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

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.

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.

Study Overview

• Status: Terminated
• Conditions: COVID-19; Pneumonia; Acute Respiratory Distress Syndrome; Community-acquired Pneumonia; Respiratory Infection; Bacterial Pneumonia; Viral Pneumonia; Fungal Pneumonia
• Intervention / Treatment: Drug: Trimodulin; Drug: Placebo (human albumin 1%)

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.

• Study Type: Interventional
• Enrollment (Actual): 107
• Phase: Phase 3

Contacts and Locations

Study Locations

• Argentina
  • Buenos Aires, Argentina, 1602
    • Investigational Site #5401
  • Cordoba, Argentina, 5000
    • Investigational Site #5403
  • Córdoba, Argentina, X5021FPQ
    • Investigational Site #5402
• Austria
  • Klagenfurt, Austria, 9020
    • Investigational Site #4303
  • Linz, Austria, 4020
    • Investigational Site #4302
  • Wien, Austria, 1090
    • Investigational Site #4304
• Belgium
  • Edegem, Belgium, 2650
    • Investigational Site #3203
  • Mechelen, Belgium, 2800
    • Investigational Site #3202
  • Ottignies, Belgium, 1340
    • Investigational Site #3201
• Brazil
  • Botucatu, Brazil, 18618-686
    • Investigational Site #5505
  • Porto Alegre, Brazil, 90020-090
    • Investigational Site #5503
  • Porto Alegre, Brazil, 90035-903
    • Investigational Site #5507
  • Porto Alegre, Brazil, 90610-000
    • Investigational Site #5506
  • Santo André, Brazil, 09030-10
    • Investigational Site #5502
  • Santos, Brazil, 11075-101
    • Investigational Site #5510
  • São José Do Rio Preto, Brazil, 15090-000
    • Investigational Site #5504
  • São Paulo, Brazil, 09530-700
    • Investigational Site #5501
  • Sao Paulo
    • Campo Largo, Sao Paulo, Brazil, 83606-177
      • Investigational Site #5508
    • Ribeirão Preto, Sao Paulo, Brazil, 14048-900
      • Investigational Site #5509
    • São Paulo, Sao Paulo, Brazil, 01323-903
      • Investigational Site #5511
• France
  • Melun, France, 77000
    • Investigational Site #3303
  • Paris, France, 75020
    • Investigational Site #3304
  • Paris, France, 75877
    • Investigational Site #3301
  • Saint-Étienne, France, 42055
    • Investigational Site #3305
  • Salouël, France, 80054
    • Investigational Site #3307
  • Strasbourg, France, 67091
    • Investigational Site #3306
  • Strasbourg, France, 67098
    • Investigational Site #3308
  • Trévenans, France, 90400
    • Investigational Site #3302
• Germany
  • Berlin, Germany, 10117
    • Investigational Site #4904
  • Bochum, Germany, 44892
    • Investigational Site #4901
  • Cottbus, Germany, 03048
    • Investogational Site #4902
  • Hannover, Germany, 30625
    • Investigational Site #4903
  • München, Germany, 81377
    • Investigational Site #4907
• Hungary
  • Debrecen, Hungary, 4031
    • Investigational SIte #3603
  • Szeged, Hungary, 6725
    • Investigational Site #3601
• Latvia
  • Daugavpils, Latvia, LV-5417
    • Investigational Site #7102
  • Riga, Latvia, LV-1002
    • Investigational Site #7101
• Lithuania
  • Kaunas, Lithuania, 47116
    • Investigational Site #7002
  • Kaunas, Lithuania, LT-44320
    • Investigational Site #7007
  • Kaunas, Lithuania, LT-50161
    • Investigational Site #7005
  • Klaipėda, Lithuania, LT-92288
    • Investigational Site #7003
  • Vilnius, Lithuania, 08661
    • Investigational Site #7006
  • Vilnius, Lithuania, LT-08406
    • Investigational Site #7001
  • Šiauliai, Lithuania, LT-76231
    • Investigational Site #7004
• Portugal
  • Guimarães, Portugal, 4835-044
    • Investigational Site #3502
  • Lisboa, Portugal, 1500-650
    • Investogational SIte #3501
• Slovakia
  • Banská Bystrica, Slovakia, 97517
    • Investigational Site #2103
  • Malacky, Slovakia, 90122
    • Investigational Site #2102
  • Michalovce, Slovakia, 07101
    • Investigational Site #2105
  • Nitra, Slovakia, 95991
    • Investigational Site #2101
  • Svidník, Slovakia, 08901
    • Investigational Site #2104
• South Africa
  • Kimberley, South Africa, 8301
    • Investigational site #2706
  • Klerksdorp, South Africa, 1864
    • Investigational Site #2702
  • Mthatha, South Africa, 5100
    • Investigational Site #2703
  • Plettenberg Bay, South Africa, 6600
    • Investigational Site #2705
  • Pretoria, South Africa, 0001
    • Investigational Site #2701
  • Pretoria, South Africa, 0002
    • Investigational Site #2707
  • Pretoria, South Africa, 0204
    • Investigational Site #2704
• Spain
  • Barcelona, Spain, 08036
    • Investigational Site #3401
  • Madrid, Spain, 28040
    • Investigational Site #3403
  • Madrona, Spain, 28222
    • Investigational Site #3404
• Turkey
  • Ankara, Turkey, 06800
    • Investigational Site #9005
  • Istanbul, Turkey, 34303
    • Investigational Site #9004
  • Trabzon, Turkey, 61100
    • Investigational Site #9001

Participation Criteria

Eligibility Criteria

• Ages Eligible for Study: 18 years and older (Adult, Older Adult)
• Accepts Healthy Volunteers: No

Description

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.

Study Plan

How is the study designed?

Design Details

• Primary Purpose: Treatment
• Allocation: Randomized
• Interventional Model: Parallel Assignment
• Masking: Quadruple

Number of Arms

2

Arms and Interventions

Participant Group / Arm	Intervention / Treatment
Experimental: Trimodulin; Trimodulin (human IgM, IgA, IgG solution) for intravenous (IV) administration.	Drug: Trimodulin; IMP will be administered via IV infusion on 5 consecutive days; Other Names: BT588
Placebo Comparator: Placebo; Human albumin 1%	Drug: Placebo (human albumin 1%); IMP will be administered via IV infusion on 5 consecutive days

What is the study measuring?

Primary Outcome Measures

Outcome Measure	Measure Description	Time Frame
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 Outcome Measures

Outcome Measure	Measure Description	Time Frame
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
28-days all-cause mortality rate	Percentage of subjects with a change to 8 on 9-category ordinal scale.	Day 29
90-days all-cause mortality rate	Percentage of subjects with a change to 8 on 9-category ordinal scale.	Day 91
Time to recovery	Number of days to score ≤ 2 until day 29	Between days 1-29
Proportion of subjects with score ≤ 2	Proportion of subjects that improved to score ≤ 2	Day 29
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
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
Days of invasive mechanical ventilation (IMV)/ extracorporeal membrane oxygenation (ECMO)	Days of IMV/ECMO	Day 29
Proportion of subjects on IMV/ECMO	Proportion of subjects on IMV/ECMO	Day 29
Days with oxygen supply	Days with oxygen supply	Day 29
Proportion of subjects with oxygen supply	Proportion of subjects with oxygen supply	Days 7, 14, 21, 29
Days in intensive care unit (ICU)	Days in intensive care unit	Day 29
Proportion of subjects in ICU	Proportion of subjects in ICU	Day 29
Days of hospitalization	Days of hospitalization	Day 29
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
SAEs	Number, severity, causality, and outcome of all serious adverse events (SAEs)	Until day 29
Dose modifications	Dose modifications (incl. reductions and changes in infusion rate)	Day 1-5
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
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
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
TEAEs	Number of all related TEAEs	Until day 29

Other Outcome Measures

Outcome Measure	Measure Description	Time Frame
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
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

Collaborators and Investigators

• Sponsor: Biotest
• Investigators: Principal Investigator: Antoni Torres, Prof, Hospital Clinic de Barcelona, Barcelona, Spain

Study record dates

Study Major Dates

• Study Start (Actual): December 22, 2022
• Primary Completion (Actual): May 5, 2025
• Study Completion (Actual): May 5, 2025

Study Registration Dates

• First Submitted: August 26, 2022
• First Submitted That Met QC Criteria: September 5, 2022
• First Posted (Actual): September 7, 2022

Study Record Updates

• Last Update Posted (Actual): June 8, 2025
• Last Update Submitted That Met QC Criteria: June 5, 2025
• Last Verified: June 1, 2025

More Information

Terms related to this study

• Keywords: SARS-CoV-2; COVID-19; CAP; Non severe community acquired pneumonia
• Additional Relevant MeSH Terms: Infections; RNA Virus Infections; Virus Diseases; Respiratory Tract Diseases; Lung Diseases; Respiration Disorders; Infant, Premature, Diseases; Infant, Newborn, Diseases; Coronavirus Infections; Coronaviridae Infections; Nidovirales Infections; Bacterial Infections; Bacterial Infections and Mycoses; Lung Injury; COVID-19; Respiratory Distress Syndrome; Respiratory Distress Syndrome, Newborn; Pneumonia; Respiratory Tract Infections; Acute Lung Injury; Pneumonia, Bacterial; Pneumonia, Viral
• Other Study ID Numbers: 1001 (Registro Nacional Estudios Clinicos (RNEC))

Plan for Individual participant data (IPD)

• Plan to Share Individual Participant Data (IPD)?: NO

Drug and device information, study documents

• Studies a U.S. FDA-regulated drug product: No
• Studies a U.S. FDA-regulated device product: No