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

Official title

A Randomized, Placebo-controlled, Double-blind, Multi-center, Phase III Trial to Assess the Efficacy and Safety of Trimodulin (BT588) in Hospitalized Subjects With Severe Community-acquired Pneumonia (sCAP)

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 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 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.

Interventions

• Drug Trimodulin
  IMP will be administered via IV infusion on 5 consecutive days
• Drug Placebo (human albumin 1%)
  IMP will be administered via IV infusion on 5 consecutive days

Primary outcome measures

• 28-day all-cause mortality rate [Time frame: Between days 1-29]

Secondary outcome measures (12)

• 90-day all-cause mortality rate [Time frame: Between days 1-91]
• Deterioration rate (up to day 29) [Time frame: Up to day 29]
• Change in Sequential Organ Failure Assessment (SOFA) score from baseline to day 7 [Time frame: Between baseline and Day 7]
• Proportion of subjects with clinical cure of pneumonia up to day 29 [Time frame: Up to day 29]
• Days of invasive mechanical ventilation (IMV) up to day 29 [Time frame: Up to day 29]
• Ventilator-free days (VFD) until day 29 [Time frame: Until day 29]
• Days with oxygen supply up to day 29 [Time frame: Up to day 29]
• Proportion of subjects with oxygen supply on days 7, 14, 21 and 29 [Time frame: On days 7, 14, 21 and 29]
• Days in intensive care unit (ICU) up to day 29 [Time frame: Up to day 29]
• Time to discharge from ICU [Time frame: Until day 91]
• Proportion of subjects in ICU on days 7, 14, 21 and 29 [Time frame: On days 7, 14, 21, 29]
• Days of hospitalization up to day 29 [Time frame: Up to day 29]

Eligibility criteria

Main Inclusion Criteria:

• Written informed consent.
• Hospitalized, adult (≥ 18 years of age) subject; In US only: ≥ 12 years of age
• 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.

Criteria are shown verbatim from the registry (in English). Final eligibility is always assessed by the study center.

Healthy volunteers: No

Study design

Allocation

Randomized

Model

Parallel assignment

Masking

Quadruple blind

Primary purpose

Treatment

Study locations

France · 20 centers

• Centre Hospitalier Victor Dupouy — Argenteuil
• Hôpital Louis Mourier — Colombes
• CHU de Grenoble - Hôpital Albert Michallon — Grenoble
• CHRU Lille - Hôpital Salengro — Lille
• CHU de Limoges - Hôpital Dupuytren — Limoges
• Centre Hospitalier de Melun — Melun
• CHU Nice-Hopital de l' Archet — Nice
• CHU Nice Hopital Pasteur 2 — Nice
• … and 12 more centers

United States · 19 centers

• Pulmonary Associates of Mobile, P.C. — Mobile
• University of California San Francisco-Fresno — Fresno
• UC Davis Health — Sacramento
• Augusta University — Augusta
• Sparrow Clinical Research Institute — Lansing
• William Beaumont Hospital — Royal Oak
• University of Missouri Clinical Research Center — Columbia
• Hannibal Clinic — Hannibal
• … and 11 more centers

Spain · 16 centers

Center list to be confirmed — check the primary protocol.

Argentina · 15 centers

• Sanatorio Parque S.A. Privado — San Vicente
• Sanatorio Parque S.A — Rosario
• Sanatorio Guemes — Buenos Aires
• Hospital General de Agudos Dr. J. M. Ramos Mejia — Buenos Aires
• CEMIC — Ciudad Autonoma de Buenos Aire
• Sanatorio de la Trinidad Mitre — Ciudad Autonoma de Buenos Aire
• Hospital Italiano de Buenos Aires — Ciudad Autonoma de Buenos Aire
• Hospital General de Agudos Dr. Ignacio Pirovano — Ciudad Autonoma de Buenos Aire
• … and 7 more centers

Belgium · 12 centers

• Onze Lieve Vrouw Ziekenhuis — Aalst
• AZ Sint-Jan — Bruges
• Hopital Erasme — Brussels
• Cliniques Universitaires Saint-Luc — Brussels
• Antwerp University Hospital (UZA) — Edegem
• ZOL — Genk
• AZ Maria Middelares — Ghent
• Universitair Ziekenhuis Brussel — Jette
• … and 4 more centers

Brazil · 12 centers

• UPECLIN - Unidade de Pesquisa Clínica — Botucatu
• HMCP - Hospital e Maternidade Celso Pierro - PUC-Campinas — Campinas
• Hospital do Rocio — Campo Largo
• Universidade de Caxias do Sul, IPCEM - Instituto de Pesquisa Clínica para Estudos Multicên — Caxias do Sul
• Hospital de Clínicas de Passo Fundo — Passo Fundo
• Irmandade da Santa Casa de Misericórdia de Porto Alegre — Porto Alegre
• Hospital de Clínicas de Porto Alegre — Porto Alegre
• Hospital Ernesto Dornelles — Porto Alegre
• … and 4 more centers

Israel · 8 centers

Center list to be confirmed — check the primary protocol.

Philippines · 8 centers

Center list to be confirmed — check the primary protocol.

South Africa · 7 centers

Center list to be confirmed — check the primary protocol.

Australia · 6 centers

• Princess Alexandra Hospital — Woolloongabba
• Monash Medical Centre — Clayton
• Sir Charles Gairdner Hospital — Nedlands
• Footscray Hospital — Footscray
• Austin Health — Heidelberg
• Sunshine Hospital — Saint Albans

Hungary · 6 centers

Center list to be confirmed — check the primary protocol.

Germany · 5 centers

Center list to be confirmed — check the primary protocol.

United Kingdom · 5 centers

Center list to be confirmed — check the primary protocol.

Czechia · 4 centers

• Fakultni nemocnice u sv. Anny v Brne — Brno
• Oblastni nemocnice Kolin a.s. — Kolín
• Hospital Kyjov — Kyjov
• Fakultni nemocnice Kralovske Vinohrady — Prague

Ireland · 4 centers

Center list to be confirmed — check the primary protocol.

Romania · 3 centers

Center list to be confirmed — check the primary protocol.

Austria · 2 centers

• KABEG-Klinikum Klagenfurt — Klagenfurt
• AKH - Medizinische Universität Wien — Vienna

New Zealand · 2 centers

Center list to be confirmed — check the primary protocol.

Identifiers

NCT: NCT05722938 · 996

Primary sources (government registries)

• ClinicalTrials.gov (US NIH)

View this study on ClinicalTrials.gov ↗