Evaluating the Safety and Efficacy of Anti-Influenza Intr... | NCT02287467

Name	Class
University of Minnesota	OTHER
International Network for Strategic Initiatives in Global HIV Trials (INSIGHT)	NETWORK

Description Module

Detailed Description

Influenza is responsible for thousands of hospitalizations and deaths each year in the United States and worldwide. One possible new treatment for the flu involves the use of IVIG, a blood product containing antibodies from people who have recovered from the flu or who have had a flu shot. The purpose of this study is to evaluate whether IVIG can reduce the severity and duration of flu in people who are hospitalized with the flu.

The study will enroll participants 18 years and older who are hospitalized with the flu. The study will enroll participants over one or more flu seasons. Regardless of the date of enrollment, each participant will be in the study for about 28 days.

At study entry (Day 0), participants will be randomly assigned to one of two groups (Arms A and B). Participants in both groups will receive standard of care (SOC) treatment for the flu, but those in Arm A will also receive one dose of IVIG and those in Arm B will receive a placebo for IVIG. Both IVIG and placebo will be given intravenously over at least 2 hours.

On Day 0, before receiving IVIG or placebo, participants will undergo a symptoms assessment, blood collection, and a nasopharyngeal (NP) swab to collect a sample of secretions from the nose and throat.

Additional study visits will occur on Days 1, 2, 3, 7, 14, and 28. Depending on the visit, participants may take part in the same study procedures that took place on Day 0. On Days 2, 14, and 28, visits for participants who are no longer hospitalized may be conducted over the phone.

Label	Type	Description	Intervention Names
Arm A: hIVIG	Experimental	Participants will receive a single infusion of intravenous hyperimmune immunoglobulin (hIVIG), administered over approximately 2 hours on Day 0. Participants will also receive SOC treatment for the flu.	Biological: Intravenous hyperimmune immunoglobulin (IVIG)
Arm B: Placebo	Placebo Comparator	Participants will receive a single infusion of placebo for hIVIG, administered over approximately 2 hours on Day 0. Participants will also receive SOC treatment for the flu.	Biological: Placebo for IVIG

Name	Type	Description	Arm Group Labels	Other Names
Intravenous hyperimmune immunoglobulin (IVIG)	Biological	Administered intravenously (IV) at a dose of 0.25 g/kg (up to a maximum of 24.75 g, corresponding to approximately 100 kg actual body weight)

Measure	Description	Time Frame
Number of Patients in Each of 6 Clinical Status Categories on Day 7	This is the primary outcome, a 6-category ordinal outcome ranging from death (worst) to discharged from hospital with resumption of normal activities (best).	Assessed on Day 7

Measure	Description	Time Frame
Number of Patients in Each of 5 Clinical Status Categories on Day 3	5-category ordinal outcome assessed on day 3; clinical status ranges from death (worst) to discharged from the hospital (best).	Assessed on Day 3
Number of Patients in Each of 6 Clinical Status Categories on Day 3

Eligibility Module

Eligibility Criteria

Inclusion Criteria:

Signed informed consent
Locally determined positive influenza test (by polymerase chain reaction [PCR] or other nucleic acid test, or by rapid antigen [Ag]) from a specimen obtained within 2 days prior to randomization
Onset of illness no more than 7 days before randomization, defined as when the participant first experienced at least one respiratory symptom or fever
Hospitalized (or in observation unit) for influenza, with anticipated hospitalization for more than 24 hours. Criteria for hospitalization will be up to the individual treating clinician.
For women of child-bearing potential: willingness to abstain from sexual intercourse or use at least one form of hormonal or barrier contraception through Day 28 of the study
Willingness to have blood and respiratory samples obtained and stored
NEW score greater than or equal to 2 at screening (see the protocol for more information on this criterion)

Exclusion Criteria:

Women who are pregnant or breast-feeding
Strong clinical evidence (in the judgment of the site investigator) that the etiology of illness is primarily bacterial in origin
Prior treatment with any investigational drug therapy within 30 days prior to screening
History of allergic reaction to blood or plasma products (as judged by the site investigator)
Known immunoglobulin A (IgA) deficiency
A pre-existing condition or use of a medication that, in the opinion of the site investigator, may place the participant at a substantially increased risk of thrombosis (e.g., cryoglobulinemia, severe refractory hypertriglyceridemia, or clinically significant monoclonal gammopathy)
Presence of any pre-existing illness that, in the opinion of the site investigator, would place the participant at an unreasonably increased risk through participation in this study
Participants who, in the judgment of the site investigator, will be unlikely to comply with the requirements of this protocol
Medical conditions for which receipt of a 500 mL volume of intravenous fluid may be dangerous to the participant (e.g., decompensated congestive heart failure)
Receiving extracorporeal membrane oxygenation (ECMO)
Suspicion that infection is due to an influenza strain or subtype other than A(H1N1)pdm09, H3N2, or influenza B (e.g., H5N1, H7N9)

Name	Affiliation	Role
Richard T. Davey, Jr., MD	National Institute of Allergy and Infectious Diseases (NIAID)	Study Chair
Eduardo Fernández-Cruz, MD, PhD	Hospital General Universitario Gregorio Marañón	Study Chair
Norman P. Markowitz, MD	The Henry Ford Hospital	Study Chair
Sarah L. Pett, MD, MBBS, DTM, MRCP (UK)	University College, London	Study Chair

Facility	Status	City	State	ZIP	Country	Contacts
UCSD Antiviral Research Center (A VRC)		San Diego	California	92103	United States
Denver Public Health

PubMed Identifier	Type	Citation	Retractions
37289541	Derived	Vanderven HA, Wentworth DN, Han WM, Peck H, Barr IG, Davey RT Jr, Beigel JH, Dwyer DE, Jain MK, Angus B, Brandt CT, Mykietiuk A, Law MG, Neaton JD, Kent SJ; INSIGHT FLU-IVIG Study Group. Understanding the treatment benefit of hyperimmune anti-influenza intravenous immunoglobulin (Flu-IVIG) for severe human influenza. JCI Insight. 2023 Jul 24;8(14):e167464. doi: 10.1172/jci.insight.167464.
31582358

ID	Title	Description
FG000	Arm A: hIVIG	Participants will receive a single infusion of intravenous hyperimmune immunoglobulin (IVIG), administered over approximately 2 hours on Day 0. Participants will also receive standard of care (SOC )treatment for the flu. Intravenous hyperimmune immunoglobulin (IVIG): Administered intravenously (IV) at a dose of 0.25 g/kg (up to a maximum of 24.75 g, corresponding to approximately 100 kg actual body weight)

Type	Includes Protocol	Includes SAP	Includes ICF	Document Label	Document Date	Document Uploaded Date	Document File Name
SAP	No	Yes	No	Statistical Analysis Plan	Aug 17, 2018	Aug 21, 2019

Type

Title

Description

Population Description

Reporting Status

Anticipated Posting Date

Parameter Type

Dispersion Type

Unit of Measure

Calculate Percentage

Time Frame

Units Analyzed

Denominator Units Selected

Arm/Group Information

Denominators

Classes

Analyses

Primary

Number of Patients in Each of 6 Clinical Status Categories on Day 7

This is the primary outcome, a 6-category ordinal outcome ranging from death (worst) to discharged from hospital with resumption of normal activities (best).

All infused participants, using multiple imputation to impute outcome for 4 participants with missing data.

Posted

Count of Participants

Participants

Assessed on Day 7

ID	Title	Description
OG000	Arm A: hIVIG	Participants will receive a single infusion of intravenous hyperimmune immunoglobulin (IVIG), administered over approximately 2 hours on Day 0. Participants will also receive SOC treatment for the flu. Intravenous hyperimmune immunoglobulin (IVIG): Administered intravenously (IV) at a dose of 0.25 g/kg (up to a maximum of 24.75 g, corresponding to approximately 100 kg actual body weight)
OG001	Arm B: Placebo	Participants will receive a single infusion of placebo for IVIG, administered over approximately 2 hours on Day 0. Participants will also receive SOC treatment for the flu. Placebo for IVIG: Administered IV as 500 mL of normal saline

Units	Counts
Participants	OG000156 OG001152

Title

Denominators

Categories

Died

Title	Measurements
	OG0003 OG0012

Hospitalized, in ICU

Title	Measurements
	OG000

Group IDs	Group Description	Statistical Method	Statistical Comment	P-Value	P-Value Comment	Parameter Type	Parameter Value	Dispersion Type	Dispersion Value	Confidence Interval Sides	Confidence Interval %	CI Lower Limit	CI Upper Limit	CI Lower Limit Comment	CI Upper Limit Comment	Estimate Comment	Tested Non-Inferiority	Non-Inferiority Type	Non-Inferiority Comment	Other Analysis Description
OG000 OG001	Odds ratio of being in a better category, as assessed using a proportional odds model. Multiple imputation techniques were used to impute an outcome for 4 patients for whom the outcome was unknown.	Regression, Logistic	Adjusted for baseline clinical status, region, and participation in the pilot study.	.33		Odds Ratio (OR)	1.25			2-Sided	95	0.79	1.97			Odds ratio is hIVIG vs. placebo. A value greater than 1 favors the hIVIG group.		Superiority

Secondary

Number of Patients in Each of 5 Clinical Status Categories on Day 3

5-category ordinal outcome assessed on day 3; clinical status ranges from death (worst) to discharged from the hospital (best).

All participants

Posted

Count of Participants

Participants

Assessed on Day 3

ID	Title	Description
OG000	Arm A: hIVIG	Participants will receive a single infusion of intravenous hyperimmune immunoglobulin (IVIG), administered over approximately 2 hours on Day 0. Participants will also receive SOC treatment for the flu. Intravenous hyperimmune immunoglobulin (IVIG): Administered intravenously (IV) at a dose of 0.25 g/kg (up to a maximum of 24.75 g, corresponding to approximately 100 kg actual body weight)
OG001	Arm B: Placebo	Participants will receive a single infusion of placebo for IVIG, administered over approximately 2 hours on Day 0. Participants will also receive SOC treatment for the flu. Placebo for IVIG: Administered IV as 500 mL of normal saline

Units	Counts
Participants

Secondary

Number of Patients in Each of 6 Clinical Status Categories on Day 3

6-category ordinal outcome evaluated on Day 3; clinical status ranges from death (worst) to discharged from hospital with resumption of normal activities (best).

All participants with clinical data available on Day 3

Posted

Count of Participants

Participants

Measured on Day 3

ID	Title	Description
OG000	Arm A: hIVIG	Participants will receive a single infusion of intravenous hyperimmune immunoglobulin (IVIG), administered over approximately 2 hours on Day 0. Participants will also receive SOC treatment for the flu. Intravenous hyperimmune immunoglobulin (IVIG): Administered intravenously (IV) at a dose of 0.25 g/kg (up to a maximum of 24.75 g, corresponding to approximately 100 kg actual body weight)
OG001	Arm B: Placebo	Participants will receive a single infusion of placebo for IVIG, administered over approximately 2 hours on Day 0. Participants will also receive SOC treatment for the flu. Placebo for IVIG: Administered IV as 500 mL of normal saline

Units	Counts
Participants

Secondary

Number of Patients With a Favorable Outcome on Day 7

Sliding dichotomy defined as non-ICU hospitalization or discharge if enrolled from ICU, and discharge if enrolled from the general ward.

Posted

Count of Participants

Participants

Assessed on Day 7

ID	Title	Description
OG000	Arm A: hIVIG	Participants will receive a single infusion of intravenous hyperimmune immunoglobulin (IVIG), administered over approximately 2 hours on Day 0. Participants will also receive SOC treatment for the flu. Intravenous hyperimmune immunoglobulin (IVIG): Administered intravenously (IV) at a dose of 0.25 g/kg (up to a maximum of 24.75 g, corresponding to approximately 100 kg actual body weight)
OG001	Arm B: Placebo	Participants will receive a single infusion of placebo for IVIG, administered over approximately 2 hours on Day 0. Participants will also receive SOC treatment for the flu. Placebo for IVIG: Administered IV as 500 mL of normal saline

Units	Counts
Participants	OG000

Secondary

Hospital Discharge

Number of participants alive and discharged from the hospital

All participants

Posted

Count of Participants

Participants

Measured through Day 7

ID	Title	Description
OG000	Arm A: hIVIG	Participants will receive a single infusion of intravenous hyperimmune immunoglobulin (IVIG), administered over approximately 2 hours on Day 0. Participants will also receive SOC treatment for the flu. Intravenous hyperimmune immunoglobulin (IVIG): Administered intravenously (IV) at a dose of 0.25 g/kg (up to a maximum of 24.75 g, corresponding to approximately 100 kg actual body weight)
OG001	Arm B: Placebo	Participants will receive a single infusion of placebo for IVIG (saline), administered over approximately 2 hours on Day 0. Participants will also receive SOC treatment for the flu. Placebo for IVIG: Administered IV as 500 mL of normal saline

Units	Counts
Participants	OG000

Secondary

Mortality

Number of participants dying through day 28.

all participants

Posted

Count of Participants

Participants

Measured through day 28

ID	Title	Description
OG000	Arm A: hIVIG	Participants will receive a single infusion of intravenous hyperimmune immunoglobulin (hIVIG), administered over approximately 2 hours on Day 0. Participants will also receive SOC treatment for the flu. Intravenous hyperimmune immunoglobulin (IVIG): Administered intravenously (IV) at a dose of 0.25 g/kg (up to a maximum of 24.75 g, corresponding to approximately 100 kg actual body weight)
OG001	Arm B: Placebo	Participants will receive a single infusion of placebo for hIVIG, administered over approximately 2 hours on Day 0. Participants will also receive SOC treatment for the flu. Placebo for IVIG: Administered IV as 500 mL of normal saline

Units	Counts
Participants	OG000

Secondary

Number of Patients Alive and Out of Hospital

Number and percent alive and out of hospital on day 28

All participants with vital status known on Day 28

Posted

Count of Participants

Participants

Measured through Day 28

ID	Title	Description
OG000	Arm A: hIVIG	Participants will receive a single infusion of intravenous hyperimmune immunoglobulin (IVIG), administered over approximately 2 hours on Day 0. Participants will also receive SOC treatment for the flu. Intravenous hyperimmune immunoglobulin (IVIG): Administered intravenously (IV) at a dose of 0.25 g/kg (up to a maximum of 24.75 g, corresponding to approximately 100 kg actual body weight)
OG001	Arm B: Placebo	Participants will receive a single infusion of placebo for IVIG (saline), administered over approximately 2 hours on Day 0. Participants will also receive SOC treatment for the flu. Placebo for IVIG: Administered IV as 500 mL of normal saline

Units	Counts
Participants

Secondary

Change in Viral Load

Change in nasopharyngeal viral load from baseline to day 3

Participants with viral load results at both baseline and day 3. Participants with undetectable viral load results at baseline are excluded.

Posted

Mean

Standard Error

log10 RNA

Day 3

ID	Title	Description
OG000	Arm A: hIVIG	Participants will receive a single infusion of intravenous hyperimmune immunoglobulin (hIVIG), administered over approximately 2 hours on Day 0. Participants will also receive SOC treatment for the flu. Intravenous hyperimmune immunoglobulin (IVIG): Administered intravenously (IV) at a dose of 0.25 g/kg (up to a maximum of 24.75 g, corresponding to approximately 100 kg actual body weight)
OG001	Arm B: Placebo	Participants will receive a single infusion of placebo for hIVIG, administered over approximately 2 hours on Day 0. Participants will also receive SOC treatment for the flu. Placebo for IVIG: Administered IV as 500 mL of normal saline

Units	Counts
Participants

Secondary

Death or Re-hospitalization

Number and percent of participants who died or were re-hospitalized after initial discharge

all participants with data

Posted

Count of Participants

Participants

Day 28

ID	Title	Description
OG000	Arm A: hIVIG	Participants will receive a single infusion of intravenous hyperimmune immunoglobulin (hIVIG), administered over approximately 2 hours on Day 0. Participants will also receive SOC treatment for the flu. Intravenous hyperimmune immunoglobulin (IVIG): Administered intravenously (IV) at a dose of 0.25 g/kg (up to a maximum of 24.75 g, corresponding to approximately 100 kg actual body weight)
OG001	Arm B: Placebo	Participants will receive a single infusion of placebo for IVIG (saline), administered over approximately 2 hours on Day 0. Participants will also receive SOC treatment for the flu. Placebo for IVIG: Administered IV as 500 mL of normal saline

Units	Counts
Participants

Secondary

Percent of Participants Developing Complications

Number and percent of participants developing respiratory distress syndrome, acute renal failure, sepsis, pneumonia, enteritis, or bronchitis

all participants

Posted

Count of Participants

Participants

Measured through Day 28

ID	Title	Description
OG000	Arm A: hIVIG	Participants will receive a single infusion of intravenous hyperimmune immunoglobulin (IVIG), administered over approximately 2 hours on Day 0. Participants will also receive SOC treatment for the flu. Intravenous hyperimmune immunoglobulin (IVIG): Administered intravenously (IV) at a dose of 0.25 g/kg (up to a maximum of 24.75 g, corresponding to approximately 100 kg actual body weight)
OG001	Arm B: Placebo	Participants will receive a single infusion of placebo for IVIG (saline), administered over approximately 2 hours on Day 0. Participants will also receive SOC treatment for the flu. Placebo for IVIG: Administered IV as 500 mL of normal saline

Units	Counts
Participants

Secondary

Number of Patients in Each of 6 Clinical Status Categories on Day 14

6-category ordinal outcome measured on day 14

participants with observed data on day 14

Posted

Count of Participants

Participants

Measured on day 14

ID	Title	Description
OG000	Arm A: hIVIG	Participants will receive a single infusion of intravenous hyperimmune immunoglobulin (IVIG), administered over approximately 2 hours on Day 0. Participants will also receive SOC treatment for the flu. Intravenous hyperimmune immunoglobulin (IVIG): Administered intravenously (IV) at a dose of 0.25 g/kg (up to a maximum of 24.75 g, corresponding to approximately 100 kg actual body weight)
OG001	Arm B: Placebo	Participants will receive a single infusion of placebo for IVIG (saline), administered over approximately 2 hours on Day 0. Participants will also receive SOC treatment for the flu. Placebo for IVIG: Administered IV as 500 mL of normal saline

Units	Counts
Participants

Secondary

Number of Patients Alive and Out of Hospital on Day 14

Number and percentage of participants alive and out of the hospital on Day 14

all participants

Posted

Count of Participants

Participants

day 14

ID	Title	Description
OG000	Arm A: hIVIG	Participants will receive a single infusion of intravenous hyperimmune immunoglobulin (IVIG), administered over approximately 2 hours on Day 0. Participants will also receive SOC treatment for the flu. Intravenous hyperimmune immunoglobulin (IVIG): Administered intravenously (IV) at a dose of 0.25 g/kg (up to a maximum of 24.75 g, corresponding to approximately 100 kg actual body weight)
OG001	Arm B: Placebo	Participants will receive a single infusion of placebo for IVIG (saline), administered over approximately 2 hours on Day 0. Participants will also receive SOC treatment for the flu. Placebo for IVIG: Administered IV as 500 mL of normal saline

Units	Counts
Participants

Secondary

Resumption of Normal Activities by Day 14

Participants reporting resumption of normal daily activities by Day 14

Participants with observed data

Posted

Count of Participants

Participants

day 14

ID	Title	Description
OG000	Arm A: hIVIG	Participants will receive a single infusion of intravenous hyperimmune immunoglobulin (hIVIG), administered over approximately 2 hours on Day 0. Participants will also receive SOC treatment for the flu. Intravenous hyperimmune immunoglobulin (IVIG): Administered intravenously (IV) at a dose of 0.25 g/kg (up to a maximum of 24.75 g, corresponding to approximately 100 kg actual body weight)
OG001	Arm B: Placebo	Participants will receive a single infusion of placebo for hIVIG, administered over approximately 2 hours on Day 0. Participants will also receive SOC treatment for the flu. Placebo for IVIG: Administered IV as 500 mL of normal saline

Units	Counts
Participants

Secondary

Number of Patients in Each of 6 Clinical Status Categories on Day 28

6-category ordinal outcome corresponding to clinical status on day 28

participants with observed data

Posted

Count of Participants

Participants

day 28

ID	Title	Description
OG000	Arm A: hIVIG	Participants will receive a single infusion of intravenous hyperimmune immunoglobulin (IVIG), administered over approximately 2 hours on Day 0. Participants will also receive SOC treatment for the flu. Intravenous hyperimmune immunoglobulin (IVIG): Administered intravenously (IV) at a dose of 0.25 g/kg (up to a maximum of 24.75 g, corresponding to approximately 100 kg actual body weight)
OG001	Arm B: Placebo	Participants will receive a single infusion of placebo for IVIG (saline), administered over approximately 2 hours on Day 0. Participants will also receive SOC treatment for the flu. Placebo for IVIG: Administered IV as 500 mL of normal saline

Units	Counts
Participants

Secondary

Number of Influenza A-Infected Patients in Each of 6 Clinical Status Categories on Day 7

Primary 6-category ordinal outcome for participants infected with Influenza A

all participants infected with influenza A

Posted

Count of Participants

Participants

Day 7

ID	Title	Description
OG000	Arm A: hIVIG	Participants will receive a single infusion of intravenous hyperimmune immunoglobulin (IVIG), administered over approximately 2 hours on Day 0. Participants will also receive SOC treatment for the flu. Intravenous hyperimmune immunoglobulin (IVIG): Administered intravenously (IV) at a dose of 0.25 g/kg (up to a maximum of 24.75 g, corresponding to approximately 100 kg actual body weight)
OG001	Arm B: Placebo	Participants will receive a single infusion of placebo for IVIG (saline), administered over approximately 2 hours on Day 0. Participants will also receive SOC treatment for the flu. Placebo for IVIG: Administered IV as 500 mL of normal saline

Units	Counts
Participants

Secondary

Number of Influenza B-Infected Patients in Each of 6 Clinical Status Categories on Day 7

Primary 6-category ordinal outcome for subgroup of participants infected with influenza B

Posted

Count of Participants

Participants

Day 7

ID	Title	Description
OG000	Arm A: hIVIG	Participants will receive a single infusion of intravenous hyperimmune immunoglobulin (IVIG), administered over approximately 2 hours on Day 0. Participants will also receive SOC treatment for the flu. Intravenous hyperimmune immunoglobulin (IVIG): Administered intravenously (IV) at a dose of 0.25 g/kg (up to a maximum of 24.75 g, corresponding to approximately 100 kg actual body weight)
OG001	Arm B: Placebo	Participants will receive a single infusion of placebo for IVIG (saline), administered over approximately 2 hours on Day 0. Participants will also receive SOC treatment for the flu. Placebo for IVIG: Administered IV as 500 mL of normal saline

Units	Counts
Participants	OG000

Secondary

pH1N1 Titers at Day 7

pH1N1 hemagglutination inhibition assay (HAI) titers among participants infected with pH1N1 using A/Cal/2009 as reference virus

participants infected with pH1N1 with HAI titers measured at day 7

Posted

Mean

Standard Deviation

titer

Day 7

ID	Title	Description
OG000	Arm A: hIVIG	Participants will receive a single infusion of intravenous hyperimmune immunoglobulin (IVIG), administered over approximately 2 hours on Day 0. Participants will also receive SOC treatment for the flu. Intravenous hyperimmune immunoglobulin (IVIG): Administered intravenously (IV) at a dose of 0.25 g/kg (up to a maximum of 24.75 g, corresponding to approximately 100 kg actual body weight)
OG001	Arm B: Placebo	Participants will receive a single infusion of placebo for IVIG (saline), administered over approximately 2 hours on Day 0. Participants will also receive SOC treatment for the flu. Placebo for IVIG: Administered IV as 500 mL of normal saline

Units	Counts
Participants

Secondary

H3N2 Titers at Day 7

H3N2 HAI titers among participants infected with H3N2 using A/HongKong/2014 as reference virus

participants infected with H3N2 with HAI titers measured at day 7

Posted

Mean

Standard Deviation

titer

Day 7

ID	Title	Description
OG000	Arm A: hIVIG	Participants will receive a single infusion of intravenous hyperimmune immunoglobulin (IVIG), administered over approximately 2 hours on Day 0. Participants will also receive SOC treatment for the flu. Intravenous hyperimmune immunoglobulin (IVIG): Administered intravenously (IV) at a dose of 0.25 g/kg (up to a maximum of 24.75 g, corresponding to approximately 100 kg actual body weight)
OG001	Arm B: Placebo	Participants will receive a single infusion of placebo for IVIG (saline), administered over approximately 2 hours on Day 0. Participants will also receive SOC treatment for the flu. Placebo for IVIG: Administered IV as 500 mL of normal saline

Units	Counts
Participants

Secondary

Influenza B Titers at Day 7

Flu B HAI titers among participants infected with influenza B using B/Phuket/2013 as reference virus

participants infected with influenza B with HAI titers measured at day 7

Posted

Mean

Standard Deviation

titer

Day 7

ID	Title	Description
OG000	Arm A: hIVIG	Participants will receive a single infusion of intravenous hyperimmune immunoglobulin (IVIG), administered over approximately 2 hours on Day 0. Participants will also receive SOC treatment for the flu. Intravenous hyperimmune immunoglobulin (IVIG): Administered intravenously (IV) at a dose of 0.25 g/kg (up to a maximum of 24.75 g, corresponding to approximately 100 kg actual body weight)
OG001	Arm B: Placebo	Participants will receive a single infusion of placebo for IVIG (saline), administered over approximately 2 hours on Day 0. Participants will also receive SOC treatment for the flu. Placebo for IVIG: Administered IV as 500 mL of normal saline

Units	Counts
Participants

Serious Adverse Events

Term	Organ System	Source Vocabulary	Assessment Type	Statistical Information
Anaemia	Blood and lymphatic system disorders	MedDRA 21.0	Systematic Assessment	EG0001 events1 affected156 at risk EG0010 events0 affected152 at risk
Leukopenia	Blood and lymphatic system disorders	MedDRA 21.0	Systematic Assessment	EG0000 events0 affected156 at risk EG0011 events1 affected152 at risk
Acute myocardial infarction	Cardiac disorders	MedDRA 21.0	Systematic Assessment	EG0002 events2 affected156 at risk EG0010 events0 affected152 at risk
Atrial fibrillation	Cardiac disorders	MedDRA 21.0	Systematic Assessment	EG0000 events0 affected156 at risk EG0012 events2 affected152 at risk
Cardiac failure	Cardiac disorders	MedDRA 21.0	Systematic Assessment	EG0000 events0 affected156 at risk EG0011 events1 affected152 at risk
Internal hernia	Gastrointestinal disorders	MedDRA 21.0	Systematic Assessment	EG0000 events0 affected156 at risk EG0011 events1 affected152 at risk
Nausea	Gastrointestinal disorders	MedDRA 21.0	Systematic Assessment	EG0001 events1 affected156 at risk EG0010 events0 affected152 at risk
Retroperitoneal haemorrhage	Gastrointestinal disorders	MedDRA 21.0	Systematic Assessment	EG0000 events0 affected156 at risk EG0011 events1 affected152 at risk
Vomiting	Gastrointestinal disorders	MedDRA 21.0	Systematic Assessment	EG0001 events1 affected156 at risk EG0010 events0 affected152 at risk
Breast abscess	Infections and infestations	MedDRA 21.0	Systematic Assessment	EG0000 events0 affected156 at risk EG0011 events1 affected152 at risk
Enterococcal bacteraemia	Infections and infestations	MedDRA 21.0	Systematic Assessment	EG0001 events1 affected156 at risk EG0010 events0 affected152 at risk
Influenza	Infections and infestations	MedDRA 21.0	Systematic Assessment	EG0002 events2 affected156 at risk EG0010 events0 affected152 at risk
Pneumonia	Infections and infestations	MedDRA 21.0	Systematic Assessment	EG0000 events0 affected156 at risk EG0011 events1 affected152 at risk
Pneumonia bacterial	Infections and infestations	MedDRA 21.0	Systematic Assessment	EG0001 events1 affected156 at risk EG0011 events1 affected152 at risk
Pneumonia fungal	Infections and infestations	MedDRA 21.0	Systematic Assessment	EG0000 events0 affected156 at risk EG0011 events1 affected152 at risk
Pyelonephritis	Infections and infestations	MedDRA 21.0	Systematic Assessment	EG0001 events1 affected156 at risk EG0010 events0 affected152 at risk
Sepsis	Infections and infestations	MedDRA 21.0	Systematic Assessment	EG0001 events1 affected156 at risk EG0011 events1 affected152 at risk
Septic shock	Infections and infestations	MedDRA 21.0	Systematic Assessment	EG0000 events0 affected156 at risk EG0011 events1 affected152 at risk
Post lumbar puncture syndrome	Injury, poisoning and procedural complications	MedDRA 21.0	Systematic Assessment	EG0000 events0 affected156 at risk EG0011 events1 affected152 at risk
Rib fracture	Injury, poisoning and procedural complications	MedDRA 21.0	Systematic Assessment	EG0001 events1 affected156 at risk EG0010 events0 affected152 at risk
Road traffic accident	Injury, poisoning and procedural complications	MedDRA 21.0	Systematic Assessment	EG0000 events0 affected156 at risk EG0011 events1 affected152 at risk
Blood creatinine increased	Investigations	MedDRA 21.0	Systematic Assessment	EG0001 events1 affected156 at risk EG0010 events0 affected152 at risk
Dehydration	Metabolism and nutrition disorders	MedDRA 21.0	Systematic Assessment	EG0001 events1 affected156 at risk EG0011 events1 affected152 at risk
Fluid overload	Metabolism and nutrition disorders	MedDRA 21.0	Systematic Assessment	EG0002 events1 affected156 at risk EG0010 events0 affected152 at risk
Hyperkalaemia	Metabolism and nutrition disorders	MedDRA 21.0	Systematic Assessment	EG0001 events1 affected156 at risk EG0010 events0 affected152 at risk
Hypoglycaemia	Metabolism and nutrition disorders	MedDRA 21.0	Systematic Assessment	EG0001 events1 affected156 at risk EG0010 events0 affected152 at risk
Rhabdomyolysis	Musculoskeletal and connective tissue disorders	MedDRA 21.0	Systematic Assessment	EG0001 events1 affected156 at risk EG0010 events0 affected152 at risk
Dizziness	Nervous system disorders	MedDRA 21.0	Systematic Assessment	EG0001 events1 affected156 at risk EG0010 events0 affected152 at risk
Haemorrhage intracranial	Nervous system disorders	MedDRA 21.0	Systematic Assessment	EG0001 events1 affected156 at risk EG0010 events0 affected152 at risk
Headache	Nervous system disorders	MedDRA 21.0	Systematic Assessment	EG0000 events0 affected156 at risk EG0011 events1 affected152 at risk
Vocal cord paresis	Nervous system disorders	MedDRA 21.0	Systematic Assessment	EG0000 events0 affected156 at risk EG0011 events1 affected152 at risk
Dysthymic disorders	Psychiatric disorders	MedDRA 21.0	Systematic Assessment	EG0001 events1 affected156 at risk EG0010 events0 affected152 at risk
Acute kidney injury	Renal and urinary disorders	MedDRA 21.0	Systematic Assessment	EG0000 events0 affected156 at risk EG0012 events2 affected152 at risk
Renal failure	Renal and urinary disorders	MedDRA 21.0	Systematic Assessment	EG0000 events0 affected156 at risk EG0011 events1 affected152 at risk
Acute respiratory distress syndrome	Respiratory, thoracic and mediastinal disorders	MedDRA 21.0	Systematic Assessment	EG0001 events1 affected156 at risk EG0010 events0 affected152 at risk
Acute respiratory failure	Respiratory, thoracic and mediastinal disorders	MedDRA 21.0	Systematic Assessment	EG0000 events0 affected156 at risk EG0011 events1 affected152 at risk
Aspiration	Respiratory, thoracic and mediastinal disorders	MedDRA 21.0	Systematic Assessment	EG0001 events1 affected156 at risk EG0010 events0 affected152 at risk
Asthma	Respiratory, thoracic and mediastinal disorders	MedDRA 21.0	Systematic Assessment	EG0001 events1 affected156 at risk EG0010 events0 affected152 at risk
Bronchospasm	Respiratory, thoracic and mediastinal disorders	MedDRA 21.0	Systematic Assessment	EG0000 events0 affected156 at risk EG0011 events1 affected152 at risk
Chronic obstructive pulmonary disease	Respiratory, thoracic and mediastinal disorders	MedDRA 21.0	Systematic Assessment	EG0001 events1 affected156 at risk EG0018 events5 affected152 at risk
Dyspnoea	Respiratory, thoracic and mediastinal disorders	MedDRA 21.0	Systematic Assessment	EG0001 events1 affected156 at risk EG0011 events1 affected152 at risk
Hypoxia	Respiratory, thoracic and mediastinal disorders	MedDRA 21.0	Systematic Assessment	EG0001 events1 affected156 at risk EG0010 events0 affected152 at risk
Pleural effusion	Respiratory, thoracic and mediastinal disorders	MedDRA 21.0	Systematic Assessment	EG0000 events0 affected156 at risk EG0011 events1 affected152 at risk
Pneumonia aspiration	Respiratory, thoracic and mediastinal disorders	MedDRA 21.0	Systematic Assessment	EG0001 events1 affected156 at risk EG0010 events0 affected152 at risk
Pulmonary embolism	Respiratory, thoracic and mediastinal disorders	MedDRA 21.0	Systematic Assessment	EG0002 events2 affected156 at risk EG0010 events0 affected152 at risk
Pulmonary oedema	Respiratory, thoracic and mediastinal disorders	MedDRA 21.0	Systematic Assessment	EG0001 events1 affected156 at risk EG0010 events0 affected152 at risk
Respiratory distress	Respiratory, thoracic and mediastinal disorders	MedDRA 21.0	Systematic Assessment	EG0000 events0 affected156 at risk EG0011 events1 affected152 at risk
Respiratory failure	Respiratory, thoracic and mediastinal disorders	MedDRA 21.0	Systematic Assessment	EG0001 events1 affected156 at risk EG0012 events2 affected152 at risk
Diabetic foot	Skin and subcutaneous tissue disorders	MedDRA 21.0	Systematic Assessment	EG0000 events0 affected156 at risk EG0011 events1 affected152 at risk
Hypotension	Vascular disorders	MedDRA 21.0	Systematic Assessment	EG0000 events0 affected156 at risk EG0011 events1 affected152 at risk
Thrombophlebitis superficial	Vascular disorders	MedDRA 21.0	Systematic Assessment	EG0000 events0 affected156 at risk EG0011 events1 affected152 at risk

ID	Term
D007074	Immunoglobulin G
D007132	Immunoglobulin Isotypes
D000906	Antibodies
D007136	Immunoglobulins
D007162	Immunoproteins
D001798	Blood Proteins
D011506	Proteins
D000602	Amino Acids, Peptides, and Proteins
D012712	Serum Globulins
D005916	Globulins

ID	Title	Description
BG000	Arm A: hIVIG	Participants will receive a single infusion of intravenous hyperimmune immunoglobulin (hIVIG), administered over approximately 2 hours on Day 0. Participants will also receive SOC treatment for the flu. Intravenous hyperimmune immunoglobulin (IVIG): Administered intravenously (IV) at a dose of 0.25 g/kg (up to a maximum of 24.75 g, corresponding to approximately 100 kg actual body weight)
BG001	Arm B: Placebo	Participants will receive a single infusion of placebo for IVIG (saline), administered over approximately 2 hours on Day 0. Participants will also receive SOC treatment for the flu. Placebo for IVIG: Administered IV as 500 mL of normal saline
BG002	Total	Total of all reporting groups

ID	Title	Description	Deaths (Affected)	Deaths (At Risk)	Serious Events (Affected)	Serious Events (At Risk)	Other Events (Affected)	Other Events (At Risk)
EG000	Arm A: hIVIG	Participants will receive a single infusion of intravenous hyperimmune immunoglobulin (IVIG), administered over approximately 2 hours on Day 0. Participants will also receive SOC treatment for the flu. Intravenous hyperimmune immunoglobulin (IVIG): Administered intravenously (IV) at a dose of 0.25 g/kg (up to a maximum of 24.75 g, corresponding to approximately 100 kg actual body weight)	6	156	25	156	13	156
EG001	Arm B: Placebo	Participants will receive a single infusion of placebo for IVIG (saline), administered over approximately 2 hours on Day 0. Participants will also receive SOC treatment for the flu. Placebo for IVIG: Administered IV as 500 mL of normal saline	5	152	26	152	14	152