Resumen

El objetivo principal del ensayo es evaluar la eficacia y la seguridad de trimodulina como tratamiento adyuvante al estándar de atención (SoC) en comparación con placebo más SoC en sujetos adultos hospitalizados con NAC-grave bajo ventilación mecánica invasiva (VMI). Otros objetivos son determinar las propiedades farmacocinéticas (PK) detalladas de trimodulina en un subestudio de PK y determinar sus propiedades farmacodinámicas (PD).

Descripción detallada

Este es un ensayo clínico de fase III, aleatorizado, controlado con placebo, doble ciego, multicéntrico, multinacional, para evaluar la eficacia y la seguridad de trimodulina en comparación con el tratamiento con placebo, como tratamiento adyuvante al SoC en sujetos adultos hospitalizados con NAC-grave que reciben VMI. Los sujetos serán aleatorizados en una proporción 1:1 para recibir trimodulina o placebo, con estratificación por centro. Los tratamientos con el producto medicinal en investigación (PMI) serán ciegos. Los sujetos recibirán el PMI una vez al día durante 5 días consecutivos (del día 1 al día 5) como adyuvante al SoC. La fase de seguimiento posterior comprende un máximo de 23 días (del día 6 al día 28), seguida de una visita/llamada telefónica de fin de seguimiento en el día 29 \[+3\]. Para los sujetos que aún se encuentren hospitalizados (en el centro del ensayo) después del día 29, se realizará un seguimiento ampliado hasta el alta o hasta el día 90. Para todos los sujetos vivos en el día 29, se realizará una visita/llamada telefónica de cierre en el día 91 \[+10\].

Elegibilidad

Edad mínima: 18 YearsSexo: ALL

Criterios de inclusión

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.

Criterios de exclusión

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.

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