Severe COVID-19 POSITIVE hospitalized male or female, between 18 and = 80 years of age
Conditions
Sponsors
APEIRON Biologics AG
Eligibility
Sex/Gender
All
Inclusion criteria
Inclusion criteria: 1. Hospitalised male or female, = 18 to = 80 years of age at the time of consent. The date of signing informed consent is defined as the beginning of the screening period. This inclusion criterion will only be assessed at the first screening visit. 2. Diagnosed to be COVID-19 POSITIVE (SARS-CoV-2 nucleic acid – qPCR) 3. Oxygenation criterion • Oxygen saturation =93 % (either on Room Air or while the patient is on supplement oxygen) 4. ALT =65 years) yes F.1.3.1 Number of subjects for this age range 120
Exclusion criteria
Exclusion criteria: 1. Any patient for whom the investigator does not consider there is a reasonable expectation that they will be able to complete the study. 2. Known history of positive Hepatitis B surface antigen, Hepatitis C antibody or HIV antibody 3. Current or chronic history of liver disease (Child Pugh score = 10), or known hepatic or biliary abnormalities (with the excep-tion of Gilbert's syndrome or asymptomatic gallstones). 4. The patient has participated in a clinical trial and has received an investigational product within the following time period prior to the first dosing day in the current study: 5 half-lives or twice the duration of the biological effect of the investigational product (whichever is longer). 5. Patients requiring high doses of loop diuretics (i.e. > 240 mg fu-rosemide daily) with significant intravascular volume depletion, as assessed clinically. 6. History of sensitivity to any of the study medications, or compo-nents thereof or a history of drug or other allergy that, in the opinion of the investigator or Medical Monitor, contraindicates their participation. 7. Pregnant females as determined by positive serum or urine hCG test prior to dosing. 8. Lactating females. 9. Unwillingness or inability to follow the procedures outlined in the protocol. 10. Unstable Hemoglobin (Hb 7 mg/dL at the time of drug infusion. Transfusion is permitted to increase Hb levels to allow entry into the study. 11. Malignancy or other irreversible condition for which 6 month mortality is estimated to be >50%. 12. Arterial blood pH less than 7.2 or serum HCO3- 45 mmHg) or chronic hypoxemia [(PaO2 50 mmHg or PaO2 < 55 mmHg, or oxygen saturation <88% on FiO2 = 0.21) - known chronic restrictive, obstructive, neuromuscular, chest wall, or pulmonary vascular disease resulting in severe exercise restriction (i.e. unable to climb stairs or perform household duties), known secondary polycythemia, severe pulmonary hypertension, or ventilator dependency 14. Known vasculitis with diffuse alveolar hemorrhage 15. Lung transplantation 16. Pre-existing renal failure, i.e. requiring renal replacement ther-apy with hemodialysis or peritoneal dialysis 17. There are other uncontrolled co-morbidities that increase the risks associated with the study drug administration, that are as-sessed by the medical expert team as unsuitable 18. Patient in clinical trials with an IMP for COVID-19 within 30 days before signing informed consent form (ICF) 19. Unstable hemodynamics in the preceding 4 hours (MAP = 65 mmHg, or SAP < 90 mmHg, DAP < 60 mmHg, and vaso-active agents required) 20. Immunocompromised patients (chemotherapy, HIV, organ transplants, stem cell transplants), 21. Receive any Angiotensin-Converting-Enzyme inhibitor (ACEi) or renin inhibitor treatment within 7 days before ICF
Design outcomes
Primary
| Measure | Time frame |
|---|---|
| Main Objective: To assess clinical efficacy of APN01 using a composite outcome of all cause-death or need of invasive mechanical ventilation up to 28 days;Secondary Objective: To assess efficacy of APN01 using log transformed levels of Lactate dehydrogenase (LDH) as a surrogate marker for organ damage. To evaluate the safety of APN01 in patients with severe COVID-19 To monitor other biomarker changes (e.g. IL-6, AngII) in patient with severe COVID-19 treated with APN01 ;Primary end point(s): The primary endpoint is a composite endpoint of all cause-death or invasive mechanical ventilation up to 28 days or hospital discharge.;Timepoint(s) of evaluation of this end point: Continioulsy over the duration of the trial | — |
Secondary
| Measure | Time frame |
|---|---|
| Secondary end point(s): 1. Log transformed levels of Lactate dehydrogenase (LDH) at day 5 as a surrogate marker for organ damage (powered secondary endpoint) 2. 28-day mortality (all cause-death) 3. Ventilator-free days (VFD) up to 28 days or hospital discharge 4. Proportion of responders, defined as =2 improvement in WHO’s 11-Point Score system at day 7, 10, 14 and 28 5. Time to death (all cause) 6. Proportion of patients with any use of invasive mechanical ven-tilation up to 28 days or hospital discharge 7. Time to first use of invasive mechanical ventilation up to 28 days or hospital discharge 8. Absolute values and absolute change in P/F ratio over time 9. Absolute values and absolute change in the modified Sequential organ failure assessment score (mSOFA score) over time 10. Time to a 2-point decrease in WHO scoring scheme 11. Absolute values and absolute change in lymphocyte counts over time 12. Absolute values and absolute change in C-reactive protein levels over time 13. Absolute values and absolute change in D-dimer over time 14. Absolute values and absolute change in log transformed levels of LDH over time 15. Time to hospital discharge 16. Change in viral RNA over time Biomarker endpoints: Absolute values and absolute changes in relevant biomarkers over time: 1. Angiotensin II (Ang II), Angiotensin 1-7 (Ang 1-7), Angiotensin 1-5 (Ang 1-5), renin and aldosterone, Angiotensin-converting enzyme (ACE), Angiotensin-converting enzyme 2 (ACE2), Angiotensin I (Ang I), Angiotensin 1-9 (Ang 1-9) 2. Cytokines: Interleukin 6 (IL-6), Interleukin 8 (IL-8), soluble Tumor Necrosis Factor receptor type II (sTNFrII), Plasminogen Activator Inhibitor type-1 (PAI-1), von Willebrand Factor (vWF), Tumor necrosis factor-a (TNF-a) 3. Alveolar epithelial markers: soluble Receptor for Advanced Glycation End products (sRAGE), Surfactant protein-D(SP-D) 4. Endothelial markers: Angiopoietin-2 5. Change in clinical laboratory markers associated with poor outcome ov | — |
Countries
Austria, Denmark, Germany, Russian Federation, United Kingdom, United States
Contacts
Public ContactSponsor
APEIRON Biologics AG
Outcome results
None listed