Hypercytokinemia in patients with COVID-19 and severe respiratory distress syndrome (SARS) due to CoV-2 infection Infections and Infestations
Conditions
Interventions
With both subject and the evaluating physician blinded, subjects will be administered the investigational drug injection and placebo (saline) injection at Visit 1 (Day 0), by a non-evaluating (unblind
Sponsors
Kimera Labs
Eligibility
Sex/Gender
All
Inclusion criteria
Inclusion criteria: 1. COVID-19 patients requiring invasive mechanical ventilation for respiratory failure due to pneumonia 2. Requiring treatment with vasopressors 3. Requiring artificial ventilation and PaO2/FiO2 < 300 mmHg
Exclusion criteria
Exclusion criteria: 1. Recent administration of hydroxychloroquine, chloroquine, or steroids 2. Recent administration of tocilizumab (IL-6 antibody) 3. Hospital acquired (HAP)-, Health Care acquired (HCAP)- or Ventilator associated-pneumonia (VAP) 4. Pneumonia exclusively of bacterial or fungal origin* bacterial pneumonia co-infected with viruses and/or other microorganisms may be entered into the study. *Due to the short time window (up to 18 hours) between fulfillment of severity criteria (ie initiation of invasive mechanical ventilation or vasopressors administration, whichever comes first) and the start of the first dose of study treatment, patients with a pneumonia of suspected viral origin by any established standard diagnostic method routinely applied at the study site (eg oral swap antigen test, rt-PCR) can be entered into the study (confirmation of viral origin must be obtained afterwards) 5. Known or suspected Pneumocystis jirovecii (formerly known as Pneumocystis carinii) pneumonia 6. Aspiration pneumonia 7. Known active tuberculosis 8. A history of post-obstructive pneumonia 9. Cystic fibrosis 10. Any chronic lung disease requiring oxygen therapy at home 11. Presence of infection in another organ location caused by same pathogen (eg 12. Pneumococcal meningitis in the context of pneumococcal pneumonia) 13. Expected to have rapidly fatal disease within 72 hours after randomization 14. Inability to maintain a mean arterial pressure 50 mmHg prior to Screening despite the presence of vasopressors and intravenous fluids 15. Not expected to survive for 3 months due to other pre-existing medical conditions such as end-stage neoplasm or other diseases 16. A history of malignancy in the 5 years prior to screening, except for successfully surgically treated non-melanoma skin malignancies 17. Known primary immunodeficiency disorder or with HIV infection and acquired immune deficiency syndrome (AIDS) with CD4 count 21 days prior to onset of pneumonia symptoms 20. Received stem cell therapy, or allogeneic transplantation (organ or bone marrow transplant) within the past 6 months 21. Receiving treatment with a biological agent (eg antibodies, cells), immunotherapy or plasma exchange treatment within the last 8 weeks 22. A known liver function impairment associated with liver cirrhosis (Child Pugh C) or known esophageal varices 23. Hospitalized within the previous 15 days 24. Conditions resulting in a New York Heart Association or Canadian Cardiovascular Society Class IV functional status 25. End-stage neuromuscular disorders (eg motor neuron diseases, myasthenia gravis, etc) or cerebral disorders that impair weaning 26. Patients with quadriplegi
Design outcomes
Primary
| Measure | Time frame |
|---|---|
| 1. Safety and adverse events measured using i.v. administration of 0.2mg/kg of placental, mesenchymal stem cell-derived exosome preparations (KTA 100,= XoGlo®) at day 1 and day 3 2. Improved respiration measured using PaO2/FiO2 at day 1, 2, and onwards daily | — |
Secondary
| Measure | Time frame |
|---|---|
| 1. Mechanical ventilator and vasopressors treatment-free days (number of days that a patient is alive and free from mechanical ventilation and vasopressors) over 28 days. 2. Percentage of patients alive and free of mechanical ventilation at Day 29 3. Ventilator free days (VFD) over 28 days. VFD are defined as one point for each day during the measurement period that are both alive and free of mechanical ventilation. 4. Percentage of patients alive and free of vasopressors at Day 29 5. Vasopressor treatment-free days over 28 days defined as one point for each day during the measurement period that subjects are both alive and free of vasopressors. 6. Time to end of invasive mechanical ventilation 7. Time to end of invasive and/or non-invasive mechanical ventilation 8. Time to end of vasopressors treatment 9. sVP-ARDS-COVID-19 Clinical Response at Day 14±2 assessed as follows: 9.1. Cure: complete resolution of pneumonia signs and symptoms present at baseline, no new symptoms or complications attributable to the pneumonia. 9.2. Non-response: any of the following: 9.2.1. Failure related to pneumonia: Persistence/progression of baseline signs/symptoms of pneumonia; or baseline radiographic abnormalities after at least 2 days of treatment; or development of new pulmonary/extra pulmonary findings consistent with active infection, or development of new pulmonary infection or extrapulmonary infection requiring antimicrobial therapy; or persistence/progression of baseline signs/symptoms of severe sepsis; or development of new signs/symptoms of severe sepsis; or death due to sepsis 9.2.2. Failure unrelated to pneumonia: Any other cause of clinical response failure than in the investigator's judgement is unrelated to the index pneumonia (myocardial infarction, pulmonary thromboembolism, se | — |
Countries
Germany
Outcome results
None listed