Trial Outcomes & Findings for Exploring Safety & Clinical Benefit of Anti-Influenza Immunoglobulin Intravenous in Hospitalized Adults With Influenza A (NCT NCT03315104)

NCT ID: NCT03315104

Last Updated: 2024-03-18

Results Overview

Frequency counts and percentage of subjects with Adverse Events by severity

Recruitment status

COMPLETED

Study phase

PHASE2

Target enrollment

65 participants

Primary outcome timeframe

Measured through Day 60

Results posted on

2024-03-18

Participant Flow

This study included patients hospitalized with serious illness with laboratory-confirmed influenza A infection. Total 75 subjects were screened with 10 screen failures. Out of 65 randomized subjects, 60 received study treatment and 53 completed the study.

Participant milestones

Participant milestones
Measure	FLU-IGIV High Dose (450 mL) Participants received a single infusion of high dose of FLU-IGIV, administered over approximately 3 hours on Day 1. Administered intravenously at a dose of 450 mL of 65 g/mL FLU-IGIV diluted to 500 mL with normal saline. Participants also received standard of care (SOC) antiviral treatment for flu. FLU-IGIV: Single dose, sterile liquid formulation for IV administration.	FLU-IGIV Low Dose (225 mL) Participants received a single infusion of low dose of FLU-IGIV, administered over approximately 3 hours on Day 1. Administered intravenously at a dose of 225 mL of 65 g/mL FLU-IGIV diluted to 500 mL with normal saline. Participants also received standard of care (SOC) antiviral treatment for flu. FLU-IGIV: Single dose, sterile liquid formulation for IV administration.	Placebo (500 mL Normal Saline) Participants received a single infusion of placebo for FLU-IGIV, administered over approximately 3 hours on Day 1. Administered IV as 500 mL of normal saline. Participants also received SOC antiviral treatment for flu. Placebo for FLU-IGIV: Single dose, normal saline solution for IV administration.
Overall Study STARTED	21	20	24
Overall Study Dosed (Safety Population)	19	19	22
Overall Study COMPLETED	18	16	19
Overall Study NOT COMPLETED	3	4	5

Reasons for withdrawal

Withdrawal data not reported

Baseline Characteristics

Exploring Safety & Clinical Benefit of Anti-Influenza Immunoglobulin Intravenous in Hospitalized Adults With Influenza A

Baseline characteristics by cohort

Baseline characteristics by cohort
Measure	FLU-IGIV High Dose (450 mL) n=21 Participants Participants received a single infusion of high dose of FLU-IGIV, administered over approximately 3 hours on Day 1. Administered intravenously at a dose of 450 mL of 65 g/mL FLU-IGIV diluted to 500 mL with normal saline. Participants also received standard of care (SOC) antiviral treatment for flu. FLU-IGIV: Single dose, sterile liquid formulation for IV administration.	FLU-IGIV Low Dose (225 mL) n=20 Participants Participants received a single infusion of low dose of FLU-IGIV, administered over approximately 3 hours on Day 1. Administered intravenously at a dose of 225 mL of 65 g/mL FLU-IGIV diluted to 500 mL with normal saline. Participants also received standard of care (SOC) antiviral treatment for flu. FLU-IGIV: Single dose, sterile liquid formulation for IV administration.	Placebo (500 mL Normal Saline) n=24 Participants Participants received a single infusion of placebo for FLU-IGIV, administered over approximately 3 hours on Day 1. Administered IV as 500 mL of normal saline. Participants also received SOC antiviral treatment for flu. Placebo for FLU-IGIV: Single dose, normal saline solution for IV administration.	Total n=65 Participants Total of all reporting groups
Age, Continuous	48.4 years STANDARD_DEVIATION 16.2 • n=5 Participants	49.1 years STANDARD_DEVIATION 14.2 • n=7 Participants	59.5 years STANDARD_DEVIATION 14.1 • n=5 Participants	52.7 years STANDARD_DEVIATION 15.5 • n=4 Participants
Age, Customized 18-54	13 Participants n=5 Participants	11 Participants n=7 Participants	8 Participants n=5 Participants	32 Participants n=4 Participants
Age, Customized 55 and over	8 Participants n=5 Participants	9 Participants n=7 Participants	16 Participants n=5 Participants	33 Participants n=4 Participants
Sex: Female, Male Female	12 Participants n=5 Participants	10 Participants n=7 Participants	12 Participants n=5 Participants	34 Participants n=4 Participants
Sex: Female, Male Male	9 Participants n=5 Participants	10 Participants n=7 Participants	12 Participants n=5 Participants	31 Participants n=4 Participants
Ethnicity (NIH/OMB) Hispanic or Latino	3 Participants n=5 Participants	4 Participants n=7 Participants	3 Participants n=5 Participants	10 Participants n=4 Participants
Ethnicity (NIH/OMB) Not Hispanic or Latino	18 Participants n=5 Participants	16 Participants n=7 Participants	21 Participants n=5 Participants	55 Participants n=4 Participants
Ethnicity (NIH/OMB) Unknown or Not Reported	0 Participants n=5 Participants	0 Participants n=7 Participants	0 Participants n=5 Participants	0 Participants n=4 Participants
Race (NIH/OMB) American Indian or Alaska Native	0 Participants n=5 Participants	0 Participants n=7 Participants	0 Participants n=5 Participants	0 Participants n=4 Participants
Race (NIH/OMB) Asian	0 Participants n=5 Participants	0 Participants n=7 Participants	0 Participants n=5 Participants	0 Participants n=4 Participants
Race (NIH/OMB) Native Hawaiian or Other Pacific Islander	0 Participants n=5 Participants	0 Participants n=7 Participants	0 Participants n=5 Participants	0 Participants n=4 Participants
Race (NIH/OMB) Black or African American	9 Participants n=5 Participants	9 Participants n=7 Participants	14 Participants n=5 Participants	32 Participants n=4 Participants
Race (NIH/OMB) White	12 Participants n=5 Participants	11 Participants n=7 Participants	10 Participants n=5 Participants	33 Participants n=4 Participants
Race (NIH/OMB) More than one race	0 Participants n=5 Participants	0 Participants n=7 Participants	0 Participants n=5 Participants	0 Participants n=4 Participants
Race (NIH/OMB) Unknown or Not Reported	0 Participants n=5 Participants	0 Participants n=7 Participants	0 Participants n=5 Participants	0 Participants n=4 Participants
Region of Enrollment North America	20 Participants n=5 Participants	20 Participants n=7 Participants	22 Participants n=5 Participants	62 Participants n=4 Participants
Region of Enrollment Spain	1 Participants n=5 Participants	0 Participants n=7 Participants	2 Participants n=5 Participants	3 Participants n=4 Participants

PRIMARY outcome

Timeframe: Measured through Day 60

Population: The safety population includes all subjects who receive any amount of study medication (FLU-IGIV or placebo). In the case of incorrect treatment administration, subjects are analyzed according to the treatment received. The safety population is the primary analysis population for all safety data.

Frequency counts and percentage of subjects with Adverse Events by severity

Outcome measures

Outcome measures
Measure	FLU-IGIV High Dose (450 mL) n=19 Participants Participants received a single infusion of high dose of FLU-IGIV, administered over approximately 3 hours on Day 1. Administered intravenously at a dose of 450 mL of 65 g/mL FLU-IGIV diluted to 500 mL with normal saline. Participants also received standard of care (SOC) antiviral treatment for flu. FLU-IGIV: Single dose, sterile liquid formulation for IV administration.	FLU-IGIV Low Dose (225 mL) n=19 Participants Participants received a single infusion of low dose of FLU-IGIV, administered over approximately 3 hours on Day 1. Administered intravenously at a dose of 225 mL of 65 g/mL FLU-IGIV diluted to 500 mL with normal saline. Participants also received standard of care (SOC) antiviral treatment for flu. FLU-IGIV: Single dose, sterile liquid formulation for IV administration.	Placebo (500 mL Normal Saline) n=22 Participants Participants received a single infusion of placebo for FLU-IGIV, administered over approximately 3 hours on Day 1. Administered IV as 500 mL of normal saline. Participants also received SOC antiviral treatment for flu. Placebo for FLU-IGIV: Single dose, normal saline solution for IV administration.
Frequency Counts and Percentage of Subjects With Adverse Events Mild	6 Participants	6 Participants	1 Participants
Frequency Counts and Percentage of Subjects With Adverse Events Moderate	3 Participants	5 Participants	6 Participants
Frequency Counts and Percentage of Subjects With Adverse Events Severe	1 Participants	1 Participants	4 Participants

PRIMARY outcome

Timeframe: Measured through 48 Hours post-dose

Population: The PK population includes all safety subjects who have adequate PK data for analysis that includes Day 1 baseline (pre-infusion) and at least one post-infusion time point. Subjects are analyzed according to the treatment received. See outcome measure description for subject exclusion details.

Levels of anti-influenza A antibodies circulating in blood over time. We initially intended to look at this variable through Day 8, however, potential native antibody level changes and sparse sampling confounded results from 0 to 48 hours post-dose from PK samples collected from Baseline Day 1 pre-dose (time 0), Day 1 post-dose, Day 2 and Day 3 (if continued hospitalization), and Day 8. For AUC from time 0 to 48 hours, subjects who did not have a sample collected within +/-10% of 48 hours post-dose had this parameter set to missing, which is why the number of subjects who contributed data for this outcome measure is lower than the overall number of subjects analyzed.

Outcome measures

Outcome measures
Measure	FLU-IGIV High Dose (450 mL) n=7 Participants Participants received a single infusion of high dose of FLU-IGIV, administered over approximately 3 hours on Day 1. Administered intravenously at a dose of 450 mL of 65 g/mL FLU-IGIV diluted to 500 mL with normal saline. Participants also received standard of care (SOC) antiviral treatment for flu. FLU-IGIV: Single dose, sterile liquid formulation for IV administration.	FLU-IGIV Low Dose (225 mL) n=10 Participants Participants received a single infusion of low dose of FLU-IGIV, administered over approximately 3 hours on Day 1. Administered intravenously at a dose of 225 mL of 65 g/mL FLU-IGIV diluted to 500 mL with normal saline. Participants also received standard of care (SOC) antiviral treatment for flu. FLU-IGIV: Single dose, sterile liquid formulation for IV administration.	Placebo (500 mL Normal Saline) n=13 Participants Participants received a single infusion of placebo for FLU-IGIV, administered over approximately 3 hours on Day 1. Administered IV as 500 mL of normal saline. Participants also received SOC antiviral treatment for flu. Placebo for FLU-IGIV: Single dose, normal saline solution for IV administration.
Area Under the Plasma Concentration Curve [AUC] From Time 0 to 48 Hours Post-dose by Hemagglutinin Inhibition Assay H1N1 California	8589.9 titer*hours/mL Geometric Coefficient of Variation 65.2	4955.4 titer*hours/mL Geometric Coefficient of Variation 87.8	1973.1 titer*hours/mL Geometric Coefficient of Variation 85.0
Area Under the Plasma Concentration Curve [AUC] From Time 0 to 48 Hours Post-dose by Hemagglutinin Inhibition Assay H1N1 Michigan	5266.3 titer*hours/mL Geometric Coefficient of Variation 67.6	3446.3 titer*hours/mL Geometric Coefficient of Variation 123.2	1630.2 titer*hours/mL Geometric Coefficient of Variation 106.4
Area Under the Plasma Concentration Curve [AUC] From Time 0 to 48 Hours Post-dose by Hemagglutinin Inhibition Assay H3N2 Hong Kong	11729.3 titer*hours/mL Geometric Coefficient of Variation 47.4	7054.8 titer*hours/mL Geometric Coefficient of Variation 39.1	3682.5 titer*hours/mL Geometric Coefficient of Variation 126.7
Area Under the Plasma Concentration Curve [AUC] From Time 0 to 48 Hours Post-dose by Hemagglutinin Inhibition Assay H3N2 Singapore	6754.0 titer*hours/mL Geometric Coefficient of Variation 34.2	4431.6 titer*hours/mL Geometric Coefficient of Variation 45.3	2511.3 titer*hours/mL Geometric Coefficient of Variation 219.6

PRIMARY outcome

Timeframe: Measured through Day 8 post-dose

Maximum observed concentration (reported as a titer) of anti-influenza A antibodies measured from Day 1 pre-dose (time 0) through Day 8 post-dose from PK samples collected from Baseline Day 1 pre-dose (time 0), Day 1 post-dose, Day 2 and Day 3 (if continued hospitalization), and Day 8.

Outcome measures

Outcome measures
Measure	FLU-IGIV High Dose (450 mL) n=19 Participants Participants received a single infusion of high dose of FLU-IGIV, administered over approximately 3 hours on Day 1. Administered intravenously at a dose of 450 mL of 65 g/mL FLU-IGIV diluted to 500 mL with normal saline. Participants also received standard of care (SOC) antiviral treatment for flu. FLU-IGIV: Single dose, sterile liquid formulation for IV administration.	FLU-IGIV Low Dose (225 mL) n=19 Participants Participants received a single infusion of low dose of FLU-IGIV, administered over approximately 3 hours on Day 1. Administered intravenously at a dose of 225 mL of 65 g/mL FLU-IGIV diluted to 500 mL with normal saline. Participants also received standard of care (SOC) antiviral treatment for flu. FLU-IGIV: Single dose, sterile liquid formulation for IV administration.	Placebo (500 mL Normal Saline) n=21 Participants Participants received a single infusion of placebo for FLU-IGIV, administered over approximately 3 hours on Day 1. Administered IV as 500 mL of normal saline. Participants also received SOC antiviral treatment for flu. Placebo for FLU-IGIV: Single dose, normal saline solution for IV administration.
Maximum Plasma Concentration [Cmax] Reported as a Titer for Hemagglutinin Inhibition Assay H1N1 California	408.3 titer Geometric Coefficient of Variation 99.8	152.5 titer Geometric Coefficient of Variation 81.6	54.7 titer Geometric Coefficient of Variation 135.9
Maximum Plasma Concentration [Cmax] Reported as a Titer for Hemagglutinin Inhibition Assay H1N1 Michigan	371.6 titer Geometric Coefficient of Variation 138.2	121.7 titer Geometric Coefficient of Variation 114.6	54.7 titer Geometric Coefficient of Variation 155.8
Maximum Plasma Concentration [Cmax] Reported as a Titer for Hemagglutinin Inhibition Assay H3N2 Hong Kong	309.6 titer Geometric Coefficient of Variation 38.4	239.8 titer Geometric Coefficient of Variation 97.2	117.7 titer Geometric Coefficient of Variation 317.2
Maximum Plasma Concentration [Cmax] Reported as a Titer for Hemagglutinin Inhibition Assay H3N2 Singapore	206.7 titer Geometric Coefficient of Variation 35.1	192.7 titer Geometric Coefficient of Variation 95.2	86.7 titer Geometric Coefficient of Variation 297.0

PRIMARY outcome

Timeframe: Measured through Day 8 post-dose

Time that anti-influenza A antibodies are at maximum concentration from Day 1 pre-dose (time 0) through Day 8 post-dose from PK samples collected from Baseline Day 1 pre-dose (time 0), Day 1 post-dose, Day 2 and Day 3 (if continued hospitalization), and Day 8. The rate of study drug elimination and dependent parameters were not accurately estimable due to rising or sustained levels of anti-influenza A antibodies, this includes First Order Terminal Elimination Rate Constant \[Kel\], Plasma Clearance \[Cl\] and Total Volume of Distribution \[Vz\].

Outcome measures

Outcome measures
Measure	FLU-IGIV High Dose (450 mL) n=19 Participants Participants received a single infusion of high dose of FLU-IGIV, administered over approximately 3 hours on Day 1. Administered intravenously at a dose of 450 mL of 65 g/mL FLU-IGIV diluted to 500 mL with normal saline. Participants also received standard of care (SOC) antiviral treatment for flu. FLU-IGIV: Single dose, sterile liquid formulation for IV administration.	FLU-IGIV Low Dose (225 mL) n=19 Participants Participants received a single infusion of low dose of FLU-IGIV, administered over approximately 3 hours on Day 1. Administered intravenously at a dose of 225 mL of 65 g/mL FLU-IGIV diluted to 500 mL with normal saline. Participants also received standard of care (SOC) antiviral treatment for flu. FLU-IGIV: Single dose, sterile liquid formulation for IV administration.	Placebo (500 mL Normal Saline) n=21 Participants Participants received a single infusion of placebo for FLU-IGIV, administered over approximately 3 hours on Day 1. Administered IV as 500 mL of normal saline. Participants also received SOC antiviral treatment for flu. Placebo for FLU-IGIV: Single dose, normal saline solution for IV administration.
Time Cmax is Observed [Tmax] by Hemagglutinin Inhibition Assay H1N1 California	24.4 hours Geometric Coefficient of Variation 660.7	17.4 hours Geometric Coefficient of Variation 358.8	108.7 hours Geometric Coefficient of Variation 64.3
Time Cmax is Observed [Tmax] by Hemagglutinin Inhibition Assay H1N1 Michigan	40.3 hours Geometric Coefficient of Variation 522.5	13.9 hours Geometric Coefficient of Variation 423.6	120.3 hours Geometric Coefficient of Variation 58.4
Time Cmax is Observed [Tmax] by Hemagglutinin Inhibition Assay H3N2 Hong Kong	4.8 hours Geometric Coefficient of Variation 127.1	14.6 hours Geometric Coefficient of Variation 298.4	76.8 hours Geometric Coefficient of Variation 119.9
Time Cmax is Observed [Tmax] by Hemagglutinin Inhibition Assay H3N2 Singapore	6.0 hours Geometric Coefficient of Variation 146.0	23.0 hours Geometric Coefficient of Variation 328.2	64.8 hours Geometric Coefficient of Variation 171.4

SECONDARY outcome

Timeframe: At Day 8 post-dose

Population: Intent to Treat (ITT) Population: includes all randomized subjects regardless of study medication (FLU-IGIV or placebo) dosing, influenza type or Protocol Deviations. Not all subjects had ordinal scale data available at Day 8 which is why the overall number of subjects analyzed is not consistent with the overall number of baseline subjects.

Score (physician-assessed): 1=death; 2=hospitalization in the intensive care unit (ICU); 3=non-ICU hospitalization requiring supplemental oxygen; 4=non-ICU hospitalization not requiring supplemental oxygen; 5=no longer hospitalized but unable to resume normal activities; 6=no longer hospitalized with full resumption of normal activities. A higher score reflects improved clinical status. Not all ITT subjects had ordinal scale data available at Day 8 post-dose which explains why the overall number of participants analyzed is not consistent with the overall number of subjects included at baseline. For subjects who were discharged with unknown ordinal score the more conservative of two relevant discharged categories was imputed.

Outcome measures

Outcome measures
Measure	FLU-IGIV High Dose (450 mL) n=19 Participants Participants received a single infusion of high dose of FLU-IGIV, administered over approximately 3 hours on Day 1. Administered intravenously at a dose of 450 mL of 65 g/mL FLU-IGIV diluted to 500 mL with normal saline. Participants also received standard of care (SOC) antiviral treatment for flu. FLU-IGIV: Single dose, sterile liquid formulation for IV administration.	FLU-IGIV Low Dose (225 mL) n=17 Participants Participants received a single infusion of low dose of FLU-IGIV, administered over approximately 3 hours on Day 1. Administered intravenously at a dose of 225 mL of 65 g/mL FLU-IGIV diluted to 500 mL with normal saline. Participants also received standard of care (SOC) antiviral treatment for flu. FLU-IGIV: Single dose, sterile liquid formulation for IV administration.	Placebo (500 mL Normal Saline) n=21 Participants Participants received a single infusion of placebo for FLU-IGIV, administered over approximately 3 hours on Day 1. Administered IV as 500 mL of normal saline. Participants also received SOC antiviral treatment for flu. Placebo for FLU-IGIV: Single dose, normal saline solution for IV administration.
Ordinal Scale Subject Distribution Reflecting Clinical Status 1-Death	0 Participants	0 Participants	0 Participants
Ordinal Scale Subject Distribution Reflecting Clinical Status 2-Hospitalization in the ICU	1 Participants	0 Participants	0 Participants
Ordinal Scale Subject Distribution Reflecting Clinical Status 3-Non-ICU hospitalization, requiring supp O2	0 Participants	2 Participants	4 Participants
Ordinal Scale Subject Distribution Reflecting Clinical Status 4-Non-ICU hospitalization, not requiring supp O2	0 Participants	0 Participants	0 Participants
Ordinal Scale Subject Distribution Reflecting Clinical Status 5-No longer hospitalized, no normal activities	7 Participants	7 Participants	9 Participants
Ordinal Scale Subject Distribution Reflecting Clinical Status 6-No longer hospitalized, normal activities	11 Participants	8 Participants	8 Participants

Adverse Events

FLU-IGIV High Dose (450 mL)

Serious events: 1 serious events

Other events: 5 other events

Deaths: 0 deaths

FLU-IGIV Low Dose (225 mL)

Serious events: 2 serious events

Other events: 6 other events

Deaths: 0 deaths

Placebo (Normal Saline)

Serious events: 5 serious events

Other events: 8 other events

Deaths: 0 deaths

Serious adverse events

Other adverse events

Additional Information

Dr. Christine Hall

Emergent BioSolutions

Phone: 204-275-4200

Email: [email protected]

Results disclosure agreements

Principal investigator is a sponsor employee The result of the study may not be published until prior publication of the global results by the Sponsor, in the case of multi-center studies.
Publication restrictions are in place

Restriction type: OTHER

Measure	FLU-IGIV High Dose (450 mL) n=19 participants at risk Participants received a single infusion of high dose of FLU-IGIV, administered over approximately 3 hours on Day 1. Administered intravenously at a dose of 450 mL of 65 g/mL FLU-IGIV diluted to 500 mL with normal saline. Participants also received standard of care (SOC) antiviral treatment for flu. FLU-IGIV: Single dose, sterile liquid formulation for IV administration.	FLU-IGIV Low Dose (225 mL) n=19 participants at risk Participants received a single infusion of low dose of FLU-IGIV, administered over approximately 3 hours on Day 1. Administered intravenously at a dose of 225 mL of 65 g/mL FLU-IGIV diluted to 500 mL with normal saline. Participants also received standard of care (SOC) antiviral treatment for flu. FLU-IGIV: Single dose, sterile liquid formulation for IV administration.	Placebo (Normal Saline) n=22 participants at risk Participants received a single infusion of placebo for FLU-IGIV, administered over approximately 3 hours on Day 1. Administered IV as 500 mL of normal saline. Participants also received SOC antiviral treatment for flu. Placebo for FLU-IGIV: Single dose, normal saline solution for IV administration.
Cardiac disorders Cardiac Failure	0.00% 0/19 • From start of infusion on Day 1 through Day 60 (2 months).	0.00% 0/19 • From start of infusion on Day 1 through Day 60 (2 months).	4.5% 1/22 • Number of events 1 • From start of infusion on Day 1 through Day 60 (2 months).
Cardiac disorders Supraventricular tachycardia	0.00% 0/19 • From start of infusion on Day 1 through Day 60 (2 months).	0.00% 0/19 • From start of infusion on Day 1 through Day 60 (2 months).	4.5% 1/22 • Number of events 1 • From start of infusion on Day 1 through Day 60 (2 months).
Infections and infestations Cellulitis	0.00% 0/19 • From start of infusion on Day 1 through Day 60 (2 months).	5.3% 1/19 • Number of events 1 • From start of infusion on Day 1 through Day 60 (2 months).	0.00% 0/22 • From start of infusion on Day 1 through Day 60 (2 months).
Infections and infestations Urosepsis	0.00% 0/19 • From start of infusion on Day 1 through Day 60 (2 months).	0.00% 0/19 • From start of infusion on Day 1 through Day 60 (2 months).	4.5% 1/22 • Number of events 1 • From start of infusion on Day 1 through Day 60 (2 months).
Metabolism and nutrition disorders Dehydration	0.00% 0/19 • From start of infusion on Day 1 through Day 60 (2 months).	0.00% 0/19 • From start of infusion on Day 1 through Day 60 (2 months).	4.5% 1/22 • Number of events 1 • From start of infusion on Day 1 through Day 60 (2 months).
Metabolism and nutrition disorders Hypokalaemia	0.00% 0/19 • From start of infusion on Day 1 through Day 60 (2 months).	0.00% 0/19 • From start of infusion on Day 1 through Day 60 (2 months).	4.5% 1/22 • Number of events 1 • From start of infusion on Day 1 through Day 60 (2 months).
Nervous system disorders Dizziness	0.00% 0/19 • From start of infusion on Day 1 through Day 60 (2 months).	0.00% 0/19 • From start of infusion on Day 1 through Day 60 (2 months).	4.5% 1/22 • Number of events 1 • From start of infusion on Day 1 through Day 60 (2 months).
Renal and urinary disorders Acute Kidney Injury	5.3% 1/19 • Number of events 1 • From start of infusion on Day 1 through Day 60 (2 months).	0.00% 0/19 • From start of infusion on Day 1 through Day 60 (2 months).	4.5% 1/22 • Number of events 1 • From start of infusion on Day 1 through Day 60 (2 months).
Respiratory, thoracic and mediastinal disorders Acute Respiratory Failure	0.00% 0/19 • From start of infusion on Day 1 through Day 60 (2 months).	0.00% 0/19 • From start of infusion on Day 1 through Day 60 (2 months).	4.5% 1/22 • Number of events 1 • From start of infusion on Day 1 through Day 60 (2 months).
Respiratory, thoracic and mediastinal disorders Aspiration	0.00% 0/19 • From start of infusion on Day 1 through Day 60 (2 months).	0.00% 0/19 • From start of infusion on Day 1 through Day 60 (2 months).	4.5% 1/22 • Number of events 1 • From start of infusion on Day 1 through Day 60 (2 months).
Respiratory, thoracic and mediastinal disorders Asthma	0.00% 0/19 • From start of infusion on Day 1 through Day 60 (2 months).	0.00% 0/19 • From start of infusion on Day 1 through Day 60 (2 months).	4.5% 1/22 • Number of events 2 • From start of infusion on Day 1 through Day 60 (2 months).
Respiratory, thoracic and mediastinal disorders Chronic obstructive pulmonary disease	0.00% 0/19 • From start of infusion on Day 1 through Day 60 (2 months).	0.00% 0/19 • From start of infusion on Day 1 through Day 60 (2 months).	4.5% 1/22 • Number of events 1 • From start of infusion on Day 1 through Day 60 (2 months).
Respiratory, thoracic and mediastinal disorders Dyspnoea	0.00% 0/19 • From start of infusion on Day 1 through Day 60 (2 months).	5.3% 1/19 • Number of events 1 • From start of infusion on Day 1 through Day 60 (2 months).	4.5% 1/22 • Number of events 1 • From start of infusion on Day 1 through Day 60 (2 months).
Respiratory, thoracic and mediastinal disorders Stridor	5.3% 1/19 • Number of events 1 • From start of infusion on Day 1 through Day 60 (2 months).	0.00% 0/19 • From start of infusion on Day 1 through Day 60 (2 months).	0.00% 0/22 • From start of infusion on Day 1 through Day 60 (2 months).
Vascular disorders Shock	5.3% 1/19 • Number of events 1 • From start of infusion on Day 1 through Day 60 (2 months).	0.00% 0/19 • From start of infusion on Day 1 through Day 60 (2 months).	0.00% 0/22 • From start of infusion on Day 1 through Day 60 (2 months).
Respiratory, thoracic and mediastinal disorders Acute respiratory distress syndrome	5.3% 1/19 • Number of events 1 • From start of infusion on Day 1 through Day 60 (2 months).	0.00% 0/19 • From start of infusion on Day 1 through Day 60 (2 months).	0.00% 0/22 • From start of infusion on Day 1 through Day 60 (2 months).

Measure	FLU-IGIV High Dose (450 mL) n=19 participants at risk Participants received a single infusion of high dose of FLU-IGIV, administered over approximately 3 hours on Day 1. Administered intravenously at a dose of 450 mL of 65 g/mL FLU-IGIV diluted to 500 mL with normal saline. Participants also received standard of care (SOC) antiviral treatment for flu. FLU-IGIV: Single dose, sterile liquid formulation for IV administration.	FLU-IGIV Low Dose (225 mL) n=19 participants at risk Participants received a single infusion of low dose of FLU-IGIV, administered over approximately 3 hours on Day 1. Administered intravenously at a dose of 225 mL of 65 g/mL FLU-IGIV diluted to 500 mL with normal saline. Participants also received standard of care (SOC) antiviral treatment for flu. FLU-IGIV: Single dose, sterile liquid formulation for IV administration.	Placebo (Normal Saline) n=22 participants at risk Participants received a single infusion of placebo for FLU-IGIV, administered over approximately 3 hours on Day 1. Administered IV as 500 mL of normal saline. Participants also received SOC antiviral treatment for flu. Placebo for FLU-IGIV: Single dose, normal saline solution for IV administration.
Metabolism and nutrition disorders Fluid overload	5.3% 1/19 • Number of events 1 • From start of infusion on Day 1 through Day 60 (2 months).	5.3% 1/19 • Number of events 1 • From start of infusion on Day 1 through Day 60 (2 months).	4.5% 1/22 • Number of events 1 • From start of infusion on Day 1 through Day 60 (2 months).
Metabolism and nutrition disorders Hypomagnesaemia	5.3% 1/19 • Number of events 1 • From start of infusion on Day 1 through Day 60 (2 months).	5.3% 1/19 • Number of events 1 • From start of infusion on Day 1 through Day 60 (2 months).	4.5% 1/22 • Number of events 1 • From start of infusion on Day 1 through Day 60 (2 months).
Metabolism and nutrition disorders Hyperglycaemia	5.3% 1/19 • Number of events 1 • From start of infusion on Day 1 through Day 60 (2 months).	5.3% 1/19 • Number of events 1 • From start of infusion on Day 1 through Day 60 (2 months).	0.00% 0/22 • From start of infusion on Day 1 through Day 60 (2 months).
Metabolism and nutrition disorders Hypoglycaemia	10.5% 2/19 • Number of events 3 • From start of infusion on Day 1 through Day 60 (2 months).	0.00% 0/19 • From start of infusion on Day 1 through Day 60 (2 months).	0.00% 0/22 • From start of infusion on Day 1 through Day 60 (2 months).
Gastrointestinal disorders Constipation	5.3% 1/19 • Number of events 1 • From start of infusion on Day 1 through Day 60 (2 months).	0.00% 0/19 • From start of infusion on Day 1 through Day 60 (2 months).	13.6% 3/22 • Number of events 3 • From start of infusion on Day 1 through Day 60 (2 months).
Gastrointestinal disorders Nausea	0.00% 0/19 • From start of infusion on Day 1 through Day 60 (2 months).	5.3% 1/19 • Number of events 1 • From start of infusion on Day 1 through Day 60 (2 months).	4.5% 1/22 • Number of events 1 • From start of infusion on Day 1 through Day 60 (2 months).
Investigations Transaminases increased	10.5% 2/19 • Number of events 2 • From start of infusion on Day 1 through Day 60 (2 months).	5.3% 1/19 • Number of events 1 • From start of infusion on Day 1 through Day 60 (2 months).	0.00% 0/22 • From start of infusion on Day 1 through Day 60 (2 months).
Investigations White blood cell count increased	0.00% 0/19 • From start of infusion on Day 1 through Day 60 (2 months).	5.3% 1/19 • Number of events 1 • From start of infusion on Day 1 through Day 60 (2 months).	4.5% 1/22 • Number of events 1 • From start of infusion on Day 1 through Day 60 (2 months).
General disorders Physical deconditioning	5.3% 1/19 • Number of events 1 • From start of infusion on Day 1 through Day 60 (2 months).	5.3% 1/19 • Number of events 1 • From start of infusion on Day 1 through Day 60 (2 months).	0.00% 0/22 • From start of infusion on Day 1 through Day 60 (2 months).
General disorders Pyrexia	5.3% 1/19 • Number of events 1 • From start of infusion on Day 1 through Day 60 (2 months).	0.00% 0/19 • From start of infusion on Day 1 through Day 60 (2 months).	4.5% 1/22 • Number of events 1 • From start of infusion on Day 1 through Day 60 (2 months).
Nervous system disorders Headache	0.00% 0/19 • From start of infusion on Day 1 through Day 60 (2 months).	10.5% 2/19 • Number of events 3 • From start of infusion on Day 1 through Day 60 (2 months).	4.5% 1/22 • Number of events 1 • From start of infusion on Day 1 through Day 60 (2 months).
Blood and lymphatic system disorders Leukocytosis	5.3% 1/19 • Number of events 1 • From start of infusion on Day 1 through Day 60 (2 months).	0.00% 0/19 • From start of infusion on Day 1 through Day 60 (2 months).	4.5% 1/22 • Number of events 1 • From start of infusion on Day 1 through Day 60 (2 months).
Infections and infestations Oral candidiasis	0.00% 0/19 • From start of infusion on Day 1 through Day 60 (2 months).	0.00% 0/19 • From start of infusion on Day 1 through Day 60 (2 months).	9.1% 2/22 • Number of events 2 • From start of infusion on Day 1 through Day 60 (2 months).
Respiratory, thoracic and mediastinal disorders Chronic obstructive pulmonary disease	0.00% 0/19 • From start of infusion on Day 1 through Day 60 (2 months).	5.3% 1/19 • Number of events 1 • From start of infusion on Day 1 through Day 60 (2 months).	4.5% 1/22 • Number of events 2 • From start of infusion on Day 1 through Day 60 (2 months).
Skin and subcutaneous tissue disorders Decubitus ulcer	5.3% 1/19 • Number of events 1 • From start of infusion on Day 1 through Day 60 (2 months).	0.00% 0/19 • From start of infusion on Day 1 through Day 60 (2 months).	4.5% 1/22 • Number of events 1 • From start of infusion on Day 1 through Day 60 (2 months).