participants on ventilation at baseline |
| Time to Cessation of Oxygen Support for Any Patient Requiring Supplemental Oxygen Therapy | Baseline to Day 56 | Time to cessation of oxygen support in all patients with supplemental oxygen (regardless of oxygen saturation). |
Countries
Australia, Belarus, Belgium, Bulgaria, Canada, Estonia, France, Georgia, Latvia, Malaysia, New Zealand, Russia, Serbia, Singapore, South Africa, Spain, Thailand, Turkey (Türkiye), Ukraine, United States
Participant flow
Pre-assignment details
Approximately 120 participants were planned however, a total of 89 subjects were randomized to treatment. 73 participants completed the trial. There were study discontinuations for death, consent withdrawn and participants who were enrolled, but did not receive study drug.
Participants by arm
| Arm | Count |
|---|---|
| VIS410 High Dose VIS410 liquid for infusion. Single, fixed, intravenous dose of 4000 mg in addition to oseltamivir | 29 |
| VIS410 Low Dose VIS410 liquid for infusion. Single, fixed, intravenous dose of 2000 mg in addition to oseltamivir | 28 |
| Placebo Single intravenous infusion of placebo in addition to oseltamivir | 28 |
| Total | 85 |
Withdrawals & dropouts
| Period | Reason | FG000 | FG001 | FG002 |
|---|---|---|---|---|
| Overall Study | Death | 1 | 2 | 3 |
| Overall Study | Subject did not receive study drug or was not confirmed Influenza A positive | 0 | 2 | 2 |
| Overall Study | Subject discharged to nursing home, not able to attend visits | 0 | 1 | 0 |
| Overall Study | Withdrawal by Subject | 3 | 1 | 1 |
Baseline characteristics
| Characteristic | VIS410 High Dose | Total | VIS410 Low Dose | Placebo |
|---|---|---|---|---|
| Age, Continuous Age (years) | 60 years STANDARD_DEVIATION 19 | 61.2 years STANDARD_DEVIATION 18.91 | 66.2 years STANDARD_DEVIATION 13.94 | 57.5 years STANDARD_DEVIATION 22.41 |
| Body mass index (kg/m^2) | 28.2 Kg/m^2 STANDARD_DEVIATION 6.48 | 28.6 Kg/m^2 STANDARD_DEVIATION 6.87 | 28.4 Kg/m^2 STANDARD_DEVIATION 7.93 | 29.2 Kg/m^2 STANDARD_DEVIATION 6.3 |
| Ethnicity (NIH/OMB) Hispanic or Latino | 2 Participants | 5 Participants | 00 Participants | 3 Participants |
| Ethnicity (NIH/OMB) Not Hispanic or Latino | 27 Participants | 79 Participants | 28 Participants | 24 Participants |
| Ethnicity (NIH/OMB) Unknown or Not Reported | 0 Participants | 1 Participants | 0 Participants | 1 Participants |
| Race (NIH/OMB) American Indian or Alaska Native | 0 Participants | 0 Participants | 0 Participants | 0 Participants |
| Race (NIH/OMB) Asian | 1 Participants | 6 Participants | 2 Participants | 3 Participants |
| Race (NIH/OMB) Black or African American | 0 Participants | 4 Participants | 3 Participants | 1 Participants |
| Race (NIH/OMB) More than one race | 0 Participants | 0 Participants | 0 Participants | 0 Participants |
| Race (NIH/OMB) Native Hawaiian or Other Pacific Islander | 0 Participants | 0 Participants | 0 Participants | 0 Participants |
| Race (NIH/OMB) Unknown or Not Reported | 3 Participants | 14 Participants | 6 Participants | 5 Participants |
| Race (NIH/OMB) White | 25 Participants | 61 Participants | 17 Participants | 19 Participants |
| Region of Enrollment Australia | 0 participants | 2 participants | 1 participants | 1 participants |
| Region of Enrollment Belarus | 1 participants | 1 participants | 0 participants | 0 participants |
| Region of Enrollment Belgium | 0 participants | 2 participants | 0 participants | 2 participants |
| Region of Enrollment Bulgaria | 3 participants | 4 participants | 0 participants | 1 participants |
| Region of Enrollment Estonia | 3 participants | 9 participants | 3 participants | 3 participants |
| Region of Enrollment France | 1 participants | 5 participants | 2 participants | 2 participants |
| Region of Enrollment Georgia | 0 participants | 1 participants | 1 participants | 0 participants |
| Region of Enrollment Latvia | 2 participants | 6 participants | 1 participants | 3 participants |
| Region of Enrollment Malaysia | 1 participants | 2 participants | 0 participants | 1 participants |
| Region of Enrollment Serbia | 6 participants | 14 participants | 5 participants | 3 participants |
| Region of Enrollment Singapore | 0 participants | 1 participants | 0 participants | 1 participants |
| Region of Enrollment South Africa | 2 participants | 6 participants | 1 participants | 3 participants |
| Region of Enrollment Spain | 4 participants | 12 participants | 4 participants | 4 participants |
| Region of Enrollment Thailand | 3 participants | 11 participants | 6 participants | 2 participants |
| Region of Enrollment United States | 3 participants | 9 participants | 4 participants | 2 participants |
| Sex: Female, Male Female | 13 Participants | 44 Participants | 18 Participants | 13 Participants |
| Sex: Female, Male Male | 16 Participants | 41 Participants | 10 Participants | 15 Participants |
Adverse events
| Event type | EG000 affected / at risk | EG001 affected / at risk | EG002 affected / at risk | EG003 affected / at risk |
|---|---|---|---|---|
| deaths Total, all-cause mortality | 1 / 29 | 2 / 29 | 3 / 58 | 3 / 30 |
| other Total, other adverse events | 11 / 29 | 13 / 29 | 24 / 58 | 7 / 30 |
| serious Total, serious adverse events | 7 / 29 | 6 / 29 | 13 / 58 | 9 / 30 |
Outcome results
Primary
Clinical Status of Participants on Day 7
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.
Time frame: 7 days
Population: Modified Intent to treat (MITT) population. All participants of the safety population that have an assessment of O2 support after randomization and are confirmed influenza A positive. Participants will be analyzed based on the treatment to which they were randomized, irrespective of what they actually received. This population was selected for the analysis of the primary endpoint to maintain the benefits of randomization and avoid the bias associated with the non-random loss of the participants
| Arm | Measure | Category | Value (COUNT_OF_PARTICIPANTS) |
|---|---|---|---|
| VIS410 High Dose | Clinical Status of Participants on Day 7 | Death | 1 Participants |
| VIS410 High Dose | Clinical Status of Participants on Day 7 | Discharge with partial resumption of normal activities | 7 Participants |
| VIS410 High Dose | Clinical Status of Participants on Day 7 | Non-ICU hospitalization without supplemental oxygen | 12 Participants |
| VIS410 High Dose | Clinical Status of Participants on Day 7 | ICU stay with mechanical ventilation | 1 Participants |
| VIS410 High Dose | Clinical Status of Participants on Day 7 | Discharge with full resumption of normal activities | 1 Participants |
| VIS410 High Dose | Clinical Status of Participants on Day 7 | ICU stay without mechanical ventilation | 2 Participants |
| VIS410 High Dose | Clinical Status of Participants on Day 7 | Non-ICU hospitalization with supplemental oxygen | 5 Participants |
| VIS410 Low Dose | Clinical Status of Participants on Day 7 | Discharge with partial resumption of normal activities | 5 Participants |
| VIS410 Low Dose | Clinical Status of Participants on Day 7 | Non-ICU hospitalization with supplemental oxygen | 5 Participants |
| VIS410 Low Dose | Clinical Status of Participants on Day 7 | ICU stay without mechanical ventilation | 0 Participants |
| VIS410 Low Dose | Clinical Status of Participants on Day 7 | Non-ICU hospitalization without supplemental oxygen | 8 Participants |
| VIS410 Low Dose | Clinical Status of Participants on Day 7 | Discharge with full resumption of normal activities | 7 Participants |
| VIS410 Low Dose | Clinical Status of Participants on Day 7 | ICU stay with mechanical ventilation | 2 Participants |
| VIS410 Low Dose | Clinical Status of Participants on Day 7 | Death | 1 Participants |
| VIS410 Total | Clinical Status of Participants on Day 7 | Non-ICU hospitalization with supplemental oxygen | 10 Participants |
| VIS410 Total | Clinical Status of Participants on Day 7 | Death | 2 Participants |
| VIS410 Total | Clinical Status of Participants on Day 7 | ICU stay with mechanical ventilation | 3 Participants |
| VIS410 Total | Clinical Status of Participants on Day 7 | ICU stay without mechanical ventilation | 2 Participants |
| VIS410 Total | Clinical Status of Participants on Day 7 | Non-ICU hospitalization without supplemental oxygen | 20 Participants |
| VIS410 Total | Clinical Status of Participants on Day 7 | Discharge with partial resumption of normal activities | 12 Participants |
| VIS410 Total | Clinical Status of Participants on Day 7 | Discharge with full resumption of normal activities | 8 Participants |
| Placebo | Clinical Status of Participants on Day 7 | ICU stay without mechanical ventilation | 0 Participants |
| Placebo | Clinical Status of Participants on Day 7 | Discharge with full resumption of normal activities | 2 Participants |
| Placebo | Clinical Status of Participants on Day 7 | Discharge with partial resumption of normal activities | 11 Participants |
| Placebo | Clinical Status of Participants on Day 7 | ICU stay with mechanical ventilation | 1 Participants |
| Placebo | Clinical Status of Participants on Day 7 | Death | 1 Participants |
| Placebo | Clinical Status of Participants on Day 7 | Non-ICU hospitalization without supplemental oxygen | 10 Participants |
| Placebo | Clinical Status of Participants on Day 7 | Non-ICU hospitalization with supplemental oxygen | 3 Participants |
Comparison: All p-values are presented for informational purposes only; there were no adjustments for multiple comparisons.p-value: 0.18195% CI: [1.03, 13.55]Regression, Logistic
Comparison: All p-values are presented for informational purposes only; there were no adjustments for multiple comparisons.p-value: 0.07395% CI: [0.9, 12.13]Regression, Logistic
Comparison: All p-values are presented for informational purposes only; there were no adjustments for multiple comparisons.p-value: 0.03795% CI: [1.08, 11.48]Regression, Logistic
Comparison: All p-values are presented for informational purposes only; there were no adjustments for multiple comparisons.p-value: 0.81495% CI: [0.4, 3.25]Regression, Logistic
Primary
The Number of Participants With Adverse Events and Serious Adverse Events Following Administration of VIS410
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).
Time frame: 56 days
Population: Safety Population: Included all ITT participants (participants who randomized to treatment) who received IV study drug. Participants were grouped according to the actual treatment received.
| Arm | Measure | Group | Value (COUNT_OF_PARTICIPANTS) |
|---|---|---|---|
| VIS410 High Dose | The Number of Participants With Adverse Events and Serious Adverse Events Following Administration of VIS410 | Participants with adverse events | 16 Participants |
| VIS410 High Dose | The Number of Participants With Adverse Events and Serious Adverse Events Following Administration of VIS410 | Participants with at least one serious treatment emergent adverse events | 6 Participants |
| VIS410 Low Dose | The Number of Participants With Adverse Events and Serious Adverse Events Following Administration of VIS410 | Participants with at least one serious treatment emergent adverse events | 4 Participants |
| VIS410 Low Dose | The Number of Participants With Adverse Events and Serious Adverse Events Following Administration of VIS410 | Participants with adverse events | 22 Participants |
| VIS410 Total | The Number of Participants With Adverse Events and Serious Adverse Events Following Administration of VIS410 | Participants with adverse events | 38 Participants |
| VIS410 Total | The Number of Participants With Adverse Events and Serious Adverse Events Following Administration of VIS410 | Participants with at least one serious treatment emergent adverse events | 10 Participants |
| Placebo | The Number of Participants With Adverse Events and Serious Adverse Events Following Administration of VIS410 | Participants with adverse events | 16 Participants |
| Placebo | The Number of Participants With Adverse Events and Serious Adverse Events Following Administration of VIS410 | Participants with at least one serious treatment emergent adverse events | 6 Participants |
Secondary
All Cause and Attributable Mortality at Day 14
Number of patients experiencing all-cause and attributable mortality rates at Day 14. Attributable mortality was derived from the Complication of Influenza eCRF; all-cause mortality was derived from Complication of Influenza, Seven-Level Ordinal Scale, AE and Study Completion eCRFs
Time frame: Day 14
Population: The safety population included all ITT participants who received IV study drug. Participants were grouped according to the actual treatment received.
| Arm | Measure | Group | Value (NUMBER) |
|---|---|---|---|
| VIS410 High Dose | All Cause and Attributable Mortality at Day 14 | Attributable mortality Day 14 | 1 participants |
| VIS410 High Dose | All Cause and Attributable Mortality at Day 14 | All-cause mortality Day 14 | 1 participants |
| VIS410 Low Dose | All Cause and Attributable Mortality at Day 14 | Attributable mortality Day 14 | 2 participants |
| VIS410 Low Dose | All Cause and Attributable Mortality at Day 14 | All-cause mortality Day 14 | 2 participants |
| VIS410 Total | All Cause and Attributable Mortality at Day 14 | All-cause mortality Day 14 | 3 participants |
| VIS410 Total | All Cause and Attributable Mortality at Day 14 | Attributable mortality Day 14 | 3 participants |
| Placebo | All Cause and Attributable Mortality at Day 14 | Attributable mortality Day 14 | 1 participants |
| Placebo | All Cause and Attributable Mortality at Day 14 | All-cause mortality Day 14 | 1 participants |
Secondary
All Cause and Attributable Mortality by Day 28
Number of patients experiencing all-cause and attributable mortality by Day 28. Attributable mortality was derived from the Complication of Influenza eCRF; all-cause mortality was derived from Complication of Influenza, Seven-Level Ordinal Scale, AE and Study Completion eCRFs
Time frame: Day 28
Population: The safety population included all ITT participants who received IV study drug. Participants were grouped according to the actual treatment received.
| Arm | Measure | Group | Value (NUMBER) |
|---|---|---|---|
| VIS410 High Dose | All Cause and Attributable Mortality by Day 28 | All-cause mortality Day 28 | 1 participants |
| VIS410 High Dose | All Cause and Attributable Mortality by Day 28 | Attributable mortality Day 28 | 1 participants |
| VIS410 Low Dose | All Cause and Attributable Mortality by Day 28 | Attributable mortality Day 28 | 2 participants |
| VIS410 Low Dose | All Cause and Attributable Mortality by Day 28 | All-cause mortality Day 28 | 2 participants |
| VIS410 Total | All Cause and Attributable Mortality by Day 28 | All-cause mortality Day 28 | 3 participants |
| VIS410 Total | All Cause and Attributable Mortality by Day 28 | Attributable mortality Day 28 | 3 participants |
| Placebo | All Cause and Attributable Mortality by Day 28 | All-cause mortality Day 28 | 2 participants |
| Placebo | All Cause and Attributable Mortality by Day 28 | Attributable mortality Day 28 | 2 participants |
Secondary
All Cause and Attributable Mortality Day 56
Number of patients experiencing all-cause and attributable mortality by Day 56. Attributable mortality was derived from the Complication of Influenza eCRF; all-cause mortality was derived from Complication of Influenza, Seven-Level Ordinal Scale, AE and Study Completion eCRFs
Time frame: Day 56
Population: The safety population included all ITT participants who received IV study drug. Participants were grouped according to the actual treatment received.
| Arm | Measure | Group | Value (NUMBER) |
|---|---|---|---|
| VIS410 High Dose | All Cause and Attributable Mortality Day 56 | All-cause mortality Day 56 | 1 participants |
| VIS410 High Dose | All Cause and Attributable Mortality Day 56 | Attributable mortality Day 56 | 1 participants |
| VIS410 Low Dose | All Cause and Attributable Mortality Day 56 | Attributable mortality Day 56 | 2 participants |
| VIS410 Low Dose | All Cause and Attributable Mortality Day 56 | All-cause mortality Day 56 | 2 participants |
| VIS410 Total | All Cause and Attributable Mortality Day 56 | Attributable mortality Day 56 | 3 participants |
| VIS410 Total | All Cause and Attributable Mortality Day 56 | All-cause mortality Day 56 | 3 participants |
| Placebo | All Cause and Attributable Mortality Day 56 | All-cause mortality Day 56 | 2 participants |
| Placebo | All Cause and Attributable Mortality Day 56 | Attributable mortality Day 56 | 2 participants |
Secondary
Anti-VIS410 Antibody Testing
Summary of the maximum fold increase for anti-VIS410 antibody testing for VIS410 groups and placebo.
Time frame: From anti-VIS410 antibody samples collected on days 28 and 56.
Population: The modified ITT (MITT) population included all participants who received IV study drug and were confirmed influenza A positive by qRT-PCR in central lab analysis of pre-dose Day 1 and/or post-dose Day 1. Participants were grouped according to the randomly assigned treatment.
| Arm | Measure | Category | Value (COUNT_OF_PARTICIPANTS) |
|---|---|---|---|
| VIS410 High Dose | Anti-VIS410 Antibody Testing | >64 fold | 0 Participants |
| VIS410 High Dose | Anti-VIS410 Antibody Testing | >16 to 64 fold | 1 Participants |
| VIS410 High Dose | Anti-VIS410 Antibody Testing | 1 to 4 fold | 22 Participants |
| VIS410 High Dose | Anti-VIS410 Antibody Testing | >4 to 16 fold | 2 Participants |
| VIS410 Low Dose | Anti-VIS410 Antibody Testing | >4 to 16 fold | 1 Participants |
| VIS410 Low Dose | Anti-VIS410 Antibody Testing | 1 to 4 fold | 24 Participants |
| VIS410 Low Dose | Anti-VIS410 Antibody Testing | >16 to 64 fold | 0 Participants |
| VIS410 Low Dose | Anti-VIS410 Antibody Testing | >64 fold | 1 Participants |
| VIS410 Total | Anti-VIS410 Antibody Testing | >16 to 64 fold | 1 Participants |
| VIS410 Total | Anti-VIS410 Antibody Testing | >64 fold | 1 Participants |
| VIS410 Total | Anti-VIS410 Antibody Testing | >4 to 16 fold | 3 Participants |
| VIS410 Total | Anti-VIS410 Antibody Testing | 1 to 4 fold | 46 Participants |
| Placebo | Anti-VIS410 Antibody Testing | >64 fold | 0 Participants |
| Placebo | Anti-VIS410 Antibody Testing | 1 to 4 fold | 25 Participants |
| Placebo | Anti-VIS410 Antibody Testing | >4 to 16 fold | 0 Participants |
| Placebo | Anti-VIS410 Antibody Testing | >16 to 64 fold | 0 Participants |
Secondary
Area Under the Viral Load-Time Curve (VL AUC) Based on qRT-PCR From Nasopharyngeal Swabs Through Day 14
The difference between VIS410 + oseltamivir and oseltamivir alone treatment groups in nasopharyngeal qRT-PCR area under the viral load-time curve (AUC) from baseline to Day 14.
Time frame: Day 1 Predose, Day 1 End of Infusion, Day 3, Day 5, Day 7, Day 14
Population: The modified ITT (MITT) population included all participants who received IV study drug and were confirmed influenza A positive by qRT-PCR in central lab analysis of pre-dose Day 1 and/or post-dose Day 1. Participants were grouped according to the randomly assigned treatment.
| Arm | Measure | Value (MEAN) | Dispersion |
|---|---|---|---|
| VIS410 High Dose | Area Under the Viral Load-Time Curve (VL AUC) Based on qRT-PCR From Nasopharyngeal Swabs Through Day 14 | 37.356 Day*vp/mL | Standard Deviation 17.6513 |
| VIS410 Low Dose | Area Under the Viral Load-Time Curve (VL AUC) Based on qRT-PCR From Nasopharyngeal Swabs Through Day 14 | 35.172 Day*vp/mL | Standard Deviation 18.6217 |
| VIS410 Total | Area Under the Viral Load-Time Curve (VL AUC) Based on qRT-PCR From Nasopharyngeal Swabs Through Day 14 | 36.264 Day*vp/mL | Standard Deviation 17.998 |
| Placebo | Area Under the Viral Load-Time Curve (VL AUC) Based on qRT-PCR From Nasopharyngeal Swabs Through Day 14 | 36.668 Day*vp/mL | Standard Deviation 17.2015 |
p-value: 0.88ANOVA
p-value: 0.778ANOVA
p-value: 0.94ANOVA
p-value: 0.662ANOVA
Secondary
Area Under the Viral Load-Time Curve (VL AUC) Based on qRT-PCR From Nasopharyngeal Swabs Through Day 7
The difference between VIS410 + oseltamivir and oseltamivir alone treatment groups in nasopharyngeal qRT-PCR area under the viral load-time curve (AUC) from baseline to Day 7.
Time frame: Day 1 Predose, Day 1 End of Infusion, Day 3, Day 5, Day 7
Population: The modified ITT (MITT) population included all participants who received IV study drug and were confirmed influenza A positive by qRT-PCR in central lab analysis of pre-dose Day 1 and/or post-dose Day 1. Participants were grouped according to the randomly assigned treatment.
| Arm | Measure | Value (MEAN) | Dispersion |
|---|---|---|---|
| VIS410 High Dose | Area Under the Viral Load-Time Curve (VL AUC) Based on qRT-PCR From Nasopharyngeal Swabs Through Day 7 | 25.490 Day*vp/mL | Standard Deviation 9.044 |
| VIS410 Low Dose | Area Under the Viral Load-Time Curve (VL AUC) Based on qRT-PCR From Nasopharyngeal Swabs Through Day 7 | 22.394 Day*vp/mL | Standard Deviation 7.9006 |
| VIS410 Total | Area Under the Viral Load-Time Curve (VL AUC) Based on qRT-PCR From Nasopharyngeal Swabs Through Day 7 | 23.942 Day*vp/mL | Standard Deviation 8.555 |
| Placebo | Area Under the Viral Load-Time Curve (VL AUC) Based on qRT-PCR From Nasopharyngeal Swabs Through Day 7 | 24.337 Day*vp/mL | Standard Deviation 8.8837 |
p-value: 0.624ANOVA
p-value: 0.399ANOVA
p-value: 0.837ANOVA
p-value: 0.183ANOVA
Secondary
Clinical Status Ordinal Scale Mean Area Under the Curve Through Day 14.
Summary of area under the curve (AUC) over time for seven-level ordinal scale. Area under the curve (AUC) is calculated using the linear trapezoidal rule. Seven-Level Ordinal Scale is a hierarchical scale with the classifications presented from the worst clinical outcome to the best clinical outcome in descending order with 7=death, 6=Intensive care unit (ICU) stay with mechanical ventilation , 5=ICU stay without mechanical ventilation, 4=Non-ICU hospitalization with supplemental oxygen, 3=Non-ICU hospitalization without supplemental oxygen, 2=Discharge with partial resumption of normal activities, 1=Discharge with full resumption of normal activities. Time frame is from baseline to day 14. Therefore, maximum and minimum values possible for the AUC Clinical Status Ordinal Scale scores range from 14 to 98.
Time frame: Baseline to Days 14
Population: The modified ITT (MITT) population included all participants who received IV study drug and were confirmed influenza A positive by qRT-PCR in central lab analysis of pre-dose Day 1 and/or post-dose Day 1. Participants were grouped according to the randomly assigned treatment
| Arm | Measure | Value (MEAN) | Dispersion |
|---|---|---|---|
| VIS410 High Dose | Clinical Status Ordinal Scale Mean Area Under the Curve Through Day 14. | 40.3 day*units on a scale | Standard Deviation 15.21 |
| VIS410 Low Dose | Clinical Status Ordinal Scale Mean Area Under the Curve Through Day 14. | 38.2 day*units on a scale | Standard Deviation 18.73 |
| VIS410 Total | Clinical Status Ordinal Scale Mean Area Under the Curve Through Day 14. | 39.3 day*units on a scale | Standard Deviation 16.91 |
| Placebo | Clinical Status Ordinal Scale Mean Area Under the Curve Through Day 14. | 35.8 day*units on a scale | Standard Deviation 12.54 |
Comparison: All p-values are presented for informational purposes only; there were no adjustments for multiple comparisons.p-value: 0.5436ANCOVA
Comparison: All p-values are presented for informational purposes only; there were no adjustments for multiple comparisons.p-value: 0.8215ANCOVA
Comparison: All p-values are presented for informational purposes only; there were no adjustments for multiple comparisons.p-value: 0.6319ANCOVA
Comparison: All p-values are presented for informational purposes only; there were no adjustments for multiple comparisons.p-value: 0.7011ANCOVA
Secondary
Clinical Status Ordinal Scale Mean Area Under the Curve Through Day 7
Summary of area under the curve (AUC) over time for seven-level ordinal scale. Area under the curve (AUC) is calculated using the linear trapezoidal rule. Seven-Level Ordinal Scale is a hierarchical scale with the classifications presented from the worst clinical outcome to the best clinical outcome in descending order with 7=death, 6=Intensive care unit (ICU) stay with mechanical ventilation , 5=ICU stay without mechanical ventilation, 4=Non-ICU hospitalization with supplemental oxygen, 3=Non-ICU hospitalization without supplemental oxygen, 2=Discharge with partial resumption of normal activities, 1=Discharge with full resumption of normal activities. Time frame is from baseline to day 7. Therefore, maximum and minimum values possible for the AUC Clinical Status Ordinal Scale scores range from 7 to 49.
Time frame: Baseline to Day 7
Population: The modified ITT (MITT) population included all participants who received IV study drug and were confirmed influenza A positive by qRT-PCR in central lab analysis of pre-dose Day 1 and/or post-dose Day 1. Participants were grouped according to the randomly assigned treatment
| Arm | Measure | Value (MEAN) | Dispersion |
|---|---|---|---|
| VIS410 High Dose | Clinical Status Ordinal Scale Mean Area Under the Curve Through Day 7 | 23.6 day*units on a scale | Standard Deviation 5.55 |
| VIS410 Low Dose | Clinical Status Ordinal Scale Mean Area Under the Curve Through Day 7 | 22.4 day*units on a scale | Standard Deviation 7.47 |
| VIS410 Total | Clinical Status Ordinal Scale Mean Area Under the Curve Through Day 7 | 23.0 day*units on a scale | Standard Deviation 6.53 |
| Placebo | Clinical Status Ordinal Scale Mean Area Under the Curve Through Day 7 | 21.4 day*units on a scale | Standard Deviation 4.97 |
Comparison: All p-values are presented for informational purposes only; there were no adjustments for multiple comparisons.p-value: 0.3534ANCOVA
Comparison: All p-values are presented for informational purposes only; there were no adjustments for multiple comparisons.p-value: 0.7839ANCOVA
Comparison: All p-values are presented for informational purposes only; there were no adjustments for multiple comparisons.p-value: 0.4893ANCOVA
Comparison: All p-values are presented for informational purposes only; there were no adjustments for multiple comparisons.p-value: 0.5101ANCOVA
Secondary
Comparison of Clinical Status on Seven-level Ordinal Scale Scores
Summary of Clinical Outcome on Seven-Level Ordinal Scale through Day 14. Worst post-baseline assessment observed. Seven-Level Ordinal Scale is a hierarchical scale with the classifications presented from the worst clinical outcome to the best clinical outcome in descending order with 7=death, 6=Intensive care unit (ICU) stay with mechanical ventilation , 5=ICU stay without mechanical ventilation, 4=Non-ICU hospitalization with supplemental oxygen, 3=Non-ICU hospitalization without supplemental oxygen, 2=Discharge with partial resumption of normal activities, 1=Discharge with full resumption of normal activities.
Time frame: Day 14
Population: The modified ITT (MITT) population included all participants who received IV study drug and were confirmed influenza A positive by qRT-PCR in central lab analysis of pre-dose Day 1 and/or post-dose Day 1. Participants were grouped according to the randomly assigned treatment.
| Arm | Measure | Category | Value (COUNT_OF_PARTICIPANTS) |
|---|---|---|---|
| VIS410 High Dose | Comparison of Clinical Status on Seven-level Ordinal Scale Scores | Death | 1 Participants |
| VIS410 High Dose | Comparison of Clinical Status on Seven-level Ordinal Scale Scores | Discharge with partial resumption of normal activities | 0 Participants |
| VIS410 High Dose | Comparison of Clinical Status on Seven-level Ordinal Scale Scores | Non-ICU hospitalization without supplemental oxygen | 2 Participants |
| VIS410 High Dose | Comparison of Clinical Status on Seven-level Ordinal Scale Scores | ICU stay with mechanical ventilation | 4 Participants |
| VIS410 High Dose | Comparison of Clinical Status on Seven-level Ordinal Scale Scores | Discharge with full resumption of normal activities | 0 Participants |
| VIS410 High Dose | Comparison of Clinical Status on Seven-level Ordinal Scale Scores | ICU stay without mechanical ventilation | 4 Participants |
| VIS410 High Dose | Comparison of Clinical Status on Seven-level Ordinal Scale Scores | Non-ICU hospitalization with supplemental oxygen | 18 Participants |
| VIS410 Low Dose | Comparison of Clinical Status on Seven-level Ordinal Scale Scores | Discharge with partial resumption of normal activities | 1 Participants |
| VIS410 Low Dose | Comparison of Clinical Status on Seven-level Ordinal Scale Scores | Non-ICU hospitalization with supplemental oxygen | 17 Participants |
| VIS410 Low Dose | Comparison of Clinical Status on Seven-level Ordinal Scale Scores | ICU stay without mechanical ventilation | 5 Participants |
| VIS410 Low Dose | Comparison of Clinical Status on Seven-level Ordinal Scale Scores | Non-ICU hospitalization without supplemental oxygen | 1 Participants |
| VIS410 Low Dose | Comparison of Clinical Status on Seven-level Ordinal Scale Scores | Discharge with full resumption of normal activities | 0 Participants |
| VIS410 Low Dose | Comparison of Clinical Status on Seven-level Ordinal Scale Scores | ICU stay with mechanical ventilation | 2 Participants |
| VIS410 Low Dose | Comparison of Clinical Status on Seven-level Ordinal Scale Scores | Death | 2 Participants |
| VIS410 Total | Comparison of Clinical Status on Seven-level Ordinal Scale Scores | Non-ICU hospitalization with supplemental oxygen | 35 Participants |
| VIS410 Total | Comparison of Clinical Status on Seven-level Ordinal Scale Scores | Death | 3 Participants |
| VIS410 Total | Comparison of Clinical Status on Seven-level Ordinal Scale Scores | ICU stay with mechanical ventilation | 6 Participants |
| VIS410 Total | Comparison of Clinical Status on Seven-level Ordinal Scale Scores | ICU stay without mechanical ventilation | 9 Participants |
| VIS410 Total | Comparison of Clinical Status on Seven-level Ordinal Scale Scores | Non-ICU hospitalization without supplemental oxygen | 3 Participants |
| VIS410 Total | Comparison of Clinical Status on Seven-level Ordinal Scale Scores | Discharge with partial resumption of normal activities | 1 Participants |
| VIS410 Total | Comparison of Clinical Status on Seven-level Ordinal Scale Scores | Discharge with full resumption of normal activities | 0 Participants |
| Placebo | Comparison of Clinical Status on Seven-level Ordinal Scale Scores | ICU stay without mechanical ventilation | 3 Participants |
| Placebo | Comparison of Clinical Status on Seven-level Ordinal Scale Scores | Discharge with full resumption of normal activities | 0 Participants |
| Placebo | Comparison of Clinical Status on Seven-level Ordinal Scale Scores | Discharge with partial resumption of normal activities | 0 Participants |
| Placebo | Comparison of Clinical Status on Seven-level Ordinal Scale Scores | ICU stay with mechanical ventilation | 2 Participants |
| Placebo | Comparison of Clinical Status on Seven-level Ordinal Scale Scores | Death | 1 Participants |
| Placebo | Comparison of Clinical Status on Seven-level Ordinal Scale Scores | Non-ICU hospitalization without supplemental oxygen | 2 Participants |
| Placebo | Comparison of Clinical Status on Seven-level Ordinal Scale Scores | Non-ICU hospitalization with supplemental oxygen | 20 Participants |
Comparison: All p-values are presented for informational purposes only; there were no adjustments for multiple comparisons.p-value: 0.478Regression, Logistic
Comparison: All p-values are presented for informational purposes only; there were no adjustments for multiple comparisons.p-value: 0.468Regression, Logistic
Comparison: All p-values are presented for informational purposes only; there were no adjustments for multiple comparisonsp-value: 0.412Regression, Logistic
Comparison: All p-values are presented for informational purposes only; there were no adjustments for multiple comparisonsp-value: 0.982Regression, Logistic
Secondary
Comparison of Ordinal Scale Parameters - Days in Hospital/ICU
Total number of days in hospital or intensive care for participations who were admitted to Hospital/ICU, including participants in Hospital/ICU at baseline. Better and worse outcome groups defined based on the Seven-Level Ordinal Scale scores, \<= 4 Seven-Level Ordinal Scale Score is better; \> 4 Seven-Level Ordinal Scale Score is worse group. Seven-Level Ordinal Scale is a hierarchical scale with the classifications presented from the worst clinical outcome to the best clinical outcome in descending order with 7=death, 6=Intensive care unit (ICU) stay with mechanical ventilation , 5=ICU stay without mechanical ventilation, 4=Non-ICU hospitalization with supplemental oxygen, 3=Non-ICU hospitalization without supplemental oxygen, 2=Discharge with partial resumption of normal activities, 1=Discharge with full resumption of normal activities.
Time frame: 56 days
Population: Participants requiring ventilation from the mITT population. The modified ITT (MITT) population included all participants who received IV study drug and were confirmed influenza A positive by qRT-PCR in central lab analysis of pre-dose Day 1 and/or post-dose Day 1. Participants were grouped according to the randomly assigned treatment.
| Arm | Measure | Group | Value (MEAN) | Dispersion |
|---|---|---|---|---|
| VIS410 High Dose | Comparison of Ordinal Scale Parameters - Days in Hospital/ICU | > 4 Seven-Level Ordinal Scale Score | 15.9 days | Standard Deviation 12.47 |
| VIS410 High Dose | Comparison of Ordinal Scale Parameters - Days in Hospital/ICU | <= 4 Seven-Level Ordinal Scale Score | 8.6 days | Standard Deviation 3.01 |
| VIS410 Low Dose | Comparison of Ordinal Scale Parameters - Days in Hospital/ICU | <= 4 Seven-Level Ordinal Scale Score | 7.9 days | Standard Deviation 5.13 |
| VIS410 Low Dose | Comparison of Ordinal Scale Parameters - Days in Hospital/ICU | > 4 Seven-Level Ordinal Scale Score | 12.6 days | Standard Deviation 9.08 |
| VIS410 Total | Comparison of Ordinal Scale Parameters - Days in Hospital/ICU | > 4 Seven-Level Ordinal Scale Score | 14.3 days | Standard Deviation 10.85 |
| VIS410 Total | Comparison of Ordinal Scale Parameters - Days in Hospital/ICU | <= 4 Seven-Level Ordinal Scale Score | 8.3 days | Standard Deviation 4.16 |
| Placebo | Comparison of Ordinal Scale Parameters - Days in Hospital/ICU | > 4 Seven-Level Ordinal Scale Score | 13.8 days | Standard Deviation 9.74 |
| Placebo | Comparison of Ordinal Scale Parameters - Days in Hospital/ICU | <= 4 Seven-Level Ordinal Scale Score | 8.9 days | Standard Deviation 5.64 |
Secondary
Comparison of Ordinal Scale Parameters - Days in ICU
Total number of days in intensive care for participants who admitted to ICU, including participants in ICU at baseline. Better and worse outcome groups defined based on the Seven-Level Ordinal Scale scores, \<= 4 Seven-Level Ordinal Scale Score is better; \> 4 Seven-Level Ordinal Scale Score is worse group. Seven-Level Ordinal Scale is a hierarchical scale with the classifications presented from the worst clinical outcome to the best clinical outcome in descending order with 7=death, 6=Intensive care unit (ICU) stay with mechanical ventilation , 5=ICU stay without mechanical ventilation, 4=Non-ICU hospitalization with supplemental oxygen, 3=Non-ICU hospitalization without supplemental oxygen, 2=Discharge with partial resumption of normal activities, 1=Discharge with full resumption of normal activities.
Time frame: 56 days
Population: Participants requiring ventilation from the mITT population. The modified ITT (MITT) population included all participants who received IV study drug and were confirmed influenza A positive by qRT-PCR in central lab analysis of pre-dose Day 1 and/or post-dose Day 1. Participants were grouped according to the randomly assigned treatment.
| Arm | Measure | Group | Value (MEAN) | Dispersion |
|---|---|---|---|---|
| VIS410 High Dose | Comparison of Ordinal Scale Parameters - Days in ICU | > 4 Seven-Level Ordinal Scale Score | 8.5 days | Standard Deviation 7.43 |
| VIS410 Low Dose | Comparison of Ordinal Scale Parameters - Days in ICU | > 4 Seven-Level Ordinal Scale Score | 6.8 days | Standard Deviation 3.71 |
| VIS410 Total | Comparison of Ordinal Scale Parameters - Days in ICU | > 4 Seven-Level Ordinal Scale Score | 7.7 days | Standard Deviation 5.88 |
| Placebo | Comparison of Ordinal Scale Parameters - Days in ICU | > 4 Seven-Level Ordinal Scale Score | 10.8 days | Standard Deviation 6.85 |
| Placebo | Comparison of Ordinal Scale Parameters - Days in ICU | <= 4 Seven-Level Ordinal Scale Score is better | 27.0 days | — |
Secondary
Comparison of Ordinal Scale Parameters - Days on Ventilation
Total number of days on ventilation for participations who used ventilation, including participants on ventilation at baseline. Better and worse outcome groups defined based on the Seven-Level Ordinal Scale scores, \<= 4 Seven-Level Ordinal Scale Score is better; \> 4 Seven-Level Ordinal Scale Score is worse group. Seven-Level Ordinal Scale is a hierarchical scale with the classifications presented from the worst clinical outcome to the best clinical outcome in descending order with 7=death, 6=Intensive care unit (ICU) stay with mechanical ventilation , 5=ICU stay without mechanical ventilation, 4=Non-ICU hospitalization with supplemental oxygen, 3=Non-ICU hospitalization without supplemental oxygen, 2=Discharge with partial resumption of normal activities, 1=Discharge with full resumption of normal activities.
Time frame: 56 days
Population: Participants requiring ventilation from the mITT population. The modified ITT (MITT) population included all participants who received IV study drug and were confirmed influenza A positive by qRT-PCR in central lab analysis of pre-dose Day 1 and/or post-dose Day 1. Participants were grouped according to the randomly assigned treatment.
| Arm | Measure | Group | Value (MEAN) | Dispersion |
|---|---|---|---|---|
| VIS410 High Dose | Comparison of Ordinal Scale Parameters - Days on Ventilation | > 4 Seven-Level Ordinal Scale Score | 5.2 days | Standard Deviation 4.55 |
| VIS410 Low Dose | Comparison of Ordinal Scale Parameters - Days on Ventilation | > 4 Seven-Level Ordinal Scale Score | 7.0 days | Standard Deviation 5.2 |
| VIS410 Total | Comparison of Ordinal Scale Parameters - Days on Ventilation | > 4 Seven-Level Ordinal Scale Score | 5.9 days | Standard Deviation 4.52 |
| Placebo | Comparison of Ordinal Scale Parameters - Days on Ventilation | > 4 Seven-Level Ordinal Scale Score | 8.0 days | Standard Deviation 5.66 |
| Placebo | Comparison of Ordinal Scale Parameters - Days on Ventilation | <= 4 Seven-Level Ordinal Scale Score | 19.0 days | — |
Secondary
Healthcare Resource Utilization. Days in Hospital and/or ICU
Total number of days in hospital and/or ICU from admission to discharge
Time frame: Day 56
Population: The modified ITT (MITT) population included all participants who received IV study drug and were confirmed influenza A positive by qRT-PCR in central lab analysis of pre-dose Day 1 and/or post-dose Day 1. Participants were grouped according to the randomly assigned treatment.
| Arm | Measure | Value (MEAN) | Dispersion |
|---|---|---|---|
| VIS410 High Dose | Healthcare Resource Utilization. Days in Hospital and/or ICU | 11.4 Days | Standard Deviation 8.6 |
| VIS410 Low Dose | Healthcare Resource Utilization. Days in Hospital and/or ICU | 9.6 Days | Standard Deviation 7.02 |
| VIS410 Total | Healthcare Resource Utilization. Days in Hospital and/or ICU | 10.5 Days | Standard Deviation 7.84 |
| Placebo | Healthcare Resource Utilization. Days in Hospital and/or ICU | 9.6 Days | Standard Deviation 6.38 |
Secondary
Median Time to Resolution of Viral Load by Treatment Arm by qRT-PCR - From End of Infusion
Number of days from the end of infusion until virus is no longer detectable (at or below the limit of detection) with no samples following that are greater than the BLQ through the Day 14 (quantitative reverse-transcription polymerase chain reaction - qRT-PCR)
Time frame: 14 days
Population: The modified ITT (MITT) population included all participants who received IV study drug and were confirmed influenza A positive by qRT-PCR in central lab analysis of pre-dose Day 1 and/or post-dose Day 1. Participants were grouped according to the randomly assigned treatment.
| Arm | Measure | Value (MEDIAN) |
|---|---|---|
| VIS410 High Dose | Median Time to Resolution of Viral Load by Treatment Arm by qRT-PCR - From End of Infusion | 13.5 Days |
| VIS410 Low Dose | Median Time to Resolution of Viral Load by Treatment Arm by qRT-PCR - From End of Infusion | 12.7 Days |
| VIS410 Total | Median Time to Resolution of Viral Load by Treatment Arm by qRT-PCR - From End of Infusion | 12.7 Days |
| Placebo | Median Time to Resolution of Viral Load by Treatment Arm by qRT-PCR - From End of Infusion | 11.9 Days |
p-value: 0.64Chi-squared
p-value: 0.775Chi-squared
p-value: 0.701Chi-squared
p-value: 0.638Chi-squared
Secondary
Median Time to Resolution of Viral Load by Treatment Arm by TCID50 - From End of Infusion
Number of days from the end of infusion until virus is no longer detectable (at or below the limit of detection) with no samples following that are greater than the BLQ through the Day 7 (TCID50)
Time frame: 7 Days
Population: The modified ITT (MITT) population included all participants who received IV study drug and were confirmed influenza A positive by TCID50 in central lab analysis of pre-dose Day 1 and/or post-dose Day 1. Participants were grouped according to the randomly assigned treatment, who also had a positive baseline viral culture based on TCID50.
| Arm | Measure | Value (MEDIAN) |
|---|---|---|
| VIS410 High Dose | Median Time to Resolution of Viral Load by Treatment Arm by TCID50 - From End of Infusion | 1.7 Days |
| VIS410 Low Dose | Median Time to Resolution of Viral Load by Treatment Arm by TCID50 - From End of Infusion | 1.7 Days |
| VIS410 Total | Median Time to Resolution of Viral Load by Treatment Arm by TCID50 - From End of Infusion | 1.7 Days |
| Placebo | Median Time to Resolution of Viral Load by Treatment Arm by TCID50 - From End of Infusion | 1.8 Days |
Comparison: All p-values are presented for informational purposes only; there were no adjustments for multiple comparisons.p-value: 0.25Chi-squared
Comparison: All p-values are presented for informational purposes only; there were no adjustments for multiple comparisons.p-value: 0.133Chi-squared
p-value: 0.177Chi-squared
Comparison: All p-values are presented for informational purposes only; there were no adjustments for multiple comparisonsp-value: 0.36Chi-squared
Secondary
Median Time to Resolution of Viral Load by Treatment Arm by TCID50 - From Onset of Symptoms
Number of days from the onset of symptoms until virus is no longer detectable (at or below the limit of detection) with no samples following that are greater than the BLQ through the Day 7 (TCID50)
Time frame: 7 Days
Population: The modified ITT (MITT) population included all participants who received IV study drug and were confirmed influenza A positive by TCID50 in central lab analysis of pre-dose Day 1 and/or post-dose Day 1. Participants were grouped according to the randomly assigned treatment, who also had a positive baseline viral culture based on TCID50.
| Arm | Measure | Value (MEDIAN) |
|---|---|---|
| VIS410 High Dose | Median Time to Resolution of Viral Load by Treatment Arm by TCID50 - From Onset of Symptoms | 4.7 Days |
| VIS410 Low Dose | Median Time to Resolution of Viral Load by Treatment Arm by TCID50 - From Onset of Symptoms | 4.8 Days |
| VIS410 Total | Median Time to Resolution of Viral Load by Treatment Arm by TCID50 - From Onset of Symptoms | 4.8 Days |
| Placebo | Median Time to Resolution of Viral Load by Treatment Arm by TCID50 - From Onset of Symptoms | 4.4 Days |
Comparison: All p-values are presented for informational purposes only; there were no adjustments for multiple comparisons.p-value: 0.636Chi-squared
p-value: 0.446Chi-squared
Comparison: All p-values are presented for informational purposes only; there were no adjustments for multiple comparisons.p-value: 0.53Chi-squared
Comparison: All p-values are presented for informational purposes only; there were no adjustments for multiple comparisons.p-value: 0.463Chi-squared
Secondary
Negative Viral Cultures by Study Day
Number of participants negative for viral titer by study day determined by TCID50 on nominal days 3, 5, 7
Time frame: Nominal days 3, 5, 7
Population: The modified ITT (MITT) population included all participants who received IV study drug and were confirmed influenza A positive by qRT-PCR in central lab analysis of pre-dose Day 1 and/or post-dose Day 1. Participants were grouped according to the randomly assigned treatment, who also had a positive baseline viral culture based on TCID50.
| Arm | Measure | Group | Value (COUNT_OF_PARTICIPANTS) |
|---|---|---|---|
| VIS410 High Dose | Negative Viral Cultures by Study Day | Participants with negative viral cultures by Day 3. | 23 Participants |
| VIS410 High Dose | Negative Viral Cultures by Study Day | Participants with negative viral cultures by Day 7. | 28 Participants |
| VIS410 High Dose | Negative Viral Cultures by Study Day | Participants with negative viral cultures by Day 5. | 25 Participants |
| VIS410 Low Dose | Negative Viral Cultures by Study Day | Participants with negative viral cultures by Day 3. | 24 Participants |
| VIS410 Low Dose | Negative Viral Cultures by Study Day | Participants with negative viral cultures by Day 7. | 27 Participants |
| VIS410 Low Dose | Negative Viral Cultures by Study Day | Participants with negative viral cultures by Day 5. | 26 Participants |
| VIS410 Total | Negative Viral Cultures by Study Day | Participants with negative viral cultures by Day 3. | 47 Participants |
| VIS410 Total | Negative Viral Cultures by Study Day | Participants with negative viral cultures by Day 5. | 51 Participants |
| VIS410 Total | Negative Viral Cultures by Study Day | Participants with negative viral cultures by Day 7. | 55 Participants |
| Placebo | Negative Viral Cultures by Study Day | Participants with negative viral cultures by Day 3. | 19 Participants |
| Placebo | Negative Viral Cultures by Study Day | Participants with negative viral cultures by Day 7. | 27 Participants |
| Placebo | Negative Viral Cultures by Study Day | Participants with negative viral cultures by Day 5. | 25 Participants |
Secondary
Number of Days to Resumption of Usual Activities
Number of days until resumption of usual activities by treatment group
Time frame: Day 56
Population: The modified ITT (MITT) population included all participants who received IV study drug and were confirmed influenza A positive by qRT-PCR in central lab analysis of pre-dose Day 1 and/or post-dose Day 1. Participants were grouped according to the randomly assigned treatment.
| Arm | Measure | Value (MEAN) | Dispersion |
|---|---|---|---|
| VIS410 High Dose | Number of Days to Resumption of Usual Activities | 11.9 days | Standard Deviation 3.07 |
| VIS410 Low Dose | Number of Days to Resumption of Usual Activities | 10.3 days | Standard Deviation 4.1 |
| VIS410 Total | Number of Days to Resumption of Usual Activities | 11.1 days | Standard Deviation 3.67 |
| Placebo | Number of Days to Resumption of Usual Activities | 11.5 days | Standard Deviation 3.38 |
Secondary
Number of Participants in Whom Peak Viral Load Occurred Post Baseline Measured by qRT-PCR
Number of participants in whom peak viral load is observed post-baseline based on quantitative reverse-transcription polymerase chain reaction (qRT-PCR). Post-baseline was considered the day 3 sample or later.
Time frame: 14 days
Population: The modified ITT (MITT) population included all participants who received IV study drug and were confirmed influenza A positive by qRT-PCR in central lab analysis of pre-dose Day 1 and/or post-dose Day 1. Participants were grouped according to the randomly assigned treatment.
| Arm | Measure | Value (COUNT_OF_PARTICIPANTS) |
|---|---|---|
| VIS410 High Dose | Number of Participants in Whom Peak Viral Load Occurred Post Baseline Measured by qRT-PCR | 5 Participants |
| VIS410 Low Dose | Number of Participants in Whom Peak Viral Load Occurred Post Baseline Measured by qRT-PCR | 1 Participants |
| VIS410 Total | Number of Participants in Whom Peak Viral Load Occurred Post Baseline Measured by qRT-PCR | 6 Participants |
| Placebo | Number of Participants in Whom Peak Viral Load Occurred Post Baseline Measured by qRT-PCR | 1 Participants |
p-value: 0.127Regression, Logistic
p-value: 1Regression, Logistic
p-value: 0.458Regression, Logistic
p-value: 0.127Regression, Logistic
Secondary
Number of Participants in Whom Peak Viral Load Occurred Post Baseline Measured by TCID50
Number of participants in whom peak viral load occurred post-baseline measured by TCID50. Post-baseline was considered the day 3 sample or later.
Time frame: 56 days
Population: The modified ITT (MITT) population included all participants who received IV study drug and were confirmed influenza A positive by qRT-PCR in central lab analysis of pre-dose Day 1 and/or post-dose Day 1. Participants were grouped according to the randomly assigned treatment.
| Arm | Measure | Value (COUNT_OF_PARTICIPANTS) |
|---|---|---|
| VIS410 High Dose | Number of Participants in Whom Peak Viral Load Occurred Post Baseline Measured by TCID50 | 1 Participants |
| VIS410 Low Dose | Number of Participants in Whom Peak Viral Load Occurred Post Baseline Measured by TCID50 | 0 Participants |
| VIS410 Total | Number of Participants in Whom Peak Viral Load Occurred Post Baseline Measured by TCID50 | 1 Participants |
| Placebo | Number of Participants in Whom Peak Viral Load Occurred Post Baseline Measured by TCID50 | 1 Participants |
p-value: 0.98Regression, Logistic
p-value: 0.955Regression, Logistic
p-value: 0.955Regression, Logistic
p-value: 0.955Regression, Logistic
Secondary
Number of Participants With Influenza-related Complications
Summary of influenza symptom complications, including baseline and incident complications
Time frame: Day 56
Population: The modified ITT (MITT) population included all participants who received IV study drug and were confirmed influenza A positive by qRT-PCR in central lab analysis of pre-dose Day 1 and/or post-dose Day 1. Participants were grouped according to the randomly assigned treatment.
| Arm | Measure | Group | Value (COUNT_OF_PARTICIPANTS) |
|---|---|---|---|
| VIS410 High Dose | Number of Participants With Influenza-related Complications | Participants with at least 1 complication of Influenza | 4 Participants |
| VIS410 High Dose | Number of Participants With Influenza-related Complications | Participants with pneumonia | 3 Participants |
| VIS410 High Dose | Number of Participants With Influenza-related Complications | Participants with sinusitis | 0 Participants |
| VIS410 High Dose | Number of Participants With Influenza-related Complications | Other chronic pulmonary disease | 0 Participants |
| VIS410 High Dose | Number of Participants With Influenza-related Complications | Death | 1 Participants |
| VIS410 High Dose | Number of Participants With Influenza-related Complications | Bacterial pneumonia | 3 Participants |
| VIS410 Low Dose | Number of Participants With Influenza-related Complications | Bacterial pneumonia | 1 Participants |
| VIS410 Low Dose | Number of Participants With Influenza-related Complications | Other chronic pulmonary disease | 0 Participants |
| VIS410 Low Dose | Number of Participants With Influenza-related Complications | Participants with at least 1 complication of Influenza | 4 Participants |
| VIS410 Low Dose | Number of Participants With Influenza-related Complications | Participants with sinusitis | 1 Participants |
| VIS410 Low Dose | Number of Participants With Influenza-related Complications | Participants with pneumonia | 1 Participants |
| VIS410 Low Dose | Number of Participants With Influenza-related Complications | Death | 2 Participants |
| VIS410 Total | Number of Participants With Influenza-related Complications | Participants with pneumonia | 4 Participants |
| VIS410 Total | Number of Participants With Influenza-related Complications | Participants with sinusitis | 1 Participants |
| VIS410 Total | Number of Participants With Influenza-related Complications | Other chronic pulmonary disease | 0 Participants |
| VIS410 Total | Number of Participants With Influenza-related Complications | Bacterial pneumonia | 4 Participants |
| VIS410 Total | Number of Participants With Influenza-related Complications | Death | 3 Participants |
| VIS410 Total | Number of Participants With Influenza-related Complications | Participants with at least 1 complication of Influenza | 8 Participants |
| Placebo | Number of Participants With Influenza-related Complications | Death | 2 Participants |
| Placebo | Number of Participants With Influenza-related Complications | Bacterial pneumonia | 0 Participants |
| Placebo | Number of Participants With Influenza-related Complications | Participants with pneumonia | 0 Participants |
| Placebo | Number of Participants With Influenza-related Complications | Other chronic pulmonary disease | 2 Participants |
| Placebo | Number of Participants With Influenza-related Complications | Participants with at least 1 complication of Influenza | 4 Participants |
| Placebo | Number of Participants With Influenza-related Complications | Participants with sinusitis | 0 Participants |
Secondary
Number of Participants With Rehospitalization Due to Relapse
Number of participants with rehospitalization due to influenza A relapse
Time frame: Day 56
Population: The modified ITT (MITT) population included all participants who received IV study drug and were confirmed influenza A positive by qRT-PCR in central lab analysis of pre-dose Day 1 and/or post-dose Day 1. Participants were grouped according to the randomly assigned treatment.
| Arm | Measure | Category | Value (COUNT_OF_PARTICIPANTS) |
|---|---|---|---|
| VIS410 High Dose | Number of Participants With Rehospitalization Due to Relapse | Rehospitalization due to relapse--Yes | 2 Participants |
| VIS410 High Dose | Number of Participants With Rehospitalization Due to Relapse | Rehospitalization due to relapse--No | 27 Participants |
| VIS410 Low Dose | Number of Participants With Rehospitalization Due to Relapse | Rehospitalization due to relapse--No | 27 Participants |
| VIS410 Low Dose | Number of Participants With Rehospitalization Due to Relapse | Rehospitalization due to relapse--Yes | 1 Participants |
| VIS410 Total | Number of Participants With Rehospitalization Due to Relapse | Rehospitalization due to relapse--Yes | 3 Participants |
| VIS410 Total | Number of Participants With Rehospitalization Due to Relapse | Rehospitalization due to relapse--No | 54 Participants |
| Placebo | Number of Participants With Rehospitalization Due to Relapse | Rehospitalization due to relapse--Yes | 3 Participants |
| Placebo | Number of Participants With Rehospitalization Due to Relapse | Rehospitalization due to relapse--No | 25 Participants |
Secondary
Peak Viral Load by TCID50
Peak viral load based on TCID50 from nasopharyngeal swabs
Time frame: Day 7
Population: The modified ITT (MITT) population included all participants who received IV study drug and were confirmed influenza A positive by qRT-PCR in central lab analysis of pre-dose Day 1 and/or post-dose Day 1. Participants were grouped according to the randomly assigned treatment.
| Arm | Measure | Value (MEAN) | Dispersion |
|---|---|---|---|
| VIS410 High Dose | Peak Viral Load by TCID50 | 3.047 log10 TCID50/mL | Standard Deviation 2.1651 |
| VIS410 Low Dose | Peak Viral Load by TCID50 | 2.714 log10 TCID50/mL | Standard Deviation 1.7415 |
| VIS410 Total | Peak Viral Load by TCID50 | 2.881 log10 TCID50/mL | Standard Deviation 1.9534 |
| Placebo | Peak Viral Load by TCID50 | 2.604 log10 TCID50/mL | Standard Deviation 2.0278 |
p-value: 0.371ANOVA
p-value: 0.735ANOVA
p-value: 0.476ANOVA
p-value: 0.581ANOVA
Secondary
The Area Under the Concentration/Time Curve of VIS410 in Participant's Serum
Summary of Serum VIS410 Pharmacokinetic Parameters in PK Population by the area under the concentration/time curve from 0 to infinity (AUC0-inf) of VIS410 in participant's serum.
Time frame: Baseline, end of infusion, Day 5, Day 14, Day 28, Day 56
Population: The PK population included all participants who received IV study drug and had at least 1 PK parameter that could be calculated.
| Arm | Measure | Value (MEAN) | Dispersion |
|---|---|---|---|
| VIS410 High Dose | The Area Under the Concentration/Time Curve of VIS410 in Participant's Serum | 11326.522 day*µg/mL | Standard Deviation 4205.1144 |
| VIS410 Low Dose | The Area Under the Concentration/Time Curve of VIS410 in Participant's Serum | 6934.815 day*µg/mL | Standard Deviation 2304.3093 |
Secondary
The Clearance Rate (Cl) of VIS410 in Participant's Serum
Summary of Serum VIS410 Pharmacokinetic Parameters in PK Population by the clearance rate (Cl) of VIS410 in participant's serum.
Time frame: PK samples were collected on days 1, 5, 14, 28 and 56.
Population: The PK population included all participants who received IV study drug and had at least 1 PK parameter that could be calculated.
| Arm | Measure | Value (MEAN) | Dispersion |
|---|---|---|---|
| VIS410 High Dose | The Clearance Rate (Cl) of VIS410 in Participant's Serum | 401.652 mL/day | Standard Deviation 143.6763 |
| VIS410 Low Dose | The Clearance Rate (Cl) of VIS410 in Participant's Serum | 325.926 mL/day | Standard Deviation 137.6743 |
Secondary
The Half-life of VIS410 in Participant's Serum
Summary of Serum VIS410 Pharmacokinetic Parameters in PK Population by the half-life (t1/2) of VIS410 in participant's serum.
Time frame: PK samples were collected on days 1, 5, 14, 28 and 56.
Population: The PK population included all participants who received IV study drug and had at least 1 PK parameter that could be calculated.
| Arm | Measure | Value (MEAN) | Dispersion |
|---|---|---|---|
| VIS410 High Dose | The Half-life of VIS410 in Participant's Serum | 9.407 mL/day | Standard Deviation 3.5549 |
| VIS410 Low Dose | The Half-life of VIS410 in Participant's Serum | 9.839 mL/day | Standard Deviation 3.2465 |
Secondary
The Maximum Concentration (Cmax) of VIS410 in Participant's Serum
Summary of Serum VIS410 Pharmacokinetic Parameters in PK Population by maximum concentration (Cmax) of VIS410 in participant's serum.
Time frame: Baseline, end of infusion, Day 5, Day 14, Day 28, Day 56
Population: The PK population included all participants who received IV study drug and had at least 1 PK parameter that could be calculated.
| Arm | Measure | Value (MEAN) | Dispersion |
|---|---|---|---|
| VIS410 High Dose | The Maximum Concentration (Cmax) of VIS410 in Participant's Serum | 1301.037 µg/mL | Standard Deviation 241.0838 |
| VIS410 Low Dose | The Maximum Concentration (Cmax) of VIS410 in Participant's Serum | 786.393 µg/mL | Standard Deviation 202.7963 |
Secondary
Time to Cessation of Oxygen Support Compared to Oseltamivir Alone Among Patients Requiring Supplemental Oxygen Therapy With Baseline Room Air <= 92%
Time to cessation of O2 support in patients with supplemental oxygen with baseline room air \<= 92%. Patients with treatment 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.
Time frame: Baseline to Day 56
Population: Modified intent to treat population (MITT), number of participants who had cessation of oxygen support.
| Arm | Measure | Value (MEDIAN) |
|---|---|---|
| VIS410 High Dose | Time to Cessation of Oxygen Support Compared to Oseltamivir Alone Among Patients Requiring Supplemental Oxygen Therapy With Baseline Room Air <= 92% | 92.5 Hours |
| VIS410 Low Dose | Time to Cessation of Oxygen Support Compared to Oseltamivir Alone Among Patients Requiring Supplemental Oxygen Therapy With Baseline Room Air <= 92% | 101.3 Hours |
| VIS410 Total | Time to Cessation of Oxygen Support Compared to Oseltamivir Alone Among Patients Requiring Supplemental Oxygen Therapy With Baseline Room Air <= 92% | 97.3 Hours |
| Placebo | Time to Cessation of Oxygen Support Compared to Oseltamivir Alone Among Patients Requiring Supplemental Oxygen Therapy With Baseline Room Air <= 92% | 79.0 Hours |
Comparison: The VIS410 high-dose group was compared against the placebo group. The null hypothesis was defined as no treatment difference.p-value: 0.748Chi-squared
Comparison: The VIS410 low-dose group was compared against the placebo group. The null hypothesis was defined as no treatment differencep-value: 0.94Chi-squared
Comparison: The total VIS410 high-dose group (high-dose + low-dose) was compared against the placebo group. The null hypothesis was defined as no treatment difference.p-value: 0.902Chi-squared
Comparison: The VIS410 high-dose group was compared against the VIS410 low-dose group. The null hypothesis was defined as no treatment difference.p-value: 0.283Chi-squared
Secondary
Time to Cessation of Oxygen Support for Any Patient Requiring Supplemental Oxygen Therapy
Time to cessation of oxygen support in all patients with supplemental oxygen (regardless of oxygen saturation).
Time frame: Baseline to Day 56
Population: Modified intent to treat population (MITT), number of participants who had cessation of oxygen support. NE = not estimable.
| Arm | Measure | Value (MEDIAN) |
|---|---|---|
| VIS410 High Dose | Time to Cessation of Oxygen Support for Any Patient Requiring Supplemental Oxygen Therapy | 119.2 Hours |
| VIS410 Low Dose | Time to Cessation of Oxygen Support for Any Patient Requiring Supplemental Oxygen Therapy | 129.7 Hours |
| VIS410 Total | Time to Cessation of Oxygen Support for Any Patient Requiring Supplemental Oxygen Therapy | 124.7 Hours |
| Placebo | Time to Cessation of Oxygen Support for Any Patient Requiring Supplemental Oxygen Therapy | 112.2 Hours |
Comparison: The VIS410 high-dose group was compared against the placebo group. The null hypothesis was defined as no treatment difference.p-value: 0.919Chi-squared
Comparison: The VIS410 low-dose group was compared against the placebo group. The null hypothesis was defined as no treatment difference.p-value: 0.9Chi-squared
Comparison: The combined VIS410 high- and low-dose groups was compared against the placebo group. The null hypothesis was defined as no treatment difference.p-value: 0.99Chi-squared
Comparison: The VIS410 high-dose group was compared against the VIS410 low-dose group. The null hypothesis was defined as no treatment difference.p-value: 0.521Chi-squared
Secondary
Time to Clinical Response (4 Out of 5 Vital Signs)
Median time to clinical response defined by resolution of at least 4 of 5 vital signs: * Afebrile with core temperature ≤ 37.8°C, without use of antipyretics (oral ≤ 37.2°C) * Oxygen saturation ≥ 95% on room air without support or a return to preinfection status, if pre-infection status was \< 95% * Pulse rate ≤ 100/min * Systolic blood pressure ≥ 90 mm/Hg, without vasopressor use * Respiratory rate ≤ 24 beats per minute
Time frame: Day 56
Population: The modified ITT (MITT) population included all participants who received IV study drug and were confirmed influenza A positive by qRT-PCR in central lab analysis of pre-dose Day 1 and/or post-dose Day 1. Participants were grouped according to the randomly assigned treatment.
| Arm | Measure | Value (MEDIAN) |
|---|---|---|
| VIS410 High Dose | Time to Clinical Response (4 Out of 5 Vital Signs) | 2.6 hours |
| VIS410 Low Dose | Time to Clinical Response (4 Out of 5 Vital Signs) | 2.6 hours |
| VIS410 Total | Time to Clinical Response (4 Out of 5 Vital Signs) | 2.6 hours |
| Placebo | Time to Clinical Response (4 Out of 5 Vital Signs) | 2.8 hours |
Comparison: All p-values are presented for informational purposes only; there were no adjustments for multiple comparisons.p-value: 0.152Chi-squared
Comparison: All p-values are presented for informational purposes only; there were no adjustments for multiple comparisons.p-value: 0.176Chi-squared
Comparison: All p-values are presented for informational purposes only; there were no adjustments for multiple comparisons.p-value: 0.157Chi-squared
p-value: 0.844Chi-squared
Secondary
Time to Complete Clinical Response (Resolution of All Vital Signs)
Median time to clinical response defined by resolution of at all 5 vital signs: * Afebrile with core temperature ≤ 37.8°C, without use of antipyretics (oral ≤ 37.2°C) * Oxygen saturation ≥ 95% on room air without support or a return to pre-infection status, if pre-infection status was \< 95% * Pulse rate ≤ 100/min * Systolic blood pressure ≥ 90 mm/Hg, without vasopressor use * Respiratory rate ≤ 24 beats per minute
Time frame: Day 56
Population: The modified ITT (MITT) population included all participants who received IV study drug and were confirmed influenza A positive by qRT-PCR in central lab analysis of pre-dose Day 1 and/or post-dose Day 1. Participants were grouped according to the randomly assigned treatment.
| Arm | Measure | Value (MEDIAN) |
|---|---|---|
| VIS410 High Dose | Time to Complete Clinical Response (Resolution of All Vital Signs) | 103.0 hours |
| VIS410 Low Dose | Time to Complete Clinical Response (Resolution of All Vital Signs) | 114.6 hours |
| VIS410 Total | Time to Complete Clinical Response (Resolution of All Vital Signs) | 103.0 hours |
| Placebo | Time to Complete Clinical Response (Resolution of All Vital Signs) | 99.8 hours |
Comparison: All p-values are presented for informational purposes only; there were no adjustments for multiple comparisons.p-value: 0.531Chi-squared
Comparison: All p-values are presented for informational purposes only; there were no adjustments for multiple comparisons.p-value: 0.582Chi-squared
Comparison: All p-values are presented for informational purposes only; there were no adjustments for multiple comparisons.p-value: 0.55Chi-squared
Comparison: All p-values are presented for informational purposes only; there were no adjustments for multiple comparisons.p-value: 0.84Chi-squared
Secondary
Total Number of Days in ICU
Total number of days in intensive care (ICU) for participants who admitted to the ICU, including participants in ICU at baseline
Time frame: 56 days
Population: Participants admitted to the ICU from the mITT population. The modified ITT (MITT) population included all participants who received IV study drug and were confirmed influenza A positive by qRT-PCR in central lab analysis of pre-dose Day 1 and/or post-dose Day 1. Participants were grouped according to the randomly assigned treatment.
| Arm | Measure | Value (MEAN) | Dispersion |
|---|---|---|---|
| VIS410 High Dose | Total Number of Days in ICU | 8.5 days | Standard Deviation 7.43 |
| VIS410 Low Dose | Total Number of Days in ICU | 6.8 days | Standard Deviation 3.71 |
| VIS410 Total | Total Number of Days in ICU | 7.7 days | Standard Deviation 5.88 |
| Placebo | Total Number of Days in ICU | 14.0 days | Standard Deviation 9.38 |
Secondary
Total Number of Days on Ventilation
Total number of days on ventilation for participants who used ventilation, including participants on ventilation at baseline
Time frame: 56 days
Population: Participants requiring ventilation from the mITT population. The modified ITT (MITT) population included all participants who received IV study drug and were confirmed influenza A positive by qRT-PCR in central lab analysis of pre-dose Day 1 and/or post-dose Day 1. Participants were grouped according to the randomly assigned treatment.
| Arm | Measure | Value (MEAN) | Dispersion |
|---|---|---|---|
| VIS410 High Dose | Total Number of Days on Ventilation | 5.2 days | Standard Deviation 4.55 |
| VIS410 Low Dose | Total Number of Days on Ventilation | 7.0 days | Standard Deviation 5.2 |
| VIS410 Total | Total Number of Days on Ventilation | 5.9 days | Standard Deviation 4.52 |
| Placebo | Total Number of Days on Ventilation | 11.7 days | Standard Deviation 7.51 |
Secondary
Viral Nasopharyngeal AUC
The difference between VIS410 + oseltamivir and oseltamivir alone treatment groups in nasopharyngeal qRT-PCR area under the viral load-time curve (AUC) from baseline to Day 5.
Time frame: Day 1 Predose, Day 1 End of Infusion, Day 3, Day 5
Population: The modified ITT (MITT) population included all participants who received IV study drug and were confirmed influenza A positive by qRT-PCR in central lab analysis of pre-dose Day 1 and/or post-dose Day 1. Participants were grouped according to the randomly assigned treatment.
| Arm | Measure | Value (MEAN) | Dispersion |
|---|---|---|---|
| VIS410 High Dose | Viral Nasopharyngeal AUC | 18.329 Day*Log10 virus particles/ mL | Standard Deviation 6.7272 |
| VIS410 Low Dose | Viral Nasopharyngeal AUC | 15.999 Day*Log10 virus particles/ mL | Standard Deviation 4.9232 |
| VIS410 Total | Viral Nasopharyngeal AUC | 17.164 Day*Log10 virus particles/ mL | Standard Deviation 5.9559 |
| Placebo | Viral Nasopharyngeal AUC | 17.727 Day*Log10 virus particles/ mL | Standard Deviation 5.9824 |
p-value: 0.735ANOVA
p-value: 0.259ANOVA
p-value: 0.644ANOVA
p-value: 0.146ANOVA
Secondary
Viral Nasopharyngeal AUC by TCID50
The area under the viral load-time curve (AUC) for VIS410 + oseltamivir and oseltamivir alone treatment groups from baseline to Day 5 measured by TCID50 from nasopharyngeal swabs.
Time frame: 5 days
Population: The modified ITT (MITT) population included all participants who received IV study drug and were confirmed influenza A positive by qRT-PCR in central lab analysis of pre-dose Day 1 and/or post-dose Day 1. Participants were grouped according to the randomly assigned treatment.
| Arm | Measure | Value (MEAN) | Dispersion |
|---|---|---|---|
| VIS410 High Dose | Viral Nasopharyngeal AUC by TCID50 | 3.826 Day*TCID50 log10/ml | Standard Deviation 4.2581 |
| VIS410 Low Dose | Viral Nasopharyngeal AUC by TCID50 | 2.823 Day*TCID50 log10/ml | Standard Deviation 2.4121 |
| VIS410 Total | Viral Nasopharyngeal AUC by TCID50 | 3.324 Day*TCID50 log10/ml | Standard Deviation 3.4649 |
| Placebo | Viral Nasopharyngeal AUC by TCID50 | 3.519 Day*TCID50 log10/ml | Standard Deviation 3.5317 |
p-value: 0.695ANOVA
p-value: 0.542ANOVA
p-value: 0.899ANOVA
p-value: 0.321ANOVA
Secondary
Viral Nasopharyngeal AUC by TCID50
The area under the viral load-time curve (AUC) for VIS410 + oseltamivir and oseltamivir alone treatment groups from baseline to Day 7 measured by TCID50 from nasopharyngeal swabs.
Time frame: 7 days
Population: The modified ITT (MITT) population included all participants who received IV study drug and were confirmed influenza A positive by qRT-PCR in central lab analysis of pre-dose Day 1 and/or post-dose Day 1. Participants were grouped according to the randomly assigned treatment.
| Arm | Measure | Value (MEAN) | Dispersion |
|---|---|---|---|
| VIS410 High Dose | Viral Nasopharyngeal AUC by TCID50 | 4.140 Day*TCID50 log10/ml | Standard Deviation 5.2238 |
| VIS410 Low Dose | Viral Nasopharyngeal AUC by TCID50 | 2.886 Day*TCID50 log10/ml | Standard Deviation 2.526 |
| VIS410 Total | Viral Nasopharyngeal AUC by TCID50 | 3.513 Day*TCID50 log10/ml | Standard Deviation 4.1131 |
| Placebo | Viral Nasopharyngeal AUC by TCID50 | 3.711 Day*TCID50 log10/ml | Standard Deviation 4.2207 |
p-value: 0.663ANOVA
p-value: 0.54ANOVA
p-value: 0.918ANOVA
p-value: 0.294ANOVA
Secondary
Viral Titer in Upper Respiratory Samples by qRT-PCR
The difference between VIS410 + oseltamivir and oseltamivir alone treatment groups in peak viral load by qRT-PCR from nasopharyngeal swabs through Day 14
Time frame: Day 14
Population: The modified ITT (MITT) population included all participants who received IV study drug and were confirmed influenza A positive by qRT-PCR in central lab analysis of pre-dose Day 1 and/or post-dose Day 1. Participants were grouped according to the randomly assigned treatment. All efficacy analyses including the primary efficacy analyses were performed in the MITT population
| Arm | Measure | Value (MEAN) | Dispersion |
|---|---|---|---|
| VIS410 High Dose | Viral Titer in Upper Respiratory Samples by qRT-PCR | 6.479 log10 virus particles/mL | Standard Deviation 1.386 |
| VIS410 Low Dose | Viral Titer in Upper Respiratory Samples by qRT-PCR | 6.378 log10 virus particles/mL | Standard Deviation 1.132 |
| VIS410 Total | Viral Titer in Upper Respiratory Samples by qRT-PCR | 6.429 log10 virus particles/mL | Standard Deviation 1.2544 |
| Placebo | Viral Titer in Upper Respiratory Samples by qRT-PCR | 6.169 log10 virus particles/mL | Standard Deviation 1.2489 |
Comparison: The VIS410 high-dose group was compared against the placebo group. The null hypothesis was defined as no treatment difference.p-value: 0.36ANOVA