Clinical trial NCT05212532: A Proof-of-Concept Study Evaluating EOM613 in COVID-19 Infected Patients With Severe Symptoms
Official title: A Proof-of-Concept Study Evaluating Safety, Tolerability, and Preliminary Efficacy of EOM613 in COVID-19 Infected Patients With Severe Symptoms
Study type: INTERVENTIONAL
Overall status: UNKNOWN
Phase: PHASE1
Conditions: COVID-19 Pneumonia
COVID-19 Respiratory Infection
COVID-19 Acute Respiratory Distress Syndrome
Keywords: Cytokines
Chemokines
COVID-19
SARS-CoV-2
Immune modulation
Lead sponsor: EOM Pharmaceuticals
Sponsor class: INDUSTRY
First posted: 2022-01-28
Enrollment: 40
Sex: ALL
Minimum age (years): 18
Maximum age (years): 84
Standard ages: ADULT
OLDER_ADULT
Accepts healthy volunteers: no
Allocation: NON_RANDOMIZED
Intervention model: PARALLEL
Intervention model description: Open label study will include 2 cohorts, non-ICU hospitalized and ICU hospitalized patients
Primary purpose: TREATMENT

Brief summary: 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.

Detailed description: 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.

Eligibility criteria: 1. Inclusion Criteria

   1. Non-ICU cohort:

      * Males or females ≥18 years and \< 85 years of age
      * Positive test for Severe Acute Respiratory Syndrome Coronavirus 2 (SARS- CoV-2) by nasopharyngeal sampling using a reliable nucleic acid Reverse Transcription-Polymerase Chain Reaction (RT-PCR) assay or fast serological tests confirmed by RT PCR afterward
      * Hospitalized for Acute Respiratory Distress Syndrome (ARDS) or pneumonia
      * Requires oxygen therapy by nasal catheter or mask, but not invasive mechanical ventilation at the enrollment
   2. ICU cohort:

      * Males or females ≥18 years and \< 85 years of age
      * Positive test for SARS-CoV-2 by nasopharyngeal sampling using a reliable nucleic acid RT-PCR assay
      * Hospitalized for ARDS or pneumonia and requires invasive mechanical ventilation at enrollment
   3. Both cohorts:

      * Participant or suitable proxy able to provide written informed consent before study procedures are performed
      * Able to adhere to the study schedule and other protocol requirements
      * No known contraindications for administering EOM613, including Mycobacterium tuberculosis infection (assessed by the anamnesis) or receiving immunosuppressant therapy after transplant
      * Not enrolled in another study of an investigational agent during this study
      * Patients who developed complications of COVID-19 (such as myocardial disease, kidney dysfunction, clotting disorder, encephalitis, severe fatigue, or multi-immune inflammatory syndrome) are eligible
2. Exclusion Criteria

   1. Both cohorts:

      * Active participation in any other clinical trial of an experimental treatment for COVID-19
      * Participation in another clinical trial with any investigational new drug within 12 months before enrollment, except if there is a possible benefit to the participant in the investigator's opinion (According to the Brazilian Resolution CNS 251/97 II.2-J)
      * Concurrent treatment with other agents with actual or possible direct-acting antiviral activity against SARS-CoV-2 is prohibited \<24 hours before study medication initiation
      * Sequential Organ Failure Assessment Score \>10
      * Stage 4 severe chronic kidney disease or requiring dialysis (i.e., estimated Glomerular Filtration Rate \[eGFR\] \<30)
      * Active cancer receiving any therapeutic intervention or under palliative care
   2. Both cohorts, conditions existing before COVID-19:

      * Chronic Obstructive Pulmonary Disease (COPD)
      * Heart failure or cardiomyopathies
      * Sickle cell disease
      * Solid-organ transplantation
      * Uncontrolled or poorly controlled Type 2 diabetes mellitus
      * Immunodeficiency or immunosuppressive therapy
      * Pregnant or breastfeeding
      * Consideration by the investigator, for any reason, that the subject is an unsuitable candidate to receive study treatment
      * Known active Mycobacterium tuberculosis infection (assessed by the anamnesis)
      * Patients who are unwilling or unable to follow protocol requirements
      * Patients with body mass index (BMI) \< 18 kg/m2 or \> 40 kg/m2

Primary outcomes:
measure: Change from baseline to day 11 in mean blood urea nitrogen (BUN) level.
timeFrame: Baseline and day 11 or discharge, whichever comes first.
measure: Change from baseline to day 11 in mean blood creatinine level.
timeFrame: Baseline and day 11 or discharge, whichever comes first.
measure: Change from baseline to day 11 in mean blood lymphocyte count.
timeFrame: Baseline and day 11 or discharge, whichever comes first.
measure: Change from baseline to day 11 in mean serum soluble interleukin-2 receptor (sIL-2R) level.
timeFrame: Baseline and day 11 or discharge, whichever comes first.
measure: Change from baseline to day 11 in mean serum interleukin-6 (IL-6).
timeFrame: Baseline and day 11 or discharge, whichever comes first.
measure: Change from baseline to day 11 in mean serum interleukin-10 (IL-10) levels.
timeFrame: Baseline and day 11 or discharge, whichever comes first.
Secondary outcomes:
measure: Median change from baseline to day 56 in World Health Organization (WHO) Scale Assessment of COVID-19 Symptom Severity
timeFrame: Baseline and day 56 or death, whichever comes first
measure: Percent of hospital days with ventilator and/or oxygen use, and percent of hospital days with maximum ventilator pressure and maximum oxygen use
timeFrame: Day 1 (baseline) of ventilator and/or oxygen use until ventilator and/or oxygen use is discontinued
Other outcomes:
Locations:
city: Manguinhos
country: Brazil
facility: Oswaldo Cruz
state: Rio De Janeiro
city: Barretos
country: Brazil
facility: Hospital de Amor
state: São Paulo
city: Barueri
country: Brazil
facility: Hospital Municipal de Barueri
state: São Paulo
city: Boqueirão
country: Brazil
facility: Casa De Saúde
state: São Paulo
Study officials:
affiliation: CEO and Director, EOM Pharma
name: Irach Taraporewala, PhD
role: STUDY_CHAIR
affiliation: Scientific Advisor & Chair of Scientific Advisory Board, EOM Pharma
name: Frank L Douglas, PhD, MD
role: STUDY_DIRECTOR
affiliation: Physician, Casa de Saude Hospital, Campinas, SP
name: Florentino Cardoso Filho, MD, PhD
role: PRINCIPAL_INVESTIGATOR
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