E.1 Medical condition or disease under investigation |
E.1.1 | Medical condition(s) being investigated |
|
E.1.1.1 | Medical condition in easily understood language |
|
E.1.1.2 | Therapeutic area | Diseases [C] - Virus Diseases [C02] |
MedDRA Classification |
E.1.3 | Condition being studied is a rare disease | No |
E.2 Objective of the trial |
E.2.1 | Main objective of the trial |
The primary endpoint is stabilization or improvement in modality needed to maintain oxygen supplementation as measured by modality required to maintain oxygen at entry. |
|
E.2.2 | Secondary objectives of the trial |
The secondary endpoints are change from baseline in: 1. Oxygen saturation based on average of three readings measured approximately 5 minutes apart derived by three independent readings; or by review of continuous oxygen monitoring records 2. Modified Borg Dyspnea scale 3. Quality of life (McGill Quality of Life Single-Item Scale) 4. Time to intubation 5. Time to extubation 6. Time to mechanical ventilation 7. Time to cessation of mechanical ventilation 8. Time to change of modality for oxygenation 9. Time to death 10.Imaging findings (Chest CT /Chest X-ray) 11.Clinical laboratory parameters 12.Frequency of Adverse Events (AEs) for Day 1 through Day 33 13.Frequency of Serious Adverse Events (SAEs) for Day 1 through Day 33 |
|
E.2.3 | Trial contains a sub-study | No |
E.3 | Principal inclusion criteria |
Inclusion Criteria: 1. Adult aged ≥ 18 years old 2. Provide voluntary, fully informed written and signed consent before any study-related procedures are conducted 3. Able to understand and comply with the relevant aspects of the study protocol 4. Laboratory (RT-PCR) confirmed COVID-19 infection on nares/throat swab and/or sputum and/or lower respiratory tract samples at Screening or within 7 days prior to Screening 5. Hospitalized, requiring supplemental oxygen with a resting room-air SpO2 of ≤93% or arterial oxygen partial pressure (PaO2)/fractional inspired oxygen (FiO2) ratio < 300 mmHg. Measurement can be taken from documented source records within the 24 hours prior to Screening 6. Chest imaging confirming lung involvement |
|
E.4 | Principal exclusion criteria |
Exclusion Criteria: 1. Existence of other evidence that can explain pneumonia including but not limited to: Influenza A virus, influenza B virus, bacterial pneumonia (as suggested by the combined clinical picture, radiological findings and known laboratory results [eg, elevated procalcitonin >0.5ng/mL and concomitant neutrophilia]), known fungal pneumonia, suspected fungal pneumonia based on compromised immune system with a history of past fungal infections, noninfectious causes, etc. 2. Known history of serious allergic reactions, including anaphylaxis to intravenous immunoglobulin (IVIG) or its preparation components 3. Subjects with a history of thromboembolic event (TEE) within the last 12 months, such as deep vein thrombosis, pulmonary embolism, myocardial infarction, ischemic stroke, transient ischemic attack, peripheral artery disease (Fontaine IV) 4. Subjects with an underlying medical condition that can lead to hypercoagulable states and hyperviscosity such as antithrombin III deficiency, Factor V Leiden, Protein C deficiency, antiphospholipid syndrome, and malignancy 5. Known history of selective IgA deficiency with antibodies against IgA 6. Subjects with conditions such as human immunodeficiency virus (HIV) infection, known acute or chronic hepatitis B or C (HBsAg positive or HCV ribonucleic acid (RNA) PCR positive or currently treated with antivirals), pulmonary fibrosis, elevated procalcitonin (> 0.5) with concomitant neutrophilia (elevated polys), heparin induced thrombocytopenia (HIT), and moderate to severe renal dysfunction (per investigator discretion based on estimated glomerular filtration rate [eGFR] <59 mL/min/1.73 m2, as defined by KDIGO Clinical Practice Guideline): • Moderately reduced GFR (G3a): GFR = 45 to 59 ml/min/1.73 m2 • Moderately reduced GFR (G3b): GFR = 30 to 44 ml/min/1.73 m2 • Severely reduced GFR (G4): GFR = 15 to 29 ml/min/1.73 m2 • Kidney failure (G5): GFR <15 ml/min/1.73 m2 7. Currently requiring IMV or having received IMV during the last 30 days 8. Known clinically significant preexisting lung, heart, or neuromuscular disease that, in the investigator’s opinion, would impact subject’s ability to complete study or may confound the study results 9. Body weight >125 kg 10.Women who are pregnant or breast-feeding 11.Subjects who received COVID-19 convalescent plasma, IVIG products, anti-interleukin agents (eg, Tocilizumab), or interferons for their COVID-19 disease before enrollment or plan to receive this treatment during the course of the study 12.Enrolled in other experimental interventional studies or taking experimental medications (ie, convalescent plasma). Diagnostic studies can be allowed if the anticipated total blood volume to be drawn across both studies and for therapeutic purposes does not exceed 450 mL over any 8-week period. |
|
E.5 End points |
E.5.1 | Primary end point(s) |
The primary endpoint is stabilization or improvement in clinical status defined as maintenance or improvement by one category on a 6-category clinical status scale on Day 7. Clinical status categories will be defined as: 1. Hospital discharge or meet discharge criteria (discharge criteria are defined as clinical recovery, i.e. fever, respiratory rate, oxygen saturation return to normal, and cough relief). 2. Hospitalization, not requiring supplemental oxygen. 3. Hospitalization, requiring supplemental oxygen (but not NIV/HFNC). 4. ICU/hospitalization, requiring NIV/HFNC therapy. 5. ICU, requiring Extracorporeal Membrane Oxygenation (ECMO) and/or IMV. 6. Death. |
|
E.5.1.1 | Timepoint(s) of evaluation of this end point |
|
E.5.2 | Secondary end point(s) |
The secondary endpoints are change from Baseline (Day 1) in: 1. Oxygen saturation (SpO2) based on average of three readings measured approximately 5 minutes apart derived by three independent readings, or by review of continuous oxygen monitoring records 2. Modified Borg Dyspnea Scale 3. Quality of life (McGill Quality of Life Single-Item Scale - MQoL-SIS) 4. Time to intubation 5. Time to extubation 6. Time to mechanical ventilation 7. Time to cessation of mechanical ventilation 8. Time to change of modality for oxygenation 9. Time to death 10.Imaging findings (Chest CT /Chest X-ray) 11.Clinical laboratory parameters 12.Frequency of Adverse Events (AEs) for Day 1 through Day 33 13.Frequency of Serious Adverse Events (SAEs) for Day 1 through Day 33 |
|
E.5.2.1 | Timepoint(s) of evaluation of this end point |
|
E.6 and E.7 Scope of the trial |
E.6 | Scope of the trial |
E.6.1 | Diagnosis | Yes |
E.6.2 | Prophylaxis | No |
E.6.3 | Therapy | Yes |
E.6.4 | Safety | Yes |
E.6.5 | Efficacy | Yes |
E.6.6 | Pharmacokinetic | No |
E.6.7 | Pharmacodynamic | No |
E.6.8 | Bioequivalence | No |
E.6.9 | Dose response | No |
E.6.10 | Pharmacogenetic | No |
E.6.11 | Pharmacogenomic | No |
E.6.12 | Pharmacoeconomic | No |
E.6.13 | Others | No |
E.7 | Trial type and phase |
E.7.1 | Human pharmacology (Phase I) | No |
E.7.1.1 | First administration to humans | No |
E.7.1.2 | Bioequivalence study | No |
E.7.1.3 | Other | No |
E.7.1.3.1 | Other trial type description | |
E.7.2 | Therapeutic exploratory (Phase II) | No |
E.7.3 | Therapeutic confirmatory (Phase III) | Yes |
E.7.4 | Therapeutic use (Phase IV) | No |
E.8 Design of the trial |
E.8.1 | Controlled | Yes |
E.8.1.1 | Randomised | Yes |
E.8.1.2 | Open | No |
E.8.1.3 | Single blind | No |
E.8.1.4 | Double blind | Yes |
E.8.1.5 | Parallel group | No |
E.8.1.6 | Cross over | No |
E.8.1.7 | Other | No |
E.8.2 | Comparator of controlled trial |
E.8.2.1 | Other medicinal product(s) | No |
E.8.2.2 | Placebo | Yes |
E.8.2.3 | Other | No |
E.8.2.4 | Number of treatment arms in the trial | 2 |
E.8.3 |
Will this trial be conducted at a single site globally?
| No |
E.8.4 | Will this trial be conducted at multiple sites globally? | Yes |
E.8.6 Trial involving sites outside the EEA |
E.8.6.2 | Trial being conducted completely outside of the EEA | Yes |
E.8.6.3 | Specify the countries outside of the EEA in which trial sites are planned |
|
E.8.7 | Trial has a data monitoring committee | Yes |
E.8.8 |
Definition of the end of the trial and justification where it is not the last
visit of the last subject undergoing the trial
|
|
E.8.9 Initial estimate of the duration of the trial |
E.8.9.2 | In all countries concerned by the trial years | 0 |
E.8.9.2 | In all countries concerned by the trial months | 3 |
E.8.9.2 | In all countries concerned by the trial days | 0 |