Efficacy and Safety of Trimodulin (BT588) in Subjects with Severe Community-acquired Pneumonia (sCAP)
- Conditions
- Community-acquired Pneumonia
- Interventions
- Drug: TrimodulinDrug: 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.
Recruitment & Eligibility
- Status
- RECRUITING
- Sex
- All
- Target Recruitment
- 590
- Written informed consent.
- Hospitalized, adult (≥ 18 years of age) subject.
- Severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) negative status.
- Signs of inflammation based on C-reactive protein threshold level.
- Diagnosis of active pneumonia.
- Radiological (or other imaging technology) evidence consistent with active pneumonia.
- Acute respiratory failure requiring IMV.
Main
- For an incapacitated subject: any indication that the subject's presumed will would be against inclusion in the trial.
- Pregnant or lactating women.
- Subjects not willing to use reliable contraceptive measures during the trial and for 15 weeks after the last IMP treatment.
- Suspected hospital-acquired pneumonia (HAP) including ventilator-associated pneumonia (VAP).
- Diagnosis of COVID-19 during the last 4 weeks.
- Subjects that required oxygen therapy due to COVID-19 in the last 6 months.
- Defined neutrophil counts within 24 hours prior to start of IMP treatment.
- Defined platelet counts within 24 hours prior to start of IMP treatment.
- Defined hemoglobin within 24 hours prior to start of IMP treatment.
- Known hemolytic disease.
- Known thrombosis or thromboembolic events (TEEs) or known medical history of TEEs or subjects particularly at risk for TEEs.
- Subject on dialysis or with severe renal impairment within 24 hours prior to start of IMP treatment.
- Subject with end-stage renal disease (ESRD) or known primary focal segmental glomerulosclerosis (FSGS).
- Known severe lung diseases interfering with sCAP therapy (e.g., subjects with chronic obstructive pulmonary disease [COPD], severe interstitial lung disease [incl. idiopathic pulmonary fibrosis], cystic fibrosis, active tuberculosis, chronically infected bronchiectasis, or active lung cancer).
- Known decompensated heart failure.
- Known pre-existing hepatic cirrhosis, severe hepatic impairment (Child Pugh score ≥ 9 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.
- Known treatment for thorax/head/neck/hematologic malignancies in the last 12 months before screening.
- 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.
- Known treatment with polyvalent immunoglobulin preparations, plasma, or albumin preparations during the last 21 days before screening.
- Known treatment with predefined medications, during the last 5 days before screening.
- Any type of interferon during the last 21 days before screening.
- Ongoing treatment with immunosuppressants other than guideline recommended immunosuppressants for treatment of active pneumonia.
- Participation in another interventional clinical trial within 30 days before screening or previous participation 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 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 2928-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 29Proportion 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
Days with oxygen supply until day 29 Until day 29 Days with oxygen supply
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)
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
Trial Locations
- Locations (125)
Sir Charles Gairdner Hospital
🇦🇺Nedlands, Western Australia, Australia
Bekes Megyei Kozponti Korhaz Pandy Kalman Tagkorhaza
🇭🇺Gyula, Hungary
Beaumont Hospital
🇮🇪Dublin, Ireland
Pulmonary Associates of Mobile, P.C.
🇺🇸Mobile, Alabama, United States
St Vincents University Hospital
🇮🇪Dublin, Ireland
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
Buffalo VA Medical Center
🇺🇸Buffalo, New York, United States
Lenox Hill Hospital
🇺🇸New York, New York, United States
Wake Forest Baptist
🇺🇸Winston-Salem, North Carolina, United States
University of Oklahoma Health Sciences Center
🇺🇸Oklahoma City, Oklahoma, United States
Jefferson University Hospitals
🇺🇸Philadelphia, Pennsylvania, United States
Vanderbilt University Medical Center
🇺🇸Nashville, Tennessee, United States
Medical City Fort Worth
🇺🇸Fort Worth, Texas, United States
University of Utah
🇺🇸Salt Lake City, Utah, United States
Sanatorio Parque S.A. Privado
🇦🇷San Vicente, Cordoba, Argentina
CEMIC
🇦🇷Ciudad Autonoma de Buenos Aire, Argentina
Sanatorio de la Trinidad Mitre
🇦🇷Ciudad Autonoma de Buenos Aire, Argentina
Hospital Italiano de Buenos Aires
🇦🇷Ciudad Autonoma de Buenos Aire, Argentina
Hospital General de Agudos Dr. Ignacio Pirovano
🇦🇷Ciudad Autonoma de Buenos Aire, Argentina
Clinica Adventista Belgrano
🇦🇷Ciudad Autonoma de Buenos Aire, Argentina
Clinica Chutro
🇦🇷Córdoba, Argentina
Hospital San Roque
🇦🇷Córdoba, Argentina
Sanatorio Privado de la Canada - Cordoba
🇦🇷Córdoba, Argentina
Centro Medico IPAM
🇦🇷Rosario, Argentina
Estudios Clinicos de los Arroyos
🇦🇷San Nicolas, Argentina
Sanatorio de la Canada
🇦🇷Villa María, Argentina
Princess Alexandra Hospital
🇦🇺Woolloongabba, Queensland, Australia
Monash Medical Centre
🇦🇺Clayton, Victoria, Australia
Footscray Hospital
🇦🇺Footscray, Australia
Austin Health
🇦🇺Heidelberg, Australia
Sunshine Hospital
🇦🇺Saint Albans, Australia
KABEG-Klinikum Klagenfurt
🇦🇹Klagenfurt, Austria
AKH - Medizinische Universität Wien
🇦🇹Vienna, Austria
AZ Sint-Jan
🇧🇪Brugge, Belgium
Cliniques Universitaires Saint-Luc
🇧🇪Brussel, Belgium
Hopital Erasme
🇧🇪Bruxelles, Belgium
Antwerp University Hospital (UZA)
🇧🇪Edegem, Belgium
AZ Maria Middelares
🇧🇪Gent, Belgium
Universitair Ziekenhuis Brussel
🇧🇪Jette, Belgium
C. H. R. de la Citadelle
🇧🇪Liège, Belgium
CHU Charleroi Hôpital Civil Marie Curie
🇧🇪Lodelinsart, Belgium
Clinique Saint-Pierre
🇧🇪Ottignies, Belgium
UPECLIN - Unidade de Pesquisa Clínica
🇧🇷Botucatu, Brazil
HMCP - Hospital e Maternidade Celso Pierro - PUC-Campinas
🇧🇷Campinas, Brazil
Universidade de Caxias do Sul, IPCEM - Instituto de Pesquisa Clínica para Estudos Multicêntricos
🇧🇷Caxias Do Sul, Brazil
Irmandade da Santa Casa de Misericórdia de Porto Alegre
🇧🇷Porto Alegre, Brazil
Hospital de Clínicas de Porto Alegre
🇧🇷Porto Alegre, Brazil
Hospital Ernesto Dornelles
🇧🇷Porto Alegre, Brazil
CIP - Centro Integrado de Pesquisa
🇧🇷São José Do Rio Preto, Brazil
Universidade Municipal de Sao Caetano do Sul (USCS)
🇧🇷São Paulo, Brazil
Fakultni nemocnice u sv. Anny v Brne
🇨🇿Brno, Czechia
Oblastni nemocnice Kolin a.s.
🇨🇿Kolín, Czechia
Hospital Kyjov
🇨🇿Kyjov, Czechia
Fakultni nemocnice Kralovske Vinohrady
🇨🇿Prague, Czechia
Centre Hospitalier Victor Dupouy
🇫🇷Argenteuil, France
Hôpital Louis Mourier
🇫🇷Colombes, France
CHU de Grenoble - Hôpital Albert Michallon
🇫🇷Grenoble, France
CHRU Lille - Hôpital Salengro
🇫🇷Lille, France
CHU de Limoges - Hôpital Dupuytren
🇫🇷Limoges, France
CHU Nice-Hopital de l' Archet
🇫🇷Nice, France
CHU Nice Hopital Pasteur 2
🇫🇷Nice, France
Hôpital Bichat - Claude Bernard
🇫🇷Paris, France
Groupe Hospitalier Diaconesses - Hopital De La Croix Saint Simon
🇫🇷Paris, France
Hôpital Tenon
🇫🇷Paris, France
Hôpital Cochin
🇫🇷Paris, France
Centre Hospitalier de Melun
🇫🇷Melun, France
CHU Rennes - Hôpital Pontchaillou
🇫🇷Rennes, France
CHU Saint-Etienne
🇫🇷Saint-Étienne, France
CHU Strasbourg - Nouvel Hôpital Civil
🇫🇷Strasbourg, France
CHU Tours - Hôpital Bretonneau
🇫🇷Tours, France
Hôpital Nord Franche-Comté
🇫🇷Trévenans, France
Charité Universitätsmedizin Berlin - Campus Charité Mitte
🇩🇪Berlin, Germany
Universitätsklinikum Hamburg-Eppendorf
🇩🇪Hamburg, Germany
CHU Strasbourg - Hôpital Hautepierre
🇫🇷Strasbourg, France
Medizinische Hochschule Hannover
🇩🇪Hanover, Germany
Hôpital Sainte Musse
🇫🇷Toulon, France
Bugat Pal Korhaz
🇭🇺Gyöngyös, Hungary
Pest Megyei Flor Ferenc Korhaz
🇭🇺Kistarcsa, Hungary
Aneszteziologiai es Intenziv Terapias Intezet
🇭🇺Pécs, Hungary
Szegedi Tudomanyegyetem Szent-Gyorgyi Albert Klinikai Kozpont
🇭🇺Szeged, Hungary
Fejer Megyei Szent Gyorgy Egyetemi Oktato Korhaz
🇭🇺Székesfehérvár, Hungary
Soroka Medical Center
🇮🇱Be'er Sheva, Israel
Bnai Zion Medical Center
🇮🇱Haifa, Israel
Rambam Medical Center
🇮🇱Haifa, Israel
The Lady Davis Carmel Medical Center
🇮🇱Haifa, Israel
Rabin Medical Center
🇮🇱Petach Tikva, Israel
Kaplan Medical Center
🇮🇱Reẖovot, Israel
Middlemore Hospital
🇳🇿Otahuhu, New Zealand
Baguio General Hospital and Medical Center
🇵🇭Baguio City, Philippines
Dr. Jose N. Rodriguez Memorial Hospital
🇵🇭Caloocan, Philippines
Tel Aviv Sourasky Medical Center
🇮🇱Tel Aviv, Israel
Davao Doctors Hospital
🇵🇭Davao City, Philippines
Southern Philippines Medical Center
🇵🇭Davao City, Philippines
St.Paul's Hospital
🇵🇭Iloilo City, Philippines
West Visayas State University Medical Center
🇵🇭Iloilo City, Philippines
Lung Center of the Philippines
🇵🇭Quezon City, Philippines
Institutul Clinic Fundeni
🇷🇴Bucharest, Romania
Spitalul Universitar de Urgenta Bucuresti
🇷🇴Bucharest, Romania
Spitalul Clinic Judetean de Urgenta "Pius Brinzeu"
🇷🇴Timişoara, Romania
Worthwhile Clinical Trials
🇿🇦Johannesburg, South Africa
RYEXO Clinical Research Zuid Afrikaans Hospital
🇿🇦Pretoria, South Africa
RYEXO Clinical Research
🇿🇦Pretoria, South Africa
Hospital Universitario Reina Sofia
🇪🇸Córdoba, Spain
Hospital Universitari de Girona Dr Josep Trueta
🇪🇸Girona, Spain
Hospital Universitario Clinico San Carlos
🇪🇸Madrid, Spain
Hospital Universitario La Paz
🇪🇸Madrid, Spain
Dr JM Engelbrecht Trial Site
🇿🇦Somerset West, South Africa
Hospital Clinic de Barcelona
🇪🇸Barcelona, Spain
Hospital de la Santa Creu i de Sant Pau
🇪🇸Barcelona, Spain
Hospital Universitari Vall d'Hebrón
🇪🇸Barcelona, Spain
Hospital Universitario Puerta de Hierro Majadahonda
🇪🇸Majadahonda, Spain
Hospital Universitario Son Espases
🇪🇸Palma De Mallorca, Spain
Hospital Universitari de Tarragona Joan XXIII
🇪🇸Tarragona, Spain
Hospital Universitari i Politecnic La Fe
🇪🇸Valencia, Spain
Royal Surrey County Hospital
🇬🇧Guildford, United Kingdom
St Thomas' Hospital
🇬🇧London, United Kingdom
Derriford Hospital
🇬🇧Plymouth, United Kingdom