Overview
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.
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.
Eligibility
Main Inclusion Criteria:
- Written informed consent.
- Hospitalized, adult (≥ 18 years of age) subject.
- Signs of inflammation based on C-reactive protein threshold level.
- Diagnosis of active community-acquired pneumonia (CAP) before hospital-admission or within 48 hours after admission.
- Radiological (or other imaging technology) evidence consistent with active pneumonia.
- Acute respiratory failure requiring IMV.
Main Exclusion Criteria:
- For an incapacitated subject: any indication that the subject's presumed will would be against inclusion in the trial.
- Pregnant or lactating women.
- Subjects of childbearing potential not willing to use reliable contraceptive measures during the trial and for 15 weeks after the last IMP treatment.
- Subjects on ECMO at start of IMP treatment.
- Suspected hospital-acquired pneumonia (HAP) including ventilator-associated pneumonia (VAP).
- Subjects discharged from hospital within the previous 14 days.
- Defined neutrophil counts up to one calendar day prior to start of IMP treatment.
- Defined platelet counts up to one calendar day prior to start of IMP treatment.
- Defined hemoglobin within up to one calendar day prior to start of IMP treatment.
- Pre-existing hemolytic disease.
- Thromboembolic events (TEEs) caused by other reasons than the current sCAP within 3 months before start of IMP treatment unless the risk for further TEEs can be adequately managed with standard prophylaxis or treatment.
- Severe renal impairment prior to start of IMP treatment.
- End-stage renal disease (ESRD) or known primary focal segmental glomerulosclerosis (FSGS).
- Pre-existing severe lung diseases concomitant to current sCAP (e.g. active tuberculosis, active lung cancer).
- Pre-existing decompensated heart failure.
- Pre-existing severe hepatic cirrhosis (Child Pugh score ≥ 10 points), or severe hepatic impairment (Child Pugh score ≥ 10 points), or hepatocellular carcinoma.
- Known intolerance to proteins of human origin or known allergic reactions to components of trimodulin / placebo.
- Selective immunoglobulin A (IgA) deficiency with known antibodies to IgA.
- 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.
- Morbid obesity with high body mass index (BMI) ≥ 40 kg/m2, or malnutrition with low BMI \< 16 kg/m2.
- Treatment with polyvalent immunoglobulin preparations during the last 21 days before start of IMP treatment.
- Known treatment with predefined medications, during the last 2 days before start of IMP treatment.
- Hematopoietic stem cell transplantation or previous lung transplantation.
- Treatment with investigational medications/procedures not according to SoC of the trial site, due to participation in another interventional clinical trial within 30 days before start of IMP treatment, or previous treatment with IMP in this clinical trial.
