COVID-19 pneumonia
Conditions
Interventions
The first 6 consecutive patients will receive 1 mg ANXV i.v. in 60 minutes,
(t=0) and 1 mg ANXVV i.v. in 15 minutes (t=8h), on day 1.
The next day these 6 patients, in case there have been no safety
Sponsors
Medisch Universitair Ziekenhuis Maastricht
Eligibility
Age
18 Years to 99 Years
Inclusion criteria
Inclusion criteria: 1. Patients hospitalized for laboratory documented SARS-CoV2 infection (qRT-PCR). 2. Males between 18 and 75 years or Females of non-reproductive age or capacity, i.e post-menopausal or sterile, and between 18 and 75 years. 3. Signed informed consent by patient 4. Hospitalized with a resting oxygen saturation on room air of 350U/L, n=97-247 U/l) 6. Mentally Competent
Exclusion criteria
Exclusion criteria: 1. Subject requiring mechanical ventilation/ extracorporeal membrane oxygenation and in-tubated for mechanical ventilation. 2. Severe COPD, defined by continuous use of long-acting bronchodilators or inhaled/oral corticosteroids for > 2 months in the home situation. 3. Subject with severe renal impairment (eGFR 50% within 6 months. 6. Bleeding Risk: a. Clinical: Active bleeding; head trauma, intracranial surgery or stroke within 3 months; history of intracerebral arteriovenous malformation, cerebral aneurysm or mass lesions of the central nervous system; cerebral haemorrhage; history of a bleeding diatheses; gastrointestinal bleeding within 6 weeks; presence of an epidural or spinal catheter; contraindication for IV therapeutic UFH. b. Laboratory: Platelet count 3.0 or baseline aPTT >=45 seconds prior to enrolment. 7. Use of any of the following treatments: UFH to treat a thrombotic event within 12 hours before enrolment; thrombolytic therapy within 3 previous days; 8. Confirmed antiphospholipid syndrome, systemic lupus erythematosus and other auto-immune diseases (at discretion of PI) 9. Confirmed thalassemias (e.g sickle cell disease) 10. Cardiopulmonary resuscitation in previous 7 days. 11. Liver failure defined as Child-Pugh Score Class C. 12. Abnormal liver function (AST >5xULN, ALT >5xULN) 13. Life expectancy of
Design outcomes
Primary
| Measure | Time frame |
|---|---|
| Main study parameter/endpoint: Efficacy potential: • Assessment of activated coagulation factors in complex with antithrombin before each ANXV administration, and at 5, 20, 90, 240 and 480 min after the ending of each ANXV administration. Complexes are FXIa:AT, FIXa:AT and FXa:AT. • Assessment of cytokine and inflammatory profile at baseline, at 16 and 32 hours after last ANXV administration. (CRP, IFN-*, TNF*, IL-1*, IL- 6, IL-10 and IL-18). • Assessment of coagulation profile at baseline, and at 16 and 32 hours after the start of the first ANXV administration. Endpoints: Absolute D-dimer - (Fibrin Equivalent units); aPTT (Activated Partial Thromboplastin time) - seconds; fibrinogen (g/L); INR • Assessment of complement C5a levels at baseline, and at 16 and 32 hours after the start of the first ANXV administration • Assessment of the presence or absence of free histones in plasma. • 28-day all cause mortality • Patient free of shortness of breath (respiratory rate 37,50°C) • Change from baseline in ALT and AST • Change from baseline in lymphocyte count • Change from baseline in neutrophil count Frequency, intensity and seriousness of adverse events (AEs): • Infusion reactions to IMP, including hypersensitivity or anaphylactic reactions. • Clinically relevant changes from baseline in: • Vital signs (blood pressure, pulse, body temperature, respiratory rate, pulse oximetry, FiO2) • Physical examination • Safety laboratory parameters • ADA • Electrocardiogram (ECG) • Imaging (on indication, for instance in case suspicion of thromboembolic-or hemorrhagic event) | — |
Secondary
| Measure | Time frame |
|---|---|
| Pharmaco-kinetic parameters: • Area under the plasma concentration vs time curve from time zero extrapolated to infinity (AUCinf) • AUC from time zero to time of last quantifiable analyte concentration (AUClast) • Observed maximum concentration (Cmax) • Time to Cmax (Tmax) • Terminal slope of a semi-logarithmic concentration-time curve (*z) • Terminal half-life (T*) • Clearance (CL) • Volume of distribution (Vz) • Dose proportionality after a single dose, based on AUC and Cmax | — |
Countries
Netherlands
Outcome results
None listed