COVID-19
Conditions
Keywords
Coronavirus Disease, Severe acute respiratory syndrome coronavirus 2, SARS-CoV-2, Coronavirus Infections, Coronaviridae Infections, Virus Diseases, Immunoglobulins, Antibodies, Gamma-globulins, Immunoglobulins, Intravenous, Immunologic Factors, Physiological Effects of Drugs
Brief summary
The purpose of the study is to determine if a high dose of Intravenous Immune Globulin (IVIG) plus Standard Medical Treatment (SMT) can reduce all-cause mortality versus SMT alone in hospitalized participants with COVID-19 requiring admission to the ICU through Day 29.
Interventions
BIOLOGICALGAMUNEX-C
Intravenous Immune Globulin (Human), 10% Caprylate/Chromatography Purified.
DRUGStandard Medical Treatment
SMT per local policies or guidelines.
Sponsors
Grifols Therapeutics LLC
Study design
Allocation
RANDOMIZED
Intervention model
PARALLEL
Primary purpose
TREATMENT
Masking
NONE
Eligibility
Sex/Gender
ALL
Age
18 Years to No maximum
Healthy volunteers
No
Inclusion criteria
* Hospitalized male or female subjects of ≥ 18 years of age at time of Screening who are being treated in the ICU for COVID-19 for not longer than 48 hours or for whom a decision has been made that COVID-19 disease severity warrants ICU admission. * Has laboratory-confirmed novel coronavirus {SARS-CoV-2} infection as determined by qualitative polymerase chain reaction (PCR) (reverse transcriptase \[RT\]-PCR), or other United States Food and Drug Administration (FDA)-approved diagnostic assay for COVID-19 in any specimen during the current hospital admission prior to randomization. * Illness (symptoms of COVID-19 of any duration requiring ICU level care), and the following: 1. Radiographic infiltrates by imaging (chest X-Ray, computerized tomography (CT) scan, etc.), and 2. Requiring mechanical ventilation and/or supplemental oxygen. * Any one of the following related to COVID-19: i. Ferritin \> 400 nanogram per milliliter (ng/mL), ii. Lactate dehydrogenase (LDH) \> 300 units per liter (U/L), iii. D-Dimers \> reference range, or iv. C-reactive protein (CRP) \> 40 milligram per liter (mg/L). * Subject provides informed consent prior to initiation of any study procedures.
Exclusion criteria
* Clinical evidence of any significant acute or chronic disease or pathophysiologic manifestations (eg, complications of COVID-19 standard medical treatments) that, in the opinion of the investigator, may place the subject at undue medical risk. * The subject has had a known (documented) serious anaphylactic reaction to blood, any blood-derived or plasma product or a past history of any hypersensitivity reactions to commercial immunoglobulin. * A medical condition in which the infusion of additional fluid is contraindicated. * Shock that is unresponsive to fluid challenge and/or multiple vasopressors and accompanied by multiorgan failure considered by the Principal Investigator not able to be reversed. * Subjects with known (documented) thrombotic complications to polyclonal IVIG therapy in the past. * Subjects with current or prior myocardial infarction, stroke, deep vein thrombosis, or thromboembolic event (within the past 12 months) or who have a history of thromboembolic events of unknown etiology. * Subjects with limitations of therapeutic effort. * Female subjects who are pregnant or of child-bearing potential with a positive test for pregnancy blood or urine human chorionic gonadotropin (HCG)-based assay at Screening/Baseline. * Subjects participating in another interventional clinical trial with investigational medical product or device. * Known history of prothrombin gene mutation 20210, homozygous Factor V Leiden mutations, antithrombin III deficiency, protein C deficiency, protein S deficiency or antiphospholipid syndrome. * Presence of malignancy (either new diagnosis of malignancy or known residual disease) within the past 12 months. * Creatinine at Screening is ≥ 4 mg/dL (or subject is dependent on dialysis/renal replacement therapy). * Known Immunoglobulin A (IgA) deficiency with anti-IgA serum antibodies. * Uncontrolled hypertension at the time of Screening (systolic blood pressure \> 200 mm Hg) or refractory severe hypotension with sustained systolic blood pressure \< 90 mm Hg unresponsive to vasopressors.
Design outcomes
Primary
| Measure | Time frame | Description |
|---|---|---|
| All-Cause Mortality Rate Through Day 29 | Up to Day 29 | All-cause mortality rate is percentage of participants in each treatment group who experienced mortality up to Day 29. |
Secondary
| Measure | Time frame | Description |
|---|---|---|
| Percentage of Participants With Actual Intensive Care Unit (ICU) Discharge Time | Up to Day 29 | Percentage of participants who were discharged from ICU were recorded. Time to actual ICU discharge was defined as duration of actual ICU stay from Day 1 through Day 29. |
| Duration of Mechanical Ventilation | Up to Day 29 | Duration (number of days) of ICU stay from post-randomization through Day 29 was calculated based on ICU admission and discharge (actual and medical equivalence) dates. |
| Duration of Any Oxygen Use From Day 1 Through Day 29 | Up to Day 29 | Duration (number of days) of any oxygen use from Day 1 through Day 29 was calculated based on the start/stop dates. |
| Mean Change From Baseline in Ordinal Scale | Baseline up to Day 29 | The ordinal scale is a 7-point scale ranging from 1 to 7 used to measure clinical status based on the following points: 1) Death; 2) Hospitalized, on invasive mechanical ventilation or extracorporeal membrane oxygenation (ECMO) 3) Hospitalized, on non-invasive ventilation or high flow oxygen devices; 4) Hospitalized, requiring supplemental oxygen; 5) Hospitalized, not requiring supplemental oxygen; 6) Not hospitalized, limitation on activities; 7) Not hospitalized, no limitations on activities. Higher score indicated no severe illness. Mean change in Ordinal scale was evaluated by fitting a linear mixed-effects model for repeated measures (MMRM). The data is reported for average across all postbaseline. |
| Absolute Change From Baseline in Ordinal Scale at Day 29 | Baseline, Day 29 | The ordinal scale is a 7-point scale ranging from 1 to 7 used to measure clinical status based on the following points: 1) Death; 2) Hospitalized, on invasive mechanical ventilation or extracorporeal membrane oxygenation (ECMO) 3) Hospitalized, on non-invasive ventilation or high flow oxygen devices; 4) Hospitalized, requiring supplemental oxygen; 5) Hospitalized, not requiring supplemental oxygen; 6) Not hospitalized, limitation on activities; 7) Not hospitalized, no limitations on activities. Higher score indicated no severe illness. |
| Percentage of Participants With Actual Hospital Discharge Time | Up to Day 29 | Percentage of participants who were discharged from the hospital were recorded. Time to hospital discharge was defined as duration of hospitalization from Day 1 through Day 29. |
| Percentage of Participants Who Develop Acute Respiratory Distress Syndrome (ARDS) | Days 1, 5, 15 and 29 | Acute Respiratory Distress Syndrome was defined based on Berlin criteria (chest imaging, origin of edema, oxygenation). |
| Percentage of Participants Who Develop ARDS Distributed by Severity | Days 1, 5, 15 and 29 | ARDS was defined by Berlin's criteria as: 1) Timing is usually within 1 week of a known clinical insult or new or worsening respiratory symptoms 2) Chest imaging: bilateral opacities-not fully explained by effusions, lobar/lung collapse, or nodules 3) Respiratory failure not fully explained by cardiac failure or fluid overload Need objective assessment (eg, echocardiography) to exclude hydrostatic edema if no risk factor present 4) Oxygenation: Mild 200 mm Hg \< partial pressure of oxygen/fraction of inspired oxygen (PaO2/FiO2) ≤ 300 mm Hg with positive end-expiratory pressure (PEEP) or continuous positive airway pressure (CPAP) ≥ 5 cm H2Oc; Moderate 100 mm Hg \< PaO2/FIO2 ≤ 200 mm Hg with PEEP ≥ 5 cm H2O; Severe PaO2/FIO2 ≤100 mm Hg with PEEP ≥ 5 cm H2O. |
| Change From Baseline in Sequential Organ Failure Assessment (SOFA) Score at Day 5, Day 15, and Day 29 | Days 5, 15, and 29 | SOFA score is a mortality prediction score that is based on the degree of dysfunction of six organ systems. The score is calculated on admission and every 24 hours until discharge using the worst parameters measured during the prior 24 hours SOFA score ranges from 0 (no organ dysfunction) to 24 (highest possible score / organ dysfunction). Higher score indicated severe illness. |
| Change From Baseline in National Early Warning Score (NEWS) | Baseline and Day 29 | NEWS is clinical scoring developed to improve detection of deterioration in ill participant. It is based on 7 clinical parameters: respiration rate, oxygen saturation, supplemental oxygen, systolic blood pressure (BP), pulse rate, level of consciousness, and temperature. A score of 0 and 2 was allocated to supplemental oxygen, 0 and 3 for level of consciousness and score of 0, 1, 2 and 3 for remaining parameters (i.e. respiration rate, oxygen saturation, systolic BP, pulse rate and temperature) where 0 = normal health condition to 3 = worst health condition; higher score indicated more severity. All scores were summed to get an aggregate score. Aggregate NEWS score ranged from 0 to 20, with higher scores meaning more severity/higher risk. |
| Percentage of Participants Achieving Clinical Response: NEWS ≤ 2 Maintained for 24 Hours | Day 29 | Percentage of participants who achieved clinical response (i.e the NEWS score ≤2 maintained for 24 hours from Day 1 through Day 29) was estimated using the Kaplan-Meier method. |
| Percentage of Participants in Each Severity Category of the 7-Point Ordinal Scale | Days 15 and 29 | The ordinal scale is a 7-point scale ranging from 1 to 7 used to measure clinical status based on the following points: 1) Death; 2) Hospitalized, on invasive mechanical ventilation or extracorporeal membrane oxygenation (ECMO) 3) Hospitalized, on non-invasive ventilation or high flow oxygen devices; 4) Hospitalized, requiring supplemental oxygen; 5) Hospitalized, not requiring supplemental oxygen; 6) Not hospitalized, limitation on activities; 7) Not hospitalized, no limitations on activities. |
Countries
United States
Participant flow
Recruitment details
Participants were enrolled in the study at 18 study centers in the United States. The study was conducted from 17 September 2020 to 25 October 2021.
Pre-assignment details
Participants with Coronavirus Disease 2019 (COVID-19) were randomized in 1:1 ratio to receive Standard Medical Treatment (SMT) or SMT plus a net total dose of Gamunex-C of 2 grams per kilogram (g/kg) (body weight) administered in divided doses over 4 to 5 consecutive days at the Principal Investigator's discretion. Maximum dose was capped at 160 g.
Participants by arm
| Arm | Count |
|---|---|
| GAMUNEX-C + Standard Medical Treatment Participants received 2 grams per kilogram (g/kg) of GAMUNEX-C, which was capped to a maximum of 160 g infusion intravenously (IV) for participants weighing more than 80 kg on Day 1. The 2 g/kg net total dose was divided either into infusions of 500 mg/kg body weight over 4 days or 400 mg/kg body weight over 5 days as per investigator's decision. Participants received standard of care interventions as per Principal Investigator's discretion from Day 1 up to Day 29. | 50 |
| Standard Medical Treatment Participants received all standard of care interventions required as per Principal Investigator's discretion throughout the participant's hospitalization, from Day 1 to Day 29. | 50 |
| Total | 100 |
Withdrawals & dropouts
| Period | Reason | FG000 | FG001 |
|---|---|---|---|
| Overall Study | Death | 14 | 16 |
| Overall Study | Lost to Follow-up | 3 | 3 |
| Overall Study | Reason not Specified | 5 | 5 |
| Overall Study | Withdrawal by Subject | 0 | 2 |
Baseline characteristics
| Characteristic | Standard Medical Treatment | Total | GAMUNEX-C + Standard Medical Treatment |
|---|---|---|---|
| Age, Continuous | 59.5 years | 57.5 years | 55.5 years |
| Ethnicity (NIH/OMB) Hispanic or Latino | 7 Participants | 16 Participants | 9 Participants |
| Ethnicity (NIH/OMB) Not Hispanic or Latino | 33 Participants | 71 Participants | 38 Participants |
| Ethnicity (NIH/OMB) Unknown or Not Reported | 0 Participants | 0 Participants | 0 Participants |
| Race (NIH/OMB) American Indian or Alaska Native | 2 Participants | 3 Participants | 1 Participants |
| Race (NIH/OMB) Asian | 1 Participants | 2 Participants | 1 Participants |
| Race (NIH/OMB) Black or African American | 5 Participants | 9 Participants | 4 Participants |
| Race (NIH/OMB) More than one race | 0 Participants | 0 Participants | 0 Participants |
| Race (NIH/OMB) Native Hawaiian or Other Pacific Islander | 0 Participants | 1 Participants | 1 Participants |
| Race (NIH/OMB) Unknown or Not Reported | 11 Participants | 24 Participants | 13 Participants |
| Race (NIH/OMB) White | 31 Participants | 61 Participants | 30 Participants |
| Sex: Female, Male Female | 23 Participants | 49 Participants | 26 Participants |
| Sex: Female, Male Male | 27 Participants | 51 Participants | 24 Participants |
Adverse events
| Event type | EG000 affected / at risk | EG001 affected / at risk |
|---|---|---|
| deaths Total, all-cause mortality | 16 / 50 | 18 / 50 |
| other Total, other adverse events | 42 / 50 | 44 / 50 |
| serious Total, serious adverse events | 27 / 50 | 23 / 50 |
Outcome results
Primary
All-Cause Mortality Rate Through Day 29
All-cause mortality rate is percentage of participants in each treatment group who experienced mortality up to Day 29.
Time frame: Up to Day 29
Population: The intent to treat (ITT) population included all participants who were randomized.
| Arm | Measure | Value (NUMBER) |
|---|---|---|
| GAMUNEX-C + Standard Medical Treatment | All-Cause Mortality Rate Through Day 29 | 28.0 Percentage of participants |
| Standard Medical Treatment | All-Cause Mortality Rate Through Day 29 | 32.0 Percentage of participants |
p-value: 0.827595% CI: [-22.3, 14.5]Fisher Exact
Secondary
Absolute Change From Baseline in Ordinal Scale at Day 29
The ordinal scale is a 7-point scale ranging from 1 to 7 used to measure clinical status based on the following points: 1) Death; 2) Hospitalized, on invasive mechanical ventilation or extracorporeal membrane oxygenation (ECMO) 3) Hospitalized, on non-invasive ventilation or high flow oxygen devices; 4) Hospitalized, requiring supplemental oxygen; 5) Hospitalized, not requiring supplemental oxygen; 6) Not hospitalized, limitation on activities; 7) Not hospitalized, no limitations on activities. Higher score indicated no severe illness.
Time frame: Baseline, Day 29
Population: The ITT population included all participants who were randomized.
| Arm | Measure | Value (LEAST_SQUARES_MEAN) |
|---|---|---|
| GAMUNEX-C + Standard Medical Treatment | Absolute Change From Baseline in Ordinal Scale at Day 29 | 1.05 score on scale |
| Standard Medical Treatment | Absolute Change From Baseline in Ordinal Scale at Day 29 | 0.65 score on scale |
p-value: 0.092295% CI: [-0.07, 0.86]Kenward-Roger
Secondary
Change From Baseline in National Early Warning Score (NEWS)
NEWS is clinical scoring developed to improve detection of deterioration in ill participant. It is based on 7 clinical parameters: respiration rate, oxygen saturation, supplemental oxygen, systolic blood pressure (BP), pulse rate, level of consciousness, and temperature. A score of 0 and 2 was allocated to supplemental oxygen, 0 and 3 for level of consciousness and score of 0, 1, 2 and 3 for remaining parameters (i.e. respiration rate, oxygen saturation, systolic BP, pulse rate and temperature) where 0 = normal health condition to 3 = worst health condition; higher score indicated more severity. All scores were summed to get an aggregate score. Aggregate NEWS score ranged from 0 to 20, with higher scores meaning more severity/higher risk.
Time frame: Baseline and Day 29
Population: The ITT population included all participants who were randomized.
| Arm | Measure | Value (LEAST_SQUARES_MEAN) |
|---|---|---|
| GAMUNEX-C + Standard Medical Treatment | Change From Baseline in National Early Warning Score (NEWS) | -2.56 score on a scale |
| Standard Medical Treatment | Change From Baseline in National Early Warning Score (NEWS) | -2.62 score on a scale |
p-value: 0.936695% CI: [-1.42, 1.53]LSM Difference
Secondary
Change From Baseline in Sequential Organ Failure Assessment (SOFA) Score at Day 5, Day 15, and Day 29
SOFA score is a mortality prediction score that is based on the degree of dysfunction of six organ systems. The score is calculated on admission and every 24 hours until discharge using the worst parameters measured during the prior 24 hours SOFA score ranges from 0 (no organ dysfunction) to 24 (highest possible score / organ dysfunction). Higher score indicated severe illness.
Time frame: Days 5, 15, and 29
Population: The ITT population included all participants who were randomized.
| Arm | Measure | Group | Value (LEAST_SQUARES_MEAN) |
|---|---|---|---|
| GAMUNEX-C + Standard Medical Treatment | Change From Baseline in Sequential Organ Failure Assessment (SOFA) Score at Day 5, Day 15, and Day 29 | Change from Baseline at Day 5 | 0.34 score on a scale |
| GAMUNEX-C + Standard Medical Treatment | Change From Baseline in Sequential Organ Failure Assessment (SOFA) Score at Day 5, Day 15, and Day 29 | Change from Baseline at Day 15 | 0.20 score on a scale |
| GAMUNEX-C + Standard Medical Treatment | Change From Baseline in Sequential Organ Failure Assessment (SOFA) Score at Day 5, Day 15, and Day 29 | Change from Baseline at Day 29 | -0.87 score on a scale |
| Standard Medical Treatment | Change From Baseline in Sequential Organ Failure Assessment (SOFA) Score at Day 5, Day 15, and Day 29 | Change from Baseline at Day 5 | -0.07 score on a scale |
| Standard Medical Treatment | Change From Baseline in Sequential Organ Failure Assessment (SOFA) Score at Day 5, Day 15, and Day 29 | Change from Baseline at Day 15 | 0.30 score on a scale |
| Standard Medical Treatment | Change From Baseline in Sequential Organ Failure Assessment (SOFA) Score at Day 5, Day 15, and Day 29 | Change from Baseline at Day 29 | -0.95 score on a scale |
p-value: 0.361195% CI: [-0.47, 1.28]LSM Difference
p-value: 0.923895% CI: [-2.13, 1.94]LSM Difference
p-value: 0.954195% CI: [-2.58, 2.73]LSM Difference
Secondary
Duration of Any Oxygen Use From Day 1 Through Day 29
Duration (number of days) of any oxygen use from Day 1 through Day 29 was calculated based on the start/stop dates.
Time frame: Up to Day 29
Population: The ITT population included all participants who were randomized.
| Arm | Measure | Value (LEAST_SQUARES_MEAN) |
|---|---|---|
| GAMUNEX-C + Standard Medical Treatment | Duration of Any Oxygen Use From Day 1 Through Day 29 | 23.00 days |
| Standard Medical Treatment | Duration of Any Oxygen Use From Day 1 Through Day 29 | 23.02 days |
p-value: 0.991795% CI: [-3.82, 3.78]ANOVA
Secondary
Duration of Mechanical Ventilation
Duration (number of days) of ICU stay from post-randomization through Day 29 was calculated based on ICU admission and discharge (actual and medical equivalence) dates.
Time frame: Up to Day 29
Population: The ITT population included all participants who were randomized.
| Arm | Measure | Value (LEAST_SQUARES_MEAN) |
|---|---|---|
| GAMUNEX-C + Standard Medical Treatment | Duration of Mechanical Ventilation | 11.22 days |
| Standard Medical Treatment | Duration of Mechanical Ventilation | 8.64 days |
p-value: 0.262695% CI: [-1.96, 7.12]ANOVA
Secondary
Mean Change From Baseline in Ordinal Scale
The ordinal scale is a 7-point scale ranging from 1 to 7 used to measure clinical status based on the following points: 1) Death; 2) Hospitalized, on invasive mechanical ventilation or extracorporeal membrane oxygenation (ECMO) 3) Hospitalized, on non-invasive ventilation or high flow oxygen devices; 4) Hospitalized, requiring supplemental oxygen; 5) Hospitalized, not requiring supplemental oxygen; 6) Not hospitalized, limitation on activities; 7) Not hospitalized, no limitations on activities. Higher score indicated no severe illness. Mean change in Ordinal scale was evaluated by fitting a linear mixed-effects model for repeated measures (MMRM). The data is reported for average across all postbaseline.
Time frame: Baseline up to Day 29
Population: The ITT population included all participants who were randomized.
| Arm | Measure | Value (LEAST_SQUARES_MEAN) |
|---|---|---|
| GAMUNEX-C + Standard Medical Treatment | Mean Change From Baseline in Ordinal Scale | -0.12 score on a scale |
| Standard Medical Treatment | Mean Change From Baseline in Ordinal Scale | -0.17 score on a scale |
p-value: 0.755795% CI: [-0.29, 0.4]Kenward-Roger
Secondary
Percentage of Participants Achieving Clinical Response: NEWS ≤ 2 Maintained for 24 Hours
Percentage of participants who achieved clinical response (i.e the NEWS score ≤2 maintained for 24 hours from Day 1 through Day 29) was estimated using the Kaplan-Meier method.
Time frame: Day 29
Population: The ITT population included all participants who were randomized.
| Arm | Measure | Value (NUMBER) |
|---|---|---|
| GAMUNEX-C + Standard Medical Treatment | Percentage of Participants Achieving Clinical Response: NEWS ≤ 2 Maintained for 24 Hours | 32.9 percentage of participants |
| Standard Medical Treatment | Percentage of Participants Achieving Clinical Response: NEWS ≤ 2 Maintained for 24 Hours | 28.2 percentage of participants |
Secondary
Percentage of Participants in Each Severity Category of the 7-Point Ordinal Scale
The ordinal scale is a 7-point scale ranging from 1 to 7 used to measure clinical status based on the following points: 1) Death; 2) Hospitalized, on invasive mechanical ventilation or extracorporeal membrane oxygenation (ECMO) 3) Hospitalized, on non-invasive ventilation or high flow oxygen devices; 4) Hospitalized, requiring supplemental oxygen; 5) Hospitalized, not requiring supplemental oxygen; 6) Not hospitalized, limitation on activities; 7) Not hospitalized, no limitations on activities.
Time frame: Days 15 and 29
Population: The ITT population included all participants who were randomized. Number analyzed are the number of participants with data available for analysis at the given timepoint.
| Arm | Measure | Group | Value (NUMBER) |
|---|---|---|---|
| GAMUNEX-C + Standard Medical Treatment | Percentage of Participants in Each Severity Category of the 7-Point Ordinal Scale | Day 15, Not hospitalized, limitation on activities | 13.6 percentage of participants |
| GAMUNEX-C + Standard Medical Treatment | Percentage of Participants in Each Severity Category of the 7-Point Ordinal Scale | Day 15, Death | 18.2 percentage of participants |
| GAMUNEX-C + Standard Medical Treatment | Percentage of Participants in Each Severity Category of the 7-Point Ordinal Scale | Day 15, Hospitalized, on invasive mechanical ventilation or ECMO | 31.8 percentage of participants |
| GAMUNEX-C + Standard Medical Treatment | Percentage of Participants in Each Severity Category of the 7-Point Ordinal Scale | Day 15, Hospitalized, on non-invasive ventilation or high flow oxygen devices | 11.4 percentage of participants |
| GAMUNEX-C + Standard Medical Treatment | Percentage of Participants in Each Severity Category of the 7-Point Ordinal Scale | Day 15, Hospitalized, requiring supplemental oxygen | 18.2 percentage of participants |
| GAMUNEX-C + Standard Medical Treatment | Percentage of Participants in Each Severity Category of the 7-Point Ordinal Scale | Day 15, Hospitalized, not requiring supplemental oxygen | 0 percentage of participants |
| GAMUNEX-C + Standard Medical Treatment | Percentage of Participants in Each Severity Category of the 7-Point Ordinal Scale | Day 15, Not hospitalized, no limitations on activities | 6.8 percentage of participants |
| GAMUNEX-C + Standard Medical Treatment | Percentage of Participants in Each Severity Category of the 7-Point Ordinal Scale | Day 29, Death | 31.7 percentage of participants |
| GAMUNEX-C + Standard Medical Treatment | Percentage of Participants in Each Severity Category of the 7-Point Ordinal Scale | Day 29, Hospitalized, on invasive mechanical ventilation or ECMO | 14.6 percentage of participants |
| GAMUNEX-C + Standard Medical Treatment | Percentage of Participants in Each Severity Category of the 7-Point Ordinal Scale | Day 29, Hospitalized, on non-invasive ventilation or high flow oxygen devices | 2.4 percentage of participants |
| GAMUNEX-C + Standard Medical Treatment | Percentage of Participants in Each Severity Category of the 7-Point Ordinal Scale | Day 29, Hospitalized, requiring supplemental oxygen | 4.9 percentage of participants |
| GAMUNEX-C + Standard Medical Treatment | Percentage of Participants in Each Severity Category of the 7-Point Ordinal Scale | Day 29, Hospitalized, not requiring supplemental oxygen | 2.4 percentage of participants |
| GAMUNEX-C + Standard Medical Treatment | Percentage of Participants in Each Severity Category of the 7-Point Ordinal Scale | Day 29, Not hospitalized, limitation on activities | 24.4 percentage of participants |
| GAMUNEX-C + Standard Medical Treatment | Percentage of Participants in Each Severity Category of the 7-Point Ordinal Scale | Day 29, Not hospitalized, no limitations on activities | 19.5 percentage of participants |
| Standard Medical Treatment | Percentage of Participants in Each Severity Category of the 7-Point Ordinal Scale | Day 29, Hospitalized, requiring supplemental oxygen | 12.5 percentage of participants |
| Standard Medical Treatment | Percentage of Participants in Each Severity Category of the 7-Point Ordinal Scale | Day 29, Death | 40.0 percentage of participants |
| Standard Medical Treatment | Percentage of Participants in Each Severity Category of the 7-Point Ordinal Scale | Day 15, Death | 27.3 percentage of participants |
| Standard Medical Treatment | Percentage of Participants in Each Severity Category of the 7-Point Ordinal Scale | Day 29, Not hospitalized, limitation on activities | 22.5 percentage of participants |
| Standard Medical Treatment | Percentage of Participants in Each Severity Category of the 7-Point Ordinal Scale | Day 15, Hospitalized, on invasive mechanical ventilation or ECMO | 15.9 percentage of participants |
| Standard Medical Treatment | Percentage of Participants in Each Severity Category of the 7-Point Ordinal Scale | Day 29, Hospitalized, on invasive mechanical ventilation or ECMO | 10.0 percentage of participants |
| Standard Medical Treatment | Percentage of Participants in Each Severity Category of the 7-Point Ordinal Scale | Day 15, Hospitalized, on non-invasive ventilation or high flow oxygen devices | 18.2 percentage of participants |
| Standard Medical Treatment | Percentage of Participants in Each Severity Category of the 7-Point Ordinal Scale | Day 29, Hospitalized, not requiring supplemental oxygen | 0 percentage of participants |
| Standard Medical Treatment | Percentage of Participants in Each Severity Category of the 7-Point Ordinal Scale | Day 15, Hospitalized, requiring supplemental oxygen | 15.9 percentage of participants |
| Standard Medical Treatment | Percentage of Participants in Each Severity Category of the 7-Point Ordinal Scale | Day 29, Hospitalized, on non-invasive ventilation or high flow oxygen devices | 2.5 percentage of participants |
| Standard Medical Treatment | Percentage of Participants in Each Severity Category of the 7-Point Ordinal Scale | Day 15, Hospitalized, not requiring supplemental oxygen | 0 percentage of participants |
| Standard Medical Treatment | Percentage of Participants in Each Severity Category of the 7-Point Ordinal Scale | Day 15, Not hospitalized, limitation on activities | 20.5 percentage of participants |
| Standard Medical Treatment | Percentage of Participants in Each Severity Category of the 7-Point Ordinal Scale | Day 29, Not hospitalized, no limitations on activities | 12.5 percentage of participants |
| Standard Medical Treatment | Percentage of Participants in Each Severity Category of the 7-Point Ordinal Scale | Day 15, Not hospitalized, no limitations on activities | 2.3 percentage of participants |
Secondary
Percentage of Participants Who Develop Acute Respiratory Distress Syndrome (ARDS)
Acute Respiratory Distress Syndrome was defined based on Berlin criteria (chest imaging, origin of edema, oxygenation).
Time frame: Days 1, 5, 15 and 29
Population: The ITT population included all participants who were randomized.
| Arm | Measure | Group | Value (NUMBER) |
|---|---|---|---|
| GAMUNEX-C + Standard Medical Treatment | Percentage of Participants Who Develop Acute Respiratory Distress Syndrome (ARDS) | Day 1 | 94.0 percentage of participants |
| GAMUNEX-C + Standard Medical Treatment | Percentage of Participants Who Develop Acute Respiratory Distress Syndrome (ARDS) | Day 5 | 93.9 percentage of participants |
| GAMUNEX-C + Standard Medical Treatment | Percentage of Participants Who Develop Acute Respiratory Distress Syndrome (ARDS) | Day 15 | 79.4 percentage of participants |
| GAMUNEX-C + Standard Medical Treatment | Percentage of Participants Who Develop Acute Respiratory Distress Syndrome (ARDS) | Day 29 | 28.0 percentage of participants |
| Standard Medical Treatment | Percentage of Participants Who Develop Acute Respiratory Distress Syndrome (ARDS) | Day 29 | 33.3 percentage of participants |
| Standard Medical Treatment | Percentage of Participants Who Develop Acute Respiratory Distress Syndrome (ARDS) | Day 1 | 96.0 percentage of participants |
| Standard Medical Treatment | Percentage of Participants Who Develop Acute Respiratory Distress Syndrome (ARDS) | Day 15 | 61.3 percentage of participants |
| Standard Medical Treatment | Percentage of Participants Who Develop Acute Respiratory Distress Syndrome (ARDS) | Day 5 | 94.0 percentage of participants |
Secondary
Percentage of Participants Who Develop ARDS Distributed by Severity
ARDS was defined by Berlin's criteria as: 1) Timing is usually within 1 week of a known clinical insult or new or worsening respiratory symptoms 2) Chest imaging: bilateral opacities-not fully explained by effusions, lobar/lung collapse, or nodules 3) Respiratory failure not fully explained by cardiac failure or fluid overload Need objective assessment (eg, echocardiography) to exclude hydrostatic edema if no risk factor present 4) Oxygenation: Mild 200 mm Hg \< partial pressure of oxygen/fraction of inspired oxygen (PaO2/FiO2) ≤ 300 mm Hg with positive end-expiratory pressure (PEEP) or continuous positive airway pressure (CPAP) ≥ 5 cm H2Oc; Moderate 100 mm Hg \< PaO2/FIO2 ≤ 200 mm Hg with PEEP ≥ 5 cm H2O; Severe PaO2/FIO2 ≤100 mm Hg with PEEP ≥ 5 cm H2O.
Time frame: Days 1, 5, 15 and 29
Population: The ITT population is included all participants who were randomized.
| Arm | Measure | Group | Value (NUMBER) |
|---|---|---|---|
| GAMUNEX-C + Standard Medical Treatment | Percentage of Participants Who Develop ARDS Distributed by Severity | Day 1: Mild | 4.0 percentage of participants |
| GAMUNEX-C + Standard Medical Treatment | Percentage of Participants Who Develop ARDS Distributed by Severity | Day 1: Moderate | 50.0 percentage of participants |
| GAMUNEX-C + Standard Medical Treatment | Percentage of Participants Who Develop ARDS Distributed by Severity | Day 1: Severe | 40.0 percentage of participants |
| GAMUNEX-C + Standard Medical Treatment | Percentage of Participants Who Develop ARDS Distributed by Severity | Day 5: Mild | 18.4 percentage of participants |
| GAMUNEX-C + Standard Medical Treatment | Percentage of Participants Who Develop ARDS Distributed by Severity | Day 5: Moderate | 42.9 percentage of participants |
| GAMUNEX-C + Standard Medical Treatment | Percentage of Participants Who Develop ARDS Distributed by Severity | Day 5: Severe | 32.7 percentage of participants |
| GAMUNEX-C + Standard Medical Treatment | Percentage of Participants Who Develop ARDS Distributed by Severity | Day 15: Mild | 41.2 percentage of participants |
| GAMUNEX-C + Standard Medical Treatment | Percentage of Participants Who Develop ARDS Distributed by Severity | Day 15: Moderate | 14.7 percentage of participants |
| GAMUNEX-C + Standard Medical Treatment | Percentage of Participants Who Develop ARDS Distributed by Severity | Day 15: Severe | 23.5 percentage of participants |
| GAMUNEX-C + Standard Medical Treatment | Percentage of Participants Who Develop ARDS Distributed by Severity | Day 29: Mild | 4.0 percentage of participants |
| GAMUNEX-C + Standard Medical Treatment | Percentage of Participants Who Develop ARDS Distributed by Severity | Day 29: Moderate | 12.0 percentage of participants |
| GAMUNEX-C + Standard Medical Treatment | Percentage of Participants Who Develop ARDS Distributed by Severity | Day 29: Severe | 12.0 percentage of participants |
| Standard Medical Treatment | Percentage of Participants Who Develop ARDS Distributed by Severity | Day 29: Moderate | 4.8 percentage of participants |
| Standard Medical Treatment | Percentage of Participants Who Develop ARDS Distributed by Severity | Day 1: Mild | 4.0 percentage of participants |
| Standard Medical Treatment | Percentage of Participants Who Develop ARDS Distributed by Severity | Day 15: Mild | 9.7 percentage of participants |
| Standard Medical Treatment | Percentage of Participants Who Develop ARDS Distributed by Severity | Day 1: Moderate | 58.0 percentage of participants |
| Standard Medical Treatment | Percentage of Participants Who Develop ARDS Distributed by Severity | Day 29: Mild | 23.8 percentage of participants |
| Standard Medical Treatment | Percentage of Participants Who Develop ARDS Distributed by Severity | Day 1: Severe | 34.0 percentage of participants |
| Standard Medical Treatment | Percentage of Participants Who Develop ARDS Distributed by Severity | Day 15: Moderate | 35.5 percentage of participants |
| Standard Medical Treatment | Percentage of Participants Who Develop ARDS Distributed by Severity | Day 5: Mild | 24.0 percentage of participants |
| Standard Medical Treatment | Percentage of Participants Who Develop ARDS Distributed by Severity | Day 29: Severe | 4.8 percentage of participants |
| Standard Medical Treatment | Percentage of Participants Who Develop ARDS Distributed by Severity | Day 5: Moderate | 48.0 percentage of participants |
| Standard Medical Treatment | Percentage of Participants Who Develop ARDS Distributed by Severity | Day 15: Severe | 16.1 percentage of participants |
| Standard Medical Treatment | Percentage of Participants Who Develop ARDS Distributed by Severity | Day 5: Severe | 22.0 percentage of participants |
Secondary
Percentage of Participants With Actual Hospital Discharge Time
Percentage of participants who were discharged from the hospital were recorded. Time to hospital discharge was defined as duration of hospitalization from Day 1 through Day 29.
Time frame: Up to Day 29
Population: The ITT population included all participants who were randomized.
| Arm | Measure | Value (NUMBER) |
|---|---|---|
| GAMUNEX-C + Standard Medical Treatment | Percentage of Participants With Actual Hospital Discharge Time | 62 Percentage of participants |
| Standard Medical Treatment | Percentage of Participants With Actual Hospital Discharge Time | 56 Percentage of participants |
p-value: 0.6854Gray's test
Secondary
Percentage of Participants With Actual Intensive Care Unit (ICU) Discharge Time
Percentage of participants who were discharged from ICU were recorded. Time to actual ICU discharge was defined as duration of actual ICU stay from Day 1 through Day 29.
Time frame: Up to Day 29
Population: The ITT population included all participants who were randomized.
| Arm | Measure | Value (NUMBER) |
|---|---|---|
| GAMUNEX-C + Standard Medical Treatment | Percentage of Participants With Actual Intensive Care Unit (ICU) Discharge Time | 64 Percentage of participants |
| Standard Medical Treatment | Percentage of Participants With Actual Intensive Care Unit (ICU) Discharge Time | 62 Percentage of participants |
p-value: 0.8599Gray's test