A randomized, placebo controlled, double-blind, multi-center, phase II trial investigating the efficacy and safety of trimodulin (BT588) as add-on therapy to standard of care in adult subjects with severe COVID-19
- Conditions
- Severe Corona Virus Disease 2019 (COVID-19)MedDRA version: 23.0Level: PTClassification code 10084380Term: COVID-19 pneumoniaSystem Organ Class: 10021881 - Infections and infestationsTherapeutic area: Diseases [C] - Virus Diseases [C02]
- Registration Number
- EUCTR2020-002345-42-ES
- Lead Sponsor
- Biotest AG
- Brief Summary
Not available
- Detailed Description
Not available
Recruitment & Eligibility
- Status
- ot Recruiting
- Sex
- All
- Target Recruitment
- 114
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 < PaO2/FiO2 =300 mmHg, lung infiltrates >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
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).
Study & Design
- Study Type
- Interventional clinical trial of medicinal product
- Study Design
- Not specified
- Primary Outcome Measures
Name Time Method 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<br>Clinical deterioration rate (score =6-7) between day 6 and day 29<br>28-day all-cause mortality rate (score =8) between day 1 and day 29
- Secondary Outcome Measures
Name Time Method