COVID-19 patients with confirmed sever viral infection of SARS-COV-2 MedDRA version: 20.0 Level: PT Classification code 10047461 Term: Viral infection System Organ Class: 10021881 - Infections and infestations
Conditions
Interventions
Trade Name: AZACITIDIN SANDOZ 25 mg/ml por szuszpenziós injekcióhoz
Product Name: AZACITIDIN SANDOZ
Pharmaceutical Form: Powder for suspension for injection
Sponsors
TurnSole Biologics Llc
Eligibility
Sex/Gender
All
Inclusion criteria
Inclusion criteria: 1. Trial subjects are in 18-75 years of age. 2. Severe COVID-19 infected patient (criteria applicable as one of the following): - Respiratory rate >30 breaths/min or rapidly worsening respiratory gas exchange (PaO2 50% Venturi mask, including use of non-invasive mechanical ventilation (NIMV) or High Flow Nasal Cannula, OR - Acute Lung Injury physiology confirmed by PaO2/FiO2 ratio of ?300 Hgmm, OR - CT scan of the chest: presence of bilateral pulmonary infiltrates or 50% progression within 48 hours OR - COVID-19 infection associated secondary hemophagocytic lymphohistiocytosis (sHLH)/ macrophage activation syndrome (MAS) - HS scores greater than 169 3. Confirmed SARS-CoV2 infection, by specific lab results at least one positive rt-PCR or IgA/IgM test (1x SARS-CoV-2 PCR positive or if SARS-CoV-2 PCR negative, within 48 hours must have the 2. test SARS-CoV-2 PCR positive) 4. Female subjects: with childbearing potential are under efficient contraception, or in post-menopause. 5. The trial subject has the willingness to comply with study procedures and to give voluntary written informed consent signed and dated prior to enrolment. 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 20 F.1.3 Elderly (>=65 years) yes F.1.3.1 Number of subjects for this age range 30
Exclusion criteria
Exclusion criteria: 1. Clinical signs of critical status: a) SpO2 ? 90%, while oxygen supply with FiO2 > 100% b) PaO2/FiO2 ? 200 mmHg c) Respiratory failure which requiring mechanical ventilation d) Shock e) Combined with organ failure other than lung, need to be admitted to ICU 2. Known sensitivity/allergy to azacitidine or other class effect pyrimidine nucleoside analogues, or hypersensitivity to any of the excipients listed. 3. Aspartate aminotransferase (AST) / alanine aminotransferase (ALT) /alkaline phosphatase (ALP) = 3x upper limit of normal (ULN) and Total Bilirubin (TBILI) =2x ULN; or Creatinine clearance 170/100 Hgmm) or above. 17. Dementia, or inability to give informed consent 18. Any serious medical condition or abnormal clinical laboratory tests which in the judgement of the investigator may compromise patient safety should he/she participates in the study. 19. Use of concomitant medication: - Drugs with reported antiviral activity against SARS-CoV-2 included hydroxychloroquine sulfate, chloroquine phosphate, lopinavir-ritonavir combination, ciclesonide, nafamostat mesylate, camostat mesylate, etc. at baseline or within 7 days prior randomization unless a part of standard of care. With the exception of prior or ongoing treatment with antivirals of favipiravir, remdesivir (or generics of these products) are allowed. - Concurrent immunomodulating biologics or use of Palifermin, Dipyrone, Deferiprone, interferon-alpha. 20. Individuals, in the opinion of the investigator, where progression to death is imminent and inevitable in the next 24 hours irrespective of treatment provision 21. Any medical condition, per opinion of PI that would affect subject safety and/or compliance
Design outcomes
Primary
| Measure | Time frame |
|---|---|
| Main Objective: To establish the tolerable maximal recommended Phase 2 dose (MRP2D) based on safety results and continued in Phase 2: To evaluate the responder rate out of subjects enrolled and completed the treatment period at day 10 of trial by the primary endpoint in each treatment group. The state “Responder”/ “Non-Responder” to be evaluated by the composite outcome criteria as follows. Subject will be defined as “Responder” at the time point of evaluation in case one of the three outcome criteria below is fulfilled: 1) No further worsening of respiratory function as defined below: a) Improvement of oxygen saturation >3 percentage points or >10%, with stable FiO2 or b) with a possibility to reduce FiO2 to maintain adequate saturation with 100 points. 2) Significant reduction in number of viral replicas detected:- 3) Change in clinical state assessed by a 6-point ordinal scale (6-POC). at least 1 point from baseline on a six-point ordinal scale: ;Secondary Objective: 1. To evaluate the change in clinical state compared to control group – 2. To assess and demonstrate the efficacy on the virological status of SARS-CoV-2 patients by virion replicates 3. To assess changes of Disease Severity (DiS) by the proportion of patients: 4. To obtain information on changes in Symptoms Severity (WHO SyS): 5. To assess the risk reduction effect of study treatment on overall mortality by the 28-day survival: 6. Length of stay in hospital [Time Frame: Till hospital discharge, up to 28 days] measured as duration of days from baseline to hospital discharge. 7. To obtain safety information - 8. To evaluate the ratio of “Responders”/ “Non-Responders” after day 3, 5, 10 and 14 of randomisation. 9. Time (days) to clinical improvement 10. Routine laboratory parameters assessment: total blood count, routine chemistry, IL-6, D-dimer, ferritin, CRP, pro-BNP. 11. Evaluations of CT Image scan of the chest. 12. Evaluation of cytokine status ;Primary end point(s): The primary efficacy | — |
Secondary
| Measure | Time frame |
|---|---|
| Secondary end point(s): Secondary Endpoints: 1) Ratio of subjects with no further worsening of respiratory function. No further worsening of respiratory function as defined below: a) Improvement of oxygen saturation >3 percentage points or >10%, with stable FiO2 or b) with a possibility to reduce FiO2 to maintain adequate saturation with 100 points. 2) Ratio of subjects with significant reduction in number of viral replicas detected. Significant reduction in number of viral replicas detected: as below 5% of baseline in the case of quantitative PCR was performed; or the PCR test is turned out negative at Ct18 sensitivity limit in case of qualitative PCR test performed at baseline. 3) Change in clinical state assessed by a 6-point ordinal scale (6-POC). Clinical improvement since start of treatment, defined as a decrease of at least 1 point from baseline on a six-point ordinal scale: 1. Not hospitalized/discharged; 2. Hospitalized, not requiring supplemental oxygen; 3. Hospitalized, requiring supplemental oxygen; 4. Hospitalized, requiring nasal high-flow oxygen therapy, non-invasive mechanical ventilation, or both; 5. Hospitalized, requiring invasive mechanical ventilation, extra-corporeal membrane oxygenation (ECMO), or both; and 6. Death. 4) Responder rate at Day 3, Day 5 and Day 7 in each treatment group. Responder rate is defined in the primary endpoint section. 5) Additional secondary endpoints: (5a) Change in symptom severity assessed by the World Health Organization (WHO)Coronavirus Disease 2019 (COVID19) ordinal 8-point scale (5b) Change in oxygenation index where OI is used to assess severity of hypoxic respiratory failure. OI is treated as a continuous variable. (5c) The proportion of subjects with ICU admission (ratio) (5d) The proportion of subjects requiring mechanical ventilation (ratio) (5e) The proportion subjects with a need for intubation (ratio) (5f) Duration of mechanical ventilation (days) (5g) Overall 28-day survival ratio (ratio) (5h) Time | — |
Countries
Hungary
Contacts
Public ContactGabor Heltovics, CEO
TurnSole Biologics Llc
Outcome results
None listed