Clinical trial NCT05531149: Efficacy and Safety of Trimodulin (BT588) in Subjects With CAP Including COVID-19 Pneumonia
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.
Study type: INTERVENTIONAL
Overall status: TERMINATED
Phase: PHASE3
Conditions: Respiratory Infection
Pneumonia
Community-acquired Pneumonia
Acute Respiratory Distress Syndrome
COVID-19
Viral Pneumonia
Bacterial Pneumonia
Fungal Pneumonia
Keywords: Non severe community acquired pneumonia
COVID-19
SARS-CoV-2
CAP
Lead sponsor: Biotest
Sponsor class: INDUSTRY
First posted: 2022-09-07
Enrollment: 107
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 to receive either trimodulin or placebo on a 1:1 basis, stratified by type of oxygen supply before randomization and by region
Primary purpose: TREATMENT

Brief 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.

Detailed 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.

Eligibility criteria: 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.

Primary outcomes:
measure: Composite Endpoint
timeFrame: Until day 29
Secondary outcomes:
measure: Clinical deterioration rate
timeFrame: Between days 6-29 and days 1-29
measure: 28-days all-cause mortality rate
timeFrame: Day 29
measure: 90-days all-cause mortality rate
timeFrame: Day 91
measure: Time to recovery
timeFrame: Between days 1-29
measure: Proportion of subjects with score ≤ 2
timeFrame: Day 29
measure: Proportion of subjects improved, unchanged, and deteriorated/died
timeFrame: Between days 1-29
measure: Proportion of subjects with different partial pressure of oxygen (PaO2)/ fraction of inspired oxygen (FiO2) ratios
timeFrame: Days 7, 14, 21, 29
measure: Days of invasive mechanical ventilation (IMV)/ extracorporeal membrane oxygenation (ECMO)
timeFrame: Day 29
measure: Proportion of subjects on IMV/ECMO
timeFrame: Day 29
measure: Days with oxygen supply
timeFrame: Day 29
measure: Proportion of subjects with oxygen supply
timeFrame: Days 7, 14, 21, 29
measure: Days in intensive care unit (ICU)
timeFrame: Day 29
measure: Proportion of subjects in ICU
timeFrame: Day 29
measure: Days of hospitalization
timeFrame: Day 29
measure: 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
timeFrame: Until day 29
measure: TEAEs
timeFrame: Until day 29
measure: SAEs
timeFrame: Until day 29
measure: Dose modifications
timeFrame: Day 1-5
measure: Change over time in ECG parameters
timeFrame: Days -1, 1, 3, 5 and once between days 8-13
measure: Changes over time in vital signs
timeFrame: Days -1,1-3, 5, 7 ,14, 21, 29
measure: Changes over time in clinical laboratory parameters
timeFrame: Days -1, 1-5, 7,14, 21, 29
Other outcomes:
measure: Pharmacokinetic assessment of immunoglobulins
timeFrame: Day 1, 5, 14
measure: Pharmacodynamic assessment of disease related serum proteins
timeFrame: Days 1, 3, 5, 7, 14
Locations:
city: Buenos Aires
country: Argentina
facility: Investigational Site #5401
city: Cordoba
country: Argentina
facility: Investigational Site #5403
city: Córdoba
country: Argentina
facility: Investigational Site #5402
city: Klagenfurt
country: Austria
facility: Investigational Site #4303
city: Linz
country: Austria
facility: Investigational Site #4302
city: Wien
country: Austria
facility: Investigational Site #4304
city: Edegem
country: Belgium
facility: Investigational Site #3203
city: Mechelen
country: Belgium
facility: Investigational Site #3202
city: Ottignies
country: Belgium
facility: Investigational Site #3201
city: Campo Largo
country: Brazil
facility: Investigational Site #5508
state: Sao Paulo
city: Ribeirão Preto
country: Brazil
facility: Investigational Site #5509
state: Sao Paulo
city: São Paulo
country: Brazil
facility: Investigational Site #5511
state: Sao Paulo
city: Botucatu
country: Brazil
facility: Investigational Site #5505
city: Porto Alegre
country: Brazil
facility: Investigational Site #5503
city: Porto Alegre
country: Brazil
facility: Investigational Site #5507
city: Porto Alegre
country: Brazil
facility: Investigational Site #5506
city: Santo André
country: Brazil
facility: Investigational Site #5502
city: Santos
country: Brazil
facility: Investigational Site #5510
city: São José Do Rio Preto
country: Brazil
facility: Investigational Site #5504
city: São Paulo
country: Brazil
facility: Investigational Site #5501
city: Melun
country: France
facility: Investigational Site #3303
city: Paris
country: France
facility: Investigational Site #3304
city: Paris
country: France
facility: Investigational Site #3301
city: Saint-Étienne
country: France
facility: Investigational Site #3305
city: Salouël
country: France
facility: Investigational Site #3307
city: Strasbourg
country: France
facility: Investigational Site #3306
city: Strasbourg
country: France
facility: Investigational Site #3308
city: Trévenans
country: France
facility: Investigational Site #3302
city: Berlin
country: Germany
facility: Investigational Site #4904
city: Bochum
country: Germany
facility: Investigational Site #4901
city: Cottbus
country: Germany
facility: Investogational Site #4902
city: Hannover
country: Germany
facility: Investigational Site #4903
city: München
country: Germany
facility: Investigational Site #4907
city: Debrecen
country: Hungary
facility: Investigational SIte #3603
city: Szeged
country: Hungary
facility: Investigational Site #3601
city: Daugavpils
country: Latvia
facility: Investigational Site #7102
city: Riga
country: Latvia
facility: Investigational Site #7101
city: Kaunas
country: Lithuania
facility: Investigational Site #7002
city: Kaunas
country: Lithuania
facility: Investigational Site #7007
city: Kaunas
country: Lithuania
facility: Investigational Site #7005
city: Klaipėda
country: Lithuania
facility: Investigational Site #7003
city: Vilnius
country: Lithuania
facility: Investigational Site #7006
city: Vilnius
country: Lithuania
facility: Investigational Site #7001
city: Šiauliai
country: Lithuania
facility: Investigational Site #7004
city: Guimarães
country: Portugal
facility: Investigational Site #3502
city: Lisboa
country: Portugal
facility: Investogational SIte #3501
city: Banská Bystrica
country: Slovakia
facility: Investigational Site #2103
city: Malacky
country: Slovakia
facility: Investigational Site #2102
city: Michalovce
country: Slovakia
facility: Investigational Site #2105
city: Nitra
country: Slovakia
facility: Investigational Site #2101
city: Svidník
country: Slovakia
facility: Investigational Site #2104
city: Kimberley
country: South Africa
facility: Investigational site #2706
city: Klerksdorp
country: South Africa
facility: Investigational Site #2702
city: Mthatha
country: South Africa
facility: Investigational Site #2703
city: Plettenberg Bay
country: South Africa
facility: Investigational Site #2705
city: Pretoria
country: South Africa
facility: Investigational Site #2701
city: Pretoria
country: South Africa
facility: Investigational Site #2707
city: Pretoria
country: South Africa
facility: Investigational Site #2704
city: Barcelona
country: Spain
facility: Investigational Site #3401
city: Madrid
country: Spain
facility: Investigational Site #3403
city: Madrona
country: Spain
facility: Investigational Site #3404
city: Ankara
country: Turkey
facility: Investigational Site #9005
city: Istanbul
country: Turkey
facility: Investigational Site #9004
city: Trabzon
country: Turkey
facility: Investigational Site #9001
Study officials:
affiliation: Hospital Clinic de Barcelona, Barcelona, Spain
name: Antoni Torres, Prof
role: PRINCIPAL_INVESTIGATOR
References: