E.1 Medical condition or disease under investigation |
E.1.1 | Medical condition(s) being investigated |
acute respiratory distress sydnrome (ARDS) secondary to Covid-19 |
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E.1.1.1 | Medical condition in easily understood language |
acute respiratory distress sydnrome (ARDS) secondary to Covid-19 |
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E.1.1.2 | Therapeutic area | Diseases [C] - Immune System Diseases [C20] |
MedDRA Classification |
E.1.2 Medical condition or disease under investigation |
E.1.2 | Version | 23.0 |
E.1.2 | Level | PT |
E.1.2 | Classification code | 10051905 |
E.1.2 | Term | Coronavirus infection |
E.1.2 | System Organ Class | 10021881 - Infections and infestations |
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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 aim of the study is to conduct a clinical trial of IV AAT as a prospective anti-inflammatory therapy for severely ill COVID-19 patients with ARDS requiring ICU admission.
The primary objective is to demonstrate a biological effect of IV Prolastin administered weekly at 120mg per kilogram of body weight in patients with severe COVID-19 illness requiring intubation and mechanical ventilation for ARDS by reducing circulating levels of IL-6 as measured by plasma ELISA. The study sample size is sufficient to demonstrate a significant difference in patients receiving Prolastin versus patients receiving placebo. |
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E.2.2 | Secondary objectives of the trial |
determine the safety and tolerability of [IV Prolastin administered once at 120mg/kg of body weight] and [IV Prolastin administered weekly at 120mg/kg of body weight for 4 weeks], as assessed by the number of AEs and SAEs and determine the effects of [IV Prolastin administered once at 120mg per kilogram of body weight] and [IV Prolastin administered weekly at 120mg per kilogram of body weight for 4 weeks] on: Physiological indices of respiratory dysfunction reflecting severity of ARDS, as measured by oxygenation index (OI), respiratory compliance Sequential organ failure assessment (SOFA) score Mortality Time on ventilator in days Circulating alpha-1 antitrypsin (AAT) levels Circulating levels of IL-1β, IL-8, IL-10, soluble TNF receptor 1 Development of shock Acute kidney injury Need for renal replacement therapy Clinical relapse Length of ICU stay in days |
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E.2.3 | Trial contains a sub-study | No |
E.3 | Principal inclusion criteria |
1.Laboratory confirmed diagnosis of COVID-19 infection 2. Moderate to severe ARDS with a PaO2/FiO2 ratio <200 3. >18 years of age 4. Patients receiving invasive mechanical ventilation or non-invasive ventilation
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E.4 | Principal exclusion criteria |
1. Not receiving invasive mechanical ventilation or non invasive ventilation 2. More than 96 hours from the onset of ARDS 3. Age < 18 years 4. Known to be pregnant or breastfeeding 5. Participation in a clinical trial of interferon therapies, immune plasma therapies or immunoglobulin within 30 days 6. Major trauma in the prior 5 days 7. Presence of any active malignancy (other than non-melanoma skin cancer) that required treatment within the last year 8. WHO Class III or IV pulmonary hypertension 9. Pulmonary embolism within past 3 months 10. Currently receiving extracorporeal life support (ECLS) 11. Currently receiving renal replacement therapy 12. Severe chronic liver disease with Child-Pugh score > 12 13. DNAR (Do Not Attempt Resuscitation) order in place 14. Treatment withdrawal imminent within 24 hours 15. Prisoners 16. Non-English speaking patients or those who do not adequately understand verbal or written information unless an interpreter is available. 17. Enrolled in a concomitant clinical trial of interferon therapies, immune plasma therapies or immunoglobulin. 18. IgA deficiency
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E.5 End points |
E.5.1 | Primary end point(s) |
The primary effectiveness outcome measure, a continuous variable, is IL-6 in plasma as measured by ELISA. |
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E.5.1.1 | Timepoint(s) of evaluation of this end point |
day 2 , day 7, day 14, day 21 and day 28 |
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E.5.2 | Secondary end point(s) |
Safety and tolerability of IMP in the respective groups, as defined by the number of SEAs and AEs, binary variable • PaO2/FiO2 ratio, continuous variable • Respiratory compliance, continuous variable • Sequential organ failure assessment (SOFA) score, continuous variable • Mortality, binary variable • Time on ventilator in days, continuous variable • Circulating AAT levels as measured by nephelometry, continuous variable • Plasma levels of IL-1β as measured by ELISA, continuous variable • Plasma levels of IL-8 as measured by ELISA, continuous variable • Plasma levels of IL-10 as measured by ELISA, continuous variable • Plasma levels levels of soluble TNF receptor 1 (sTNFR1, a surrogate marker for TNF-α) as measured by ELISA, continuous variable • Development of shock, defined for the purpose of this study as life-threatening organ dysfunction caused by a dysregulated response to infection, with critical reduction in tissue perfusion and acute failure of multiple organs, including the lungs, kidneys, and liver, binary variable • Acute kidney injury defined as an abrupt sustained rise in urea and creatinine, binary variable • Need for renal replacement therapy, binary variable • Clinical relapse, as defined by the need for readmission to the ICU or a marked decline in PaO2/FiO2 or development of shock or mortality following a period of sustained clinical improvement, binary variable • Secondary bacterial pneumonia as defined by the combination of radiographic findings and sputum/airway secretion microscopy and culture, binary variable
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E.5.2.1 | Timepoint(s) of evaluation of this end point |
day 2 , day 7, day 14, day 21 and day 28 |
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E.6 and E.7 Scope of the trial |
E.6 | Scope of the trial |
E.6.1 | Diagnosis | No |
E.6.2 | Prophylaxis | No |
E.6.3 | Therapy | Yes |
E.6.4 | Safety | No |
E.6.5 | Efficacy | No |
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) | Yes |
E.7.3 | Therapeutic confirmatory (Phase III) | No |
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 | Yes |
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 | 3 |
E.8.3 |
The trial involves single site in the Member State concerned
| No |
E.8.4 | The trial involves multiple sites in the Member State concerned | Yes |
E.8.4.1 | Number of sites anticipated in Member State concerned | 4 |
E.8.5 | The trial involves multiple Member States | No |
E.8.6 Trial involving sites outside the EEA |
E.8.6.1 | Trial being conducted both within and outside the EEA | No |
E.8.6.2 | Trial being conducted completely outside of the EEA | No |
E.8.7 | Trial has a data monitoring committee | No |
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
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The end of the trial will be defined as the last patient visit for the last patient enrolled to the trial. |
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E.8.9 Initial estimate of the duration of the trial |
E.8.9.1 | In the Member State concerned years | 1 |
E.8.9.1 | In the Member State concerned months | 0 |
E.8.9.1 | In the Member State concerned days | 0 |