Efficacy and Safety of Trimodulin in Subjects With Severe COVID-19

Inclusion Criteria:

1. 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.

2. Male or female subject ≥18 years of age.

3. Laboratory-confirmed SARS-CoV-2 infection from a test done in a respiratory tract
sample within the last 5 days at screening.

4. 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.

5. Subject must receive SoC treatment for COVID-19.

Exclusion Criteria:

1. Pregnant or lactating women.

2. 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.

3. Severe neutropenia (neutrophil count <500/mm³) assessed within 24 hours prior to start
of treatment.

4. Thrombocytopenia (platelet count <30,000/mm³) assessed within 24 hours prior to start
of treatment.

5. Hemoglobin <7g/dL assessed within 24 hours prior to start of treatment.

6. Known hemolysis.

7. 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.

8. 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).

9. Subject with end stage renal disease (ESRD), or known primary focal segmental
glomerulosclerosis (FSGS).

10. 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).

11. Known decompensated heart failure (New York Heart Association class III-IV).

12. Known pre-existing hepatic cirrhosis, severe hepatic impairment (Child Pugh C score ≥9
points), or hepatocellular carcinoma.

13. Known intolerance to proteins of human origin or known allergic reactions to
components of trimodulin.

14. Selective, absolute immunoglobulin A (IgA) deficiency with known antibodies to IgA.

15. Known treatment for thorax/head/neck/hematologic malignancies in the last 12 months.

16. Known human immunodeficiency virus infection.

17. 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.

18. Obesity (body mass index ≥40 kg/m²), a body weight of more than 123 kg, or anorexia
(body mass index <16 kg/m²).

19. Known immunosuppressive treatment other than acute treatment for COVID-19 (e.g.
transplant recipient, subject with autoimmune disease).

20. 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.

21. Participation in another interventional clinical trial within 30 days before entering,
or during the trial, or previous participation in this clinical trial.

22. Employee or direct relative of an employee of the contract research organization, the
trial site, or Biotest.