Trial Outcomes & Findings for Study of an Investigational Monoclonal Antibody, VIS410, in Subjects With Uncomplicated Influenza A (NCT NCT02989194)
NCT ID: NCT02989194
Last Updated: 2022-08-15
Results Overview
The percentage of participants with adverse events (AEs) and serious adverse events (SAEs) following administration of a single dose of IV VIS410.
COMPLETED
PHASE2
150 participants
100 days
2022-08-15
Participant Flow
This study was initiated in 58 study centers; 28 sites enrolled at least 1 subject.
When required, subject may have been given a pre-screening informed consent to perform a Rapid Antigen Test for influenza. Flu-positive subjects were given a full explanation of the nature of the study and written informed consent (approved by local ethics committee) was obtained according to local requirements before any study related assessments
Participant milestones
| Measure |
VIS410 High Dose
Single intravenous fixed dose of 4000 mg VIS410
|
VIS410 Low Dose
Single intravenous fixed dose of 2000 mg VIS410
|
Placebo
Single intravenous saline solution
|
|---|---|---|---|
|
Overall Study
STARTED
|
50
|
50
|
50
|
|
Overall Study
COMPLETED
|
49
|
48
|
50
|
|
Overall Study
NOT COMPLETED
|
1
|
2
|
0
|
Reasons for withdrawal
| Measure |
VIS410 High Dose
Single intravenous fixed dose of 4000 mg VIS410
|
VIS410 Low Dose
Single intravenous fixed dose of 2000 mg VIS410
|
Placebo
Single intravenous saline solution
|
|---|---|---|---|
|
Overall Study
Study on hold for safety and participant was withdrawn
|
1
|
0
|
0
|
|
Overall Study
Lost to Follow-up
|
0
|
1
|
0
|
|
Overall Study
Withdrawal by Subject
|
0
|
1
|
0
|
Baseline Characteristics
Participant was omitted if the date/time of symptom onset was missing.
Baseline characteristics by cohort
| Measure |
VIS410 High Dose
n=50 Participants
Single intravenous fixed dose of 4000 mg VIS410
|
VIS410 Low Dose
n=50 Participants
Single intravenous fixed dose of 2000 mg VIS410
|
Placebo
n=50 Participants
Single intravenous saline solution
|
Total
n=150 Participants
Total of all reporting groups
|
|---|---|---|---|---|
|
Age, Categorical
<=18 years
|
0 Participants
n=50 Participants
|
0 Participants
n=50 Participants
|
0 Participants
n=50 Participants
|
0 Participants
n=150 Participants
|
|
Age, Categorical
Between 18 and 65 years
|
50 Participants
n=50 Participants
|
50 Participants
n=50 Participants
|
50 Participants
n=50 Participants
|
150 Participants
n=150 Participants
|
|
Age, Categorical
>=65 years
|
0 Participants
n=50 Participants
|
0 Participants
n=50 Participants
|
0 Participants
n=50 Participants
|
0 Participants
n=150 Participants
|
|
Age, Continuous
|
40.3 years
STANDARD_DEVIATION 13.13 • n=50 Participants
|
39.6 years
STANDARD_DEVIATION 13.79 • n=50 Participants
|
43.1 years
STANDARD_DEVIATION 12.77 • n=50 Participants
|
41.0 years
STANDARD_DEVIATION 13.23 • n=150 Participants
|
|
Sex: Female, Male
Female
|
27 Participants
n=50 Participants
|
29 Participants
n=50 Participants
|
28 Participants
n=50 Participants
|
84 Participants
n=150 Participants
|
|
Sex: Female, Male
Male
|
23 Participants
n=50 Participants
|
21 Participants
n=50 Participants
|
22 Participants
n=50 Participants
|
66 Participants
n=150 Participants
|
|
Ethnicity (NIH/OMB)
Hispanic or Latino
|
10 Participants
n=50 Participants
|
12 Participants
n=50 Participants
|
13 Participants
n=50 Participants
|
35 Participants
n=150 Participants
|
|
Ethnicity (NIH/OMB)
Not Hispanic or Latino
|
40 Participants
n=50 Participants
|
38 Participants
n=50 Participants
|
37 Participants
n=50 Participants
|
115 Participants
n=150 Participants
|
|
Ethnicity (NIH/OMB)
Unknown or Not Reported
|
0 Participants
n=50 Participants
|
0 Participants
n=50 Participants
|
0 Participants
n=50 Participants
|
0 Participants
n=150 Participants
|
|
Race (NIH/OMB)
American Indian or Alaska Native
|
0 Participants
n=50 Participants
|
0 Participants
n=50 Participants
|
0 Participants
n=50 Participants
|
0 Participants
n=150 Participants
|
|
Race (NIH/OMB)
Asian
|
1 Participants
n=50 Participants
|
1 Participants
n=50 Participants
|
1 Participants
n=50 Participants
|
3 Participants
n=150 Participants
|
|
Race (NIH/OMB)
Native Hawaiian or Other Pacific Islander
|
0 Participants
n=50 Participants
|
0 Participants
n=50 Participants
|
0 Participants
n=50 Participants
|
0 Participants
n=150 Participants
|
|
Race (NIH/OMB)
Black or African American
|
10 Participants
n=50 Participants
|
11 Participants
n=50 Participants
|
10 Participants
n=50 Participants
|
31 Participants
n=150 Participants
|
|
Race (NIH/OMB)
White
|
38 Participants
n=50 Participants
|
38 Participants
n=50 Participants
|
36 Participants
n=50 Participants
|
112 Participants
n=150 Participants
|
|
Race (NIH/OMB)
More than one race
|
0 Participants
n=50 Participants
|
0 Participants
n=50 Participants
|
0 Participants
n=50 Participants
|
0 Participants
n=150 Participants
|
|
Race (NIH/OMB)
Unknown or Not Reported
|
1 Participants
n=50 Participants
|
0 Participants
n=50 Participants
|
3 Participants
n=50 Participants
|
4 Participants
n=150 Participants
|
|
Region of Enrollment
Latvia
|
6 participants
n=50 Participants
|
2 participants
n=50 Participants
|
7 participants
n=50 Participants
|
15 participants
n=150 Participants
|
|
Region of Enrollment
United States
|
19 participants
n=50 Participants
|
21 participants
n=50 Participants
|
18 participants
n=50 Participants
|
58 participants
n=150 Participants
|
|
Region of Enrollment
South Africa
|
24 participants
n=50 Participants
|
25 participants
n=50 Participants
|
24 participants
n=50 Participants
|
73 participants
n=150 Participants
|
|
Region of Enrollment
Estonia
|
1 participants
n=50 Participants
|
2 participants
n=50 Participants
|
0 participants
n=50 Participants
|
3 participants
n=150 Participants
|
|
Region of Enrollment
Bulgaria
|
0 participants
n=50 Participants
|
0 participants
n=50 Participants
|
1 participants
n=50 Participants
|
1 participants
n=150 Participants
|
|
Subjects Body Mass Index
|
29.01 kg/m^2
n=50 Participants
|
30.80 kg/m^2
n=50 Participants
|
28.82 kg/m^2
n=50 Participants
|
29.54 kg/m^2
n=150 Participants
|
|
Time since onset of influenza (hours)
|
27.69 hours
n=49 Participants • Participants who did not have a start date/time for symptom onset were excluded.
|
28.88 hours
n=49 Participants • Participants who did not have a start date/time for symptom onset were excluded.
|
28.07 hours
n=50 Participants • Participants who did not have a start date/time for symptom onset were excluded.
|
28.60 hours
n=148 Participants • Participants who did not have a start date/time for symptom onset were excluded.
|
PRIMARY outcome
Timeframe: 100 daysPopulation: Safety Population The safety population included all subjects randomized who received IV study drug. The safety population summaries were based on the actual treatment received.
The percentage of participants with adverse events (AEs) and serious adverse events (SAEs) following administration of a single dose of IV VIS410.
Outcome measures
| Measure |
VIS410 High Dose
n=49 Participants
Single intravenous dose of 4000 mg VIS410
|
VIS410 Low Dose
n=49 Participants
Single intravenous dose of 2000 mg VIS410
|
VIS410 Total
n=98 Participants
Summation of the VIS410 high and low dose groups.
|
Placebo
n=50 Participants
Single intravenous dose of saline solution
|
|---|---|---|---|---|
|
Assess the Safety and Tolerability of a Single IV Dose of VIS410 in Participants With Uncomplicated Influenza Infection
Percentage of subjects with any adverse events
|
57.1 percentage of participants
Interval 42.21 to 71.18
|
34.7 percentage of participants
Interval 21.67 to 49.64
|
45.9 percentage of participants
Interval 35.8 to 56.29
|
26.0 percentage of participants
Interval 14.63 to 40.34
|
|
Assess the Safety and Tolerability of a Single IV Dose of VIS410 in Participants With Uncomplicated Influenza Infection
Percentage of subjects with any serious adverse events
|
0 percentage of participants
Interval 0.0 to 7.25
|
0 percentage of participants
Interval 0.0 to 7.25
|
0 percentage of participants
Interval 0.0 to 3.69
|
4 percentage of participants
Interval 0.49 to 13.71
|
PRIMARY outcome
Timeframe: 100 daysPopulation: Safety Population. The safety population included all participants randomized who received IV study drug. The safety population summaries were based on the actual treatment received.
Percentage of participants experiencing any TEAE, TEAEs considered related to study treatment and the number of participants experiencing adverse events of special interest (AESI). A TEAE is defined as an adverse event that starts on or after the date of study drug IV infusion. AESIs included hypersensitivity reaction, anaphylactic reaction, or injection site adverse event.
Outcome measures
| Measure |
VIS410 High Dose
n=49 Participants
Single intravenous dose of 4000 mg VIS410
|
VIS410 Low Dose
n=49 Participants
Single intravenous dose of 2000 mg VIS410
|
VIS410 Total
n=98 Participants
Summation of the VIS410 high and low dose groups.
|
Placebo
n=50 Participants
Single intravenous dose of saline solution
|
|---|---|---|---|---|
|
Percentage of Participants With Any Treatment-emergent Adverse Event (TEAE) and TEAEs of Special Interest
Percentage of subjects with treatment related TEAEs
|
30.6 percentage of participants
Interval 18.25 to 45.42
|
14.3 percentage of participants
Interval 5.94 to 27.24
|
22.4 percentage of participants
Interval 14.64 to 31.99
|
12.0 percentage of participants
Interval 4.53 to 24.31
|
|
Percentage of Participants With Any Treatment-emergent Adverse Event (TEAE) and TEAEs of Special Interest
Percentage of subjects with any TEAE
|
55.1 percentage of participants
Interval 40.23 to 69.33
|
34.7 percentage of participants
Interval 21.67 to 49.64
|
44.9 percentage of participants
Interval 34.83 to 55.28
|
24.0 percentage of participants
Interval 13.06 to 38.17
|
|
Percentage of Participants With Any Treatment-emergent Adverse Event (TEAE) and TEAEs of Special Interest
Percentage of subjects with any TEAEs of Special Interest
|
34.7 percentage of participants
Interval 21.67 to 49.64
|
16.3 percentage of participants
Interval 7.32 to 29.66
|
25.5 percentage of participants
Interval 17.24 to 35.31
|
12 percentage of participants
Interval 4.53 to 24.31
|
|
Percentage of Participants With Any Treatment-emergent Adverse Event (TEAE) and TEAEs of Special Interest
Percentage of Subjects with any hypersensitivity Reactions
|
0 percentage of participants
Interval 0.0 to 7.25
|
0 percentage of participants
Interval 0.0 to 7.25
|
0 percentage of participants
Interval 0.0 to 3.69
|
0 percentage of participants
Interval 0.0 to 7.11
|
|
Percentage of Participants With Any Treatment-emergent Adverse Event (TEAE) and TEAEs of Special Interest
Percentage of subjects with any anaphylactic reactions
|
0 percentage of participants
Interval 0.0 to 7.25
|
0 percentage of participants
Interval 0.0 to 7.25
|
0 percentage of participants
Interval 0.0 to 3.69
|
0 percentage of participants
Interval 0.0 to 7.11
|
|
Percentage of Participants With Any Treatment-emergent Adverse Event (TEAE) and TEAEs of Special Interest
Percentage of subjects with any injection site AEs.
|
2.0 percentage of participants
Interval 0.05 to 10.85
|
0.0 percentage of participants
Interval 0.0 to 7.25
|
1.0 percentage of participants
Interval 0.03 to 5.55
|
0 percentage of participants
Interval 0.0 to 7.11
|
SECONDARY outcome
Timeframe: 10 daysPopulation: Modified Intent-to-Treat Population. The modified intent-to-treat (mITT) population included all subjects who received IV study drug and were confirmed influenza A positive by a molecular test at the central virological laboratory.
The Influenza Patient Reported Outcome (FluPRO) questionnaire is a 32-question instrument that assesses the occurrence and intensity of influenza associated symptoms (scale of 0 to 4, with 0 representing no symptoms) over 24 hours (lower scores indicate better outcomes). FluPRO data were recorded by subjects at Baseline (Day 1), then daily thereafter through Day 10. These data were summarized at each visit by treatment group. The data below show the percent change in mean total symptom scores over time by treatment arm.
Outcome measures
| Measure |
VIS410 High Dose
n=46 Participants
Single intravenous dose of 4000 mg VIS410
|
VIS410 Low Dose
n=44 Participants
Single intravenous dose of 2000 mg VIS410
|
VIS410 Total
n=90 Participants
Summation of the VIS410 high and low dose groups.
|
Placebo
n=48 Participants
Single intravenous dose of saline solution
|
|---|---|---|---|---|
|
Percentage Change From Baseline in Signs and Symptoms of Influenza-like Illness as Assessed by the Influenza Patient Reported Outcomes Questionnaire After a Single IV Dose of VIS410
Percentage change from baseline to day 6
|
-69.31 Percent Change
Standard Deviation 20.90
|
-66.80 Percent Change
Standard Deviation 33.42
|
-68.08 Percent Change
Standard Deviation 27.61
|
64.01 Percent Change
Standard Deviation 23.35
|
|
Percentage Change From Baseline in Signs and Symptoms of Influenza-like Illness as Assessed by the Influenza Patient Reported Outcomes Questionnaire After a Single IV Dose of VIS410
Percentage change from baseline to day 8
|
-77.98 Percent Change
Standard Deviation 20.76
|
-76.03 Percent Change
Standard Deviation 25.53
|
-77.02 Percent Change
Standard Deviation 23.13
|
-76.16 Percent Change
Standard Deviation 21.01
|
|
Percentage Change From Baseline in Signs and Symptoms of Influenza-like Illness as Assessed by the Influenza Patient Reported Outcomes Questionnaire After a Single IV Dose of VIS410
Percent Change from Baseline to Day 2
|
-26.12 Percent Change
Standard Deviation 27.00
|
-29.98 Percent Change
Standard Deviation 29.55
|
-28.01 Percent Change
Standard Deviation 28.18
|
-19.53 Percent Change
Standard Deviation 26.51
|
|
Percentage Change From Baseline in Signs and Symptoms of Influenza-like Illness as Assessed by the Influenza Patient Reported Outcomes Questionnaire After a Single IV Dose of VIS410
Percentage change from baseline to day 3
|
-38.65 Percent Change
Standard Deviation 28.78
|
-49.37 Percent Change
Standard Deviation 29.62
|
-43.89 Percent Change
Standard Deviation 29.53
|
-33.63 Percent Change
Standard Deviation 23.60
|
|
Percentage Change From Baseline in Signs and Symptoms of Influenza-like Illness as Assessed by the Influenza Patient Reported Outcomes Questionnaire After a Single IV Dose of VIS410
Percentage change from baseline to day 4
|
-53.46 Percent Change
Standard Deviation 26.16
|
-59.08 Percent Change
Standard Deviation 31.12
|
-56.21 Percent Change
Standard Deviation 28.67
|
-44.55 Percent Change
Standard Deviation 28.20
|
|
Percentage Change From Baseline in Signs and Symptoms of Influenza-like Illness as Assessed by the Influenza Patient Reported Outcomes Questionnaire After a Single IV Dose of VIS410
Percentage change from baseline to day 5
|
-60.85 Percent Change
Standard Deviation 25.52
|
-64.61 Percent Change
Standard Deviation 29.91
|
-62.69 Percent Change
Standard Deviation 27.66
|
-56.75 Percent Change
Standard Deviation 24.31
|
|
Percentage Change From Baseline in Signs and Symptoms of Influenza-like Illness as Assessed by the Influenza Patient Reported Outcomes Questionnaire After a Single IV Dose of VIS410
Percentage change from baseline to day 7
|
-74.03 Percent Change
Standard Deviation 19.31
|
-70.76 Percent Change
Standard Deviation 31.18
|
-72.43 Percent Change
Standard Deviation 25.71
|
-71.51 Percent Change
Standard Deviation 20.61
|
|
Percentage Change From Baseline in Signs and Symptoms of Influenza-like Illness as Assessed by the Influenza Patient Reported Outcomes Questionnaire After a Single IV Dose of VIS410
Percentage change from baseline to day 9
|
-80.05 Percent Change
Standard Deviation 19.78
|
-78.48 Percent Change
Standard Deviation 25.95
|
-79.27 Percent Change
Standard Deviation 22.91
|
-79.52 Percent Change
Standard Deviation 19.84
|
|
Percentage Change From Baseline in Signs and Symptoms of Influenza-like Illness as Assessed by the Influenza Patient Reported Outcomes Questionnaire After a Single IV Dose of VIS410
Percentage change from baseline to day 10
|
-82.30 Percent Change
Standard Deviation 20.07
|
-81.38 Percent Change
Standard Deviation 20.43
|
-81.85 Percent Change
Standard Deviation 20.14
|
-84.35 Percent Change
Standard Deviation 17.52
|
SECONDARY outcome
Timeframe: 100 daysPopulation: Modified Intent-to-Treat Population The modified intent-to-treat (mITT) population included all subjects who received IV study drug and were confirmed influenza A positive by a molecular test at the central virological laboratory.
Number of participants requiring hospitalization for influenza-related complications
Outcome measures
| Measure |
VIS410 High Dose
n=46 Participants
Single intravenous dose of 4000 mg VIS410
|
VIS410 Low Dose
n=44 Participants
Single intravenous dose of 2000 mg VIS410
|
VIS410 Total
n=90 Participants
Summation of the VIS410 high and low dose groups.
|
Placebo
n=48 Participants
Single intravenous dose of saline solution
|
|---|---|---|---|---|
|
Hospitalization for Influenza-related Complications
|
0 Participants
|
0 Participants
|
0 Participants
|
0 Participants
|
SECONDARY outcome
Timeframe: 100 daysPopulation: Modified Intent-to-Treat Population. The modified intent-to-treat (mITT) population included all subjects who received IV study drug and were confirmed influenza A positive by a molecular test at the central virological laboratory.
Duration of hospitalization for participants with at least 1 complication of influenza. There were no participants hospitalized for complications of influenza.
Outcome measures
| Measure |
VIS410 High Dose
n=46 Participants
Single intravenous dose of 4000 mg VIS410
|
VIS410 Low Dose
n=44 Participants
Single intravenous dose of 2000 mg VIS410
|
VIS410 Total
n=90 Participants
Summation of the VIS410 high and low dose groups.
|
Placebo
n=48 Participants
Single intravenous dose of saline solution
|
|---|---|---|---|---|
|
Duration of Hospitalization for Complications of Influenza
|
0 days
|
0 days
|
0 days
|
0 days
|
SECONDARY outcome
Timeframe: 100 daysPopulation: Modified Intent-to-Treat Population. The modified intent-to-treat (mITT) population included all subjects who received IV study drug and were confirmed influenza A positive by a molecular test at the central virological laboratory.
Count of participants with at least 1 complication of influenza
Outcome measures
| Measure |
VIS410 High Dose
n=46 Participants
Single intravenous dose of 4000 mg VIS410
|
VIS410 Low Dose
n=44 Participants
Single intravenous dose of 2000 mg VIS410
|
VIS410 Total
n=90 Participants
Summation of the VIS410 high and low dose groups.
|
Placebo
n=48 Participants
Single intravenous dose of saline solution
|
|---|---|---|---|---|
|
Count of Participants With Complications of Influenza
|
1 participants
Interval 0.06 to 11.53
|
3 participants
Interval 1.43 to 18.66
|
4 participants
Interval 1.22 to 10.99
|
3 participants
Interval 1.31 to 17.2
|
SECONDARY outcome
Timeframe: 100 daysPopulation: Modified Intent-to-Treat Population The modified intent-to-treat (mITT) population included all subjects who received IV study drug and were confirmed influenza A positive by a molecular test at the central virological laboratory.
Number of participants with influenza A relapse/reinfection
Outcome measures
| Measure |
VIS410 High Dose
n=46 Participants
Single intravenous dose of 4000 mg VIS410
|
VIS410 Low Dose
n=44 Participants
Single intravenous dose of 2000 mg VIS410
|
VIS410 Total
n=90 Participants
Summation of the VIS410 high and low dose groups.
|
Placebo
n=48 Participants
Single intravenous dose of saline solution
|
|---|---|---|---|---|
|
Influenza A Relapse/Reinfection
|
0 Participants
|
0 Participants
|
0 Participants
|
0 Participants
|
SECONDARY outcome
Timeframe: 1, 3, 5, 7, 14, 28, 56, 100 daysPopulation: The Pharmacokinetics (PK) population included all subjects who received IV study drug and had at least 1 PK concentration that could be calculated
The maximum observed concentration of VIS410 in serum (Cmax).
Outcome measures
| Measure |
VIS410 High Dose
n=47 Participants
Single intravenous dose of 4000 mg VIS410
|
VIS410 Low Dose
n=49 Participants
Single intravenous dose of 2000 mg VIS410
|
VIS410 Total
Summation of the VIS410 high and low dose groups.
|
Placebo
Single intravenous dose of saline solution
|
|---|---|---|---|---|
|
VIS410 Maximum Plasma Concentration
|
1013.559 mcg/mL
Geometric Coefficient of Variation 35.5
|
627.640 mcg/mL
Geometric Coefficient of Variation 54.6
|
—
|
—
|
SECONDARY outcome
Timeframe: 1, 3, 5, 7, 14, 28, 56, 100 daysPopulation: The PK population included all subjects who received IV study drug and had at least 1 PK concentration that could be calculated
Time corresponding to the maximum serum concentration of VIS410.
Outcome measures
| Measure |
VIS410 High Dose
n=47 Participants
Single intravenous dose of 4000 mg VIS410
|
VIS410 Low Dose
n=49 Participants
Single intravenous dose of 2000 mg VIS410
|
VIS410 Total
Summation of the VIS410 high and low dose groups.
|
Placebo
Single intravenous dose of saline solution
|
|---|---|---|---|---|
|
Pharmacokinetics of VIS410 Concentration in Serum
|
0.119 day
Geometric Coefficient of Variation 79.0624
|
0.133 day
Geometric Coefficient of Variation 131.4255
|
—
|
—
|
SECONDARY outcome
Timeframe: 1, 3, 5, 7, 14, 28, 56, 100 daysPopulation: The PK population included all subjects who received IV study drug and had at least 1 PK concentration that could be calculated
VIS410 area under the plasma concentration time curve in serum. AUC 0-infinity is from the time of dosing extrapolated to infinity.
Outcome measures
| Measure |
VIS410 High Dose
n=46 Participants
Single intravenous dose of 4000 mg VIS410
|
VIS410 Low Dose
n=48 Participants
Single intravenous dose of 2000 mg VIS410
|
VIS410 Total
Summation of the VIS410 high and low dose groups.
|
Placebo
Single intravenous dose of saline solution
|
|---|---|---|---|---|
|
VIS410 Plasma Concentration ( AUC 0-infinity)
|
8598.909 day*mcg/mL
Geometric Coefficient of Variation 38.3172
|
5371.988 day*mcg/mL
Geometric Coefficient of Variation 30.0631
|
—
|
—
|
SECONDARY outcome
Timeframe: 1, 3, 5, 7, 14, 28, 56, 100 daysPopulation: The PK population included all subjects who received IV study drug and had at least 1 PK concentration that could be calculated
VIS410 area under the plasma concentration time curve in serum. AUC 0-last is the area under the plasma concentration time curve from time 0 to the last measurable concentration.
Outcome measures
| Measure |
VIS410 High Dose
n=47 Participants
Single intravenous dose of 4000 mg VIS410
|
VIS410 Low Dose
n=49 Participants
Single intravenous dose of 2000 mg VIS410
|
VIS410 Total
Summation of the VIS410 high and low dose groups.
|
Placebo
Single intravenous dose of saline solution
|
|---|---|---|---|---|
|
VIS410 Plasma Concentration (AUC 0-last)
|
8441.244 day*mcg/mL
Geometric Coefficient of Variation 39.5852
|
5385.491 day*mcg/mL
Geometric Coefficient of Variation 31.2065
|
—
|
—
|
SECONDARY outcome
Timeframe: 1, 3, 5, 7, 14, 28, 56, 100 daysPopulation: The PK population included all subjects who received IV study drug and had at least 1 PK concentration that could be calculated
Terminal elimination half-life of VIS410 in serum (t1/2) in serum.
Outcome measures
| Measure |
VIS410 High Dose
n=46 Participants
Single intravenous dose of 4000 mg VIS410
|
VIS410 Low Dose
n=48 Participants
Single intravenous dose of 2000 mg VIS410
|
VIS410 Total
Summation of the VIS410 high and low dose groups.
|
Placebo
Single intravenous dose of saline solution
|
|---|---|---|---|---|
|
Half-life of VIS410 in Serum.
|
9.941 day
Geometric Coefficient of Variation 40.6241
|
10.119 day
Geometric Coefficient of Variation 34.2559
|
—
|
—
|
SECONDARY outcome
Timeframe: 1, 3, 5, 7, 14, 28, 56, 100 daysPopulation: The PK population included all subjects who received IV study drug and had at least 1 PK concentration that could be calculated.
Summary of VIS410 total clearance (CL) in serum.
Outcome measures
| Measure |
VIS410 High Dose
n=46 Participants
Single intravenous dose of 4000 mg VIS410
|
VIS410 Low Dose
n=48 Participants
Single intravenous dose of 2000 mg VIS410
|
VIS410 Total
Summation of the VIS410 high and low dose groups.
|
Placebo
Single intravenous dose of saline solution
|
|---|---|---|---|---|
|
Clearance (CL) of VIS410 in Serum.
|
465.175 mL/day
Geometric Coefficient of Variation 38.3172
|
372.302 mL/day
Geometric Coefficient of Variation 30.0631
|
—
|
—
|
SECONDARY outcome
Timeframe: 7 daysPopulation: Modified Intent-to-Treat Population The modified intent-to-treat (mITT) population included all subjects who received IV study drug and were confirmed influenza A positive by a molecular test at the central virological laboratory.
The difference between VIS410 and placebo treatment groups in viral AUC based on the half-maximal tissue culture infective dose (TCID50) from nasopharyngeal swab samples taken from the first 50 participants.
Outcome measures
| Measure |
VIS410 High Dose
n=46 Participants
Single intravenous dose of 4000 mg VIS410
|
VIS410 Low Dose
n=44 Participants
Single intravenous dose of 2000 mg VIS410
|
VIS410 Total
n=90 Participants
Summation of the VIS410 high and low dose groups.
|
Placebo
n=48 Participants
Single intravenous dose of saline solution
|
|---|---|---|---|---|
|
Area Under the Viral Load-Time Curve (VL AUC) From Nasopharyngeal Swab Day 7.
|
3.726 d x log10 TCID50/mL
Interval 0.15 to 14.44
|
3.570 d x log10 TCID50/mL
Interval 0.14 to 13.37
|
3.660 d x log10 TCID50/mL
Interval 0.14 to 14.44
|
4.782 d x log10 TCID50/mL
Interval 0.28 to 16.57
|
SECONDARY outcome
Timeframe: 7 daysPopulation: Modified Intent-to-Treat Population The modified intent-to-treat (mITT) population included all subjects who received IV study drug and were confirmed influenza A positive by a molecular test at the central virological laboratory.
The difference between VIS410 and placebo treatment groups in peak viral load based on the half-maximal tissue culture infective dose (TCID50) from nasopharyngeal swab samples taken from the first 50 participants.
Outcome measures
| Measure |
VIS410 High Dose
n=46 Participants
Single intravenous dose of 4000 mg VIS410
|
VIS410 Low Dose
n=44 Participants
Single intravenous dose of 2000 mg VIS410
|
VIS410 Total
n=90 Participants
Summation of the VIS410 high and low dose groups.
|
Placebo
n=48 Participants
Single intravenous dose of saline solution
|
|---|---|---|---|---|
|
Peak Viral Load by TCID50
|
3.125 log10 TCID50/mL
Interval 0.38 to 5.75
|
2.50 log10 TCID50/mL
Interval 0.38 to 4.75
|
2.625 log10 TCID50/mL
Interval 0.38 to 5.75
|
3.375 log10 TCID50/mL
Interval 0.38 to 6.75
|
SECONDARY outcome
Timeframe: 7 daysPopulation: Modified Intent-to-Treat Population The modified intent-to-treat (mITT) population included all subjects who received IV study drug and were confirmed influenza A positive by a molecular test at the central virological laboratory.
The number of days for the median time to resolution of peak viral load from end of infusion by nasopharyngeal swabs collected from the first 50 participants and tested by half maximal tissue culture infective dose (TCID50)
Outcome measures
| Measure |
VIS410 High Dose
n=46 Participants
Single intravenous dose of 4000 mg VIS410
|
VIS410 Low Dose
n=44 Participants
Single intravenous dose of 2000 mg VIS410
|
VIS410 Total
n=90 Participants
Summation of the VIS410 high and low dose groups.
|
Placebo
n=48 Participants
Single intravenous dose of saline solution
|
|---|---|---|---|---|
|
Time to Resolution of Peak Viral Load From Nasopharyngeal Samples by TCID50.
|
2.0 days
Interval 1.81 to 2.9
|
1.9 days
Interval 1.83 to 2.87
|
1.9 days
Interval 1.84 to 2.1
|
3.6 days
Interval 1.83 to 3.85
|
SECONDARY outcome
Timeframe: 100 daysPopulation: Safety Population The safety population included all ITT subjects who received IV study drug. The safety population summaries were based on the actual treatment received. Not all participants had samples for all timepoints. For participants receiving placebo, all participants were tested on Day 1 and Day 100; only samples from two participants were tested at Days 14 and 56.
Count of subjects testing positive for anti-VIS410 antibodies on days 1, 14, 56 and 100. A positive result includes samples confirmed positive and above titer cut point factor (and titer ≥ 1). Negative results include screened or confirmed negative or confirmed positive but below titer cut point factor (titer \< 1). For participants receiving placebo, only samples from two participants were tested at Days 14 and 56.
Outcome measures
| Measure |
VIS410 High Dose
n=49 Participants
Single intravenous dose of 4000 mg VIS410
|
VIS410 Low Dose
n=49 Participants
Single intravenous dose of 2000 mg VIS410
|
VIS410 Total
n=98 Participants
Summation of the VIS410 high and low dose groups.
|
Placebo
n=50 Participants
Single intravenous dose of saline solution
|
|---|---|---|---|---|
|
Summary of Anti-VIS410 Antibody (ADA) Titers.
Visit day 1 anti-VIS410 antibody titer · ADA Titer > 4 to 16
|
1 Participants
|
1 Participants
|
2 Participants
|
0 Participants
|
|
Summary of Anti-VIS410 Antibody (ADA) Titers.
Day 14 anti-VIS410 antibody titer · ADA Titer ≤ 1
|
46 Participants
|
43 Participants
|
89 Participants
|
1 Participants
|
|
Summary of Anti-VIS410 Antibody (ADA) Titers.
Day 14 anti-VIS410 antibody titer · ADA Titer > 1 to 4
|
2 Participants
|
3 Participants
|
5 Participants
|
1 Participants
|
|
Summary of Anti-VIS410 Antibody (ADA) Titers.
Day 14 anti-VIS410 antibody titer · ADA Titer > 64
|
0 Participants
|
0 Participants
|
0 Participants
|
0 Participants
|
|
Summary of Anti-VIS410 Antibody (ADA) Titers.
Day 56 anti-VIS410 antibody titer · ADA Titer ≤ 1
|
42 Participants
|
34 Participants
|
76 Participants
|
2 Participants
|
|
Summary of Anti-VIS410 Antibody (ADA) Titers.
Day 100 anti-VIS410 antibody titer · ADA Titer > 1 to 4
|
6 Participants
|
8 Participants
|
14 Participants
|
3 Participants
|
|
Summary of Anti-VIS410 Antibody (ADA) Titers.
Day 100 anti-VIS410 antibody titer · ADA Titer > 64
|
0 Participants
|
0 Participants
|
0 Participants
|
0 Participants
|
|
Summary of Anti-VIS410 Antibody (ADA) Titers.
Visit day 1 anti-VIS410 antibody titer · ADA Titer ≤ 1
|
45 Participants
|
43 Participants
|
88 Participants
|
45 Participants
|
|
Summary of Anti-VIS410 Antibody (ADA) Titers.
Visit day 1 anti-VIS410 antibody titer · ADA Titer > 1 to 4
|
3 Participants
|
3 Participants
|
6 Participants
|
4 Participants
|
|
Summary of Anti-VIS410 Antibody (ADA) Titers.
Visit day 1 anti-VIS410 antibody titer · ADA Titer > 16 to 64
|
0 Participants
|
0 Participants
|
0 Participants
|
0 Participants
|
|
Summary of Anti-VIS410 Antibody (ADA) Titers.
Visit day 1 anti-VIS410 antibody titer · ADA Titer > 64
|
0 Participants
|
0 Participants
|
0 Participants
|
0 Participants
|
|
Summary of Anti-VIS410 Antibody (ADA) Titers.
Day 14 anti-VIS410 antibody titer · ADA Titer > 4 to 16
|
1 Participants
|
1 Participants
|
2 Participants
|
0 Participants
|
|
Summary of Anti-VIS410 Antibody (ADA) Titers.
Day 14 anti-VIS410 antibody titer · ADA Titer > 16 to 64
|
0 Participants
|
0 Participants
|
0 Participants
|
0 Participants
|
|
Summary of Anti-VIS410 Antibody (ADA) Titers.
Day 56 anti-VIS410 antibody titer · ADA Titer > 1 to 4
|
5 Participants
|
8 Participants
|
13 Participants
|
0 Participants
|
|
Summary of Anti-VIS410 Antibody (ADA) Titers.
Day 56 anti-VIS410 antibody titer · ADA Titer > 4 to 16
|
1 Participants
|
3 Participants
|
4 Participants
|
0 Participants
|
|
Summary of Anti-VIS410 Antibody (ADA) Titers.
Day 56 anti-VIS410 antibody titer · ADA Titer > 16 to 64
|
1 Participants
|
3 Participants
|
4 Participants
|
0 Participants
|
|
Summary of Anti-VIS410 Antibody (ADA) Titers.
Day 56 anti-VIS410 antibody titer · ADA Titer > 64
|
0 Participants
|
0 Participants
|
0 Participants
|
0 Participants
|
|
Summary of Anti-VIS410 Antibody (ADA) Titers.
Day 100 anti-VIS410 antibody titer · ADA Titer ≤ 1
|
32 Participants
|
26 Participants
|
58 Participants
|
47 Participants
|
|
Summary of Anti-VIS410 Antibody (ADA) Titers.
Day 100 anti-VIS410 antibody titer · ADA Titer > 4 to 16
|
10 Participants
|
11 Participants
|
21 Participants
|
0 Participants
|
|
Summary of Anti-VIS410 Antibody (ADA) Titers.
Day 100 anti-VIS410 antibody titer · ADA Titer > 16 to 64
|
1 Participants
|
2 Participants
|
3 Participants
|
0 Participants
|
SECONDARY outcome
Timeframe: 10 daysPopulation: Modified Intent-to-Treat Population. The modified intent-to-treat (mITT) population included all subjects who received IV study drug and were confirmed influenza A positive by a molecular test at the central virological laboratory.
The Influenza Patient Reported Outcome (FluPRO) questionnaire is a 32-question instrument that assesses the occurrence and intensity of influenza associated symptoms (scale of 0 to 4, with 0 representing no symptoms) over 24 hours (lower scores indicate better outcomes). FluPRO data were recorded by subjects at Baseline (Day 1), then daily thereafter through Day 10. Data below show the time to symptom resolution for Total Symptom Score.
Outcome measures
| Measure |
VIS410 High Dose
n=46 Participants
Single intravenous dose of 4000 mg VIS410
|
VIS410 Low Dose
n=44 Participants
Single intravenous dose of 2000 mg VIS410
|
VIS410 Total
n=90 Participants
Summation of the VIS410 high and low dose groups.
|
Placebo
n=48 Participants
Single intravenous dose of saline solution
|
|---|---|---|---|---|
|
Duration of Signs and Symptoms of Influenza-like Illness as Assessed by the Influenza Patient Reported Outcomes Questionnaire After a Single IV Dose of VIS410
|
2.7 days
Interval 1.4 to 4.1
|
2.0 days
Interval 1.0 to 3.0
|
2.1 days
Interval 1.0 to 3.8
|
2.6 days
Interval 1.3 to 4.0
|
Adverse Events
VIS410 High Dose
VIS410 Low Dose
Placebo
Serious adverse events
| Measure |
VIS410 High Dose
n=49 participants at risk
Single intravenous fixed dose of 4000 mg VIS410
|
VIS410 Low Dose
n=49 participants at risk
Single intravenous fixed dose of 2000 mg VIS410
|
Placebo
n=50 participants at risk
Single intravenous saline solution
|
|---|---|---|---|
|
Gastrointestinal disorders
Upper gastrointestinal haemorrhage
|
0.00%
0/49 • Adverse events were monitored continuously from signing of informed consent until the last study related activity (100 days).
New or worsening symptoms of influenza, including cough, sore throat, nasal congestion, fatigue, headache, myalgia or low-grade fever were in general, considered a component of the presenting illness, and were not reported as AEs unless they resulted in an SAE
|
0.00%
0/49 • Adverse events were monitored continuously from signing of informed consent until the last study related activity (100 days).
New or worsening symptoms of influenza, including cough, sore throat, nasal congestion, fatigue, headache, myalgia or low-grade fever were in general, considered a component of the presenting illness, and were not reported as AEs unless they resulted in an SAE
|
2.0%
1/50 • Number of events 1 • Adverse events were monitored continuously from signing of informed consent until the last study related activity (100 days).
New or worsening symptoms of influenza, including cough, sore throat, nasal congestion, fatigue, headache, myalgia or low-grade fever were in general, considered a component of the presenting illness, and were not reported as AEs unless they resulted in an SAE
|
|
Nervous system disorders
Cerebrovascular accident
|
0.00%
0/49 • Adverse events were monitored continuously from signing of informed consent until the last study related activity (100 days).
New or worsening symptoms of influenza, including cough, sore throat, nasal congestion, fatigue, headache, myalgia or low-grade fever were in general, considered a component of the presenting illness, and were not reported as AEs unless they resulted in an SAE
|
0.00%
0/49 • Adverse events were monitored continuously from signing of informed consent until the last study related activity (100 days).
New or worsening symptoms of influenza, including cough, sore throat, nasal congestion, fatigue, headache, myalgia or low-grade fever were in general, considered a component of the presenting illness, and were not reported as AEs unless they resulted in an SAE
|
2.0%
1/50 • Number of events 1 • Adverse events were monitored continuously from signing of informed consent until the last study related activity (100 days).
New or worsening symptoms of influenza, including cough, sore throat, nasal congestion, fatigue, headache, myalgia or low-grade fever were in general, considered a component of the presenting illness, and were not reported as AEs unless they resulted in an SAE
|
Other adverse events
| Measure |
VIS410 High Dose
n=49 participants at risk
Single intravenous fixed dose of 4000 mg VIS410
|
VIS410 Low Dose
n=49 participants at risk
Single intravenous fixed dose of 2000 mg VIS410
|
Placebo
n=50 participants at risk
Single intravenous saline solution
|
|---|---|---|---|
|
Gastrointestinal disorders
Diarrhea
|
26.5%
13/49 • Number of events 13 • Adverse events were monitored continuously from signing of informed consent until the last study related activity (100 days).
New or worsening symptoms of influenza, including cough, sore throat, nasal congestion, fatigue, headache, myalgia or low-grade fever were in general, considered a component of the presenting illness, and were not reported as AEs unless they resulted in an SAE
|
16.3%
8/49 • Number of events 8 • Adverse events were monitored continuously from signing of informed consent until the last study related activity (100 days).
New or worsening symptoms of influenza, including cough, sore throat, nasal congestion, fatigue, headache, myalgia or low-grade fever were in general, considered a component of the presenting illness, and were not reported as AEs unless they resulted in an SAE
|
12.0%
6/50 • Number of events 6 • Adverse events were monitored continuously from signing of informed consent until the last study related activity (100 days).
New or worsening symptoms of influenza, including cough, sore throat, nasal congestion, fatigue, headache, myalgia or low-grade fever were in general, considered a component of the presenting illness, and were not reported as AEs unless they resulted in an SAE
|
|
Gastrointestinal disorders
Vomiting
|
8.2%
4/49 • Number of events 4 • Adverse events were monitored continuously from signing of informed consent until the last study related activity (100 days).
New or worsening symptoms of influenza, including cough, sore throat, nasal congestion, fatigue, headache, myalgia or low-grade fever were in general, considered a component of the presenting illness, and were not reported as AEs unless they resulted in an SAE
|
0.00%
0/49 • Adverse events were monitored continuously from signing of informed consent until the last study related activity (100 days).
New or worsening symptoms of influenza, including cough, sore throat, nasal congestion, fatigue, headache, myalgia or low-grade fever were in general, considered a component of the presenting illness, and were not reported as AEs unless they resulted in an SAE
|
2.0%
1/50 • Number of events 1 • Adverse events were monitored continuously from signing of informed consent until the last study related activity (100 days).
New or worsening symptoms of influenza, including cough, sore throat, nasal congestion, fatigue, headache, myalgia or low-grade fever were in general, considered a component of the presenting illness, and were not reported as AEs unless they resulted in an SAE
|
|
Nervous system disorders
Headache
|
6.1%
3/49 • Number of events 3 • Adverse events were monitored continuously from signing of informed consent until the last study related activity (100 days).
New or worsening symptoms of influenza, including cough, sore throat, nasal congestion, fatigue, headache, myalgia or low-grade fever were in general, considered a component of the presenting illness, and were not reported as AEs unless they resulted in an SAE
|
4.1%
2/49 • Number of events 2 • Adverse events were monitored continuously from signing of informed consent until the last study related activity (100 days).
New or worsening symptoms of influenza, including cough, sore throat, nasal congestion, fatigue, headache, myalgia or low-grade fever were in general, considered a component of the presenting illness, and were not reported as AEs unless they resulted in an SAE
|
4.0%
2/50 • Number of events 2 • Adverse events were monitored continuously from signing of informed consent until the last study related activity (100 days).
New or worsening symptoms of influenza, including cough, sore throat, nasal congestion, fatigue, headache, myalgia or low-grade fever were in general, considered a component of the presenting illness, and were not reported as AEs unless they resulted in an SAE
|
Additional Information
Results disclosure agreements
- Principal investigator is a sponsor employee
- Publication restrictions are in place