The purpose of this study is to evaluate the safety, tolerability and preliminary efficacy of EOM613, a peptide nucleic acid with novel immune-modulating properties, in treating patients with severe COVID-19 infections. This proof-of-concept study is the first clinical trial of EOM613 in this patient population.
Much of the morbidity and mortality in COVID-19 infection is thought to be the result of an overly zealous attack by the immune system (e.g., cytokine storm and IL-6 elevations) as it attempts to counteract the viral infection. Some drugs with immunomodulatory effects (e.g., dexamethasone, tocilizumab) have been shown to reduce virus-induced cytokine storms and key pro-inflammatory cytokines, including IL-6. EOM613 is a peptide nucleic acid with novel immune-modulating properties, including modulation of IL-6 expression. It has an excellent safety profile and has yielded promising therapeutic results in patients with Acquired Immunodeficiency Syndrome (AIDS), cancer cachexia and severe rheumatoid arthritis. EOM613 was reported to have antiviral activity in cell cultures inoculated with Human Immunodeficiency Virus (HIV) or adenovirus. This proof-of-concept study is the first clinical trial of EOM613 in patients with COVID-19 infection. This study will include two cohorts of hospitalized patients, non-ICU and ICU. In non-ICU patients, EOM613 is to be administered subcutaneously (SC) at a dose of 2 mL once daily (QD) for 10 days, for a total of 20 mL. In ICU patients, EOM613 is to be administered SC at a dose of 2 mL twice daily (BID) for 5 days followed by 2 mL QD for 5 days, for a total of 30 mL. The primary objective and outcome measures include assessment of safety and tolerability of EOM613, based on clinical laboratory, physical exams, and assessment of adverse events (AEs). The secondary objectives and outcome measures are 1) The proportions of non-ICU patients discharged with and without progression to invasive mechanical ventilation or ICU; 2) The proportion of ICU patients who die, are discharged to the infirmary, or discharged from the hospital; and 3) Assessment of levels of pro- and anti-inflammatory cytokines in Cytokine Panel 13, and their correlations with primary and secondary endpoints.
Study Type
INTERVENTIONAL
Allocation
NON_RANDOMIZED
Purpose
TREATMENT
Masking
NONE
Enrollment
40
peptide nucleic acid (PNA)
Oswaldo Cruz
Manguinhos, Rio de Janeiro, Brazil
RECRUITINGHospital de Amor
Barretos, São Paulo, Brazil
RECRUITINGHospital Municipal de Barueri
Barueri, São Paulo, Brazil
RECRUITINGChange from baseline to day 11 in mean blood urea nitrogen (BUN) level.
The BUN primary outcome measure is its change from baseline to day 11 or to discharge, whichever comes first (BUN is also assessed on days 2, 5, and 8). BUN is obtained from a venous blood draw and measured in millimoles of urea per liter. 2.1 to 8.5 mmol/L is considered normal; values above 8.5 mmol/L may indicate renal impairment.
Time frame: Baseline and day 11 or discharge, whichever comes first.
Change from baseline to day 11 in mean blood creatinine level.
The blood creatinine primary outcome measure is its change from baseline to day 11 or to discharge, whichever comes first (blood creatinine is also assessed on days 2, 5, and 8). Blood creatinine is obtained from a venous blood draw and measured in micromoles of creatinine per liter. 65.4 to 119.3 micromoles/L in adult women and 52.2 to 91.9 micromoles/L in adult men are considered normal; values above these ranges may indicate renal impairment.
Time frame: Baseline and day 11 or discharge, whichever comes first.
Change from baseline to day 11 in mean blood lymphocyte count.
The blood lymphocyte count primary outcome measure is its change from baseline to day 11 or to discharge, whichever comes first (blood lymphocyte count is also assessed on days 2, 5, and 8). Blood lymphocyte count is obtained from a venous blood draw and measured as the number of lymphocytes per microliter of blood. Between 1,000 and 3000 lymphocytes per microliter of blood is considered normal. Values below this range have correlated with the severity of COVID-19 infection; values above this range can be indicative of an infection, cancer of the blood or lymphatic system, or an autoimmune disorder.
Time frame: Baseline and day 11 or discharge, whichever comes first.
Change from baseline to day 11 in mean serum soluble interleukin-2 receptor (sIL-2R) level.
The serum sIL-2R primary outcome measure is its change from baseline to day 11 or to discharge, whichever comes first (serum sIL-2R will also be assessed on days 2, 5, 8, 14 and 28). Serum sIL-2R levels are measured with a Quantitative Multiplex Bead Assay. The normal range has been reported as 175.3 - 858.2 pg/mL. Elevated levels are found in individuals with severe inflammatory conditions and solid tumors.
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Casa De Saúde
Boqueirão, São Paulo, Brazil
RECRUITINGTime frame: Baseline and day 11 or discharge, whichever comes first.
Change from baseline to day 11 in mean serum interleukin-6 (IL-6).
The serum IL-6 primary outcome measure is its change from baseline to day 11 or to discharge, whichever comes first (serum IL-6 will also be assessed on days 2, 5, 8, 14 and 28). Serum IL-6 levels are measured with a Quantitative Multiplex Bead Assay. Normal values have been reported as \<2.0 pg/mL. Elevated levels are associated with inflammatory conditions and predict lower chances of survival in COVID-19 patients.
Time frame: Baseline and day 11 or discharge, whichever comes first.
Change from baseline to day 11 in mean serum interleukin-10 (IL-10) levels.
The serum IL-10 primary outcome measure is its change from baseline to day 11 or discharge, whichever comes first (serum IL-10 will also be assessed on days 2, 5, 8, 14 and 28). Serum IL-10 levels are measured with a Quantitative Multiplex Bead Assay. Normal values have been reported as \<2.8 pg/mL. Elevated levels are associated with inflammatory conditions and predict lower chances of survival in COVID-19 patients.
Time frame: Baseline and day 11 or discharge, whichever comes first.
Median change from baseline to day 56 in World Health Organization (WHO) Scale Assessment of COVID-19 Symptom Severity
The WHO Scale secondary outcome measure is the median change from baseline to day 56. This ordinal Scale is from 0 (no clinical/virological evidence of infection) to 8 (death). Scale assessments are made on patients on days 1-14, 21, 28, 42 and 56. Scale assessments of discharged patients are made during a home visit by a study nurse.
Time frame: Baseline and day 56 or death, whichever comes first
Percent of hospital days with ventilator and/or oxygen use, and percent of hospital days with maximum ventilator pressure and maximum oxygen use
Daily recording of ventilator and oxygen use (on or off), ventilator pressure, and oxygen use (percent and flow rate) in the morning and evening for patients requiring respiratory assistance. These data will be used to calculate the mean percent of total hospital days with ventilator and/or oxygen use, and the mean percent of days of maximum ventilator pressure and maximum oxygen use from day 1 of ventilator and/or oxygen use to subsequent days.
Time frame: Day 1 (baseline) of ventilator and/or oxygen use until ventilator and/or oxygen use is discontinued