moderate or severe Coronavirus Disease 2019 (COVID-19) MedDRA version: 23.0 Level: PT Classification code 10084268 Term: COVID-19 System Organ Class: 10021881 - Infections and infestations
Conditions
Interventions
Product Name: Trimodulin
Product Code: BT588
Pharmaceutical Form: Solution for infusion
INN or Proposed INN: Trimodulin (human IgM, IgA, IgG solution)
Other descriptive name: Trimodulin (human IgM, Ig
Sponsors
Biotest AG
Eligibility
Sex/Gender
All
Inclusion criteria
Inclusion criteria: 1. Written informed consent obtained from the subject or legally acceptable/authorized representative (LAR) or informed verbal consent in case of pandemic restrictions, in compliance with all local legal requirements. 2. Hospitalized, adult (= 18 years of age) subject (any gender). 3. Laboratory-confirmed acute SARS-CoV-2 infection within 5 days prior to screening. 4. Receiving oxygen supply via low-flow oxygen (LFO, by mask or nasal prongs) or on non-invasive ventilation (NIV) or high-flow oxygen (HFO) at start of treatment. 5. Fulfilling at least one of the following clinical respiratory parameters within 24 hours prior to start of treatment: - SpO2 = 94% (on room air, and without preceding chronic lung disease); - 100 mm Hg =65 years) yes F.1.3.1 Number of subjects for this age range 134
Exclusion criteria
Exclusion criteria: 1. Pregnant or lactating women. 2. Subject on invasive mechanical ventilation (IMV) and/or extracorporeal membrane oxygenation (ECMO) or predicted to be on IMV and/or ECMO at start of treatment. 3. 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. 4. Severe neutropenia (neutrophil count < 0.5 x109/L) assessed within 24 hours prior to start of treatment. 5. Hemoglobin < 7g/dL assessed within 24 hours prior to start of treatment. 6. Known hemolytic disease. 7. Known thrombosis or acute thromboembolic events (TEEs) or known medical history of 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 COVID-19 infection (e.g. history of thrombophilia). 8. 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 (details in Appendix 3: Estimated Glomerular Filtration Rate). 9. Subject with end stage renal disease (ESRD), or known primary focal segmental glomerulosclerosis (FSGS). 10. Known severe lung diseases interfering with COVID-19 therapy (e.g. COPD (GOLD stage III-IV / Group D), severe interstitial lung disease, cystic fibrosis, idiopathic pulmonary fibrosis, active tuberculosis, chronically infected bronchiectasis, or active lung cancer). 11. Known decompensated heart failure (New York Heart Association class III–IV). 12. Known pre-existing hepatic cirrhosis, severe hepatic impairment (Child Pugh C score = 9 points), or hepatocellular carcinoma. 13. Known intolerance to proteins of human origin or known allergic reactions to components of trimodulin. 14. Selective, absolute immunoglobulin A (IgA) deficiency with known antibodies to IgA. 15. Known treatment for thorax/head/neck/hematologic malignancies in the last 12 months. 16. Known human immunodeficiency virus infection. 17. Life expectancy of less than 90 days, according to the Investigator’s clinical judgment, because of medical conditions neither related to COVID-19 nor to associated medical complications. 18. Morbid obesity with high body mass index = 40 kg/m², or malnutrition with low body mass index < 16 kg/m². 19. Known treatment with polyvalent immunoglobulin preparations, plasma, or albumin preparations during the last 21 days before entering the trial. 20. Known treatment with exploratory selective immune suppressors (cytokine inhibitors, cytokine receptor inhibitors, kinase inhibitors) during the last 10 days before entering the trial. 21. Known treatment with fluoroquinolone preparations, during the last 5 days before entering the trial. 22. Known treatment with any type of interferon during the last 21 days before entering the trial. 23. Known treatment with immunosuppressants other than guideline recommended immunosuppressants for treatment of acute COVID-19. 24. Participation in another interventional clinical trial within 30 days before entering, or previous participation in this clinical trial. 25. Employee or direct relative of an employee of the contract research organization, the trial site, or Biotest.
Design outcomes
Primary
| Measure | Time frame |
|---|---|
| Main Objective: 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 moderate or severe COVID-19.;Secondary Objective: Other objectives are to determine pharmacokinetic (PK) and pharmacodynamic (PD) properties of trimodulin.;Primary end point(s): Composite primary endpoint: Deterioration / mortality rate;Timepoint(s) of evaluation of this end point: - Clinical deterioration (increment of at least 1 category on the 9-category ordinal-scale from baseline) between day 6 and day 29 - 28-day all-cause mortality between day 1 and day 29 | — |
Secondary
| Measure | Time frame |
|---|---|
| Secondary end point(s): 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 - Proportion of subjects with PaO2/FiO2 ratio < 100, 100 to < 200, 200 to < 300 or = 300 on days 7, 14, 21, 29 - Days of IMV/ECMO until day 29 - Proportion of subjects on IMV/ECMO until day 29 - Days with oxygen supply until day 29 - Proportion of subjects with oxygen supply on days 7, 14, 21, 29 - Days in intensive care unit (ICU) until day 29 - Proportion of subjects in ICU until day 29 - Days of hospitalization until day 29 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 infusion-related TEAEs through day 29 [+3] - Number, severity, causality, and outcome of all serious adverse events (SAEs) through day 29 [+3] - Dose modifications (incl. reductions and changes in infusion rate) - Distribution and changes over time for safety, laboratory, vital signs parameters, and ECG Secondary PK endpoints: Changes from baseline, during and after treatment: - Serum concentration of IgM, IgA, and IgG 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 titers;Timepoint(s) of evaluation of this end point: Included in E.5.2 | — |
Countries
Argentina, Austria, Belgium, Brazil, Chile, Colombia, Denmark, Estonia, France, Germany, Hungary, Israel, Italy, Latvia, Lithuania, Mexico, Peru, Poland, Portugal, Slovakia, South Africa, Spain, Turkey, United Kingdom
Contacts
Public ContactClinical Trial Information
Biotest AG
Outcome results
None listed