Efficacy and Safety of Trimodulin (BT588) in Subjects With CAP Including COVID-19 Pneumonia

COVID-19 Clinical Trial

— TRICOVID  

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 CAP Including COVID-19 Pneumonia.

Clinical Trial Details — Status: Recruiting

Administrative data

• NCT number: NCT05531149
• Other study ID #: 1001
• Status: Recruiting
• Phase: Phase 3
• Start date: December 22, 2022
• Est. completion date: August 31, 2025

Study information

• Verified date: April 2024
• Source: Biotest
• Contact: Patrick Langohr
• Phone: +491732947122
• Email: patrick.langohr[@]biotest.com
• Is FDA regulated: No
• Study type: Interventional

Clinical Trial Summary

The main objectives of the trial are 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. Other objectives are to determine pharmacokinetic (PK) and pharmacodynamic (PD) properties of trimodulin.

Description:

This is a randomized, placebo-controlled, double-blind, multi-center, phase III trial to assess the efficacy and safety of trimodulin compared to placebo treatment, adjunctive to SoC in adult hospitalized subjects with non-severe community-acquired pneumonia (CAP) or moderate / severe Coronavirus Disease 2019 (COVID-19) pneumonia. Patients requiring low-flow oxygen, non-invasive ventilation or high-flow oxygen and with signs of early systemic inflammation (defined by C reactive protein (CRP), D-dimer and platelet levels) will be enrolled. Subjects will be randomized to receive either trimodulin or placebo on a 1:1 basis, stratified by type of oxygen supply before randomization and by region. Investigational Medicinal Product (IMP) treatments will be blinded. Subjects will be administered IMP once daily on five 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 all subjects still in the hospital after day 29, an extended follow-up visit is conducted until day 90 or until discharge. For all subjects a closing visit/telephone call on day 91 [+10] will be done. For the evaluation of the primary and several secondary endpoints of the trial, a 9-category ordinal scale will be used. The primary objective is to assess efficacy of trimodulin based on clinical deterioration and mortality to demonstrate superiority to treatment with placebo. Secondary objectives are to assess efficacy and safety and to determine PK and PD properties of trimodulin compared to placebo.

Recruitment information / eligibility

• Status: Recruiting
• Enrollment: 390
• Est. completion date: August 31, 2025
• Est. primary completion date: August 31, 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) subjects.

3. Diagnosis of CAP or COVID- 19 pneumonia (e.g. according to local guidelines) and with radiologic evidence showing new pulmonary lobar or multilobar infiltrates consistent with CAP or COVID-19 pneumonia.

4. Receiving oxygen supply via low-flow oxygen, high-flow oxygen or on non-invasive ventilation.

5. Fulfilling at least one clinical respiratory parameter (SpO2 = 94% and/or 100 mm Hg < PaO2/FiO2 = 300 mm Hg).

6. Signs of early systemic inflammation based on CRP and coagulation parameter threshold levels.

Main Exclusion Criteria:

1. Pregnant or lactating women.

2. Subject on invasive mechanical ventilation and/or extracorporeal membrane oxygenation.

3. Subject with septic shock and in need for vasopressors.

4. Severe neutropenia prior to start of treatment.

5. Hemoglobin >7 g/dL prior to start of treatment.

6. Pre-existing hemolytic disease.

7. Pre-existing thromboembolic events (TEEs).

8. Subject on dialysis or with severe renal impairment prior to start of treatment.

9. Subject with end stage renal disease, or known primary focal segmental glomerulosclerosis.

10. Pre-existing severe lung diseases to current pneumonia.

11. Pre-existing decompensated heart failure.

12. Pre-existing hepatic cirrhosis, severe hepatic impairment , or hepatocellular carcinoma.

13. Known intolerance to proteins of human origin or known allergic reactions to components of trimodulin/placebo.

14. Selective, absolute immunoglobulin A (IgA) deficiency with known antibodies to IgA.

15. Known human immunodeficiency virus infection.

16. Life expectancy of less than 90 days.

17. Morbid obesity or malnutrition.

18. Treatment with predefined medications (certain immune modulators or immunosuppressants) before entering the trial.

Related Conditions & MeSH terms

• Acute Lung Injury
• Acute Respiratory Distress Syndrome
• Bacterial Pneumonia
• Community-acquired Pneumonia
• COVID-19
• Pneumonia
• Pneumonia, Bacterial
• Pneumonia, Viral
• Respiratory Distress Syndrome
• Respiratory Distress Syndrome, Newborn
• Respiratory Infection
• Respiratory Tract Infections
• Viral Pneumonia

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	Investigational Site #5401	Buenos Aires
Argentina	Investigational Site #5403	Cordoba
Argentina	Investigational Site #5402	Córdoba
Austria	Investigational Site #4303	Klagenfurt
Austria	Investigational Site #4302	Linz
Austria	Investigational Site #4304	Wien
Belgium	Investigational Site #3203	Edegem
Belgium	Investigational Site #3202	Mechelen
Belgium	Investigational Site #3201	Ottignies
Brazil	Investigational Site #5505	Botucatu
Brazil	Investigational Site #5503	Porto Alegre
Brazil	Investigational Site #5506	Porto Alegre
Brazil	Investigational Site #5507	Porto Alegre
Brazil	Investigational Site #5502	Santo André
Brazil	Investigational Site #5504	São José Do Rio Preto
Brazil	Investigational Site #5501	São Paulo
France	Investigational Site #3303	Melun
France	Investigational Site #3301	Paris
France	Investigational Site #3304	Paris
France	Investigational Site #3305	Saint-Étienne
France	Investigational Site #3307	Salouël
France	Investigational Site #3306	Strasbourg
France	Investigational Site #3308	Strasbourg
France	Investigational Site #3302	Trévenans
Germany	Investigational Site #4904	Berlin
Germany	Investigational Site #4901	Bochum
Germany	Investogational Site #4902	Cottbus
Germany	Investigational Site #4903	Hannover
Germany	Investigational Site #4907	München
Hungary	Investigational SIte #3603	Debrecen
Hungary	Investigational Site #3601	Szeged
Latvia	Investigational Site #7102	Daugavpils
Latvia	Investigational Site #7101	Riga
Lithuania	Investigational Site #7004	Šiauliai
Lithuania	Investigational Site #7002	Kaunas
Lithuania	Investigational Site #7005	Kaunas
Lithuania	Investigational Site #7007	Kaunas
Lithuania	Investigational Site #7003	Klaipeda
Lithuania	Investigational Site #7001	Vilnius
Portugal	Investigational Site #3502	Guimarães
Portugal	Investogational SIte #3501	Lisboa
Slovakia	Investigational Site #2103	Banská Bystrica
Slovakia	Investigational Site #2102	Malacky
Slovakia	Investigational Site #2105	Michalovce
Slovakia	Investigational Site #2101	Nitra
Slovakia	Investigational Site #2104	Svidník
South Africa	Investigational site #2706	Kimberley
South Africa	Investigational Site #2702	Klerksdorp
South Africa	Investigational Site #2703	Mthatha
South Africa	Investigational Site #2705	Plettenberg Bay
South Africa	Investigational Site #2701	Pretoria
South Africa	Investigational Site #2704	Pretoria
South Africa	Investigational Site #2707	Pretoria
Spain	Investigational Site #3401	Barcelona
Spain	Investigational Site #3403	Madrid
Spain	Investigational Site #3404	Madrona
Turkey	Investigational Site #9005	Ankara
Turkey	Investigational Site #9004	Istanbul
Turkey	Investigational Site #9001	Trabzon

Sponsors (1)

Lead Sponsor	Collaborator
Biotest

Countries where clinical trial is conducted

Argentina,  Austria,  Belgium,  Brazil,  France,  Germany,  Hungary,  Latvia,  Lithuania,  Portugal,  Slovakia,  South Africa,  Spain,  Turkey, 

Outcome

Type	Measure	Description	Time frame	Safety issue
Other	Pharmacokinetic assessment of immunoglobulins	Assessment of changes in serum concentrations (g/L) of immunoglobulin M (IgM), immunoglobulin A (IgA), and immunoglobulin G (IgG) before, during and after treatment	Day 1, 5, 14
Other	Pharmacodynamic assessment of disease related serum proteins	Assessment of relative changes in serum concentrations from baseline before, during and after treatment including markers of inflammation, coagulation, complement factors and biomarkers (e.g. % change in Interleukin-6)	Days 1, 3, 5, 7, 14
Primary	Composite Endpoint	Composite of percentage of subjects with a change of at least 1 category on the 9-category ordinal scale from baseline (between days 6-29) and 28-day all-cause mortality rate (between days 1-29)	Until day 29
Secondary	Clinical deterioration rate	Percentage of subjects with a change of at least 1 category on the category ordinal-scale	Between days 6-29 and days 1-29
Secondary	28-days all-cause mortality rate	Percentage of subjects with a change to 8 on 9-category ordinal scale.	Day 29
Secondary	90-days all-cause mortality rate	Percentage of subjects with a change to 8 on 9-category ordinal scale.	Day 91
Secondary	Time to recovery	Number of days to score = 2 until day 29	Between days 1-29
Secondary	Proportion of subjects with score = 2	Proportion of subjects that improved to score = 2	Day 29
Secondary	Proportion of subjects improved, unchanged, and deteriorated/died	Proportion of subjects improved, unchanged, and deteriorated/died compared to baseline at several days	Between days 1-29
Secondary	Proportion of subjects with different partial pressure of oxygen (PaO2)/ fraction of inspired oxygen (FiO2) ratios	Proportion of subjects with PaO2/FiO2 ratio < 100, 100 to < 200, 200 to < 300 or = 300	Days 7, 14, 21, 29
Secondary	Days of invasive mechanical ventilation (IMV)/ extracorporeal membrane oxygenation (ECMO)	Days of IMV/ECMO	Day 29
Secondary	Proportion of subjects on IMV/ECMO	Proportion of subjects on IMV/ECMO	Day 29
Secondary	Days with oxygen supply	Days with oxygen supply	Day 29
Secondary	Proportion of subjects with oxygen supply	Proportion of subjects with oxygen supply	Days 7, 14, 21, 29
Secondary	Days in intensive care unit (ICU)	Days in intensive care unit	Day 29
Secondary	Proportion of subjects in ICU	Proportion of subjects in ICU	Day 29
Secondary	Days of hospitalization	Days of hospitalization	Day 29
Secondary	All 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 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	Until day 29
Secondary	TEAEs	Number of all related TEAEs	Until day 29
Secondary	SAEs	Number, severity, causality, and outcome of all serious adverse events (SAEs)	Until day 29
Secondary	Dose modifications	Dose modifications (incl. reductions and changes in infusion rate)	Day 1-5
Secondary	Change over time in ECG parameters	ECG recordings, (including heart rate, QT-interval, QTcF) showing abnormal, clinically relevant findings will be reported as adverse event	Days -1, 1, 3, 5 and once between days 8-13
Secondary	Changes over time in vital signs	Changes in recordings of vital sign parameters showing clinically significant measurements outside the normal range will be reported as adverse event.	Days -1,1-3, 5, 7 ,14, 21, 29
Secondary	Changes over time in clinical laboratory parameters	Changes in recordings for clinical laboratory values (including chemistry, hematology and coagulation) showing clinically significant measurements outside the normal range will be reported as adverse event.	Days -1, 1-5, 7,14, 21, 29