Study of an Investigational Monoclonal Antibody, VIS410, in Subjects With Uncomplicated Influenza A

• Sponsor: Visterra, Inc. (Industry)
• Overall Status: Completed
• CT.gov ID: NCT02989194
• Collaborator: Biomedical Advanced Research and Development Authority (U.S. Fed)
• Enrollment: 150
• Locations: 54
• Arms: 3
• Actual Duration (Months): 9.7
• Patients Per Site: 2.8
• Patients Per Site Per Month: 0.3

Study Details

Study Description

Brief Summary

This is a Phase 2a randomized, double-blind, placebo-controlled study designed to assess the safety and tolerability of an investigational monoclonal antibody, VIS410, in subjects with uncomplicated influenza.

Condition or Disease	Intervention/Treatment	Phase
Influenza	Drug: VIS410 low dose; Drug: VIS410 high dose; Drug: Placebo	Phase 2

Detailed Description

Subjects will be admitted to an infusion unit for drug administration and observation following infusion. The study is designed to compare an infusion of a single high or low IV dose of VIS410 against placebo. Subjects will be followed for 100 (±7 days).

Study Design

• Study Type: Interventional
• Actual Enrollment: 150 participants
• Allocation: Randomized
• Intervention Model: Parallel Assignment
• Masking: Quadruple (Participant, Care Provider, Investigator, Outcomes Assessor)
• Primary Purpose: Treatment
• Official Title: A Phase 2a Double-blind, Placebo-controlled Study to Assess the Safety and Tolerability of a Single Intravenous Dose of an Investigational Monoclonal Antibody With Code Name VIS410 in Subjects With Uncomplicated Influenza A Infection
• Actual Study Start Date: Jan 6, 2017
• Actual Primary Completion Date: Oct 27, 2017
• Actual Study Completion Date: Oct 27, 2017

Arms and Interventions

Arm	Intervention/Treatment
Experimental: VIS410 low dose Single intravenous fixed low dose of VIS410	Drug: VIS410 low dose; Single intravenous fixed low dose of VIS410
Experimental: VIS410 high dose Single intravenous fixed high dose of VIS410	Drug: VIS410 high dose; Single intravenous fixed high dose of VIS410
Placebo Comparator: Placebo Single intravenous placebo infusion	Drug: Placebo; Single intravenous infusion of placebo

Outcome Measures

Primary Outcome Measures

1. Assess the Safety and Tolerability of a Single IV Dose of VIS410 in Participants With Uncomplicated Influenza Infection [100 days]

   The percentage of participants with adverse events (AEs) and serious adverse events (SAEs) following administration of a single dose of IV VIS410.

2. Percentage of Participants With Any Treatment-emergent Adverse Event (TEAE) and TEAEs of Special Interest [100 days]

   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.

Secondary Outcome Measures

1. 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 [10 days]

   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.

2. Hospitalization for Influenza-related Complications [100 days]

   Number of participants requiring hospitalization for influenza-related complications

3. Duration of Hospitalization for Complications of Influenza [100 days]

   Duration of hospitalization for participants with at least 1 complication of influenza. There were no participants hospitalized for complications of influenza.

4. Count of Participants With Complications of Influenza [100 days]

   Count of participants with at least 1 complication of influenza

5. Influenza A Relapse/Reinfection [100 days]

   Number of participants with influenza A relapse/reinfection

6. VIS410 Maximum Plasma Concentration [1, 3, 5, 7, 14, 28, 56, 100 days]

   The maximum observed concentration of VIS410 in serum (Cmax).

7. Pharmacokinetics of VIS410 Concentration in Serum [1, 3, 5, 7, 14, 28, 56, 100 days]

   Time corresponding to the maximum serum concentration of VIS410.

8. VIS410 Plasma Concentration ( AUC 0-infinity) [1, 3, 5, 7, 14, 28, 56, 100 days]

   VIS410 area under the plasma concentration time curve in serum. AUC 0-infinity is from the time of dosing extrapolated to infinity.

9. VIS410 Plasma Concentration (AUC 0-last) [1, 3, 5, 7, 14, 28, 56, 100 days]

   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.

10. Half-life of VIS410 in Serum. [1, 3, 5, 7, 14, 28, 56, 100 days]

    Terminal elimination half-life of VIS410 in serum (t1/2) in serum.

11. Clearance (CL) of VIS410 in Serum. [1, 3, 5, 7, 14, 28, 56, 100 days]

    Summary of VIS410 total clearance (CL) in serum.

12. Area Under the Viral Load-Time Curve (VL AUC) From Nasopharyngeal Swab Day 7. [7 days]

    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.

13. Peak Viral Load by TCID50 [7 days]

    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.

14. Time to Resolution of Peak Viral Load From Nasopharyngeal Samples by TCID50. [7 days]

    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)

15. Summary of Anti-VIS410 Antibody (ADA) Titers. [100 days]

    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.

16. 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 [10 days]

    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.

Eligibility Criteria

Criteria

• Ages Eligible for Study: 18 Years to 65 Years
• Sexes Eligible for Study: All
• Accepts Healthy Volunteers: No

Inclusion Criteria:

• Male and female subjects aged ≥18 years and ˂65 years

• Women should fulfill one of the following criteria:

1. Post-menopausal; either amenorrhea ≥12 months or follicle stimulating hormone >40 mIU/mL (milli-international units/milliliter) as documented in their medical history

2. Surgically sterile; hysterectomy, bilateral oophorectomy, or tubal ligation

3. Women of childbearing potential participating in heterosexual sexual relations must be willing to use adequate contraception from screening until 60 days post 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 when having heterosexual intercourse, from screening until 60 days post infusion

• Test positive for influenza A by Rapid Antigen Test performed with a commercially available test on an adequate nasopharyngeal specimen in accordance with the manufacturer's instructions

• Presence of at least one respiratory symptom (cough, sore throat, or nasal symptoms) of moderate to severe intensity, or presence of at least one constitutional symptom (myalgia [aches and pains], headache, feverishness, or fatigue) of moderate to severe intensity

• Onset of symptoms (time when the temperature was first measured as elevated [temperature of ≥100.4°F or ≥38°C], OR the time when the subject experienced at least one respiratory symptom or at least one constitutional symptom) no more than 72 hours before the start of infusion

Exclusion Criteria:

• Use of NSAIDs or antihistamines within 6 hours of study drug dosing with the exception of those used as part of the pretreatment regimen

• History of intolerance or allergic response to monoclonal antibodies and/or pretreatment medications (diphenhydramine, ibuprofen and acetylsalicylic acid)

• Subject weight less than (<) 45 kg

• Subjects with clinical history that would lead to increased risk of influenza complications including but not limited to clinically significant cardiac disease, moderate to severe asthma, or other moderate to severe chronic obstructive pulmonary disease, metabolic syndrome including moderate to severe diabetes or active tuberculosis

• History of chronic GI disease, including bleeding, ulceration, Irritable Bowel Syndrome, systemic mastocytosis or chronic diarrhea

• Women who are pregnant, breast-feeding, or considering becoming pregnant

• Patients with hypoxemia requiring oxygen support

• Clinical evidence of worsening of any chronic medical condition (temporally associated with the onset of symptoms of influenza) which, in the Investigator's opinion, indicates that such finding(s) could represent complications of influenza

• Presence of immunocompromised status due to chronic illness, previous organ transplant, or use of immunosuppressive medical therapy including systemic steroids

• Presence of known Acquired Immune Deficiency Syndrome-defining illness, chronic hepatitis B or hepatitis C

• Receipt of any dose of antiviral therapy such as, but not limited to, rimantadine, amantadine, peramivir, zanamivir, laninamivir or oseltamivir in the 7 days prior to screening

• 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

• Subjects unable to take oral predose medication

• 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

• Subjects on chronic medications where the dose has not been stable for at least 3 months

Contacts and Locations

Locations

	Site	City	State	Country	Postal Code
1		Huntsville	Alabama	United States	35801
2		Coral Gables	Florida	United States	33134
3		Homestead	Florida	United States	33033
4		Miami	Florida	United States	33165
5		Miami	Florida	United States	33185
6		Orlando	Florida	United States	32811
7		Eunice	Louisiana	United States	70535
8		New Orleans	Louisiana	United States	70115
9		Shelby	North Carolina	United States	28150
10		Houston	Texas	United States	77058
11		McAllen	Texas	United States	78504
12		Asenovgrad		Bulgaria	4230
13		Lom		Bulgaria	3600
14		Ruse		Bulgaria	7002
15		Sofia		Bulgaria	1202
16		Sofia		Bulgaria	1407
17		Velingrad		Bulgaria	4600
18		Paide		Estonia	72713
19		Tallinn		Estonia	10617
20		Tallinn		Estonia	11615
21		Tallinn		Estonia	13415
22		Daugavpils		Latvia	LV-5417
23		Liepaja		Latvia	LV-3414
24		Rezekne		Latvia	LV-4600
25		Riga		Latvia	LV-1010
26		Valmiera		Latvia	LV-4201
27		Ventspils		Latvia	LV-3601
28		Kragujevac		Serbia	34000
29		Nis		Serbia	18000
30		Novi Sad		Serbia	21000
31		Welkom	Free State	South Africa	9460
32		Benoni	Gauteng	South Africa	1500
33		Centurion	Gauteng	South Africa	1692
34		Johannesburg	Gauteng	South Africa	2113
35		Kempton Park	Gauteng	South Africa	1619
36		Pretoria West	Gauteng	South Africa	0183
37		Pretoria	Gauteng	South Africa	0121
38		Soshanguve	Gauteng	South Africa	0152
39		Soweto	Gauteng	South Africa	2013
40		Durban	Kwazulu Natal	South Africa	4092
41		Thabazimbi	Limpopo	South Africa	0380
42		Middelburg	Mpumalanga	South Africa	1055
43		Witbank	Mpumalanga	South Africa	1035
44		Cape Town	Western Cape	South Africa	7570
45		Worcester	Western Cape	South Africa	6850
46		Kharkiv		Ukraine	61064
47		Kharkiv		Ukraine	61106
48		Kiev		Ukraine	03049
49		Kiev		Ukraine	03110
50		Kiev		Ukraine	04050
51		Odesa		Ukraine	65023
52		Sumy		Ukraine	40021
53		Vinnytsya		Ukraine	21001
54		Vinnytsya		Ukraine	21029

Sponsors and Collaborators

• Visterra, Inc.
• Biomedical Advanced Research and Development Authority

Investigators

• Study Director: Clinical Development, Visterra, Inc.

Study Documents (Full-Text)

• Study Protocol - Mar 14, 2017
• Statistical Analysis Plan - Jan 5, 2018

More Information

Publications

None provided.

• Responsible Party: Visterra, Inc.
• ClinicalTrials.gov Identifier: NCT02989194
• Other Study ID Numbers: VIS410-202
• First Posted: Dec 12, 2016
• Last Update Posted: Aug 15, 2022
• Last Verified: Aug 1, 2022

• Individual Participant Data (IPD) Sharing Statement: No
• Plan to Share IPD: No
• Additional relevant MeSH terms: Influenza, Human

Study Results

Participant Flow

Recruitment Details	This study was initiated in 58 study centers; 28 sites enrolled at least 1 subject.
Pre-assignment Detail	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

Arm/Group Title	VIS410 High Dose	VIS410 Low Dose	Placebo
Arm/Group Description	Single intravenous fixed dose of 4000 mg VIS410	Single intravenous fixed dose of 2000 mg VIS410	Single intravenous saline solution
Period Title: Overall Study
STARTED	50	50	50
COMPLETED	49	48	50
NOT COMPLETED	1	2	0

Baseline Characteristics

Arm/Group Title	VIS410 High Dose	VIS410 Low Dose	Placebo	Total
Arm/Group Description	Single intravenous fixed dose of 4000 mg VIS410	Single intravenous fixed dose of 2000 mg VIS410	Single intravenous saline solution	Total of all reporting groups
Overall Participants	50	50	50	150
Age (Count of Participants)
<=18 years	0 0%	0 0%	0 0%	0 0%
Between 18 and 65 years	50 100%	50 100%	50 100%	150 100%
>=65 years	0 0%	0 0%	0 0%	0 0%
Age (years) [Mean (Standard Deviation) ]
Mean (Standard Deviation) [years]	40.3 (13.13)	39.6 (13.79)	43.1 (12.77)	41.0 (13.23)
Sex: Female, Male (Count of Participants)
Female	27 54%	29 58%	28 56%	84 56%
Male	23 46%	21 42%	22 44%	66 44%
Ethnicity (NIH/OMB) (Count of Participants)
Hispanic or Latino	10 20%	12 24%	13 26%	35 23.3%
Not Hispanic or Latino	40 80%	38 76%	37 74%	115 76.7%
Unknown or Not Reported	0 0%	0 0%	0 0%	0 0%
Race (NIH/OMB) (Count of Participants)
American Indian or Alaska Native	0 0%	0 0%	0 0%	0 0%
Asian	1 2%	1 2%	1 2%	3 2%
Native Hawaiian or Other Pacific Islander	0 0%	0 0%	0 0%	0 0%
Black or African American	10 20%	11 22%	10 20%	31 20.7%
White	38 76%	38 76%	36 72%	112 74.7%
More than one race	0 0%	0 0%	0 0%	0 0%
Unknown or Not Reported	1 2%	0 0%	3 6%	4 2.7%
Region of Enrollment (participants) [Number]
Latvia	6 12%	2 4%	7 14%	15 10%
United States	19 38%	21 42%	18 36%	58 38.7%
South Africa	24 48%	25 50%	24 48%	73 48.7%
Estonia	1 2%	2 4%	0 0%	3 2%
Bulgaria	0 0%	0 0%	1 2%	1 0.7%
Subjects Body Mass Index (kg/m^2) [Mean (Full Range) ]
Mean (Full Range) [kg/m^2]	29.01	30.80	28.82	29.54
Time since onset of influenza (hours) (hours) [Mean (Standard Deviation) ]
Mean (Standard Deviation) [hours]	43.31 (16.479)	40.57 (11.563)	38.19 (13.859)	40.67 (14.170)
Time since onset of influenza (hours) (hours) [Median (Full Range) ]
Median (Full Range) [hours]	27.69	28.88	28.07	28.60

Outcome Measures

1. Primary Outcome

Title	Assess the Safety and Tolerability of a Single IV Dose of VIS410 in Participants With Uncomplicated Influenza Infection
Description	The percentage of participants with adverse events (AEs) and serious adverse events (SAEs) following administration of a single dose of IV VIS410.
Time Frame	100 days

Outcome Measure Data

Analysis Population Description

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.

Arm/Group Title	VIS410 High Dose	VIS410 Low Dose	VIS410 Total	Placebo
Arm/Group Description	Single intravenous dose of 4000 mg VIS410	Single intravenous dose of 2000 mg VIS410	Summation of the VIS410 high and low dose groups.	Single intravenous dose of saline solution
Measure Participants	49	49	98	50
Percentage of subjects with any adverse events	57.1 114.2%	34.7 69.4%	45.9 91.8%	26.0 17.3%
Percentage of subjects with any serious adverse events	0 0%	0 0%	0 0%	4 2.7%

2. Primary Outcome

Title	Percentage of Participants With Any Treatment-emergent Adverse Event (TEAE) and TEAEs of Special Interest
Description	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.
Time Frame	100 days

Outcome Measure Data

Analysis Population Description

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.

Arm/Group Title	VIS410 High Dose	VIS410 Low Dose	Total VIS410	Placebo
Arm/Group Description	Single intravenous fixed dose of 4000 mg VIS410	Single intravenous fixed dose of 2000 mg VIS410	Summation of 4000 mg and 2000 mg VIS410 dose groups.	Single intravenous saline solution
Measure Participants	49	49	98	50
Percentage of subjects with any TEAE	55.1 110.2%	34.7 69.4%	44.9 89.8%	24.0 16%
Percentage of subjects with treatment related TEAEs	30.6 61.2%	14.3 28.6%	22.4 44.8%	12.0 8%
Percentage of subjects with any TEAEs of Special Interest	34.7 69.4%	16.3 32.6%	25.5 51%	12 8%
Percentage of Subjects with any hypersensitivity Reactions	0 0%	0 0%	0 0%	0 0%
Percentage of subjects with any anaphylactic reactions	0 0%	0 0%	0 0%	0 0%
Percentage of subjects with any injection site AEs.	2.0 4%	0.0 0%	1.0 2%	0 0%

3. Secondary Outcome

Title	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
Description	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.
Time Frame	10 days

Outcome Measure Data

Analysis Population Description

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.

Arm/Group Title	VIS410 High Dose	VIS410 Low Dose	VIS410 Total	Placebo
Arm/Group Description	Single intravenous dose of 4000 mg VIS410	Single intravenous dose of 2000 mg VIS410	Summation of the 4000 and 2000 mg dose groups	Single dose intravenous saline solution
Measure Participants	46	44	90	48
Percent Change from Baseline to Day 2	-26.12 (27.00)	-29.98 (29.55)	-28.01 (28.18)	-19.53 (26.51)
Percentage change from baseline to day 3	-38.65 (28.78)	-49.37 (29.62)	-43.89 (29.53)	-33.63 (23.60)
Percentage change from baseline to day 4	-53.46 (26.16)	-59.08 (31.12)	-56.21 (28.67)	-44.55 (28.20)
Percentage change from baseline to day 5	-60.85 (25.52)	-64.61 (29.91)	-62.69 (27.66)	-56.75 (24.31)
Percentage change from baseline to day 6	-69.31 (20.90)	-66.80 (33.42)	-68.08 (27.61)	64.01 (23.35)
Percentage change from baseline to day 7	-74.03 (19.31)	-70.76 (31.18)	-72.43 (25.71)	-71.51 (20.61)
Percentage change from baseline to day 8	-77.98 (20.76)	-76.03 (25.53)	-77.02 (23.13)	-76.16 (21.01)
Percentage change from baseline to day 9	-80.05 (19.78)	-78.48 (25.95)	-79.27 (22.91)	-79.52 (19.84)
Percentage change from baseline to day 10	-82.30 (20.07)	-81.38 (20.43)	-81.85 (20.14)	-84.35 (17.52)

Statistical Analysis 1

Statistical Analysis Overview	Comparison Group Selection	VIS410 Total, Placebo
	Comments	Percent Change from Baseline to Day 2. All null hypotheses were defined as no treatment difference.
	Type of Statistical Test	Superiority
	Comments	Descriptive statistics. All statistical comparisons were performed using 2-sided tests at the 0.05 significance level.
Statistical Test of Hypothesis	p-Value	0.158
	Comments	All p-values are presented for informational purposes only, there were no adjustments for multiple comparisons.
	Method	Wilcoxon (Mann-Whitney)
	Comments

Statistical Analysis 2

Statistical Analysis Overview	Comparison Group Selection	VIS410 Total, Placebo
	Comments	Percent Change from Baseline to Day 3. All null hypotheses were defined as no treatment difference.
	Type of Statistical Test	Superiority
	Comments	Descriptive statistics. All statistical comparisons were performed using 2-sided tests at the 0.05 significance level.
Statistical Test of Hypothesis	p-Value	0.025
	Comments	All p-values are presented for informational purposes only, there were no adjustments for multiple comparisons.
	Method	Wilcoxon (Mann-Whitney)
	Comments

Statistical Analysis 3

Statistical Analysis Overview	Comparison Group Selection	VIS410 Total, Placebo
	Comments	Percent Change from Baseline to Day 4. All null hypotheses were defined as no treatment difference.
	Type of Statistical Test	Superiority
	Comments	Descriptive statistics. All statistical comparisons were performed using 2-sided tests at the 0.05 significance level.
Statistical Test of Hypothesis	p-Value	0.007
	Comments	All p-values are presented for informational purposes only, there were no adjustments for multiple comparisons.
	Method	Wilcoxon (Mann-Whitney)
	Comments

Statistical Analysis 4

Statistical Analysis Overview	Comparison Group Selection	VIS410 Total, Placebo
	Comments	Percent Change from Baseline to Day 5. All null hypotheses were defined as no treatment difference.
	Type of Statistical Test	Superiority
	Comments	Descriptive statistics. All statistical comparisons were performed using 2-sided tests at the 0.05 significance level.
Statistical Test of Hypothesis	p-Value	0.061
	Comments	All p-values are presented for informational purposes only, there were no adjustments for multiple comparisons.
	Method	Wilcoxon (Mann-Whitney)
	Comments

Statistical Analysis 5

Statistical Analysis Overview	Comparison Group Selection	VIS410 Total, Placebo
	Comments	Percent Change from Baseline to Day 6. All null hypotheses were defined as no treatment difference.
	Type of Statistical Test	Superiority
	Comments	Descriptive statistics. All statistical comparisons were performed using 2-sided tests at the 0.05 significance level.
Statistical Test of Hypothesis	p-Value	0.107
	Comments	All p-values are presented for informational purposes only, there were no adjustments for multiple comparisons.
	Method	Wilcoxon (Mann-Whitney)
	Comments

Statistical Analysis 6

Statistical Analysis Overview	Comparison Group Selection	VIS410 Total, Placebo
	Comments	Percent Change from Baseline to Day 7. All null hypotheses were defined as no treatment difference.
	Type of Statistical Test	Superiority
	Comments	Descriptive statistics. All statistical comparisons were performed using 2-sided tests at the 0.05 significance level.
Statistical Test of Hypothesis	p-Value	0.237
	Comments	All p-values are presented for informational purposes only, there were no adjustments for multiple comparisons.
	Method	Wilcoxon (Mann-Whitney)
	Comments

Statistical Analysis 7

Statistical Analysis Overview	Comparison Group Selection	VIS410 Total, Placebo
	Comments	Percent Change from Baseline to Day 8. All null hypotheses were defined as no treatment difference.
	Type of Statistical Test	Superiority
	Comments	Descriptive statistics. All statistical comparisons were performed using 2-sided tests at the 0.05 significance level.
Statistical Test of Hypothesis	p-Value	0.497
	Comments	All p-values are presented for informational purposes only, there were no adjustments for multiple comparisons.
	Method	Wilcoxon (Mann-Whitney)
	Comments

Statistical Analysis 8

Statistical Analysis Overview	Comparison Group Selection	VIS410 Total, Placebo
	Comments	Percent Change from Baseline to Day 9. All null hypotheses were defined as no treatment difference.
	Type of Statistical Test	Superiority
	Comments	Descriptive statistics. All statistical comparisons were performed using 2-sided tests at the 0.05 significance level.
Statistical Test of Hypothesis	p-Value	0.704
	Comments	All p-values are presented for informational purposes only, there were no adjustments for multiple comparisons.
	Method	Wilcoxon (Mann-Whitney)
	Comments

Statistical Analysis 9

Statistical Analysis Overview	Comparison Group Selection	VIS410 Total, Placebo
	Comments	Percent Change from Baseline to Day 10. All null hypotheses were defined as no treatment difference.
	Type of Statistical Test	Superiority
	Comments	Descriptive statistics. All statistical comparisons were performed using 2-sided tests at the 0.05 significance level.
Statistical Test of Hypothesis	p-Value	0.585
	Comments	All p-values are presented for informational purposes only, there were no adjustments for multiple comparisons.
	Method	Wilcoxon (Mann-Whitney)
	Comments

4. Secondary Outcome

Title	Hospitalization for Influenza-related Complications
Description	Number of participants requiring hospitalization for influenza-related complications
Time Frame	100 days

Outcome Measure Data

Analysis Population Description

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.

Arm/Group Title	VIS410 High Dose	VIS410 Low Dose	VIS410 Total	Placebo
Arm/Group Description	Single intravenous fixed dose of 4000 mg VIS410	Single intravenous fixed dose of 2000 mg VIS410	Summation of 4000 and 2000 mg VIS410 dose groups	Single intravenous saline solution
Measure Participants	46	44	90	48
Count of Participants [Participants]	0 0%	0 0%	0 0%	0 0%

5. Secondary Outcome

Title	Duration of Hospitalization for Complications of Influenza
Description	Duration of hospitalization for participants with at least 1 complication of influenza. There were no participants hospitalized for complications of influenza.
Time Frame	100 days

Outcome Measure Data

Analysis Population Description

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.

Arm/Group Title	VIS410 High Dose	VIS410 Low Dose	VIS410 Total	Placebo
Arm/Group Description	Single intravenous fixed dose of 4000 mg VIS410	Single intravenous fixed dose of 2000 mg VIS410	Summation of 4000 and 2000 mg VIS410 dose groups.	Single intravenous saline solution
Measure Participants	46	44	90	48
Number [days]	0	0	0	0

6. Secondary Outcome

Title	Count of Participants With Complications of Influenza
Description	Count of participants with at least 1 complication of influenza
Time Frame	100 days

Outcome Measure Data

Analysis Population Description

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.

Arm/Group Title	VIS410 High Dose	VIS410 Low Dose	VIS410 Total	Placebo
Arm/Group Description	Single intravenous fixed dose of 4000 mg VIS410	Single intravenous fixed dose of 2000 mg VIS410	Summation of 4000 and 2000 mg VIS410 dose groups.	Single intravenous saline solution
Measure Participants	46	44	90	48
Number (95% Confidence Interval) [participants]	1 2%	3 6%	4 8%	3 2%

7. Secondary Outcome

Title	Influenza A Relapse/Reinfection
Description	Number of participants with influenza A relapse/reinfection
Time Frame	100 days

Outcome Measure Data

Analysis Population Description

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.

Arm/Group Title	VIS410 High Dose	VIS410 Low Dose	VIS410 Total	Placebo
Arm/Group Description	Single intravenous fixed dose of 4000 mg VIS410	Single intravenous fixed dose of 2000 mg VIS410	Summation of 4000 and 2000 mg VIS410 dose groups.	Single intravenous saline solution
Measure Participants	46	44	90	48
Count of Participants [Participants]	0 0%	0 0%	0 0%	0 0%

8. Secondary Outcome

Title	VIS410 Maximum Plasma Concentration
Description	The maximum observed concentration of VIS410 in serum (Cmax).
Time Frame	1, 3, 5, 7, 14, 28, 56, 100 days

Outcome Measure Data

Analysis Population Description

The Pharmacokinetics (PK) population included all subjects who received IV study drug and had at least 1 PK concentration that could be calculated

Arm/Group Title	VIS410 High Dose	VIS410 Low Dose
Arm/Group Description	Single intravenous fixed dose of 4000 mg VIS410	Single intravenous fixed dose of 2000 mg VIS410
Measure Participants	47	49
Geometric Mean (Geometric Coefficient of Variation) [mcg/mL]	1013.559 (35.5)	627.640 (54.6)

9. Secondary Outcome

Title	Pharmacokinetics of VIS410 Concentration in Serum
Description	Time corresponding to the maximum serum concentration of VIS410.
Time Frame	1, 3, 5, 7, 14, 28, 56, 100 days

Outcome Measure Data

Analysis Population Description

The PK population included all subjects who received IV study drug and had at least 1 PK concentration that could be calculated

Arm/Group Title	VIS410 High Dose	VIS410 Low Dose
Arm/Group Description	Single intravenous fixed dose of 4000 mg VIS410	Single intravenous fixed dose of 2000 mg VIS410
Measure Participants	47	49
Geometric Mean (Geometric Coefficient of Variation) [day]	0.119 (79.0624)	0.133 (131.4255)

10. Secondary Outcome

Title	VIS410 Plasma Concentration ( AUC 0-infinity)
Description	VIS410 area under the plasma concentration time curve in serum. AUC 0-infinity is from the time of dosing extrapolated to infinity.
Time Frame	1, 3, 5, 7, 14, 28, 56, 100 days

Outcome Measure Data

Analysis Population Description

The PK population included all subjects who received IV study drug and had at least 1 PK concentration that could be calculated

Arm/Group Title	VIS410 High Dose	VIS410 Low Dose
Arm/Group Description	Single intravenous fixed dose of 4000 mg VIS410	Single intravenous fixed dose of 2000 mg VIS410
Measure Participants	46	48
Geometric Mean (Geometric Coefficient of Variation) [day*mcg/mL]	8598.909 (38.3172)	5371.988 (30.0631)

11. Secondary Outcome

Title	VIS410 Plasma Concentration (AUC 0-last)
Description	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.
Time Frame	1, 3, 5, 7, 14, 28, 56, 100 days

Outcome Measure Data

Analysis Population Description

The PK population included all subjects who received IV study drug and had at least 1 PK concentration that could be calculated

Arm/Group Title	VIS410 High Dose	VIS410 Low Dose
Arm/Group Description	Single intravenous fixed dose of 4000 mg VIS410	Single intravenous fixed dose of 2000 mg VIS410
Measure Participants	47	49
Geometric Mean (Geometric Coefficient of Variation) [day*mcg/mL]	8441.244 (39.5852)	5385.491 (31.2065)

12. Secondary Outcome

Title	Half-life of VIS410 in Serum.
Description	Terminal elimination half-life of VIS410 in serum (t1/2) in serum.
Time Frame	1, 3, 5, 7, 14, 28, 56, 100 days

Outcome Measure Data

Analysis Population Description

The PK population included all subjects who received IV study drug and had at least 1 PK concentration that could be calculated

Arm/Group Title	VIS410 High Dose	VIS410 Low Dose
Arm/Group Description	Single intravenous fixed dose of 4000 mg VIS410	Single intravenous fixed dose of 2000 mg VIS410
Measure Participants	46	48
Geometric Mean (Geometric Coefficient of Variation) [day]	9.941 (40.6241)	10.119 (34.2559)

13. Secondary Outcome

Title	Clearance (CL) of VIS410 in Serum.
Description	Summary of VIS410 total clearance (CL) in serum.
Time Frame	1, 3, 5, 7, 14, 28, 56, 100 days

Outcome Measure Data

Analysis Population Description

The PK population included all subjects who received IV study drug and had at least 1 PK concentration that could be calculated.

Arm/Group Title	VIS410 High Dose	VIS410 Low Dose
Arm/Group Description	Single intravenous fixed dose of 4000 mg VIS410	Single intravenous fixed dose of 2000 mg VIS410
Measure Participants	46	48
Geometric Mean (Geometric Coefficient of Variation) [mL/day]	465.175 (38.3172)	372.302 (30.0631)

14. Secondary Outcome

Title	Area Under the Viral Load-Time Curve (VL AUC) From Nasopharyngeal Swab Day 7.
Description	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.
Time Frame	7 days

Outcome Measure Data

Analysis Population Description

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.

Arm/Group Title	VIS410 High Dose	VIS410 Low Dose	VIS410 Total	Placebo
Arm/Group Description	Single intravenous fixed dose of 4000 mg VIS410	Single intravenous fixed dose of 2000 mg VIS410	Summation of 4000 and 2000 mg VIS410 dose groups.	Single intravenous saline solution
Measure Participants	46	44	90	48
Median (Full Range) [d x log10 TCID50/mL]	3.726	3.570	3.660	4.782

Statistical Analysis 1

Statistical Analysis Overview	Comparison Group Selection	VIS410 Total, Placebo
	Comments	A t-test was used to assess the difference between the VIS410 total and placebo treatment groups from nasopharyngeal swabs based on the TCID50.
	Type of Statistical Test	Superiority
	Comments	All statistical comparisons were performed using 2-sided tests at the 0.05 significance level.
Statistical Test of Hypothesis	p-Value	0.083
	Comments
	Method	t-test, 2 sided
	Comments

15. Secondary Outcome

Title	Peak Viral Load by TCID50
Description	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.
Time Frame	7 days

Outcome Measure Data

Analysis Population Description

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.

Arm/Group Title	VIS410 High Dose	VIS410 Low Dose	VIS410 Total	Placebo
Arm/Group Description	Single intravenous fixed dose of 4000 mg VIS410	Single intravenous fixed dose of 2000 mg VIS410	Summation of 4000 and 2000 mg VIS410 dose groups.	Single intravenous saline solution
Measure Participants	46	44	90	48
Median (Full Range) [log10 TCID50/mL]	3.125	2.50	2.625	3.375

Statistical Analysis 1

Statistical Analysis Overview	Comparison Group Selection	VIS410 Total, Placebo
	Comments	The null hypothesis was defined as no treatment difference.
	Type of Statistical Test	Superiority
	Comments	All statistical comparisons were performed using 2-sided tests at the 0.05 significance level.
Statistical Test of Hypothesis	p-Value	0.169
	Comments	All p-values are presented for informational purposes only; there were no adjustments for multiple comparisons.
	Method	t-test, 2 sided
	Comments

16. Secondary Outcome

Title	Time to Resolution of Peak Viral Load From Nasopharyngeal Samples by TCID50.
Description	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)
Time Frame	7 days

Outcome Measure Data

Analysis Population Description

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.

Arm/Group Title	VIS410 High Dose	VIS410 Low Dose	VIS649 Total	Placebo
Arm/Group Description	Single intravenous fixed dose of 4000 mg VIS410	Single intravenous fixed dose of 2000 mg VIS410	Summation of 4000 and 2000 mg VIS410 dose groups.	Single intravenous saline solution
Measure Participants	46	44	90	48
Median (95% Confidence Interval) [days]	2.0	1.9	1.9	3.6

Statistical Analysis 1

Statistical Analysis Overview	Comparison Group Selection	VIS410 Total, Placebo
	Comments	Kaplan-Meier methods were used to calculate the median time. All null hypotheses were defined as no treatment difference.
	Type of Statistical Test	Superiority
	Comments	Descriptive Statistics. Statistical comparisons were performed using log rank test.
Statistical Test of Hypothesis	p-Value	0.028
	Comments	All p-values are presented for informational purposes only; there were no adjustments for multiple comparisons.
	Method	Log Rank
	Comments
Other Statistical Analysis		All statistical comparisons were performed using 2-sided tests at the 0.05 significance level, unless specifically stated otherwise. All null hypotheses were defined as no treatment difference. All p-values are presented for informational purposes only; there were no adjustments for multiple comparisons.

17. Secondary Outcome

Title	Summary of Anti-VIS410 Antibody (ADA) Titers.
Description	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.
Time Frame	100 days

Outcome Measure Data

Analysis Population Description

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.

Arm/Group Title	VIS410 High Dose	VIS410 Low Dose	VIS410 Total	Placebo
Arm/Group Description	Single intravenous fixed dose of 4000 mg VIS410	Single intravenous fixed dose of 2000 mg VIS410	All participants receiving VIS410	Single intravenous saline solution
Measure Participants	49	49	98	50
ADA Titer ≤ 1	45 90%	43 86%	88 176%	45 30%
ADA Titer > 1 to 4	3 6%	3 6%	6 12%	4 2.7%
ADA Titer > 4 to 16	1 2%	1 2%	2 4%	0 0%
ADA Titer > 16 to 64	0 0%	0 0%	0 0%	0 0%
ADA Titer > 64	0 0%	0 0%	0 0%	0 0%
ADA Titer ≤ 1	46 92%	43 86%	89 178%	1 0.7%
ADA Titer > 1 to 4	2 4%	3 6%	5 10%	1 0.7%
ADA Titer > 4 to 16	1 2%	1 2%	2 4%	0 0%
ADA Titer > 16 to 64	0 0%	0 0%	0 0%	0 0%
ADA Titer > 64	0 0%	0 0%	0 0%	0 0%
ADA Titer ≤ 1	42 84%	34 68%	76 152%	2 1.3%
ADA Titer > 1 to 4	5 10%	8 16%	13 26%	0 0%
ADA Titer > 4 to 16	1 2%	3 6%	4 8%	0 0%
ADA Titer > 16 to 64	1 2%	3 6%	4 8%	0 0%
ADA Titer > 64	0 0%	0 0%	0 0%	0 0%
ADA Titer ≤ 1	32 64%	26 52%	58 116%	47 31.3%
ADA Titer > 1 to 4	6 12%	8 16%	14 28%	3 2%
ADA Titer > 4 to 16	10 20%	11 22%	21 42%	0 0%
ADA Titer > 16 to 64	1 2%	2 4%	3 6%	0 0%
ADA Titer > 64	0 0%	0 0%	0 0%	0 0%

18. Secondary Outcome

Title	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
Description	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.
Time Frame	10 days

Outcome Measure Data

Analysis Population Description

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.

Arm/Group Title	VIS410 High Dose	VIS410 Low Dose	VIS410 Total	Placebo
Arm/Group Description	Single intravenous dose of 4000 mg VIS410	Single intravenous dose of 2000 mg VIS410	Summation of the 4000 and 2000 mg dose groups	Single dose intravenous saline solution
Measure Participants	46	44	90	48
Median (Inter-Quartile Range) [days]	2.7	2.0	2.1	2.6

Statistical Analysis 1

Statistical Analysis Overview	Comparison Group Selection	VIS410 Total, Placebo
	Comments	All null hypotheses were defined as no treatment difference.
	Type of Statistical Test	Equivalence
	Comments	Descriptive Statistics. All statistical comparisons were performed at the 0.05 significance level.
Statistical Test of Hypothesis	p-Value	0.173
	Comments	All p-values are presented for informational purposes only; there were no adjustments for multiple comparisons.
	Method	Log Rank
	Comments	Kaplan-Meier methods were used to calculate the median time, 25th percentile and 75th percentile.

Adverse Events

Time Frame	Adverse events were monitored continuously from signing of informed consent until the last study related activity (100 days).
Adverse Event Reporting Description	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
Arm/Group Title	VIS410 High Dose		VIS410 Low Dose		Placebo
Arm/Group Description	Single intravenous fixed dose of 4000 mg VIS410		Single intravenous fixed dose of 2000 mg VIS410		Single intravenous saline solution
All Cause Mortality
	VIS410 High Dose		VIS410 Low Dose		Placebo
	Affected / at Risk (%)	# Events	Affected / at Risk (%)	# Events	Affected / at Risk (%)	# Events
Total	0/49 (0%)		0/49 (0%)		0/50 (0%)
Serious Adverse Events
	VIS410 High Dose		VIS410 Low Dose		Placebo
	Affected / at Risk (%)	# Events	Affected / at Risk (%)	# Events	Affected / at Risk (%)	# Events
Total	0/49 (0%)		0/49 (0%)		2/50 (4%)
Gastrointestinal disorders
Upper gastrointestinal haemorrhage	0/49 (0%)	0	0/49 (0%)	0	1/50 (2%)	1
Nervous system disorders
Cerebrovascular accident	0/49 (0%)	0	0/49 (0%)	0	1/50 (2%)	1
Other (Not Including Serious) Adverse Events
	VIS410 High Dose		VIS410 Low Dose		Placebo
	Affected / at Risk (%)	# Events	Affected / at Risk (%)	# Events	Affected / at Risk (%)	# Events
Total	16/49 (32.7%)		10/49 (20.4%)		7/50 (14%)
Gastrointestinal disorders
Diarrhea	13/49 (26.5%)	13	8/49 (16.3%)	8	6/50 (12%)	6
Vomiting	4/49 (8.2%)	4	0/49 (0%)	0	1/50 (2%)	1
Nervous system disorders
Headache	3/49 (6.1%)	3	2/49 (4.1%)	2	2/50 (4%)	2

Limitations/Caveats

[Not Specified]

More Information

Certain Agreements

Principal Investigators are NOT employed by the organization sponsoring the study.

There is NOT an agreement between Principal Investigators and the Sponsor (or its agents) that restricts the PI's rights to discuss or publish trial results after the trial is completed.