Trial Review

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Trial details imported from ClinicalTrials.gov

For full trial details, please see the original record at https://clinicaltrials.gov/ct2/show/NCT05722938




Registration number
NCT05722938
Ethics application status
Date submitted
11/01/2023
Date registered
10/02/2023
Date last updated
26/04/2024

Titles & IDs
Public title
Efficacy and Safety of Trimodulin (BT588) in Subjects With Severe Community-acquired Pneumonia (sCAP)
Scientific 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)
Secondary ID [1] 0 0
996
Universal Trial Number (UTN)
Trial acronym
ESsCAPE
Linked study record

Health condition
Health condition(s) or problem(s) studied:
Community-acquired Pneumonia 0 0
Condition category
Condition code
Respiratory 0 0 0 0
Other respiratory disorders / diseases
Infection 0 0 0 0
Other infectious diseases
Infection 0 0 0 0
Studies of infection and infectious agents

Intervention/exposure
Study type
Interventional
Description of intervention(s) / exposure
Treatment: Drugs - Trimodulin
Treatment: Drugs - Placebo (human albumin 1%)

Experimental: Trimodulin - Trimodulin (human IgM, IgA, IgG solution) for intravenous (IV) administration.

Placebo Comparator: Placebo - Human albumin 1%


Treatment: Drugs: Trimodulin
IMP will be administered via IV infusion on 5 consecutive days

Treatment: Drugs: Placebo (human albumin 1%)
IMP will be administered via IV infusion on 5 consecutive days
Intervention code [1] 0 0
Treatment: Drugs
Comparator / control treatment
Control group

Outcomes
Primary outcome [1] 0 0
28-day all-cause mortality rate
Timepoint [1] 0 0
Between days 1-29
Secondary outcome [1] 0 0
90-day all-cause mortality rate
Timepoint [1] 0 0
Between days 1-91
Secondary outcome [2] 0 0
28-day all-cause mortality rate plus day 6-29 deterioration rate
Timepoint [2] 0 0
1. Between days 1-29; 2. Between days 6-29
Secondary outcome [3] 0 0
Deterioration rate (day 6-29)
Timepoint [3] 0 0
Between days 6-29
Secondary outcome [4] 0 0
28-day all-cause mortality rate plus day 1-29 deterioration rate
Timepoint [4] 0 0
1.+2. Between days 1-29
Secondary outcome [5] 0 0
Deterioration rate (day 1-29)
Timepoint [5] 0 0
Between days 1-29
Secondary outcome [6] 0 0
Change in Sequential Organ Failure Assessment (SOFA) score from baseline to days 3, 5, 7, 14, 21, 29 and discharge
Timepoint [6] 0 0
Between baseline and Days 3, 5, 7, 14, 21, 29 and discharge
Secondary outcome [7] 0 0
Proportion of subjects with clinical cure of pneumonia on days 7, 14, 21, 29 and discharge
Timepoint [7] 0 0
On days 7, 14, 21, 29 or on the day of discharge
Secondary outcome [8] 0 0
Days of invasive mechanical ventilation (IMV) until day 29
Timepoint [8] 0 0
Until day 29
Secondary outcome [9] 0 0
Ventilator-free days (VFD) until day 29
Timepoint [9] 0 0
Until day 29
Secondary outcome [10] 0 0
Days with oxygen supply until day 29
Timepoint [10] 0 0
Until day 29
Secondary outcome [11] 0 0
Proportion of subjects with oxygen supply on days 7, 14, 21, 29 and discharge
Timepoint [11] 0 0
On days 7, 14, 21, 29 or on the day of discharge
Secondary outcome [12] 0 0
Proportion of subjects with PaO2/FiO2 ratio < 100, 100 to < 200, 200 to < 300 or = 300 on days 7, 14, 21, and 29
Timepoint [12] 0 0
On days 7, 14, 21, 29
Secondary outcome [13] 0 0
Vasopressor-free days until day 29
Timepoint [13] 0 0
Until day 29
Secondary outcome [14] 0 0
Days in intensive care unit (ICU) until day 29
Timepoint [14] 0 0
Until day 29
Secondary outcome [15] 0 0
Time to discharge from ICU
Timepoint [15] 0 0
Until day 91
Secondary outcome [16] 0 0
Proportion of subjects in ICU on days 7, 14, 21 and 29
Timepoint [16] 0 0
On days 7, 14, 21, 29
Secondary outcome [17] 0 0
Days of hospitalization until day 29
Timepoint [17] 0 0
Until day 29
Secondary outcome [18] 0 0
Time to discharge from hospital
Timepoint [18] 0 0
Until day 91
Secondary outcome [19] 0 0
Proportion of subjects in hospital on days 7, 14, 21 and 29
Timepoint [19] 0 0
On days 7, 14, 21, 29
Secondary outcome [20] 0 0
28-day readmission rate
Timepoint [20] 0 0
Day 29
Secondary outcome [21] 0 0
Rate of unscheduled return(s) to the emergency department or primary physician between day 29 and day 91
Timepoint [21] 0 0
Between Days 29 - 91
Secondary outcome [22] 0 0
Time to return to normal activities until day 91
Timepoint [22] 0 0
Until day 91
Secondary outcome [23] 0 0
Health status based on Clinical Frailty Scale (CFS) on day 91
Timepoint [23] 0 0
Between Days 29 - 91
Secondary outcome [24] 0 0
Quality of life based on Nottingham Health Profile (NHP) on days 29 and 91
Timepoint [24] 0 0
Day 29 and day 91
Secondary outcome [25] 0 0
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
Timepoint [25] 0 0
Until day 29
Secondary outcome [26] 0 0
Infusion-related TEAEs
Timepoint [26] 0 0
Until day 29
Secondary outcome [27] 0 0
Serious adverse events (SAEs)
Timepoint [27] 0 0
Until day 29
Secondary outcome [28] 0 0
Dose modifications
Timepoint [28] 0 0
Day 1-5
Secondary outcome [29] 0 0
Change over time in electrocardiogram (ECG) parameters
Timepoint [29] 0 0
Days -1, 1, 3, 5 and once between days 8-13
Secondary outcome [30] 0 0
Number and changes in observed Adverse Events in vital signs over time
Timepoint [30] 0 0
Days -1, 1-3, 5, 7, 14, 21, 29
Secondary outcome [31] 0 0
Number and changes in observed Adverse Events in clinical laboratory parameters over time
Timepoint [31] 0 0
Days -1, 1-5, 7, 14, 21, 29

Eligibility
Key inclusion criteria
Main

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
Minimum age
18 Years
Maximum age
No limit
Sex
Both males and females
Can healthy volunteers participate?
No
Key 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
Purpose of the study
Treatment
Allocation to intervention
Randomised controlled trial
Procedure for enrolling a subject and allocating the treatment (allocation concealment procedures)
Methods used to generate the sequence in which subjects will be randomised (sequence generation)
Masking / blinding
Blinded (masking used)
Who is / are masked / blinded?
The people receiving the treatment/s
The people administering the treatment/s
The people assessing the outcomes
The people analysing the results/data
Intervention assignment
Parallel
Other design features
Phase
Phase 3
Type of endpoint/s
Statistical methods / analysis

Recruitment
Recruitment status
Recruiting
Data analysis
Reason for early stopping/withdrawal
Other reasons
Date of first participant enrolment
Anticipated
Actual
9/09/2023
Date of last participant enrolment
Anticipated
Actual
Date of last data collection
Anticipated
30/04/2025
Actual
Sample size
Target
590
Accrual to date
Final
Recruitment in Australia
Recruitment state(s)
QLD
Recruitment hospital [1] 0 0
Princess Alexandra Hospital - Woolloongabba
Recruitment hospital [2] 0 0
Footscray Hospital - Footscray
Recruitment hospital [3] 0 0
Austin Health - Heidelberg
Recruitment hospital [4] 0 0
Sunshine Hospital - Saint Albans
Recruitment postcode(s) [1] 0 0
4102 - Woolloongabba
Recruitment postcode(s) [2] 0 0
3011 - Footscray
Recruitment postcode(s) [3] 0 0
3084 - Heidelberg
Recruitment postcode(s) [4] 0 0
3021 - Saint Albans
Recruitment outside Australia
Country [1] 0 0
United States of America
State/province [1] 0 0
California
Country [2] 0 0
United States of America
State/province [2] 0 0
Michigan
Country [3] 0 0
United States of America
State/province [3] 0 0
Missouri
Country [4] 0 0
United States of America
State/province [4] 0 0
Montana
Country [5] 0 0
United States of America
State/province [5] 0 0
New Jersey
Country [6] 0 0
United States of America
State/province [6] 0 0
New York
Country [7] 0 0
United States of America
State/province [7] 0 0
North Carolina
Country [8] 0 0
United States of America
State/province [8] 0 0
Pennsylvania
Country [9] 0 0
United States of America
State/province [9] 0 0
Texas
Country [10] 0 0
United States of America
State/province [10] 0 0
Utah
Country [11] 0 0
Argentina
State/province [11] 0 0
Ciudad Autonoma de Buenos Aire
Country [12] 0 0
Argentina
State/province [12] 0 0
Córdoba
Country [13] 0 0
Argentina
State/province [13] 0 0
Rosario
Country [14] 0 0
Argentina
State/province [14] 0 0
San Nicolas
Country [15] 0 0
Argentina
State/province [15] 0 0
Villa María
Country [16] 0 0
Austria
State/province [16] 0 0
Klagenfurt
Country [17] 0 0
Austria
State/province [17] 0 0
Vienna
Country [18] 0 0
Belgium
State/province [18] 0 0
Brugge
Country [19] 0 0
Belgium
State/province [19] 0 0
Brussel
Country [20] 0 0
Belgium
State/province [20] 0 0
Bruxelles
Country [21] 0 0
Belgium
State/province [21] 0 0
Edegem
Country [22] 0 0
Belgium
State/province [22] 0 0
Gent
Country [23] 0 0
Belgium
State/province [23] 0 0
Liège
Country [24] 0 0
Belgium
State/province [24] 0 0
Ottignies
Country [25] 0 0
Brazil
State/province [25] 0 0
Botucatu
Country [26] 0 0
Brazil
State/province [26] 0 0
Campinas
Country [27] 0 0
Brazil
State/province [27] 0 0
Caxias Do Sul
Country [28] 0 0
Brazil
State/province [28] 0 0
Porto Alegre
Country [29] 0 0
Brazil
State/province [29] 0 0
São José Do Rio Preto
Country [30] 0 0
Brazil
State/province [30] 0 0
São Paulo
Country [31] 0 0
Czechia
State/province [31] 0 0
Brno
Country [32] 0 0
Czechia
State/province [32] 0 0
Kolín
Country [33] 0 0
Czechia
State/province [33] 0 0
Kyjov
Country [34] 0 0
Czechia
State/province [34] 0 0
Prague
Country [35] 0 0
France
State/province [35] 0 0
Argenteuil
Country [36] 0 0
France
State/province [36] 0 0
Colombes
Country [37] 0 0
France
State/province [37] 0 0
Grenoble
Country [38] 0 0
France
State/province [38] 0 0
Lille
Country [39] 0 0
France
State/province [39] 0 0
Limoges
Country [40] 0 0
France
State/province [40] 0 0
Melun
Country [41] 0 0
France
State/province [41] 0 0
Nice
Country [42] 0 0
France
State/province [42] 0 0
Paris
Country [43] 0 0
France
State/province [43] 0 0
Saint-Étienne
Country [44] 0 0
France
State/province [44] 0 0
Strasbourg
Country [45] 0 0
France
State/province [45] 0 0
Toulon
Country [46] 0 0
France
State/province [46] 0 0
Tours
Country [47] 0 0
France
State/province [47] 0 0
Trévenans
Country [48] 0 0
Germany
State/province [48] 0 0
Berlin
Country [49] 0 0
Germany
State/province [49] 0 0
Hamburg
Country [50] 0 0
Germany
State/province [50] 0 0
Hanover
Country [51] 0 0
Hungary
State/province [51] 0 0
Gyöngyös
Country [52] 0 0
Hungary
State/province [52] 0 0
Pécs
Country [53] 0 0
Hungary
State/province [53] 0 0
Szeged
Country [54] 0 0
Israel
State/province [54] 0 0
Haifa
Country [55] 0 0
Israel
State/province [55] 0 0
Petach Tikva
Country [56] 0 0
New Zealand
State/province [56] 0 0
Otahuhu
Country [57] 0 0
Philippines
State/province [57] 0 0
Baguio City
Country [58] 0 0
Philippines
State/province [58] 0 0
Caloocan
Country [59] 0 0
Philippines
State/province [59] 0 0
Davao City
Country [60] 0 0
Philippines
State/province [60] 0 0
Iloilo City
Country [61] 0 0
Philippines
State/province [61] 0 0
Quezon City
Country [62] 0 0
Romania
State/province [62] 0 0
Bucharest
Country [63] 0 0
Romania
State/province [63] 0 0
Timisoara
Country [64] 0 0
South Africa
State/province [64] 0 0
Johannesburg
Country [65] 0 0
South Africa
State/province [65] 0 0
Pretoria
Country [66] 0 0
South Africa
State/province [66] 0 0
Somerset West
Country [67] 0 0
Spain
State/province [67] 0 0
Barcelona
Country [68] 0 0
Spain
State/province [68] 0 0
Córdoba
Country [69] 0 0
Spain
State/province [69] 0 0
Girona
Country [70] 0 0
Spain
State/province [70] 0 0
Madrid
Country [71] 0 0
Spain
State/province [71] 0 0
Majadahonda
Country [72] 0 0
Spain
State/province [72] 0 0
Tarragona
Country [73] 0 0
Spain
State/province [73] 0 0
Valencia
Country [74] 0 0
United Kingdom
State/province [74] 0 0
Guildford
Country [75] 0 0
United Kingdom
State/province [75] 0 0
Plymouth

Funding & Sponsors
Primary sponsor type
Commercial sector/Industry
Name
Biotest
Address
Country

Ethics approval
Ethics application status

Summary
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.
Trial website
https://clinicaltrials.gov/ct2/show/NCT05722938
Trial related presentations / publications
Public notes

Contacts
Principal investigator
Name 0 0
Tobias Welte, Prof.
Address 0 0
Hannover Medical School
Country 0 0
Phone 0 0
Fax 0 0
Email 0 0
Contact person for public queries
Name 0 0
Iris Bobenhausen, PhD
Address 0 0
Country 0 0
Phone 0 0
+4915222801073
Fax 0 0
Email 0 0
iris.bobenhausen@biotest.com
Contact person for scientific queries



Summary Results

For IPD and results data, please see https://clinicaltrials.gov/ct2/show/NCT05722938