Patients with acute SARS-CoV-2 infection, proven by a positive SARS-CoV-2 PCR test. The health status of the patients at inclusion in the clinical trial is rated 5 - 6 according to the WHO scale (see protocol, CATCOVID_v1.2, 27.09.2021, page 13). Patients are at high risk of severe disease progression with ARDS and/or multiple organ failure, and at high risk of mortality.
Conditions
Interventions
Product Name: BAY 86-5277
Pharmaceutical Form: Oral solution
INN or Proposed INN: BAY 86-5277
Other descriptive name: [5-chloro-2-[2-[(2R)-4-[(4-fluorophenyl)methyl]-2-methyl-piperazin-1-yl]-2-oxo-eth
Sponsors
Charité – Universitätsmedizin Berlin
Eligibility
Sex/Gender
All
Inclusion criteria
Inclusion criteria: In order to be eligible to participate in this study, a patient must meet all of the following inclusion criteria: 1. Age = 18 years 2. Male or non-pregnant*/non-breast-feeding female 3. Subject understands the clinical trial and signed the informed consent form 4. Positive laboratory-confirmed SARS-CoV-2 PCR test Allergy to dexamethasone 5. WHO clinical progression scale 5-6 6. Onset of COVID-19 symptoms =65 years) yes F.1.3.1 Number of subjects for this age range 208
Exclusion criteria
Exclusion criteria: Exclusion Criteria: 1. Patient has a chance of survival 72 hours before randomization 4. Other indications for systemic or inhaled glucocorticoid treatment 5. Immunosuppressive medication within the last 30 days before randomization 6. Immunosuppressive disease 7. Chronic inflammatory airways disease (e.g., COPD) 8. Renal failure requiring dialysis 9. Acute (or acute on chronic) liver failure, Chronic liver failure (Child-Pugh class C) 10. Chronic heart failure NYHA III/IV 11. Acute right heart failure 12. Clear evidence of active tuberculosis, bacterial, fungal, viral, or other infection (besides SARS-CoV-2) 13. Current or regular treatment with Chloramphenicol* 14. Current or regular treatment with Nefazodone* 15. Current or regular treatment with Cimetidin* 16. Current or regular treatment with macrolide antibiotics* 17. Current or regular treatment with azole antimycotics* 18. Treatment with Phenytoin** 19. Person is placed in an institution based on an official or judicial order 20. Person who is dependent on the Sponsor, Principal Investigators, or the study site *Please note that only clinically relevant strong CYP3A4 inhibitors were considered, please note that protease inhibitors will not be relevant for this study as patients with an immunosuppressive disease are excluded (see also section 8.1.4). ** Please note that only strong CYP3A4 inducers were considered (see also section 8.1.4) See protocol, CATCOVID_v1.2, 27.09.2021: Chapter 7 (Study Population); Subchapter 7.1, page 37f.
Design outcomes
Primary
| Measure | Time frame |
|---|---|
| Main Objective: The overall objective of the study is to evaluate the clinical efficacy and safety of the CCR1 antagonist BAY 86-5277 in comparison to the placebo control arm of the study in patients hospitalized with COVID-19. The primary objective is the reduction of a critical disease progression in hospitalized COVID-19 patients with the need for oxygen supplementation. Mechanical ventilation is one of the key clinical features of severe COVID-19. The primary endpoint is the number of ventilator-free days during the study period of 28 days. The survey of ventilator-free days, i.e. the reduced need for mechanical ventilation, allows an assessment of whether BAY 86-5277 reduces progression to more severe courses of COVID-19. See protocol, CATCOVID_v1.2, 27.09.2021: Chapter 5 (Objectives and Endpoints); Subchapter 5.1, page 30.;Secondary Objective: We will monitor several clinical parameters as secondary outcomes and a detailed assessment of the clinical course of the COVID-19 patients. Additionally, we will monitor the pharmacokinetics in a sub-cohort during the initial phase of the clinical trial. Besides the assessment of the efficacy, we will also evaluate the safety of BAY 86-5277.;Primary end point(s): The primary endpoint is the number of ventilator-free days during the study period of 28 days. Ventilator-free days are defined as the number of days after the last extubation: • Each day after the discharge of a Subject will be counted as ventilator-free day. • In case of a tracheal cannula, the equivalent to extubation is 48 hours without respirator. • Death will be counted as “zero ventilator-free days”, regardless of whether the patient was intubated at any point or not For further definitions, see Protocol_CATCOVID_v1.2 (27.09.2021), Chapter 5.1 and Figure 1 (page 30).;Timepoint(s) of evaluation of this end point: Ventilator-free days at day 28 | — |
Secondary
| Measure | Time frame |
|---|---|
| Secondary end point(s): Secondary Endpoints 1. WHO clinical progression scale*; 2. Severity of gas exchange impairment (paO2/FiO2)*; 3. Duration in days of supplemental oxygen*; 4. Duration in days of MV*; 5. ICU-free days*; 6. Duration in days of hospitalization*; 7. SOFA at Day 1, 10, 28; 8. Mortality; date & cause of death (if applicable); 9. Documentation of AEs and SAEs (if applicable); 10. Determination of total and unbound drug concentration in a sub-cohort during the 10 days study medication treatment period *at Day 28 See Protocol, CATCOVID_ v1.2, 27.09.2021: Chapter 5 (Objectives and Endpoints); Subchapter 5.2, page 31.;Timepoint(s) of evaluation of this end point: 1. WHO clinical progression scale*; 2. Severity of gas exchange impairment (paO2/FiO2)*; 3. Duration in days of supplemental oxygen*; 4. Duration in days of MV*; 5. ICU-free days*; 6. Duration in days of hospitalization*; 7. SOFA at Day 1, 10, 28; 8. Mortality; date & cause of death (if applicable); 9. Documentation of AEs and SAEs (if applicable); 10. Determination of total and unbound drug concentration in a sub-cohort during the 10 days study medication treatment period *at Day 28 | — |
Countries
Germany
Contacts
Public ContactBIH - Center for Digital Health
Berlin Institute of Health at Charité
Outcome results
None listed