A study to test trimodulin in adult hospitalized patients with CAP including COVID-19 pneumonia.

Overview

Sponsor-declared trial summary

Key facts

Sponsor

Biotest AG

Participant type

Patients

Age range

18-64 years, 65+ years

Gender

Male and Female

Therapeutic area

Diseases [C] - Respiratory Tract Diseases [C08]

Trial duration

26 Oct 2022 → 5 May 2025

Decision date (initial)

2024-07-22

Transition trial

Yes

Low-intervention

No

Rare-disease indication

No

Vulnerable population

Yes

External identifiers

EU CT number

2024-513002-60-00

EudraCT number

2022-000736-37

ClinicalTrials.gov

NCT05531149

Trial design

CTIS Part I — objectives, methods, condition coding

Main objective

Scope: Efficacy, Therapy, Safety, Pharmacodynamic, Pharmacokinetic

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 non-severe community-acquired pneumonia (CAP) or moderate / severe Coronavirus Disease 2019 (COVID-19) pneumonia

Secondary objectives 1

1. To determine pharmacokinetic (PK) and pharmacodynamic (PD) properties of trimodulin.

Conditions and MedDRA coding

Non-severe community-acquired pneumonia (CAP) or moderate or severe Coronavirus Disease 2019 (COVID-19)

Regulatory references

Scientific advice from competent authorities

European Medicines Agency, Paul-Ehrlich-Institut, Food And Drug Administration

Plan to share IPD

No

IPD plan description

N/A

Eligibility criteria

Principal inclusion / exclusion criteria as submitted by sponsor

Inclusion criteria 7

1. Written informed consent obtained from the subject or legally acceptable/authorized representative (LAR)* in compliance with all local legal requirements . *Informed consent process by LAR is not applicable in Lithuania
2. Hospitalized, adult (≥ 18 years of age) subject (any gender).
3. Diagnosis of CAP (e.g., according to ATS/IDSA guideline) or COVID-19 pneumonia (e.g., according to local guidelines) before or within 48 hours after hospital admission, and with radiologic evidence (available from routine SoC done before or after hospital admission) showing new pulmonary lobar or multilobar infiltrates consistent with CAP or COVID-19 pneumonia.
4. Receiving oxygen supply via low-flow oxygen (LFO, by mask or nasal prongs with > 2 L/min) or on non-invasive ventilation (NIV) or high-flow oxygen (HFO) at start of treatment with investigational medicinal product (IMP).
5. Fulfilling at least one of the following clinical respiratory parameters within 24 hours prior to start of treatment with IMP: • SpO2 ≤ 94% (on room air, and without preceding chronic lung disease); • 100 mm Hg < PaO2/FiO2 ≤ 300 mm Hg under HFO or NIV.
6. Treatment with IMP has to be started within 7 days after first hospital-admission for CAP or COVID-19 pneumonia.
7. Subject must receive SoC treatment for CAP or COVID-19 pneumonia.

Exclusion criteria 27

1. Pregnant or lactating women.
2. Subjects of child bearing potential not willing to use reliable contraceptive measures during the trial and for 15 weeks after the last IMP treatment.
3. Subject on invasive mechanical ventilation (IMV) and/or extracorporeal membrane oxygenation (ECMO) or predicted to be on IMV and/or ECMO at start of IMP treatment.
4. Subject with septic shock and in need for vasopressors at start of IMP treatment.
5. Subject with sustained improvement in any form of oxygen supply (e.g., change from IMV to NIV/HFO/LFO, or change from HFO to LFO) during the last 7 days or with predicted cessation of oxygen supply at start of treatment.
6. Severe neutropenia (neutrophil count < 0.5 x10^9/L) assessed within 24 hours prior to start of treatment.
7. Hemoglobin < 7g/dL assessed within 24 hours prior to start of treatment.
8. Pre-existing hemolytic disease.
9. Pre-existing thrombosis or thromboembolic events (TEEs) (e.g., cerebrovascular accidents, transient ischemic attack, myocardial infarction, pulmonary embolism, and deep vein thrombosis) within 3 months before entering the trial. Subjects particularly at risk for TEEs caused by other reasons than the current pneumonia (e.g., history of thrombophilia, permanent immobilization, or permanent paralysis of lower extremities).
10. Subject on dialysis or with severe renal impairment, estimated glomerular filtration rate (eGFR) < 30 mL/min/1.73 m² assessed within 24 hours prior to start of treatment.
11. Subject with end stage renal disease (ESRD), or primary focal segmental glomerulosclerosis (FSGS).
12. Pre-existing severe lung diseases concomitant to current pneumonia (e.g., COPD (GOLD stage III-IV / Group D), severe interstitial lung disease [including idiopathic pulmonary fibrosis], cystic fibrosis, active tuberculosis, chronically infected bronchiectasis, aspiration pneumonia or active lung cancer).
13. Pre-existing decompensated heart failure (New York Heart Association class III–IV).
14. Pre-existing hepatic cirrhosis, severe hepatic impairment (Child Pugh score ≥ 9 points), or hepatocellular carcinoma.
15. Known intolerance to proteins of human origin or known allergic reactions to any of the components of trimodulin / placebo.
16. Selective immunoglobulin A (IgA) deficiency with known antibodies to IgA.
17. Known human immunodeficiency virus infection.
18. Life expectancy of less than 90 days, according to the Investigator's clinical judgment, because of medical conditions related neither to current pneumonia, nor to associated medical complications.
19. Morbid obesity with high body mass index ≥ 40 kg/m², or malnutrition with low body mass index < 16 kg/m².
20. Treatment with polyvalent immunoglobulin preparations, plasma, or albumin preparations during the last 21 days before entering the trial.
21. Ongoing treatment with selective immune modulators (targeted and anti-inflammatory drugs) like cytokine inhibitors, receptor inhibitors, kinase inhibitors (Exceptions: corticosteroids, non-steroidal anti-inflammatory drugs [NSAIDs] and previous use of COVID-19 guideline-recommended immune modulating drugs if for treatment of COVID-19).
22. Treatment with fluoroquinolone preparations during the last 5 days before entering the trial.
23. Treatment with any type of interferon during the last 21 days before entering the trial.
24. Ongoing treatment with immunosuppressants like anti-proliferative/anti-cancer drugs, drugs used in transplantation or autoimmune diseases (Exception: corticosteroids).
25. Participation in another interventional clinical trial (using medications and/or procedures not according to SoC of the trial site) within 30 days before screening, or previous participation in this clinical trial.
26. Employee or direct relative of an employee of the contract research organization, the trial site, or Biotest.
27. Persons, subject to legal protection measures, if applicable according to local laws.

Endpoints

Primary and secondary outcome measures (English text)

Primary endpoints 1

1. Composite primary endpoint: Deterioration / mortality rate

Secondary endpoints 4

1. Secondary efficacy endpoints: • Clinical deterioration rate (day 6-29) • Clinical deterioration rate (day 1-29) • 28-days all-cause mortality rate on day 29 • 90-days all-cause mortality rate on day 91 • Time to recovery to score ≤ 2 until day 29 • Proportion of subjects with score ≤ 2 on day 29 •Proportion of subjects improved, unchanged, and deteriorated/died compared to baseline at several days
2. Secondary safety endpoints: • Number, severity, causality, outcome, and seriousness of all adverse events (AEs), treatment-emergent AEs (TEAEs), AEs of special interest (AESIs), infusional TEAEs, TEAEs that led to permanent withdrawal of IMP, and TEAEs that led to discontinuation of the trial through day 29 [+3] • Number of all related TEAEs through day 29 [+3]
3. Secondary PK endpoints: Changes from baseline, during and after treatment: - Serum concentration of IgM, IgA, and IgG
4. Secondary PD endpoints: Changes from baseline, during and after treatment: - Factors and markers of coagulation - Markers of inflammation - Complement factors - Biomarkers - Anti-SARS-CoV-2 and anti-S. pneumoniae titers

Investigational products

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

Test 1

Placebo 1

Sponsors and contacts

Sponsor organisations, regulatory contacts, third parties

Biotest AG

Sponsor organisation

Biotest AG

Address

Landsteinerstrasse 5, Dreieichenhain Dreieichenhain

City

Dreieich

Postcode

63303

Country

Germany

Scientific contact point

Organisation

Biotest AG

Contact name

Patrick Langohr

Public contact point

Organisation

Biotest AG

Contact name

Patrick Langohr

Third parties 11

Locations

9 EU/EEA countries · 33 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

Summary of results Art. 37(4) CTR

Layperson summary Annex V

Documents 114 files

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

Application history

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