Efficacy and Safety of Trimodulin in Subjects With Severe COVID-19 (ESsCOVID)
Covid19
About this trial
This is an interventional treatment trial for Covid19 focused on measuring Covid19, Severe community acquired pneumonia, Acute Respiratory Distress Syndrome, SARS-CoV-2, Severe Corona Virus Disease
Eligibility Criteria
Inclusion Criteria:
- Written informed consent obtained from the subject or legally authorized representative or informed verbal or administration consent due to pandemic situation, in compliance with all local legal requirements.
- Male or female subject ≥18 years of age.
- Laboratory-confirmed SARS-CoV-2 infection from a test done in a respiratory tract sample within the last 5 days at screening.
Diagnosis of community-acquired severe COVID-19 within 10 days after hospital-admission, with severe defined as:
Need for non-invasive ventilation (NIV), or high-flow oxygen therapy (score =5 on the 9-category ordinal scale).
At least one of the following clinical respiratory parameters is fulfilled: dyspnea, respiratory frequency ≥30/min, SpO2 ≤93%, 100 mmHg < PaO2/FiO2 ≤300 mmHg, and/or lung infiltrates >50% within 24 to 48 hours.
At least one measurement of C-reactive protein ≥50 mg/L within 36 hours prior to start of treatment.
- Subject must receive SoC treatment for COVID-19.
Exclusion Criteria:
- Pregnant or lactating women.
- Subjects that deteriorated to score >5 on the 9-category ordinal scale (e.g. receiving invasive mechanical ventilation (IMV), and/or extracorporeal membrane oxygenation (ECMO)) or subjects that improved to score <5 prior to randomization.
- Severe neutropenia (neutrophil count <500/mm³) assessed within 24 hours prior to start of treatment.
- Thrombocytopenia (platelet count <30,000/mm³) assessed within 24 hours prior to start of treatment.
- Hemoglobin <7g/dL assessed within 24 hours prior to start of treatment.
- Known hemolysis.
- Known thrombosis or thromboembolic events (TEEs) or known medical history of TEEs (e.g. cerebrovascular accidents, transient ischemic attack, myocardial infarction, pulmonary embolism, and deep vein thrombosis) within the previous 3 months or those subjects particularly at risk for TEEs (e.g. history of thrombophilia, permanent immobilization, or permanent paralysis of the lower extremities) caused by other reasons than COVID-19.
- Subject on dialysis or with severe renal impairment, estimated glomerular filtration rate (eGFR) <30 mL/min/1.73 m² assessed within 24 hours prior to start of treatment (details in Appendix 3: Estimated Glomerular Filtration Rate).
- Subject with end stage renal disease (ESRD), or known primary focal segmental glomerulosclerosis (FSGS).
- Known severe lung diseases interfering with COVID-19 therapy (e.g. severe interstitial lung disease, cystic fibrosis, idiopathic pulmonary fibrosis, active tuberculosis, chronically infected bronchiectasis, or active lung cancer).
- Known decompensated heart failure (New York Heart Association class III-IV).
- Known pre-existing hepatic cirrhosis, severe hepatic impairment (Child Pugh C score ≥9 points), or hepatocellular carcinoma.
- Known intolerance to proteins of human origin or known allergic reactions to components of trimodulin.
- Selective, absolute immunoglobulin A (IgA) deficiency with known antibodies to IgA.
- Known treatment for thorax/head/neck/hematologic malignancies in the last 12 months.
- Known human immunodeficiency virus infection.
- Life expectancy of less than 90 days, according to the Investigator's clinical judgment, because of medical conditions neither related to COVID-19 nor to associated medical complications.
- Obesity (body mass index ≥40 kg/m²), a body weight of more than 123 kg, or anorexia (body mass index <16 kg/m²).
- Known immunosuppressive treatment other than acute treatment for COVID-19 (e.g. transplant recipient, subject with autoimmune disease).
- Known treatment with polyvalent immunoglobulin preparations, any type of blood product, or any type of interferon during the last 21 days before entering the trial.
- Participation in another interventional clinical trial within 30 days before entering, or during the trial, or previous participation in this clinical trial.
- Employee or direct relative of an employee of the contract research organization, the trial site, or Biotest.
Sites / Locations
- Investigational site # 5503
- Investigational site # 5502
- Investigational site # 5505
- Investigational site # 5501
- Investigational site # 3304
- Investigational Site # 3301
- Investigational site # 3305
- Investigational site # 0707
- Investigational site # 0709
- Investigational site # 0702
- Investigational site # 0706
- Investigational site # 0711
- Investigational Site # 0704
- Investigational site # 0708
- Investigational site # 0701
- Investigational Site # 3401
- Investigational Site # 3402
Arms of the Study
Arm 1
Arm 2
Experimental
Placebo Comparator
Trimodulin
Placebo
Trimodulin (human IgM, IgA, IgG solution) for intravenous (IV) administration.
Human albumin 1%