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Clinical Trial Details — Status: Recruiting

Administrative data

NCT number NCT05722938
Other study ID # 996
Secondary ID
Status Recruiting
Phase Phase 3
First received
Last updated
Start date September 9, 2023
Est. completion date April 30, 2025

Study information

Verified date June 2024
Source Biotest
Contact Iris Bobenhausen, PhD
Phone +4915222801073
Email iris.bobenhausen@biotest.com
Is FDA regulated No
Health authority
Study type Interventional

Clinical Trial 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.


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 information / eligibility

Status Recruiting
Enrollment 590
Est. completion date April 30, 2025
Est. primary completion date February 28, 2025
Accepts healthy volunteers No
Gender All
Age group 18 Years and older
Eligibility Main Inclusion Criteria: 1. Written informed consent. 2. Hospitalized, adult (= 18 years of age) subject. 3. Severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) negative status. 4. Signs of inflammation based on C-reactive protein threshold level. 5. Diagnosis of active pneumonia. 6. Radiological (or other imaging technology) evidence consistent with active pneumonia. 7. 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 not willing to use reliable contraceptive measures during the trial and for 15 weeks after the last IMP treatment. 4. Suspected hospital-acquired pneumonia (HAP) including ventilator-associated pneumonia (VAP). 5. Diagnosis of COVID-19 during the last 4 weeks. 6. Subjects that required oxygen therapy due to COVID-19 in the last 6 months. 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. Known hemolytic disease. 11. Known thrombosis or thromboembolic events (TEEs) or known medical history of TEEs or subjects particularly at risk for TEEs. 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. 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). 15. Known decompensated heart failure. 16. Known pre-existing hepatic cirrhosis, severe hepatic impairment (Child Pugh score = 9 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. Known treatment for thorax/head/neck/hematologic malignancies in the last 12 months before screening. 20. 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. 21. Morbid obesity with high body mass index (BMI) = 40 kg/m2, or malnutrition with low BMI < 16 kg/m2. 22. Known treatment with polyvalent immunoglobulin preparations, plasma, or albumin preparations during the last 21 days before screening. 23. Known treatment with predefined medications, during the last 5 days before screening. 24. Any type of interferon during the last 21 days before screening. 25. Ongoing treatment with immunosuppressants other than guideline recommended immunosuppressants for treatment of active pneumonia. 26. Participation in another interventional clinical trial within 30 days before screening or previous participation in this clinical trial.

Study Design


Related Conditions & MeSH terms


Intervention

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

Locations

Country Name City State
Argentina Clinica Adventista Belgrano Ciudad Autonoma de Buenos Aire
Argentina Hospital General de Agudos Dr. Ignacio Pirovano Ciudad Autonoma de Buenos Aire
Argentina Hospital Italiano de Buenos Aires Ciudad Autonoma de Buenos Aire
Argentina Sanatorio de la Trinidad Mitre 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 Parque S.A. Privado San Vicente Cordoba
Argentina Sanatorio de la Canada Villa María
Australia Footscray Hospital Footscray
Australia Austin Health Heidelberg
Australia Sunshine Hospital Saint Albans
Australia Princess Alexandra Hospital Woolloongabba Queensland
Austria KABEG-Klinikum Klagenfurt Klagenfurt
Austria AKH - Medizinische Universität Wien Vienna
Belgium 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
Brazil 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 Hospital de Clínicas de Porto Alegre Porto Alegre
Brazil Hospital Ernesto Dornelles Porto Alegre
Brazil Irmandade da Santa Casa de Misericórdia de Porto Alegre Porto Alegre
Brazil CIP - Centro Integrado de Pesquisa São José Do Rio Preto
Brazil Universidade Municipal de Sao Caetano do Sul (USCS) São Paulo
Czechia 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
France 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 Centre Hospitalier de Melun Melun
France CHU Nice Hopital Pasteur 2 Nice
France CHU Nice-Hopital de l' Archet Nice
France Groupe Hospitalier Diaconesses - Hopital De La Croix Saint Simon Paris
France Hôpital Bichat - Claude Bernard Paris
France Hôpital Cochin Paris
France Hôpital Tenon Paris
France CHU Saint-Etienne Saint-Étienne
France CHU Strasbourg - Hôpital Hautepierre Strasbourg
France CHU Strasbourg - Nouvel Hôpital Civil Strasbourg
France Hôpital Sainte Musse Toulon
France CHU Tours - Hôpital Bretonneau Tours
France Hôpital Nord Franche-Comté Trévenans
Germany Charité Universitätsmedizin Berlin - Campus Charité Mitte Berlin
Germany Universitätsklinikum Hamburg-Eppendorf Hamburg
Germany Medizinische Hochschule Hannover Hanover
Hungary 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
Israel Soroka Medical Center Be'er Sheva
Israel Rambam Medical Center Haifa
Israel The Lady Davis Carmel Medical Center Haifa
Israel Rabin Medical Center Petach Tikva
Israel Kaplan Medical Center Re?ovot
New Zealand Middlemore Hospital Otahuhu
Philippines Baguio General Hospital and Medical Center Baguio City
Philippines Dr. Jose N. Rodriguez Memorial Hospital Caloocan
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
Romania Institutul Clinic Fundeni Bucharest
Romania Spitalul Universitar de Urgenta Bucuresti Bucharest
Romania Spitalul Clinic Judetean de Urgenta "Pius Brinzeu" Timisoara
South Africa Worthwhile Clinical Trials Johannesburg
South Africa RYEXO Clinical Research Pretoria
South Africa RYEXO Clinical Research Zuid Afrikaans Hospital Pretoria
South Africa Dr JM Engelbrecht Trial Site Somerset West
Spain 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 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 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
United Kingdom Royal Surrey County Hospital Guildford
United Kingdom St Thomas' Hospital London
United Kingdom Derriford Hospital Plymouth
United States Augusta University Augusta Georgia
United States Buffalo VA Medical Center Buffalo New York
United States Mercury Street Medical Group Butte Montana
United States Medical City Fort Worth Fort Worth Texas
United States University of California San Francisco-Fresno Fresno California
United States Hannibal Clinic Hannibal Missouri
United States Sparrow Clinical Research Institute Lansing Michigan
United States Vanderbilt University Medical Center Nashville Tennessee
United States Lenox Hill Hospital New York New York
United States St. Michael's Medical Center Newark New Jersey
United States University of Oklahoma Health Sciences Center Oklahoma City Oklahoma
United States Jefferson University Hospitals Philadelphia Pennsylvania
United States William Beaumont Hospital Royal Oak Michigan
United States University of Utah Salt Lake City Utah
United States Wake Forest Baptist Winston-Salem North Carolina

Sponsors (1)

Lead Sponsor Collaborator
Biotest

Countries where clinical trial is conducted

United States,  Argentina,  Australia,  Austria,  Belgium,  Brazil,  Czechia,  France,  Germany,  Hungary,  Israel,  New Zealand,  Philippines,  Romania,  South Africa,  Spain,  United Kingdom, 

Outcome

Type Measure Description Time frame Safety issue
Other Serum concentration of immunoglobulins Changes of serum concentration of IgM, IgA, and IgG from baseline, during and after treatment Day 1, 5, 14
Other Pharmacokinetic assessment of immunoglobulins Assessment of changes in serum concentrations (g/L) of IgM, IgA, and IgG before, during and after treatment Day 1, 2, 3, 4, 5, 6, 7, 9, 14, 21, 29
Other Pharmacodynamic assessment of disease related serum proteins Assessment of relative changes in serum concentrations from baseline, during and after treatment of factors and markers of coagulation (e.g. % change in D-dimer), markers of inflammation (e.g. % change in CRP), complement factors (e.g. % change in C3, C4), specific antibody titers against sCAP-related pathogens (e.g. % change in Streptococcus pneumoniae antibody titers) Day 1, 2, 3, 4, 5, 7, 14, 21, 29
Primary 28-day all-cause mortality rate Percentage of subjects that died until day 29 regardless of cause of death Between days 1-29
Secondary 90-day all-cause mortality rate Percentage of subjects that died until day 91 regardless of cause of death Between days 1-91
Secondary 28-day all-cause mortality rate plus day 6-29 deterioration rate Percentage of subjects that died until day 29
Percentage of subjects with at least one deterioration event between day 6 and day 29
1. Between days 1-29; 2. Between days 6-29
Secondary Deterioration rate (day 6-29) Percentage of subjects with at least one deterioration event between day 6 and day 29 Between days 6-29
Secondary 28-day all-cause mortality rate plus day 1-29 deterioration rate Percentage of subjects that died until day 29
Percentage of subjects with at least one deterioration event between day 1 and day 29
1.+2. Between days 1-29
Secondary Deterioration rate (day 1-29) Percentage of subjects with at least one deterioration event between day 1 and day 29 Between days 1-29
Secondary Change in Sequential Organ Failure Assessment (SOFA) score from baseline to days 3, 5, 7, 14, 21, 29 and discharge Change in Sequential Organ Failure Assessment (SOFA) Between baseline and Days 3, 5, 7, 14, 21, 29 and discharge
Secondary Proportion of subjects with clinical cure of pneumonia on days 7, 14, 21, 29 and discharge Percentage of subjects with clinical cure of pneumonia On days 7, 14, 21, 29 or on the day of discharge
Secondary Days of invasive mechanical ventilation (IMV) until day 29 Days of invasive mechanical ventilation (IMV) until day 29 Until day 29
Secondary Ventilator-free days (VFD) until day 29 Ventilator-free days (VFD) Until day 29
Secondary Days with oxygen supply until day 29 Days with oxygen supply Until day 29
Secondary Proportion of subjects with oxygen supply on days 7, 14, 21, 29 and discharge Percentage of subjects with oxygen supply On days 7, 14, 21, 29 or on the day of discharge
Secondary Proportion of subjects with PaO2/FiO2 ratio < 100, 100 to < 200, 200 to < 300 or = 300 on days 7, 14, 21, and 29 Percentage of subjects with PaO2/FiO2 ratio < 100, 100 to < 200, 200 to < 300 or = 300 On days 7, 14, 21, 29
Secondary Vasopressor-free days until day 29 Vasopressor-free days until day 29 Until day 29
Secondary Days in intensive care unit (ICU) until day 29 Days in intensive care unit (ICU) until day 29 Until day 29
Secondary Time to discharge from ICU Time to discharge from ICU Until day 91
Secondary Proportion of subjects in ICU on days 7, 14, 21 and 29 Percentage of subjects in ICU On days 7, 14, 21, 29
Secondary Days of hospitalization until day 29 Days of hospitalization Until day 29
Secondary Time to discharge from hospital Time to discharge from hospital Until day 91
Secondary Proportion of subjects in hospital on days 7, 14, 21 and 29 Percentage of subjects in hospital On days 7, 14, 21, 29
Secondary 28-day readmission rate Percentage of subjects readmitted to the hospital Day 29
Secondary Rate of unscheduled return(s) to the emergency department or primary physician between day 29 and day 91 Percentage of subjects returning to the emergency department or primary physician Between Days 29 - 91
Secondary Time to return to normal activities until day 91 Time to return to normal activities Until day 91
Secondary Health status based on Clinical Frailty Scale (CFS) on day 91 Change in Health status from Baseline assessment based on Clinical Frailty Scale (score 1 very fit to score 9 terminally ill) Between Days 29 - 91
Secondary Quality of life based on Nottingham Health Profile (NHP) on days 29 and 91 Change in Quality of life based on Nottingham Health Profile (NHP) Day 29 and day 91
Secondary 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 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 Until day 29
Secondary Infusion-related TEAEs Number of all infusion-related TEAEs Until day 29
Secondary Serious adverse events (SAEs) Number, severity, causality, and outcome of all SAEs Until day 29
Secondary Dose modifications Dose modifications (including reductions and changes in infusion rate) Day 1-5
Secondary Change over time in electrocardiogram (ECG) parameters ECG output (diagram including QT-interval and QTcF) showing abnormal, clinically relevant findings will be reported as adverse event Days -1, 1, 3, 5 and once between days 8-13
Secondary Number and changes in observed Adverse Events in vital signs over time 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 Days -1, 1-3, 5, 7, 14, 21, 29
Secondary Number and changes in observed Adverse Events in clinical laboratory parameters over time 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 Days -1, 1-5, 7, 14, 21, 29
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