Efficacy and Safety of Trimodulin (BT588) in Subjects With Severe Community-acquired Pneumonia (sCAP)

Phase 3

Recruiting

• Conditions: Community-acquired Pneumonia
• Interventions: Drug: Trimodulin; Drug: Placebo (human albumin 1%)

• Registration Number: NCT05722938
• Lead Sponsor: Biotest

Brief Summary

The main objective of the trial is 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 sCAP on invasive mechanical ventilation (IMV).

Other objectives are to determine detailed pharmacokinetic (PK) properties of trimodulin in a PK substudy and to determine its pharmacodynamic (PD) properties.

Detailed Description

This is a randomized, placebo-controlled, double-blind, multi-center, multi-national, phase III trial, to assess the efficacy and safety of trimodulin compared to placebo treatment, as adjunctive treatment to SoC in adult hospitalized subjects with sCAP receiving IMV.

Subjects will be randomized on a 1:1 basis to receive trimodulin or placebo, stratified by center. Investigational medicinal product (IMP) treatments will be blinded.

Subject will be administered IMP once daily on 5 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 subjects still in the hospital (trial site) after day 29, an extended follow-up is conducted until discharge or until day 90. For all subjects alive on day 29, a closing visit/telephone call on day 91 \[+10\] will be done.

Study Timeline

• Study First Submitted: 2023-01-11
• Study First Submitted QC: 2023-01-31
• Study First Posted: 2023-02-10
• Study Start: 2023-09-09
• Status Verified: 2025-03
• Last Update Submitted: 2025-05-05
• Last Update Posted: 2025-05-07
• Primary Completion: 2026-10-31
• Study Completion: 2026-12-31

Recruitment & Eligibility

• Status: RECRUITING
• Sex: All
• Target Recruitment: 590

Inclusion Criteria

1. Written informed consent.
2. Hospitalized, adult (≥ 18 years of age) subject.
3. Signs of inflammation based on C-reactive protein threshold level.
4. Diagnosis of active community-acquired pneumonia (CAP) before hospital-admission or within 48 hours after admission.
5. Radiological (or other imaging technology) evidence consistent with active pneumonia.
6. Acute respiratory failure requiring IMV.

Main

Exclusion Criteria

1. For an incapacitated subject: any indication that the subject's presumed will would be against inclusion in the trial.
2. Pregnant or lactating women.
3. Subjects of childbearing potential not willing to use reliable contraceptive measures during the trial and for 15 weeks after the last IMP treatment.
4. Subjects on ECMO or predicted to be on ECMO at start of IMP treatment.
5. Suspected hospital-acquired pneumonia (HAP) including ventilator-associated pneumonia (VAP).
6. Subjects discharged from hospital within the previous 14 days.
7. Defined neutrophil counts within 24 hours prior to start of IMP treatment.
8. Defined platelet counts within 24 hours prior to start of IMP treatment.
9. Defined hemoglobin within 24 hours prior to start of IMP treatment.
10. Pre-existing hemolytic disease.
11. Pre-existing thrombosis or other thromboembolic events (TEEs) within 3 months before start of IMP treatment. Subjects particularly at risk for TEEs caused by other reasons than the current sCAP.
12. Subject on dialysis or with severe renal impairment within 24 hours prior to start of IMP treatment.
13. Subject with end-stage renal disease (ESRD) or known primary focal segmental glomerulosclerosis (FSGS).
14. Pre-existing severe lung diseases concomitant to current sCAP (e.g., subjects with chronic obstructive pulmonary disease [COPD] Gold Stage III or IV, severe interstitial lung disease [incl. idiopathic pulmonary fibrosis], cystic fibrosis, active tuberculosis, chronically infected bronchiectasis, or active lung cancer).
15. Pre-existing decompensated heart failure.
16. Pre-existing severe hepatic cirrhosis (Child Pugh score ≥ 10 points), or severe hepatic impairment (Child Pugh score ≥ 10 points), or hepatocellular carcinoma.
17. Known intolerance to proteins of human origin or known allergic reactions to components of trimodulin / placebo.
18. Selective immunoglobulin A (IgA) deficiency with known antibodies to IgA.
19. Life expectancy of less than 90 days, according to the investigator's clinical judgment, because of medical conditions related neither to sCAP nor to sCAP-associated septic conditions.
20. Morbid obesity with high body mass index (BMI) ≥ 40 kg/m2, or malnutrition with low BMI < 16 kg/m2.
21. Treatment with polyvalent immunoglobulin preparations during the last 21 days before start of IMP treatment.
22. Known treatment with predefined medications, during the last 2 days before start of IMP treatment.
23. Treatment with any type of interferon during the last 21 days before start of IMP treatment
24. Subject with previous organ or hematopoietic stem cell transplantation receiving ongoing treatment with immunosuppressants (exception: corticosteroids) at start of IMP treatment.
25. Participation in another interventional clinical trial (using medications and/or procedures not according to SoC of the trial site) within 30 days before start of IMP treatment or previous IMP treatment in this clinical trial.

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
28-day all-cause mortality rate	Between days 1-29	Percentage of subjects that died until day 29 regardless of cause of death

Secondary Outcome Measures

Name	Time	Method
Days with oxygen supply until day 29	Until day 29	Days with oxygen supply
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 AEs and TEAEs, AESIs, infusional TEAEs, TEAEs that led to permanent withdrawal of IMP, and TEAEs that led to discontinuation of the trial
28-day all-cause mortality rate plus day 6-29 deterioration rate	1. Between days 1-29; 2. Between days 6-29	1. Percentage of subjects that died until day 29; 2. Percentage of subjects with at least one deterioration event between day 6 and day 29
28-day all-cause mortality rate plus day 1-29 deterioration rate	1.+2. Between days 1-29	1. Percentage of subjects that died until day 29; 2. Percentage of subjects with at least one deterioration event between day 1 and day 29
Proportion of subjects in ICU on days 7, 14, 21 and 29	On days 7, 14, 21, 29	Percentage of subjects in ICU
Deterioration rate (day 6-29)	Between days 6-29	Percentage of subjects with at least one deterioration event between day 6 and day 29
Change in Sequential Organ Failure Assessment (SOFA) score from baseline to days 3, 5, 7, 14, 21, 29 and discharge	Between baseline and Days 3, 5, 7, 14, 21, 29 and discharge	Change in Sequential Organ Failure Assessment (SOFA)
Days of invasive mechanical ventilation (IMV) until day 29	Until day 29	Days of invasive mechanical ventilation (IMV) until day 29
Days of hospitalization until day 29	Until day 29	Days of hospitalization
Deterioration rate (day 1-29)	Between days 1-29	Percentage of subjects with at least one deterioration event between day 1 and day 29
Proportion of subjects with clinical cure of pneumonia on days 7, 14, 21, 29 and discharge	On days 7, 14, 21, 29 or on the day of discharge	Percentage of subjects with clinical cure of pneumonia
Ventilator-free days (VFD) until day 29	Until day 29	Ventilator-free days (VFD)
Time to discharge from hospital	Until day 91	Time to discharge from hospital
Proportion of subjects with oxygen supply on days 7, 14, 21, 29 and discharge	On days 7, 14, 21, 29 or on the day of discharge	Percentage of subjects with oxygen supply
Time to discharge from ICU	Until day 91	Time to discharge from ICU
Proportion of subjects with PaO2/FiO2 ratio < 100, 100 to < 200, 200 to < 300 or ≥ 300 on days 7, 14, 21, and 29	On days 7, 14, 21, 29	Percentage of subjects with PaO2/FiO2 ratio \< 100, 100 to \< 200, 200 to \< 300 or ≥ 300
Vasopressor-free days until day 29	Until day 29	Vasopressor-free days until day 29
90-day all-cause mortality rate	Between days 1-91	Percentage of subjects that died until day 91 regardless of cause of death
Days in intensive care unit (ICU) until day 29	Until day 29	Days in intensive care unit (ICU) until day 29
Proportion of subjects in hospital on days 7, 14, 21 and 29	On days 7, 14, 21, 29	Percentage of subjects in hospital
Infusion-related TEAEs	Until day 29	Number of all infusion-related TEAEs
Dose modifications	Day 1-5	Dose modifications (including reductions and changes in infusion rate)
Change over time in electrocardiogram (ECG) parameters	Days -1, 1, 3, 5 and once between days 8-13	ECG output (diagram including QT-interval and QTcF) showing abnormal, clinically relevant findings will be reported as adverse event
28-day readmission rate	Day 29	Percentage of subjects readmitted to the hospital
Quality of life based on Nottingham Health Profile (NHP) on days 29 and 91	Day 29 and day 91	Change in Quality of life based on Nottingham Health Profile (NHP)
Serious adverse events (SAEs)	Until day 29	Number, severity, causality, and outcome of all SAEs
Number and changes in observed Adverse Events in vital signs over time	Days -1, 1-3, 5, 7, 14, 21, 29	Clinically significant changes in values of vital signs (including systolic and diastolic blood pressure, arterial oxygen saturation, heart rate, respiratory rate and body temperature) are rated as adverse events. The number of adverse events and changes in numbers of the adverse events over time will be reported
Number and changes in observed Adverse Events in clinical laboratory parameters over time	Days -1, 1-5, 7, 14, 21, 29	Clinically significant changes in clinical laboratory values (including chemistry, hematology and coagulation) are rated as adverse events. The number of adverse events and changes in numbers of the adverse events over time will be reported
Rate of unscheduled return(s) to the emergency department or primary physician between day 29 and day 91	Between Days 29 - 91	Percentage of subjects returning to the emergency department or primary physician
Time to return to normal activities until day 91	Until day 91	Time to return to normal activities
Health status based on Clinical Frailty Scale (CFS) on day 91	Between Days 29 - 91	Change in Health status from Baseline assessment based on Clinical Frailty Scale (score 1 very fit to score 9 terminally ill)

Trial Locations

Locations (134)

Pulmonary Associates of Mobile, P.C.; 🇺🇸 Mobile, Alabama, United States

University of California San Francisco-Fresno; 🇺🇸 Fresno, California, United States

UC Davis Health; 🇺🇸 Sacramento, California, United States

Augusta University; 🇺🇸 Augusta, Georgia, United States

Sparrow Clinical Research Institute; 🇺🇸 Lansing, Michigan, United States

William Beaumont Hospital; 🇺🇸 Royal Oak, Michigan, United States

University of Missouri Clinical Research Center; 🇺🇸 Columbia, Missouri, United States

Hannibal Clinic; 🇺🇸 Hannibal, Missouri, United States

Mercury Street Medical Group; 🇺🇸 Butte, Montana, United States

St. Michael's Medical Center; 🇺🇸 Newark, New Jersey, United States

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