None listed
Conditions
Interventions
DFV890 50 mg b.i.d. + standar of care Type of group
• DFV890 50 mg will be administered orally twice per day approximately 12 hours apart (morning and evening).
• For participants unable to ingest tablets, study drug can be administered through a nasogastric tube (8 French or greater) as follows:
• Suspend both tablets in approximately 40 mL of water with stirring for approximately 3 minutes
• The suspension can then be administered through a nasogastric tube using an appropriate syringe. This needs to take place within a maximum of 6
The treatment is assigned considering the evaluation perfomed by the physician up to 14 days.
Sponsors
Novartis Pharma AG.,
Eligibility
Inclusion criteria
Inclusion criteria: • Male and female patients aged 18-80 years inclusive at screening • Clinically diagnosed with the SARS-CoV-2 virus by polymerase chain reaction (PCR) or by other approved diagnostic methodology within 7 days prior to randomization • Hospitalized with COVID-19-induced pneumonia evidenced by chest X-ray, computed tomography scan (CT scan) or magnetic resonance scan (MR scan), taken within 5 days prior to randomization (within 24 hours in patients in the Netherlands) • Impaired respiratory function, defined as peripheral oxygen saturation (SpO2) ≤93% on room air or partial pressure of oxygen (PaO2) / fraction of inspired oxygen (FiO2) <300 millimeter of mercury (mmHg) at screening. For cities located at altitudes greater than 2500 m above sea level, these will be substituted with SpO2 <90% and PaO2/FiO2 <250 mmHg. • APACHE II score of ≥10 at screening • C-reactive protein (CRP) ≥20 mg/L and/or ferritin level ≥600 μg/L at screening • Body mass index of ≥18 to <40kg/m2 at screening
Exclusion criteria
Exclusion criteria: • Suspected active or chronic bacterial (including Mycobacterium tuberculosis), fungal, viral, or other infection (besides SARS-CoV-2) • In the opinion of the investigator, progression to death is imminent and inevitable within the next 24 hours, irrespective of the provision of treatment • Intubated prior to randomization • Suspected active or chronic bacterial (including Mycobacterium tuberculosis), fungal, viral, or other infection (besides SARS-CoV-2) • In the opinion of the investigator, progression to death is imminent and inevitable within the next 24 hours, irrespective of the provision of treatment • Intubated prior to randomization • Previous treatment with anti-rejection and immunomodulatory drugs within the past 2 weeks, or within the past 30 days or 5 half-lives (whichever is the longer) for immunomodulatory therapeutic antibodies or prohibited drugs (see Section 6.2.1.2), with the exception of hydroxychloroquine, chloroquine or corticosteroids: • For COVID-19 infection, ongoing corticosteroid treatment is permitted at doses as per local SoC • For non-COVID-19 disorders, ongoing corticosteroid treatment is permitted at doses up to and including prednisolone 10 mg daily (or equivalent). (see Section 6.2.1) • In patients in the Netherlands only, the use of hydroxychloroquine and/or chloroquine in the past 2 weeks are exclusionary. • Serum alanine transaminase (ALT) or aspartate transaminase (AST) >5 times upper limit of normal detected within 24 hours at screening or at baseline (according to local laboratory reference ranges) or other evidence if severe hepatic impairment (Child-Pugh Class C, see Appendix 4) • Absolute peripheral blood neutrophil count of ≤1000/mm3 • Estimated GFR (eGFR) ≤30 mL/min/1.73m2 (based on CKD-EPI formula) • Patients currently being treated with drugs known to be strong or moderate inducers of isoenzyme CYP2C9 and/or strong inhibitors of CYP2C9 and/or strong inducers of cytochrome P450, family 3, subfamily A (CYP3A) (see list of prohibited drugs: Section 6.2.1.2) and the treatment cannot be discontinued or switched to a different medication prior to starting study treatment • Patients with innate or acquired immunodeficiencies • Patients who have undergone solid organ or stem cell transplantation
Design outcomes
Primary
| Measure | Time frame |
|---|---|
| Outcome name:clinical and in-hospital outcomes, and laboratory values, including serum CRP, a key biomarker of inflammasome inhibition and safety during and after the 14-day treatment period. Measure:the APACHE II score (range 0 to 71) on day 15 or on day of discharge (whichever is earlier) with worst case imputation for death as this disease severity score provides a comprehensive structured assessment of the clinical, physiological and laboratory parameters that have been routinely employed by physicians in the current situation to access the overall clinical status of COVID-19 patients with pneumonia and respiratory failure Timepoints:day 15 or on day of discharge | — |
Secondary
| Measure | Time frame |
|---|---|
| Outcome name:a log-scale fitting a repeated measures mixed model including treatment group, study day, the three stratification factors and log transformed baseline CRP as a covariate Measure:Serum C-reactive protein (CRP) levels Timepoints:during and after the 14-day treatment period ; Outcome name:a 9-point ordinal scale (WHO 2020 Measure:Clinical status Timepoints:Day 15 y Day 29 ; Outcome name:Adverse Events (AE), Serious Adverse Events (SAE), clinically significant changes in laboratory measures, and vital signs Measure:Safety Endpoints Timepoints:Tretament Period up to D29 and D45 | — |
Countries
Argentina, Brazil, Denmark, Germany, Hungaria, India, Mexico, Peru, South Africa, Spain
Contacts
Public ContactJacqueline Giron
NOVARTIS BIOSCIENCES PERU S.A.
Outcome results
None listed