Trial Outcomes & Findings for A Study to Evaluate the Safety and Efficacy of C19-IG 20% in SARS-CoV-2 Infected Asymptomatic Ambulatory Outpatients (NCT NCT04847141)

Participants were enrolled in the study at 5 centers in Spain. The study was conducted from 28 April 2021 to 27 December 2021.

Participants with Severe Acute Respiratory Syndrome Coronavirus 2 (SARS-Cov-2) infection were randomized in 1:1:1 ratio to receive anti-COVID-19 Immune Globulin (Human) 20% \[C19-IG 20%\] 1 gram (g), C19-IG 20% 2 g, and placebo. A total of 555 participants were screened and 465 participants were randomized in the study. Among these, 461 participants were dosed, and 430 participants completed the study.

A Study to Evaluate the Safety and Efficacy of C19-IG 20% in SARS-CoV-2 Infected Asymptomatic Ambulatory Outpatients

Participants were described as symptomatic if they a. experienced at least two of the following systemic symptoms: fever (≥38 ºC), chills, myalgia, headache, sore throat, cough, fatigue that interferes with activities of daily living, new olfactory/taste disorder(s), and vomiting/diarrhea, b. experienced at least one of the following respiratory signs/symptoms: new or worsening shortness of breath or difficulty breathing; c. experienced a peripheral oxygen saturation by pulse oximetry (SpO2) \<94% on room air; or d. had radiographical evidence of pneumonia. The percentage of participants who meet the primary endpoint within each treatment group was presented along with a two-sided exact (Clopper-Pearson) 95% confidence interval (CI).

Mean change from baseline (CFB) in log10 SARS-CoV-2 viral load at Days 7 and 14 was assessed.

An outpatient setting was defined as no hospitalization or intensive care unit (ICU) admission through Days 3, 7, and 14. The percentage of participants who remained in an outpatient setting and maintained SpO2 ≥94% on room air at each timepoint within each treatment group were presented along with a two-sided exact (Clopper-Pearson) 95% CI. p-value and 95% CI were not estimable for C19-IG 20% 1 g vs placebo as all participants had remained in an outpatient setting and maintained SpO2 ≥94% on Room Air in C19-IG 20% 1 g and placebo arm on Day 3.

The percentage of participants with negative SARS-CoV-2 by PCR through Day 14 and Day 29 within each treatment group was presented along with a two-sided exact (Clopper-Pearson) 95% CI.

The first negative test result was defined as the first PCR negative result after the first PCR positive result. Kaplan-Meier method was used for analysis. Participants who did not have any viral load data or had negative test results through the study were excluded from the KM analysis.

The percentage of participants requiring oxygen supplementation through Day 29 within each treatment group was presented along with a two-sided exact (Clopper-Pearson) 95% CI.

The duration (number of days) of any oxygen use from Day 1 through Day 29 was calculated based on the start/stop date of using oxygen supplementation.

The ordinal scale is a 7-point scale ranging from 1 to 7 used to measure clinical status of a participant 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; and 7) not hospitalized, no limitations on activities. A higher score indicates less severity.

The ordinal scale is a 7-point scale ranging from 1 to 7 used to measure clinical status of a participant based on the following points: 1) death; 2) hospitalized, on invasive mechanical ventilation or 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; and 7) not hospitalized, no limitations on activities. A higher score indicates less severity. The analysis was performed by using a linear mixed-effects model for repeated measures (MMRM).

The ordinal scale is a 7-point scale ranging from 1 to 7 used to measure clinical status of a participant based on the following points: 1) death; 2) hospitalized, on invasive mechanical ventilation or 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; and 7) not hospitalized, no limitations on activities.

The NEWS has demonstrated an ability to classify participants at risk of poor outcomes. This score is based on 7 clinical parameters (respiration rate, oxygen saturation, any supplemental oxygen, temperature, systolic blood pressure (BP), heart rate, level of consciousness \[Alert, Voice, Pain, Unresponsive\]). A score of 0 to 3 was allocated to each parameter except supplemental oxygen use (score of 0 or 2) and level of consciousness (score of 0 \[alert, normal health condition\] or 3 \[altered mental state/confusion, worst health condition\]). All parameter scores were summed to get an aggregate NEWS assessment. Scoring for NEWS ranges from 0 to 20, with higher scores meaning more severity/higher clinical risk: low risk (score 1 to 4); medium risk (score 5 to 6); high risk (score 7 to 20). The analysis is performed by using a linear MMRM.

MAV for management/treatment of COVID-19 may have occurred in any setting e.g., emergency department, urgent care, outpatient clinic, or professional setting wherein direct in-person/telemedicine medical assessment and escalation of care for COVID-19 was provided by licensed healthcare personnel. The percentage of participants requiring at least one COVID-19-related MAV for management/treatment of COVID-19 (apart from routinely scheduled study-directed visits) within each treatment group was presented along with a two-sided exact (Clopper-Pearson) 95% CI.

The percentage of participants requiring hospital admission through Day 29 within each treatment group was presented along with a two-sided exact (Clopper-Pearson) 95% CI.

The duration (number of days) of hospitalization from post-randomization through Day 29 was calculated based on hospital admission and discharge dates recorded.

The percentage of participants requiring ICU admission through Day 29 within each treatment group was presented along with a two-sided exact (Clopper-Pearson) 95% CI. ICU level care is defined as the medical need for intensive or invasive monitoring; the immediate or impending need for the support of the airway, breathing, or circulation; and/or stabilization of acute severe, or life-threatening complications of COVID-19.

The duration (number of days) of ICU stay from post-randomization through Day 29 was calculated based on ICU admission and discharge dates recorded.

The percentage of participants requiring invasive mechanical ventilation through Day 29 within each treatment group was presented along with a two-sided exact (Clopper-Pearson) 95% CI.

The duration (number of days) on invasive mechanical ventilation from post randomization through Day 29 was calculated based on the start/stop dates of invasive mechanical ventilation.

All-cause mortality rate is the percentage of participants in each treatment group who experienced mortality up to Day 29.

Critical COVID-19 illness was defined as any one of the following: (a) requiring ICU admission or ICU level of care, (b) invasive mechanical ventilation, or (c) resulting in death by Day 29. The percentage of participants with critical COVID-19 illness defined above within each treatment group was presented along with a two-sided exact (Clopper-Pearson) 95% CI.

Length of time to clinical progression to critical COVID-19 illness was defined as the time to death, invasive mechanical ventilation, or ICU admission/requiring ICU level of care. ICU level care is defined as the medical need for intensive or invasive monitoring; the immediate or impending need for the support of the airway, breathing, or circulation; and/or stabilization of acute severe, or life-threatening complications of COVID-19. The time to clinical progression was estimated using the KM method.

Participants were described as symptomatic if they a. experienced at least two of the following systemic symptoms: fever (≥38℃), chills, myalgia, headache, sore throat, cough, fatigue that interferes with activities of daily living, new olfactory/taste disorder(s), and vomiting/diarrhea, b. experienced at least one of the following respiratory signs/symptoms: new or worsening shortness of breath or difficulty breathing, c. experienced a peripheral oxygen saturation by pulse oximetry (SpO2) \<94% on room air, or d. had radiographical evidence of pneumonia. Time to COVID-19 symptoms was defined as the time from study drug administration to the first time point when any of the above elements was fulfilled through Day 14. The time to COVID-19 symptoms was estimated using the KM method.