COVID-19 trials registries data warehouse

https://www.clinicaltrialsregister.eu/ctr-search/trial/2021-000516-37/HU

TurnSole Biologics Llc - Gabor Heltovics, CEO

info@turnsolebiologics.com

2021-02-04

Completed

RCT

Randomized

Adaptive

Open label

single-center

Treatment

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 <80 Hgmm on room air) OR - Evidence of rales/crackles on physical examination and SpO2 93% on room air, OR - increasing need for O2 supplementation greater than >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.

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 <30 mL/min. 4. Neutrophil count (ANC) below 1500/mcl, 5. Haemoglobin (Hgb)<7.0 mmol/L 6. Platelet count below 100,000/mcl 7. Advanced malignant hepatic tumors / patients at risk of tumor lysis syndrome are those with high tumor burden prior to treatment. 8. Cardial disorders by Echocardiography or by medical history (arrhythmia, atrialfibrillation or fluttern, sick sinus syndrome (SSS) ventricular arrhythmia, coronary disorders, AMI, EF 50% or valve disorders (excl. mitralis prolapsus). Severe heart failure/ with a history of severe congestive heart failure, (NYHA III-IV, or NYHA IV) 9. Severe chronic renal disorder, or renal impairment requiring dialysis (eGFR<30) 10. Ongoing/suspected sever bacterial infection 11. Acute cerebrovascular disease within 3 months prior to enrolment 12. Pregnancy or breast-feeding (latter can be stopped) 13. Has received other immunomodulatory drug in the past for the treatment of other medical conditions 14. Previously diagnosed with HIV (HIV-Ab test positive) or anti-HCV antibodies positive 15. Obesity of 35 BMI or above 16. Uncontrolled hypertension (RR >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

2

TurnSole Biologics Llc

18

75

Hungary

Severe disease at enrollment

6: Severe disease at enrollment

50

The primary efficacy endpoint in the study is the responder rate at Day 10 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: 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: If none of the above three criteria is fulfilled, then the subject will be considered as “Non-Responder” at the time point of evaluation.

Declared number of arm (2.0) differs from found arms (1.0)

Phase 1/Phase 2

[{"arm_notes": "", "treatment_id": 160, "treatment_name": "Azacitidine", "treatment_type": "Others pharmacological treatment", "pharmacological_treatment": "Pharmacological treatment"}, {"arm_notes": "", "treatment_id": 2188, "treatment_name": "Standard of care", "treatment_type": "Standard of care", "pharmacological_treatment": "Standard of care"}]