Efficacy and Safety of Trimodulin (BT588) in Subjects With CAP Including COVID-19 Pneumonia

A Randomized, Placebo-controlled, Double-blind, Multi-center, Phase III Trial to Assess the Efficacy and Safety of Trimodulin (BT588) in Adult Hospitalized Subjects With CAP Including COVID-19 Pneumonia.

The main objectives of the trial are to assess the efficacy and safety of trimodulin as adjunctive treatment to standard of care (SoC) compared to placebo plus SoC in adult hospitalized subjects with non-severe community-acquired pneumonia (CAP) or moderate / severe Coronavirus Disease 2019 (COVID-19) pneumonia.

Other objectives are to determine pharmacokinetic (PK) and pharmacodynamic (PD) properties of trimodulin.

This is a randomized, placebo-controlled, double-blind, multi-center, phase III trial to assess the efficacy and safety of trimodulin compared to placebo treatment, adjunctive to SoC in adult hospitalized subjects with non-severe community-acquired pneumonia (CAP) or moderate / severe Coronavirus Disease 2019 (COVID-19) pneumonia. Patients requiring low-flow oxygen, non-invasive ventilation or high-flow oxygen and with signs of early systemic inflammation (defined by C reactive protein (CRP), D-dimer and platelet levels) will be enrolled.

Subjects will be randomized to receive either trimodulin or placebo on a 1:1 basis, stratified by type of oxygen supply before randomization and by region. Investigational Medicinal Product (IMP) treatments will be blinded. Subjects will be administered IMP once daily on five consecutive days (day 1 through day 5) adjunctive to SoC. The subsequent follow-up phase comprises maximally 23 days (day 6 through day 28) followed by an end-of-follow-up visit/telephone call on day 29 [+3]. For all subjects still in the hospital after day 29, an extended follow-up visit is conducted until day 90 or until discharge. For all subjects a closing visit/telephone call on day 91 [+10] will be done.

For the evaluation of the primary and several secondary endpoints of the trial, a 9-category ordinal scale will be used. The primary objective is to assess efficacy of trimodulin based on clinical deterioration and mortality to demonstrate superiority to treatment with placebo. Secondary objectives are to assess efficacy and safety and to determine PK and PD properties of trimodulin compared to placebo.

Main Inclusion Criteria:

1. Written informed consent.
2. Hospitalized, adult (≥ 18 years of age) subjects.
3. Diagnosis of CAP or COVID- 19 pneumonia (e.g. according to local guidelines) and with radiologic evidence showing new pulmonary lobar or multilobar infiltrates consistent with CAP or COVID-19 pneumonia.
4. Receiving oxygen supply via low-flow oxygen, high-flow oxygen or on non-invasive ventilation.
5. Fulfilling at least one clinical respiratory parameter (SpO2 ≤ 94% and/or 100 mm Hg < PaO2/FiO2 ≤ 300 mm Hg).
6. Signs of early systemic inflammation based on CRP and coagulation parameter threshold levels.

Main Exclusion Criteria:

1. Pregnant or lactating women.
2. Subject on invasive mechanical ventilation and/or extracorporeal membrane oxygenation.
3. Subject with septic shock and in need for vasopressors.
4. Severe neutropenia prior to start of treatment.
5. Hemoglobin >7 g/dL prior to start of treatment.
6. Pre-existing hemolytic disease.
7. Pre-existing thromboembolic events (TEEs).
8. Subject on dialysis or with severe renal impairment prior to start of treatment.
9. Subject with end stage renal disease, or known primary focal segmental glomerulosclerosis.
10. Pre-existing severe lung diseases to current pneumonia.
11. Pre-existing decompensated heart failure.
12. Pre-existing hepatic cirrhosis, severe hepatic impairment , or hepatocellular carcinoma.
13. Known intolerance to proteins of human origin or known allergic reactions to components of trimodulin/placebo.
14. Selective, absolute immunoglobulin A (IgA) deficiency with known antibodies to IgA.
15. Known human immunodeficiency virus infection.
16. Life expectancy of less than 90 days.
17. Morbid obesity or malnutrition.
18. Treatment with predefined medications (certain immune modulators or immunosuppressants) before entering the trial.