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

Phase 3TerminatedNCT05531149

Biotest107 enrolled

Overview

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.

Study Type

INTERVENTIONAL

Allocation

RANDOMIZED

Purpose

TREATMENT

Masking

Eligibility

Sex: ALLMin age: 18 Years

Medical Language ↔ Plain English

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.

Locations (64)

Investigational Site #5401

Buenos Aires, Argentina

Investigational Site #5403

Córdoba, Argentina

Investigational Site #5402

Córdoba, Argentina

Investigational Site #4303

Klagenfurt, Austria

Investigational Site #4302

Linz, Austria

Investigational Site #4304

Outcomes

Primary Outcomes

Composite Endpoint

Composite of percentage of subjects with a change of at least 1 category on the 9-category ordinal scale from baseline (between days 6-29) and 28-day all-cause mortality rate (between days 1-29)

Time frame: Until day 29

Secondary Outcomes

Clinical deterioration rate

Percentage of subjects with a change of at least 1 category on the category ordinal-scale

Time frame: Between days 6-29 and days 1-29

28-days all-cause mortality rate

Percentage of subjects with a change to 8 on 9-category ordinal scale.

Time frame: Day 29

90-days all-cause mortality rate

Percentage of subjects with a change to 8 on 9-category ordinal scale.

Time frame: Day 91

Time to recovery

Number of days to score ≤ 2 until day 29

Time frame: Between days 1-29

Proportion of subjects with score ≤ 2

Proportion of subjects that improved to score ≤ 2

Time frame: Day 29

Proportion of subjects improved, unchanged, and deteriorated/died

Proportion of subjects improved, unchanged, and deteriorated/died compared to baseline at several days

Time frame: Between days 1-29

Proportion of subjects with different partial pressure of oxygen (PaO2)/ fraction of inspired oxygen (FiO2) ratios

Proportion of subjects with PaO2/FiO2 ratio \< 100, 100 to \< 200, 200 to \< 300 or ≥ 300

Time frame: Days 7, 14, 21, 29

Days of invasive mechanical ventilation (IMV)/ extracorporeal membrane oxygenation (ECMO)

Days of IMV/ECMO

Time frame: Day 29

Proportion of subjects on IMV/ECMO

Time frame: Day 29

Days with oxygen supply

Time frame: Day 29

Proportion of subjects with oxygen supply

Time frame: Days 7, 14, 21, 29

Days in intensive care unit (ICU)

Days in intensive care unit

Time frame: Day 29

Proportion of subjects in ICU

Time frame: Day 29

Days of hospitalization

Time frame: Day 29

All adverse events (AEs), treatment-emergent AEs (TEAEs), AEs of special interest (AESIs), infusional TEAEs, TEAEs that led to permanent withdrawal of IMP and/or discontinuation of trial

Number, severity, causality, outcome, and seriousness of all adverse events (AEs), treatment-emergent AEs (TEAEs), AEs of special interest (AESIs), infusional TEAEs, TEAEs that led to permanent withdrawal of IMP, and TEAEs that led to discontinuation of the trial

Time frame: Until day 29

TEAEs

Number of all related TEAEs

Time frame: Until day 29

SAEs

Number, severity, causality, and outcome of all serious adverse events (SAEs)

Time frame: Until day 29

Dose modifications

Dose modifications (incl. reductions and changes in infusion rate)

Time frame: Day 1-5

Change over time in ECG parameters

ECG recordings, (including heart rate, QT-interval, QTcF) showing abnormal, clinically relevant findings will be reported as adverse event

Time frame: Days -1, 1, 3, 5 and once between days 8-13

Changes over time in vital signs

Changes in recordings of vital sign parameters showing clinically significant measurements outside the normal range will be reported as adverse event.

Time frame: Days -1,1-3, 5, 7 ,14, 21, 29

Changes over time in clinical laboratory parameters

Changes in recordings for clinical laboratory values (including chemistry, hematology and coagulation) showing clinically significant measurements outside the normal range will be reported as adverse event.

Time frame: Days -1, 1-5, 7,14, 21, 29

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

Overview

Conditions

Interventions

Eligibility

Locations (64)

Outcomes

Primary Outcomes

Secondary Outcomes