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

Phase 3

Recruiting

• Conditions: COVID-19; Pneumonia; Community-acquired Pneumonia; Bacterial Pneumonia; Respiratory Infection; Viral Pneumonia; Fungal Pneumonia; Acute Respiratory Distress Syndrome
• Interventions: Drug: Trimodulin; Drug: Placebo (human albumin 1%)

• Registration Number: NCT05531149
• Lead Sponsor: Biotest

Brief Summary

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.

Detailed Description

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 Timeline

• Study First Submitted: 2022-08-26
• Study First Submitted QC: 2022-09-05
• Study First Posted: 2022-09-07
• Study Start: 2022-12-22
• Status Verified: 2024-04
• Last Update Submitted: 2024-04-10
• Last Update Posted: 2024-04-11
• Primary Completion: 2025-08-31
• Study Completion: 2025-08-31

Recruitment & Eligibility

• Status: RECRUITING
• Sex: All
• Target Recruitment: 390

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

Read More

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.

Read More

Study & Design

• Study Type: INTERVENTIONAL
• Study Design: PARALLEL

Arm && Interventions

Group	Intervention	Description
Trimodulin	Trimodulin	Trimodulin (human IgM, IgA, IgG solution) for intravenous (IV) administration.
Placebo	Placebo (human albumin 1%)	Human albumin 1%

Primary Outcome Measures

Name	Time	Method
Composite Endpoint	Until day 29	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)

Secondary Outcome Measures

Name	Time	Method
Proportion of subjects improved, unchanged, and deteriorated/died	Between days 1-29	Proportion of subjects improved, unchanged, and deteriorated/died compared to baseline at several days
28-days all-cause mortality rate	Day 29	Percentage of subjects with a change to 8 on 9-category ordinal scale.
Proportion of subjects in ICU	Day 29	Proportion of subjects in ICU
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	Until day 29	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
90-days all-cause mortality rate	Day 91	Percentage of subjects with a change to 8 on 9-category ordinal scale.
Days of invasive mechanical ventilation (IMV)/ extracorporeal membrane oxygenation (ECMO)	Day 29	Days of IMV/ECMO
Days in intensive care unit (ICU)	Day 29	Days in intensive care unit
Dose modifications	Day 1-5	Dose modifications (incl. reductions and changes in infusion rate)
Changes over time in clinical laboratory parameters	Days -1, 1-5, 7,14, 21, 29	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.
Proportion of subjects on IMV/ECMO	Day 29	Proportion of subjects on IMV/ECMO
Proportion of subjects with oxygen supply	Days 7, 14, 21, 29	Proportion of subjects with oxygen supply
TEAEs	Until day 29	Number of all related TEAEs
Clinical deterioration rate	Between days 6-29 and days 1-29	Percentage of subjects with a change of at least 1 category on the category ordinal-scale
Proportion of subjects with score ≤ 2	Day 29	Proportion of subjects that improved to score ≤ 2
Proportion of subjects with different partial pressure of oxygen (PaO2)/ fraction of inspired oxygen (FiO2) ratios	Days 7, 14, 21, 29	Proportion of subjects with PaO2/FiO2 ratio \< 100, 100 to \< 200, 200 to \< 300 or ≥ 300
Days with oxygen supply	Day 29	Days with oxygen supply
Days of hospitalization	Day 29	Days of hospitalization
SAEs	Until day 29	Number, severity, causality, and outcome of all serious adverse events (SAEs)
Change over time in ECG parameters	Days -1, 1, 3, 5 and once between days 8-13	ECG recordings, (including heart rate, QT-interval, QTcF) showing abnormal, clinically relevant findings will be reported as adverse event
Changes over time in vital signs	Days -1,1-3, 5, 7 ,14, 21, 29	Changes in recordings of vital sign parameters showing clinically significant measurements outside the normal range will be reported as adverse event.
Time to recovery	Between days 1-29	Number of days to score ≤ 2 until day 29

Trial Locations

Locations (59)

Investigational Site #5402; 🇦🇷 Córdoba, Argentina

Investigational Site #5403; 🇦🇷 Cordoba, Argentina

Investigational Site #5506; 🇧🇷 Porto Alegre, Brazil

Investigational Site #3201; 🇧🇪 Ottignies, Belgium

Investigational Site #2703; 🇿🇦 Mthatha, South Africa

Investigational Site #3401; 🇪🇸 Barcelona, Spain

Investigational site #2706; 🇿🇦 Kimberley, South Africa

Investigational Site #7001; 🇱🇹 Vilnius, Lithuania

Investigational Site #7002; 🇱🇹 Kaunas, Lithuania

Investigational Site #2705; 🇿🇦 Plettenberg Bay, South Africa

Investigational Site #3403; 🇪🇸 Madrid, Spain

Investigational Site #3301; 🇫🇷 Paris, France

Investigational Site #2707; 🇿🇦 Pretoria, South Africa

Investigational Site #2704; 🇿🇦 Pretoria, South Africa

Investogational SIte #3501; 🇵🇹 Lisboa, Portugal

Investigational Site #3404; 🇪🇸 Madrona, Spain

Investigational Site #2701; 🇿🇦 Pretoria, South Africa

Investigational Site #2702; 🇿🇦 Klerksdorp, South Africa

Investigational Site #4901; 🇩🇪 Bochum, Germany

Investigational Site #5401; 🇦🇷 Buenos Aires, Argentina

Investigational Site #4304; 🇦🇹 Wien, Austria

Investigational Site #5501; 🇧🇷 São Paulo, Brazil

Investigational Site #3305; 🇫🇷 Saint-Étienne, France

Investigational Site #4903; 🇩🇪 Hannover, Germany

Investigational Site #3502; 🇵🇹 Guimarães, Portugal

Investigational Site #2105; 🇸🇰 Michalovce, Slovakia

Investigational Site #3304; 🇫🇷 Paris, France

Investigational Site #3203; 🇧🇪 Edegem, Belgium

Investigational Site #4303; 🇦🇹 Klagenfurt, Austria

Investigational Site #3202; 🇧🇪 Mechelen, Belgium

Investigational Site #5502; 🇧🇷 Santo André, Brazil

Investigational Site #3307; 🇫🇷 Salouël, France

Investigational Site #3306; 🇫🇷 Strasbourg, France

Investigational Site #7101; 🇱🇻 Riga, Latvia

Investigational Site #7003; 🇱🇹 Klaipėda, Lithuania

Investigational Site #2102; 🇸🇰 Malacky, Slovakia

Investigational Site #2101; 🇸🇰 Nitra, Slovakia

Investigational Site #9001; 🇹🇷 Trabzon, Turkey

Investigational Site #5505; 🇧🇷 Botucatu, Brazil

Investigational Site #5503; 🇧🇷 Porto Alegre, Brazil

Investigational Site #3303; 🇫🇷 Melun, France

Investigational SIte #3603; 🇭🇺 Debrecen, Hungary

Investigational Site #7102; 🇱🇻 Daugavpils, Latvia

Investigational Site #2103; 🇸🇰 Banská Bystrica, Slovakia

Investigational Site #2104; 🇸🇰 Svidník, Slovakia

Investigational Site #5507; 🇧🇷 Porto Alegre, Brazil

Investigational Site #4302; 🇦🇹 Linz, Austria

Investigational Site #5504; 🇧🇷 São José Do Rio Preto, Brazil

Investigational Site #3308; 🇫🇷 Strasbourg, France

Investigational Site #3302; 🇫🇷 Trévenans, France

Investogational Site #4902; 🇩🇪 Cottbus, Germany

Investigational Site #4904; 🇩🇪 Berlin, Germany

Investigational Site #4907; 🇩🇪 München, Germany

Investigational Site #3601; 🇭🇺 Szeged, Hungary

Investigational Site #7007; 🇱🇹 Kaunas, Lithuania

Investigational Site #7005; 🇱🇹 Kaunas, Lithuania

Investigational Site #9005; 🇹🇷 Ankara, Turkey

Investigational Site #9004; 🇹🇷 Istanbul, Turkey

Investigational Site #7004; 🇱🇹 Šiauliai, Lithuania