Influenza A H1N1, Influenza A H3N2
Conditions
Keywords
influenza A, hospitalized, H1N1, H3N2, human flu, respiratory tract infection, serious illness, flu
Brief summary
Influenza, or the flu, is an infectious respiratory disease that can range in severity from mild to severe to even death. This study aims to evaluate a treatment for people who are hospitalized with the flu. The study is looking to see if antibodies collected from people who have recovered from the seasonal flu or who have had the seasonal flu shot can be used safely as a study drug to treat hospitalized patients with severe flu infections. Also, this study will help to find the right dose for this study drug for treatment of severe flu in hospitalized patients. Overall, this study will evaluate if the hospitalized patients receiving standard of care along with the study drug get better more quickly than those treated with standard of care and placebo. The study drug that contains antibodies against the flu is called anti-influenza immunoglobulin intravenous (FLU-IGIV).
Interventions
BIOLOGICALFLU-IGIV
Single dose, sterile liquid formulation for IV administration.
OTHERPlacebo for FLU-IGIV
Single dose, normal saline solution for IV administration.
Sponsors
Emergent BioSolutions
Study design
Allocation
RANDOMIZED
Intervention model
PARALLEL
Primary purpose
TREATMENT
Masking
QUADRUPLE (Subject, Caregiver, Investigator, Outcomes Assessor)
Intervention model description
Staggered enrollment for the first 9 subjects, then parallel low and high dose treatment with a placebo group
Eligibility
Sex/Gender
ALL
Age
18 Years to No maximum
Healthy volunteers
No
Inclusion criteria
* Provision of voluntary informed consent in writing by patient, or legally authorized representative. * Age ≥ 18 years of age. * Locally determined positive influenza A infection (Rapid Antigen (Ag) Test or PCR) from a specimen obtained within 2 days prior to randomization. * Onset of symptoms ≤ 6 days before randomization, defined as when the patient first experienced at least one respiratory symptom or fever. * Hospitalized (or in observation unit) with influenza, with anticipated hospitalization for more than 24 hours and will be/already are receiving antiviral SOC. * Experiencing ≥ 1 respiratory symptom (ex. cough, sore throat, nasal congestion) and ≥ 1 constitutional symptom (ex. headache, myalgia, feverishness or fatigue). * For women of child-bearing potential: willingness to abstain from sexual intercourse or use at least 1 form of hormonal or barrier contraception through Day 60 of the study. * Willingness to have blood and respiratory samples obtained and stored. * National Early Warning Score (NEW score) ≥ 3 at screening.
Exclusion criteria
* Use of any investigational product within the past 30 days prior to screening. * History of hypersensitivity to blood or plasma products (as judged by the site investigator). * History of allergy to latex or rubber. * Known medical history of IgA deficiency. * Pregnancy or lactation. * Medical conditions for which receipt of a 500 mL volume of intravenous fluid may be dangerous to the patient (e.g. decompensated congestive heart failure), based on investigator's medical opinion with careful consideration of lab results. * Liver function: liver function test (LFT) \> 2.5 times upper limit of normal (ULN). * Renal Function: glomerular filtration rate (GFR) \< 60 mL/min/1.73 m2 (age and sex adjusted). * A pre-existing condition or use of a medication that, in the opinion of the site investigator, may place the individual at a substantially increased risk of thrombosis (e.g. cryoglobulinemia, severe refractory hypertriglyceridemia, or clinically significant monoclonal gammopathy). * An opinion of the investigator that it would be unwise to allow participation of the patient in the study (the reason for exclusion of the patient must be documented). * Receiving extracorporeal membrane oxygenation (ECMO). * Anticipated life expectancy of \< 90 days. * Confirmed bacterial pneumonia or any concurrent respiratory viral infection that is not influenza A (ex. respiratory syncytial virus (RSV) infection).
Design outcomes
Primary
| Measure | Time frame | Description |
|---|---|---|
| Frequency Counts and Percentage of Subjects With Adverse Events | Measured through Day 60 | Frequency counts and percentage of subjects with Adverse Events by severity |
| Area Under the Plasma Concentration Curve [AUC] From Time 0 to 48 Hours Post-dose by Hemagglutinin Inhibition Assay | Measured through 48 Hours post-dose | 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. |
| Maximum Plasma Concentration [Cmax] Reported as a Titer for Hemagglutinin Inhibition Assay | 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. |
| Time Cmax is Observed [Tmax] by Hemagglutinin Inhibition Assay | 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 \[Vz\]. |
Secondary
| Measure | Time frame | Description |
|---|---|---|
| Ordinal Scale Subject Distribution Reflecting Clinical Status | At Day 8 post-dose | 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. |
Countries
Canada, Puerto Rico, Spain, United States
Participant flow
Recruitment details
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.
Participants by arm
| Arm | Count |
|---|---|
| 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. | 21 |
| 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. | 20 |
| 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. | 24 |
| Total | 65 |
Baseline characteristics
| Characteristic | FLU-IGIV High Dose (450 mL) | FLU-IGIV Low Dose (225 mL) | Placebo (500 mL Normal Saline) | Total |
|---|---|---|---|---|
| Age, Continuous | 48.4 years STANDARD_DEVIATION 16.2 | 49.1 years STANDARD_DEVIATION 14.2 | 59.5 years STANDARD_DEVIATION 14.1 | 52.7 years STANDARD_DEVIATION 15.5 |
| Age, Customized 18-54 | 13 Participants | 11 Participants | 8 Participants | 32 Participants |
| Age, Customized 55 and over | 8 Participants | 9 Participants | 16 Participants | 33 Participants |
| Ethnicity (NIH/OMB) Hispanic or Latino | 3 Participants | 4 Participants | 3 Participants | 10 Participants |
| Ethnicity (NIH/OMB) Not Hispanic or Latino | 18 Participants | 16 Participants | 21 Participants | 55 Participants |
| Ethnicity (NIH/OMB) Unknown or Not Reported | 0 Participants | 0 Participants | 0 Participants | 0 Participants |
| Race (NIH/OMB) American Indian or Alaska Native | 0 Participants | 0 Participants | 0 Participants | 0 Participants |
| Race (NIH/OMB) Asian | 0 Participants | 0 Participants | 0 Participants | 0 Participants |
| Race (NIH/OMB) Black or African American | 9 Participants | 9 Participants | 14 Participants | 32 Participants |
| Race (NIH/OMB) More than one race | 0 Participants | 0 Participants | 0 Participants | 0 Participants |
| Race (NIH/OMB) Native Hawaiian or Other Pacific Islander | 0 Participants | 0 Participants | 0 Participants | 0 Participants |
| Race (NIH/OMB) Unknown or Not Reported | 0 Participants | 0 Participants | 0 Participants | 0 Participants |
| Race (NIH/OMB) White | 12 Participants | 11 Participants | 10 Participants | 33 Participants |
| Region of Enrollment North America | 20 Participants | 20 Participants | 22 Participants | 62 Participants |
| Region of Enrollment Spain | 1 Participants | 0 Participants | 2 Participants | 3 Participants |
| Sex: Female, Male Female | 12 Participants | 10 Participants | 12 Participants | 34 Participants |
| Sex: Female, Male Male | 9 Participants | 10 Participants | 12 Participants | 31 Participants |
Adverse events
| Event type | EG000 affected / at risk | EG001 affected / at risk | EG002 affected / at risk |
|---|---|---|---|
| deaths Total, all-cause mortality | 0 / 19 | 0 / 19 | 0 / 22 |
| other Total, other adverse events | 5 / 19 | 6 / 19 | 8 / 22 |
| serious Total, serious adverse events | 1 / 19 | 2 / 19 | 5 / 22 |
Outcome results
Primary
Area Under the Plasma Concentration Curve [AUC] From Time 0 to 48 Hours Post-dose by Hemagglutinin Inhibition Assay
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.
Time frame: 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.
| Arm | Measure | Group | Value (GEOMETRIC_MEAN) | Dispersion |
|---|---|---|---|---|
| FLU-IGIV High Dose (450 mL) | 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 |
| FLU-IGIV High Dose (450 mL) | 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 |
| FLU-IGIV High Dose (450 mL) | 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 |
| FLU-IGIV High Dose (450 mL) | 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 |
| FLU-IGIV Low Dose (225 mL) | Area Under the Plasma Concentration Curve [AUC] From Time 0 to 48 Hours Post-dose by Hemagglutinin Inhibition Assay | H3N2 Singapore | 4431.6 titer*hours/mL | Geometric Coefficient of Variation 45.3 |
| FLU-IGIV Low Dose (225 mL) | Area Under the Plasma Concentration Curve [AUC] From Time 0 to 48 Hours Post-dose by Hemagglutinin Inhibition Assay | H3N2 Hong Kong | 7054.8 titer*hours/mL | Geometric Coefficient of Variation 39.1 |
| FLU-IGIV Low Dose (225 mL) | Area Under the Plasma Concentration Curve [AUC] From Time 0 to 48 Hours Post-dose by Hemagglutinin Inhibition Assay | H1N1 California | 4955.4 titer*hours/mL | Geometric Coefficient of Variation 87.8 |
| FLU-IGIV Low Dose (225 mL) | Area Under the Plasma Concentration Curve [AUC] From Time 0 to 48 Hours Post-dose by Hemagglutinin Inhibition Assay | H1N1 Michigan | 3446.3 titer*hours/mL | Geometric Coefficient of Variation 123.2 |
| Placebo (500 mL Normal Saline) | Area Under the Plasma Concentration Curve [AUC] From Time 0 to 48 Hours Post-dose by Hemagglutinin Inhibition Assay | H1N1 California | 1973.1 titer*hours/mL | Geometric Coefficient of Variation 85 |
| Placebo (500 mL Normal Saline) | Area Under the Plasma Concentration Curve [AUC] From Time 0 to 48 Hours Post-dose by Hemagglutinin Inhibition Assay | H1N1 Michigan | 1630.2 titer*hours/mL | Geometric Coefficient of Variation 106.4 |
| Placebo (500 mL Normal Saline) | Area Under the Plasma Concentration Curve [AUC] From Time 0 to 48 Hours Post-dose by Hemagglutinin Inhibition Assay | H3N2 Hong Kong | 3682.5 titer*hours/mL | Geometric Coefficient of Variation 126.7 |
| Placebo (500 mL Normal Saline) | Area Under the Plasma Concentration Curve [AUC] From Time 0 to 48 Hours Post-dose by Hemagglutinin Inhibition Assay | H3N2 Singapore | 2511.3 titer*hours/mL | Geometric Coefficient of Variation 219.6 |
Primary
Frequency Counts and Percentage of Subjects With Adverse Events
Frequency counts and percentage of subjects with Adverse Events by severity
Time frame: 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.
| Arm | Measure | Group | Value (COUNT_OF_PARTICIPANTS) |
|---|---|---|---|
| FLU-IGIV High Dose (450 mL) | Frequency Counts and Percentage of Subjects With Adverse Events | Mild | 6 Participants |
| FLU-IGIV High Dose (450 mL) | Frequency Counts and Percentage of Subjects With Adverse Events | Moderate | 3 Participants |
| FLU-IGIV High Dose (450 mL) | Frequency Counts and Percentage of Subjects With Adverse Events | Severe | 1 Participants |
| FLU-IGIV Low Dose (225 mL) | Frequency Counts and Percentage of Subjects With Adverse Events | Moderate | 5 Participants |
| FLU-IGIV Low Dose (225 mL) | Frequency Counts and Percentage of Subjects With Adverse Events | Mild | 6 Participants |
| FLU-IGIV Low Dose (225 mL) | Frequency Counts and Percentage of Subjects With Adverse Events | Severe | 1 Participants |
| Placebo (500 mL Normal Saline) | Frequency Counts and Percentage of Subjects With Adverse Events | Moderate | 6 Participants |
| Placebo (500 mL Normal Saline) | Frequency Counts and Percentage of Subjects With Adverse Events | Severe | 4 Participants |
| Placebo (500 mL Normal Saline) | Frequency Counts and Percentage of Subjects With Adverse Events | Mild | 1 Participants |
Primary
Maximum Plasma Concentration [Cmax] Reported as a Titer for Hemagglutinin Inhibition Assay
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.
Time frame: Measured through Day 8 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.
| Arm | Measure | Group | Value (GEOMETRIC_MEAN) | Dispersion |
|---|---|---|---|---|
| FLU-IGIV High Dose (450 mL) | Maximum Plasma Concentration [Cmax] Reported as a Titer for Hemagglutinin Inhibition Assay | H1N1 California | 408.3 titer | Geometric Coefficient of Variation 99.8 |
| FLU-IGIV High Dose (450 mL) | Maximum Plasma Concentration [Cmax] Reported as a Titer for Hemagglutinin Inhibition Assay | H1N1 Michigan | 371.6 titer | Geometric Coefficient of Variation 138.2 |
| FLU-IGIV High Dose (450 mL) | Maximum Plasma Concentration [Cmax] Reported as a Titer for Hemagglutinin Inhibition Assay | H3N2 Hong Kong | 309.6 titer | Geometric Coefficient of Variation 38.4 |
| FLU-IGIV High Dose (450 mL) | Maximum Plasma Concentration [Cmax] Reported as a Titer for Hemagglutinin Inhibition Assay | H3N2 Singapore | 206.7 titer | Geometric Coefficient of Variation 35.1 |
| FLU-IGIV Low Dose (225 mL) | Maximum Plasma Concentration [Cmax] Reported as a Titer for Hemagglutinin Inhibition Assay | H3N2 Singapore | 192.7 titer | Geometric Coefficient of Variation 95.2 |
| FLU-IGIV Low Dose (225 mL) | Maximum Plasma Concentration [Cmax] Reported as a Titer for Hemagglutinin Inhibition Assay | H1N1 California | 152.5 titer | Geometric Coefficient of Variation 81.6 |
| FLU-IGIV Low Dose (225 mL) | Maximum Plasma Concentration [Cmax] Reported as a Titer for Hemagglutinin Inhibition Assay | H3N2 Hong Kong | 239.8 titer | Geometric Coefficient of Variation 97.2 |
| FLU-IGIV Low Dose (225 mL) | Maximum Plasma Concentration [Cmax] Reported as a Titer for Hemagglutinin Inhibition Assay | H1N1 Michigan | 121.7 titer | Geometric Coefficient of Variation 114.6 |
| Placebo (500 mL Normal Saline) | Maximum Plasma Concentration [Cmax] Reported as a Titer for Hemagglutinin Inhibition Assay | H3N2 Singapore | 86.7 titer | Geometric Coefficient of Variation 297 |
| Placebo (500 mL Normal Saline) | Maximum Plasma Concentration [Cmax] Reported as a Titer for Hemagglutinin Inhibition Assay | H1N1 Michigan | 54.7 titer | Geometric Coefficient of Variation 155.8 |
| Placebo (500 mL Normal Saline) | Maximum Plasma Concentration [Cmax] Reported as a Titer for Hemagglutinin Inhibition Assay | H3N2 Hong Kong | 117.7 titer | Geometric Coefficient of Variation 317.2 |
| Placebo (500 mL Normal Saline) | Maximum Plasma Concentration [Cmax] Reported as a Titer for Hemagglutinin Inhibition Assay | H1N1 California | 54.7 titer | Geometric Coefficient of Variation 135.9 |
Primary
Time Cmax is Observed [Tmax] by Hemagglutinin Inhibition Assay
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 \[Vz\].
Time frame: Measured through Day 8 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.
| Arm | Measure | Group | Value (GEOMETRIC_MEAN) | Dispersion |
|---|---|---|---|---|
| FLU-IGIV High Dose (450 mL) | Time Cmax is Observed [Tmax] by Hemagglutinin Inhibition Assay | H1N1 California | 24.4 hours | Geometric Coefficient of Variation 660.7 |
| FLU-IGIV High Dose (450 mL) | Time Cmax is Observed [Tmax] by Hemagglutinin Inhibition Assay | H1N1 Michigan | 40.3 hours | Geometric Coefficient of Variation 522.5 |
| FLU-IGIV High Dose (450 mL) | Time Cmax is Observed [Tmax] by Hemagglutinin Inhibition Assay | H3N2 Hong Kong | 4.8 hours | Geometric Coefficient of Variation 127.1 |
| FLU-IGIV High Dose (450 mL) | Time Cmax is Observed [Tmax] by Hemagglutinin Inhibition Assay | H3N2 Singapore | 6.0 hours | Geometric Coefficient of Variation 146 |
| FLU-IGIV Low Dose (225 mL) | Time Cmax is Observed [Tmax] by Hemagglutinin Inhibition Assay | H3N2 Singapore | 23.0 hours | Geometric Coefficient of Variation 328.2 |
| FLU-IGIV Low Dose (225 mL) | Time Cmax is Observed [Tmax] by Hemagglutinin Inhibition Assay | H1N1 California | 17.4 hours | Geometric Coefficient of Variation 358.8 |
| FLU-IGIV Low Dose (225 mL) | Time Cmax is Observed [Tmax] by Hemagglutinin Inhibition Assay | H3N2 Hong Kong | 14.6 hours | Geometric Coefficient of Variation 298.4 |
| FLU-IGIV Low Dose (225 mL) | Time Cmax is Observed [Tmax] by Hemagglutinin Inhibition Assay | H1N1 Michigan | 13.9 hours | Geometric Coefficient of Variation 423.6 |
| Placebo (500 mL Normal Saline) | Time Cmax is Observed [Tmax] by Hemagglutinin Inhibition Assay | H3N2 Singapore | 64.8 hours | Geometric Coefficient of Variation 171.4 |
| Placebo (500 mL Normal Saline) | Time Cmax is Observed [Tmax] by Hemagglutinin Inhibition Assay | H1N1 Michigan | 120.3 hours | Geometric Coefficient of Variation 58.4 |
| Placebo (500 mL Normal Saline) | Time Cmax is Observed [Tmax] by Hemagglutinin Inhibition Assay | H3N2 Hong Kong | 76.8 hours | Geometric Coefficient of Variation 119.9 |
| Placebo (500 mL Normal Saline) | Time Cmax is Observed [Tmax] by Hemagglutinin Inhibition Assay | H1N1 California | 108.7 hours | Geometric Coefficient of Variation 64.3 |
Secondary
Ordinal Scale Subject Distribution Reflecting Clinical Status
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.
Time frame: 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.
| Arm | Measure | Category | Value (COUNT_OF_PARTICIPANTS) |
|---|---|---|---|
| FLU-IGIV High Dose (450 mL) | Ordinal Scale Subject Distribution Reflecting Clinical Status | 3-Non-ICU hospitalization, requiring supp O2 | 0 Participants |
| FLU-IGIV High Dose (450 mL) | Ordinal Scale Subject Distribution Reflecting Clinical Status | 1-Death | 0 Participants |
| FLU-IGIV High Dose (450 mL) | Ordinal Scale Subject Distribution Reflecting Clinical Status | 4-Non-ICU hospitalization, not requiring supp O2 | 0 Participants |
| FLU-IGIV High Dose (450 mL) | Ordinal Scale Subject Distribution Reflecting Clinical Status | 6-No longer hospitalized, normal activities | 11 Participants |
| FLU-IGIV High Dose (450 mL) | Ordinal Scale Subject Distribution Reflecting Clinical Status | 2-Hospitalization in the ICU | 1 Participants |
| FLU-IGIV High Dose (450 mL) | Ordinal Scale Subject Distribution Reflecting Clinical Status | 5-No longer hospitalized, no normal activities | 7 Participants |
| FLU-IGIV Low Dose (225 mL) | Ordinal Scale Subject Distribution Reflecting Clinical Status | 2-Hospitalization in the ICU | 0 Participants |
| FLU-IGIV Low Dose (225 mL) | Ordinal Scale Subject Distribution Reflecting Clinical Status | 1-Death | 0 Participants |
| FLU-IGIV Low Dose (225 mL) | Ordinal Scale Subject Distribution Reflecting Clinical Status | 3-Non-ICU hospitalization, requiring supp O2 | 2 Participants |
| FLU-IGIV Low Dose (225 mL) | Ordinal Scale Subject Distribution Reflecting Clinical Status | 4-Non-ICU hospitalization, not requiring supp O2 | 0 Participants |
| FLU-IGIV Low Dose (225 mL) | Ordinal Scale Subject Distribution Reflecting Clinical Status | 5-No longer hospitalized, no normal activities | 7 Participants |
| FLU-IGIV Low Dose (225 mL) | Ordinal Scale Subject Distribution Reflecting Clinical Status | 6-No longer hospitalized, normal activities | 8 Participants |
| Placebo (500 mL Normal Saline) | Ordinal Scale Subject Distribution Reflecting Clinical Status | 2-Hospitalization in the ICU | 0 Participants |
| Placebo (500 mL Normal Saline) | Ordinal Scale Subject Distribution Reflecting Clinical Status | 6-No longer hospitalized, normal activities | 8 Participants |
| Placebo (500 mL Normal Saline) | Ordinal Scale Subject Distribution Reflecting Clinical Status | 5-No longer hospitalized, no normal activities | 9 Participants |
| Placebo (500 mL Normal Saline) | Ordinal Scale Subject Distribution Reflecting Clinical Status | 3-Non-ICU hospitalization, requiring supp O2 | 4 Participants |
| Placebo (500 mL Normal Saline) | Ordinal Scale Subject Distribution Reflecting Clinical Status | 1-Death | 0 Participants |
| Placebo (500 mL Normal Saline) | Ordinal Scale Subject Distribution Reflecting Clinical Status | 4-Non-ICU hospitalization, not requiring supp O2 | 0 Participants |
Comparison: Pairwise Wilcoxon rank-sum test for a location shiftp-value: 0.17495% CI: [0, 1]Wilcoxon (Mann-Whitney)
Comparison: Pairwise Wilcoxon rank-sum test for a location shiftp-value: 0.57295% CI: [0, 1]Wilcoxon (Mann-Whitney)
Comparison: Pairwise Wilcoxon rank-sum test for a location shiftp-value: 0.53495% CI: [0, 1]Wilcoxon (Mann-Whitney)
Comparison: Pairwise Wilcoxon rank-sum test for a location shift where the two active dose groups were pooled and compared to placebo.p-value: 0.53495% CI: [0, 1]Wilcoxon (Mann-Whitney)