Severe Corona Virus Disease 2019 (COVID-19) MedDRA version: 23.0 Level: PT Classification code 10084380 Term: COVID-19 pneumonia 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)
Current Sponsor code: BT588
Other descriptive nam
Sponsors
Biotest AG
Eligibility
Sex/Gender
All
Inclusion criteria
Inclusion criteria: 1. Written informed consent obtained from the subject or legally authorized representative or informed verbal or administration consent due to pandemic situation, in compliance with all local legal requirements. 2. Male or female subject =18 years of age. 3. Laboratory-confirmed SARS-CoV-2 infection. 4. Diagnosis of community-acquired severe COVID-19 within 5 days after hospital-admission, with severe defined as: o Need for non-invasive ventilation (NIV), or high-flow oxygen therapy (score =5 on the 9-category ordinal scale). o At least one clinical respiratory parameter: dyspnea, respiratory frequency =30/min, SpO2 =93%, 100 mmHg 50% within 24 to 48 hours. o At least one measurement of C-reactive protein =50 mg/L within 18 hours prior to start of treatment. 5. Subject must receive SoC treatment for COVID-19. Are the trial subjects under 18? no Number of subjects for this age range: F.1.2 Adults (18-64 years) yes F.1.2.1 Number of subjects for this age range 100 F.1.3 Elderly (>=65 years) yes F.1.3.1 Number of subjects for this age range 64
Exclusion criteria
Exclusion criteria: 2. Subjects that deteriorated to score >5 on the 9-category ordinal scale (e.g. receiving invasive mechanical ventilation (IMV), and/or extracorporeal membrane oxygenation (ECMO)) or subjects that improved to score <5 prior to randomization. 3. Severe neutropenia (neutrophil count <500/mm³) assessed within 18 hours prior to start of treatment. 4. Thrombocytopenia (platelet count <30,000/mm³) assessed within 18 hours prior to start of treatment. 5. Hemoglobin <7g/dL assessed within 18 hours prior to start of treatment. 6. Known hemolysis. 7. Known thrombosis or 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 the previous 3 months or those subjects particularly at risk for TEEs (e.g. history of thrombophilia, permanent immobilization, or permanent paralysis of the lower extremities) caused by other reasons than COVID-19. 8. Subject on dialysis or with severe renal impairment, estimated glomerular filtration rate (eGFR) <30 mL/min/1.73 m² assessed within 18 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. 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. 15. Known treatment for thorax/head/neck/hematologic malignancies in the last 12 months. 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. Obesity (body mass index =40 kg/m²), a body weight of more than 123 kg, or anorexia (body mass index <16 kg/m²).
Design outcomes
Primary
| Measure | Time frame |
|---|---|
| Main Objective: The objectives of the trial are to evaluate the efficacy and safety of trimodulin as add-on therapy to standard of care (SoC) compared to placebo treatment in adult hospitalized subjects with severe COVID-19.;Secondary Objective: Pharmacodynamic (PD) and pharmacokinetic (PK) properties of trimodulin will be evaluated in all subjects.;Primary end point(s): The composite endpoint is evaluated on day 29 [+3];Timepoint(s) of evaluation of this end point: Included in E.5.1 Clinical deterioration rate (score =6-7) between day 6 and day 29 28-day all-cause mortality rate (score =8) 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 • Time to clinical deterioration (change to score 6-7, day 6-29) • Time to clinical deterioration (change to score 6-7, day 1-29) • Time to mortality (change to score =8) • Proportion of subjects in each of the 9-categories of the ordinal scale on days 7, 14, 21, 29 • Time to clinical improvement to score =4 until day 29 • Time to clinical improvement to score =3 until day 29 • Time to recovery to score =2 until day 29 • Proportion of subjects with score =2 on day 29 • Days of IMV • Days without oxygen supply until day 29 • Time to discontinuation from any form of oxygen supply • Proportion of subjects without any form of oxygen supply on day 29 • Intensive care unit (ICU)-free days until day 29 • Hospital-free days until day 29 • Time to SARS-CoV-2 negative status Secondary safety endpoints: • Number, severity, causality, outcome, and seriousness of all adverse events (AEs), treatment-emergent AEs (TEAEs), AEs of special interest, 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 SAEs through day 29 [+3] • Dose modifications (incl. reductions and changes in infusion rate) • Distribution and changes over time for safety and vital signs parameters, and of overall evaluation of ECG and of ECG parameters Secondary pharmacokinetic endpoints: Changes from baseline, during and after treatment: • Serum concentration of IgM, IgA, and IgG Secondary pharmaodynamic endpoints: Changes from baseline, during and after treatment: • Markers for inflammation • Complement factors;Timepoint(s) of evaluation of this end point: Included in E.5.2 | — |
Countries
Brazil, France, Russian Federation, Spain, Sweden
Contacts
Public ContactClinical Trial Information
Biotest AG
Outcome results
None listed