Clinical trial NCT05722938: 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 Adult Hospitalized Subjects With Severe Community-acquired Pneumonia (sCAP)
Study type: INTERVENTIONAL
Overall status: RECRUITING
Phase: PHASE3
Conditions: Community-acquired Pneumonia
Keywords: Severe Community-acquired Pneumonia
Lead sponsor: Biotest
Sponsor class: INDUSTRY
First posted: 2023-02-10
Enrollment: 590
Sex: ALL
Minimum age (years): 18
Standard ages: ADULT
OLDER_ADULT
Accepts healthy volunteers: no
Allocation: RANDOMIZED
Intervention model: PARALLEL
Intervention model description: Subjects will be randomized on a 1:1 basis to receive trimodulin or placebo, stratified by center
Primary purpose: TREATMENT

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.

Eligibility criteria: Main Inclusion Criteria:

1. Written informed consent.
2. Hospitalized, adult (≥ 18 years of age) subject.
3. Signs of inflammation based on C-reactive protein threshold level.
4. Diagnosis of active community-acquired pneumonia (CAP) before hospital-admission or within 48 hours after admission.
5. Radiological (or other imaging technology) evidence consistent with active pneumonia.
6. 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 of childbearing potential not willing to use reliable contraceptive measures during the trial and for 15 weeks after the last IMP treatment.
4. Subjects on ECMO or predicted to be on ECMO at start of IMP treatment.
5. Suspected hospital-acquired pneumonia (HAP) including ventilator-associated pneumonia (VAP).
6. Subjects discharged from hospital within the previous 14 days.
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. Pre-existing hemolytic disease.
11. Pre-existing thrombosis or other thromboembolic events (TEEs) within 3 months before start of IMP treatment. Subjects particularly at risk for TEEs caused by other reasons than the current sCAP.
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. Pre-existing severe lung diseases concomitant to current sCAP (e.g., subjects with chronic obstructive pulmonary disease \[COPD\] Gold Stage III or IV, severe interstitial lung disease \[incl. idiopathic pulmonary fibrosis\], cystic fibrosis, active tuberculosis, chronically infected bronchiectasis, or active lung cancer).
15. Pre-existing decompensated heart failure.
16. Pre-existing severe hepatic cirrhosis (Child Pugh score ≥ 10 points), or severe hepatic impairment (Child Pugh score ≥ 10 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. 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.
20. Morbid obesity with high body mass index (BMI) ≥ 40 kg/m2, or malnutrition with low BMI \< 16 kg/m2.
21. Treatment with polyvalent immunoglobulin preparations during the last 21 days before start of IMP treatment.
22. Known treatment with predefined medications, during the last 2 days before start of IMP treatment.
23. Treatment with any type of interferon during the last 21 days before start of IMP treatment
24. Subject with previous organ or hematopoietic stem cell transplantation receiving ongoing treatment with immunosuppressants (exception: corticosteroids) at start of IMP treatment.
25. Participation in another interventional clinical trial (using medications and/or procedures not according to SoC of the trial site) within 30 days before start of IMP treatment or previous IMP treatment in this clinical trial.

Primary outcomes:
measure: 28-day all-cause mortality rate
timeFrame: Between days 1-29
Secondary outcomes:
measure: 90-day all-cause mortality rate
timeFrame: Between days 1-91
measure: 28-day all-cause mortality rate plus day 6-29 deterioration rate
timeFrame: 1. Between days 1-29; 2. Between days 6-29
measure: Deterioration rate (day 6-29)
timeFrame: Between days 6-29
measure: 28-day all-cause mortality rate plus day 1-29 deterioration rate
timeFrame: 1.+2. Between days 1-29
measure: Deterioration rate (day 1-29)
timeFrame: Between days 1-29
measure: Change in Sequential Organ Failure Assessment (SOFA) score from baseline to days 3, 5, 7, 14, 21, 29 and discharge
timeFrame: Between baseline and Days 3, 5, 7, 14, 21, 29 and discharge
measure: Proportion of subjects with clinical cure of pneumonia on days 7, 14, 21, 29 and discharge
timeFrame: On days 7, 14, 21, 29 or on the day of discharge
measure: Days of invasive mechanical ventilation (IMV) until day 29
timeFrame: Until day 29
measure: Ventilator-free days (VFD) until day 29
timeFrame: Until day 29
measure: Days with oxygen supply until day 29
timeFrame: Until day 29
measure: Proportion of subjects with oxygen supply on days 7, 14, 21, 29 and discharge
timeFrame: On days 7, 14, 21, 29 or on the day of discharge
measure: Proportion of subjects with PaO2/FiO2 ratio < 100, 100 to < 200, 200 to < 300 or ≥ 300 on days 7, 14, 21, and 29
timeFrame: On days 7, 14, 21, 29
measure: Vasopressor-free days until day 29
timeFrame: Until day 29
measure: Days in intensive care unit (ICU) until day 29
timeFrame: Until day 29
measure: Time to discharge from ICU
timeFrame: Until day 91
measure: Proportion of subjects in ICU on days 7, 14, 21 and 29
timeFrame: On days 7, 14, 21, 29
measure: Days of hospitalization until day 29
timeFrame: Until day 29
measure: Time to discharge from hospital
timeFrame: Until day 91
measure: Proportion of subjects in hospital on days 7, 14, 21 and 29
timeFrame: On days 7, 14, 21, 29
measure: 28-day readmission rate
timeFrame: Day 29
measure: Rate of unscheduled return(s) to the emergency department or primary physician between day 29 and day 91
timeFrame: Between Days 29 - 91
measure: Time to return to normal activities until day 91
timeFrame: Until day 91
measure: Health status based on Clinical Frailty Scale (CFS) on day 91
timeFrame: Between Days 29 - 91
measure: Quality of life based on Nottingham Health Profile (NHP) on days 29 and 91
timeFrame: Day 29 and day 91
measure: 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
timeFrame: Until day 29
measure: Infusion-related TEAEs
timeFrame: Until day 29
measure: Serious adverse events (SAEs)
timeFrame: Until day 29
measure: Dose modifications
timeFrame: Day 1-5
measure: Change over time in electrocardiogram (ECG) parameters
timeFrame: Days -1, 1, 3, 5 and once between days 8-13
measure: Number and changes in observed Adverse Events in vital signs over time
timeFrame: Days -1, 1-3, 5, 7, 14, 21, 29
measure: Number and changes in observed Adverse Events in clinical laboratory parameters over time
timeFrame: Days -1, 1-5, 7, 14, 21, 29
Other outcomes:
measure: Serum concentration of immunoglobulins
timeFrame: Day 1, 5, 14
measure: Pharmacokinetic assessment of immunoglobulins
timeFrame: Day 1, 2, 3, 4, 5, 6, 7, 9, 14, 21, 29
measure: Pharmacodynamic assessment of disease related serum proteins
timeFrame: Day 1, 2, 3, 4, 5, 7, 14, 21, 29
Locations:
city: Mobile
country: United States
facility: Pulmonary Associates of Mobile, P.C.
state: Alabama
city: Fresno
country: United States
facility: University of California San Francisco-Fresno
state: California
city: Sacramento
country: United States
facility: UC Davis Health
state: California
city: Augusta
country: United States
facility: Augusta University
state: Georgia
city: Lansing
country: United States
facility: Sparrow Clinical Research Institute
state: Michigan
city: Royal Oak
country: United States
facility: William Beaumont Hospital
state: Michigan
city: Columbia
country: United States
facility: University of Missouri Clinical Research Center
state: Missouri
city: Hannibal
country: United States
facility: Hannibal Clinic
state: Missouri
city: Butte
country: United States
facility: Mercury Street Medical Group
state: Montana
city: Newark
country: United States
facility: St. Michael's Medical Center
state: New Jersey
city: Buffalo
country: United States
facility: Buffalo VA Medical Center
state: New York
city: New York
country: United States
facility: Lenox Hill Hospital
state: New York
city: Winston-Salem
country: United States
facility: Wake Forest Baptist
state: North Carolina
city: Oklahoma City
country: United States
facility: University of Oklahoma Health Sciences Center
state: Oklahoma
city: Philadelphia
country: United States
facility: Jefferson University Hospitals
state: Pennsylvania
city: Nashville
country: United States
facility: Vanderbilt University Medical Center
state: Tennessee
city: Fort Worth
country: United States
facility: Medical City Fort Worth
state: Texas
city: Houston
country: United States
facility: Houston Methodist Hospital
state: Texas
city: Salt Lake City
country: United States
facility: University of Utah
state: Utah
city: San Vicente
country: Argentina
facility: Sanatorio Parque S.A. Privado
state: Cordoba
city: Ciudad Autonoma de Buenos Aire
country: Argentina
facility: CEMIC
city: Ciudad Autonoma de Buenos Aire
country: Argentina
facility: Sanatorio de la Trinidad Mitre
city: Ciudad Autonoma de Buenos Aire
country: Argentina
facility: Hospital Italiano de Buenos Aires
city: Ciudad Autonoma de Buenos Aire
country: Argentina
facility: Hospital General de Agudos Dr. Ignacio Pirovano
city: Ciudad Autonoma de Buenos Aire
country: Argentina
facility: Clinica Adventista Belgrano
city: Córdoba
country: Argentina
facility: Clinica Chutro
city: Córdoba
country: Argentina
facility: Hospital San Roque
city: Córdoba
country: Argentina
facility: Sanatorio Privado de la Canada - Cordoba
city: Rosario
country: Argentina
facility: Centro Medico IPAM
city: San Nicolas
country: Argentina
facility: Estudios Clinicos de los Arroyos
city: Villa María
country: Argentina
facility: Sanatorio de la Canada
city: Woolloongabba
country: Australia
facility: Princess Alexandra Hospital
state: Queensland
city: Clayton
country: Australia
facility: Monash Medical Centre
state: Victoria
city: Nedlands
country: Australia
facility: Sir Charles Gairdner Hospital
state: Western Australia
city: Footscray
country: Australia
facility: Footscray Hospital
city: Heidelberg
country: Australia
facility: Austin Health
city: Saint Albans
country: Australia
facility: Sunshine Hospital
city: Klagenfurt
country: Austria
facility: KABEG-Klinikum Klagenfurt
city: Vienna
country: Austria
facility: AKH - Medizinische Universität Wien
city: Brugge
country: Belgium
facility: AZ Sint-Jan
city: Brussel
country: Belgium
facility: Cliniques Universitaires Saint-Luc
city: Bruxelles
country: Belgium
facility: Hopital Erasme
city: Edegem
country: Belgium
facility: Antwerp University Hospital (UZA)
city: Gent
country: Belgium
facility: AZ Maria Middelares
city: Jette
country: Belgium
facility: Universitair Ziekenhuis Brussel
city: Liège
country: Belgium
facility: C. H. R. de la Citadelle
city: Lodelinsart
country: Belgium
facility: CHU Charleroi Hôpital Civil Marie Curie
city: Ottignies
country: Belgium
facility: Clinique Saint-Pierre
city: Botucatu
country: Brazil
facility: UPECLIN - Unidade de Pesquisa Clínica
city: Campinas
country: Brazil
facility: HMCP - Hospital e Maternidade Celso Pierro - PUC-Campinas
city: Caxias Do Sul
country: Brazil
facility: Universidade de Caxias do Sul, IPCEM - Instituto de Pesquisa Clínica para Estudos Multicêntricos
city: Passo Fundo
country: Brazil
facility: Hospital de Clínicas de Passo Fundo
city: Porto Alegre
country: Brazil
facility: Irmandade da Santa Casa de Misericórdia de Porto Alegre
city: Porto Alegre
country: Brazil
facility: Hospital de Clínicas de Porto Alegre
city: Porto Alegre
country: Brazil
facility: Hospital Ernesto Dornelles
city: São José Do Rio Preto
country: Brazil
facility: CIP - Centro Integrado de Pesquisa
city: São Paulo
country: Brazil
facility: Hospital Alemão Oswaldo Cruz
city: São Paulo
country: Brazil
facility: Universidade Municipal de Sao Caetano do Sul (USCS)
city: Brno
country: Czechia
facility: Fakultni nemocnice u sv. Anny v Brne
city: Kolín
country: Czechia
facility: Oblastni nemocnice Kolin a.s.
city: Kyjov
country: Czechia
facility: Hospital Kyjov
city: Prague
country: Czechia
facility: Fakultni nemocnice Kralovske Vinohrady
city: Argenteuil
country: France
facility: Centre Hospitalier Victor Dupouy
city: Colombes
country: France
facility: Hôpital Louis Mourier
city: Grenoble
country: France
facility: CHU de Grenoble - Hôpital Albert Michallon
city: Lille
country: France
facility: CHRU Lille - Hôpital Salengro
city: Limoges
country: France
facility: CHU de Limoges - Hôpital Dupuytren
city: Melun
country: France
facility: Centre Hospitalier de Melun
city: Nice
country: France
facility: CHU Nice-Hopital de l' Archet
city: Nice
country: France
facility: CHU Nice Hopital Pasteur 2
city: Paris
country: France
facility: Hôpital Bichat - Claude Bernard
city: Paris
country: France
facility: Groupe Hospitalier Diaconesses - Hopital De La Croix Saint Simon
city: Paris
country: France
facility: Hôpital Tenon
city: Paris
country: France
facility: Hôpital Cochin
city: Rennes
country: France
facility: CHU Rennes - Hôpital Pontchaillou
city: Saint-Étienne
country: France
facility: CHU Saint-Etienne
city: Strasbourg
country: France
facility: CHU Strasbourg - Nouvel Hôpital Civil
city: Strasbourg
country: France
facility: CHU Strasbourg - Hôpital Hautepierre
city: Toulon
country: France
facility: Hôpital Sainte Musse
city: Tours
country: France
facility: CHU Tours - Hôpital Bretonneau
city: Trévenans
country: France
facility: Hôpital Nord Franche-Comté
city: Berlin
country: Germany
facility: Charité Universitätsmedizin Berlin - Campus Charité Mitte
city: Hamburg
country: Germany
facility: Universitätsklinikum Hamburg-Eppendorf
city: Hanover
country: Germany
facility: Medizinische Hochschule Hannover
city: Gyula
country: Hungary
facility: Bekes Megyei Kozponti Korhaz Pandy Kalman Tagkorhaza
city: Gyöngyös
country: Hungary
facility: Bugat Pal Korhaz
city: Kistarcsa
country: Hungary
facility: Pest Megyei Flor Ferenc Korhaz
city: Pécs
country: Hungary
facility: Aneszteziologiai es Intenziv Terapias Intezet
city: Szeged
country: Hungary
facility: Szegedi Tudomanyegyetem Szent-Gyorgyi Albert Klinikai Kozpont
city: Székesfehérvár
country: Hungary
facility: Fejer Megyei Szent Gyorgy Egyetemi Oktato Korhaz
city: Dublin
country: Ireland
facility: St James's Hospital
city: Dublin
country: Ireland
facility: Beaumont Hospital
city: Dublin
country: Ireland
facility: St Vincents University Hospital
city: Be'er Sheva
country: Israel
facility: Soroka Medical Center
city: Haifa
country: Israel
facility: Bnai Zion Medical Center
city: Haifa
country: Israel
facility: Rambam Medical Center
city: Haifa
country: Israel
facility: The Lady Davis Carmel Medical Center
city: Petach Tikva
country: Israel
facility: Rabin Medical Center
city: Reẖovot
country: Israel
facility: Kaplan Medical Center
city: Tel Aviv
country: Israel
facility: Tel Aviv Sourasky Medical Center
city: Otahuhu
country: New Zealand
facility: Middlemore Hospital
city: Baguio City
country: Philippines
facility: Baguio General Hospital and Medical Center
city: Caloocan
country: Philippines
facility: Dr. Jose N. Rodriguez Memorial Hospital
city: Davao City
country: Philippines
facility: Davao Doctors Hospital
city: Davao City
country: Philippines
facility: Southern Philippines Medical Center
city: Iloilo City
country: Philippines
facility: St.Paul's Hospital
city: Iloilo City
country: Philippines
facility: West Visayas State University Medical Center
city: Manila
country: Philippines
facility: Philippine General Hospital
city: Quezon City
country: Philippines
facility: Lung Center of the Philippines
city: Bucharest
country: Romania
facility: Institutul Clinic Fundeni
city: Bucharest
country: Romania
facility: Spitalul Universitar de Urgenta Bucuresti
city: Timişoara
country: Romania
facility: Spitalul Clinic Judetean de Urgenta "Pius Brinzeu"
city: Centurion
country: South Africa
facility: Johese Clinical Research
state: Gauteng
city: Pretoria
country: South Africa
facility: Emmed Clinical Research
state: Gauteng
city: Pretoria
country: South Africa
facility: Into Research
state: Gauteng
city: Johannesburg
country: South Africa
facility: Worthwhile Clinical Trials
city: Pretoria
country: South Africa
facility: RYEXO Clinical Research Zuid Afrikaans Hospital
city: Pretoria
country: South Africa
facility: RYEXO Clinical Research
city: Somerset West
country: South Africa
facility: Dr JM Engelbrecht Trial Site
city: Barcelona
country: Spain
facility: Hospital Clinic de Barcelona
city: Barcelona
country: Spain
facility: Hospital de la Santa Creu i de Sant Pau
city: Barcelona
country: Spain
facility: Hospital Universitari Vall d'Hebrón
city: Córdoba
country: Spain
facility: Hospital Universitario Reina Sofia
city: Girona
country: Spain
facility: Hospital Universitari de Girona Dr Josep Trueta
city: Madrid
country: Spain
facility: Hospital Universitario Clinico San Carlos
city: Madrid
country: Spain
facility: Hospital Universitario La Paz
city: Majadahonda
country: Spain
facility: Hospital Universitario Puerta de Hierro Majadahonda
city: Palma De Mallorca
country: Spain
facility: Hospital Universitario Son Espases
city: Tarragona
country: Spain
facility: Hospital Universitari de Tarragona Joan XXIII
city: Valencia
country: Spain
facility: Hospital Universitari i Politecnic La Fe
city: Glasgow
country: United Kingdom
facility: Queen Elizabeth University Campus
city: Guildford
country: United Kingdom
facility: Royal Surrey County Hospital
city: London
country: United Kingdom
facility: St Thomas' Hospital
city: Plymouth
country: United Kingdom
facility: Derriford Hospital
Study officials:
affiliation: Hospital Vall d'Hebron
name: Ricard Ferrer Roca, Dr.
role: PRINCIPAL_INVESTIGATOR
References: