A study to test trimodulin in adult hospitalized patients with severe pneumonia

Overview

Sponsor-declared trial summary

Key facts

Sponsor

Biotest GmbH & Co. KGaA

Participant type

Patients

Age range

18-64 years, 65+ years

Gender

Male and Female

Therapeutic area

Diseases [C] - Respiratory Tract Diseases [C08]

Trial duration

7 Jun 2023 → ongoing

Decision date (initial)

2023-04-24

Transition trial

No

Low-intervention

No

Rare-disease indication

No

Vulnerable population

Yes

Trial design

CTIS Part I — objectives, methods, condition coding

Main objective

Scope: Efficacy, Safety, Pharmacokinetic, Pharmacodynamic

To assess the efficacy of trimodulin based on 28-day all-cause mortality to demonstrate superiority to treatment with placebo

Secondary objectives 1

1. To assess efficacy and safety and to determine PK and PD properties of trimodulin compared to placebo

Conditions and MedDRA coding

Severe community-acquired pneumonia (sCAP)

Study design 1 period

Regulatory references

Scientific advice from competent authorities

Paul Ehrlich Institute, European Medicines Agency, Food And Drug Administration

Plan to share IPD

No

Eligibility criteria

Principal inclusion / exclusion criteria as submitted by sponsor

Inclusion criteria 8

1. Written informed consent obtained from subject or legally acceptable/authorized representative (LAR)
2. Hospitalized, adult (≥ 18 years of age) subject (any gender).
3. C-reactive protein (CRP) ≥ 70 mg/L up to 1 calendar day prior to start of treatment with IMP.
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 must be available from routine SoC.
6. Acute respiratory failure requiring IMV, defining sCAP (Appendix 9: sCAP Diagnostic Criteria According to the ATS/IDSA Guideline)
7. Treatment with IMP must be started between 1 and 24 hours after initiation of IMV.
8. Subject must receive SoC treatment for sCAP according to applicable regional and global sCAP guidelines.

Exclusion criteria 26

1. 01. For an incapacitated subject: any indication that the subject’s presumed will would be against inclusion in the trial.
2. 10. Pre-existing hemolytic disease.
3. 11. Thromboembolic events (TEEs) caused by other reasons than the current sCAP (e.g., cerebrovascular accidents, transient ischemic attack, myocardial infarction, pulmonary embolism, and deep vein thrombosis) within 3 months before start of IMP treatment.. unless the risk for further TEEs can be adequately managed with standard prophylaxis or treatment.
4. 12. Severe renal impairment, estimated glomerular filtration rate (eGFR) < 30 mL/min/1.73 m² per most recent test performed up to 1 calendar day prior to start of IMP treatment (details in Appendix 2: Estimated Glomerular Filtration Rate).*), unless the subject is already on dialysis or continuous replacement therapy.
5. 13. End-stage renal disease (ESRD) or known primary focal segmental glomerulosclerosis (FSGS).
6. 14. Pre-existing severe lung diseases concomitant to current sCAP (e.g., subjects with active tuberculosis, or active lung cancer).
7. 15. Pre-existing decompensated heart failure (New York Heart Association class III–IV).
8. 16. Pre-existing severe hepatic cirrhosis, (Child Pugh score ≥ 10 points), or severe hepatic impairment (Child Pugh score ≥ 10 points), or hepatocellular carcinoma.
9. 17. Known intolerance to proteins of human origin or known allergic reactions to any of the components of trimodulin / placebo.
10. 18. Selective IgA deficiency with known antibodies to IgA.
11. 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.
12. 02. Pregnant or lactating women.
13. 20. Morbid obesity with high body mass index (BMI) ≥ 40 kg/m2, or malnutrition with low BMI < 16 kg/m2.
14. 21. Treatment with > 1 g/kg body weight of polyvalent immunoglobulin preparation in total during the last 21 days before start of IMP treatment
15. 22. Treatment with fluoroquinolone preparations, during the last 2 days before start of IMP treatment
16. 23. Hematopoietic stem cell transplantation within 1 year, or previous lung transplantation
17. 24. Treatment with investigational medications procedures not according to SoC of the trial site , due to participation in another interventional clinical tria within 30 days before start of IMP treatment or previous IMP treatment with IMP in this clinical trial.
18. 25. Employee or direct relative of an employee of the CRO, or the trial site, if employee is directly involved in the trial or otherwise in a dependent relationship with the site staff.
19. 26. Persons, subject to legal protection measures, if applicable according to local laws.
20. 03. Subjects of childbearing potential not willing to use reliable contraceptive measures during the trial and for 15 weeks after the last IMP treatment.
21. 04. Subjects on extracorporeal membrane oxygenation (ECMO) at start of IMP treatment.
22. 05. Suspected hospital-acquired pneumonia (HAP) including ventilator associated pneumonia (VAP).
23. 06. Subjects discharged from hospital within the previous 14 days.
24. 07. Severe neutropenia (neutrophil count <500/mm³) per most recent test performed up to 1 calendar day prior to start of IMP treatment.
25. 08. Thrombocytopenia (platelet count <30,000/mm³) per most recent test performed up to 1 calendar day prior to start of IMP treatment.
26. 09. Hemoglobin (Hb) < 7 g/dL hours per most recent test performed up to 1 calendar day prior to start of IMP treatment.

Endpoints

Primary and secondary outcome measures (English text)

Primary endpoints 1

1. Efficacy Endpoint: 28-day all-cause mortality rate

Secondary endpoints 27

1. 90-day all-cause mortality rate
2. Change in Sequential Organ Failure Assessment (SOFA) score from baseline to day 7
3. Proportion of subjects with clinical cure of pneumonia up to day 29
4. Days of IMV up to day 29
5. Ventilator-free days (VFD) up to day 29
6. Days with oxygen supply up to day 29
7. Proportion of subjects with oxygen supply on days 7, 14, 21, 29
8. Days in intensive care unit (ICU) up to day 29
9. Time to discharge from ICU
10. Proportion of subjects in ICU on days 7, 14, 21 and 29
11. Days of hospitalization up to day 29
12. Time to discharge from hospital
13. Proportion of subjects in hospital on days 7, 14, 21 and 29
14. 28-day readmission rate
15. Rate of unscheduled return(s) to the emergency department or primary physician between day 29 and day 91
16. Time to return to normal activities up to day 91
17. Health status based on Clinical Frailty Scale (CFS) on day 91
18. Number, severity, causality, outcome, and seriousness of all adverse events (AEs) and treatment-emergent AEs (TEAEs), AEs of special interest (AESIs), infusional TEAEs, TEAEs that led to permanent discontinuation of IMP, and TEAEs that led to discontinuation of the trial through day 29 [+3]
19. Number of all related TEAEs through day 91 [+10]
20. Number, severity, causality, and outcome of all SAEs through day 29 [+3]
21. Dose modifications (including reductions and changes in infusion rate)
22. Distribution and changes over time of clinical laboratory vital signs parameters, and electrocardiogram (ECG)
23. For subjects in main study: Changes from baseline, during and after treatment: Serum concentration of IgM, IgA, and IgG
24. For subjects in the PK substudy: Serum concentration of IgM, IgA, and IgG
25. For subjects in the PK substudy: Pharmacokinetic parameters of IgM, IgA and IgG
26. Changes from baseline, during and after treatment: Markers of inflammation, Markers of coagulation, Complement factors, Biomarkers, Anti-pathogen titers
27. Deterioration rate up to day 29

Investigational products

Investigational medicinal products (IMPs), comparators, placebo, auxiliary

Test 1

Placebo 1

Sponsors and contacts

Sponsor organisations, regulatory contacts, third parties

Biotest GmbH & Co. KGaA

Sponsor organisation

Biotest GmbH & Co. KGaA

Address

Landsteinerstrasse 5, Dreieichenhain Dreieichenhain

City

Dreieich

Postcode

63303

Country

Germany

Scientific contact point

Organisation

Biotest GmbH & Co. KGaA

Contact name

Iris Bobenhausen

Public contact point

Organisation

Biotest GmbH & Co. KGaA

Contact name

Iris Bobenhausen

Third parties 6

Locations

9 EU/EEA countries · 61 investigational sites

By country

Investigational sites

Country notifications

Trial-start, recruitment-start, end and early-termination notifications submitted per Member State

Results and documents

Annex IV summary of results, Annex V layperson summary, and all documents registered in CTIS for this trial

Documents 182 files

Public protocol annexes, IB summaries, regulatory submissions and post-authorisation documents registered in CTIS.

Application history

28 submissions — initial application plus substantial / non-substantial modifications