A Proof-of-Concept Study Evaluating EOM613 in COVID-19 Infected Patients With Severe Symptoms

NCT05212532 | Unknown Phase 1 DMC

• 1 other identifier: CL-EOM613-001
• Study Type: interventional
• Target: 40
• Locations: 1 country
• Sites: 4

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.

Conditions

COVID-19 Pneumonia; COVID-19 Respiratory Infection; COVID-19 Acute Respiratory Distress Syndrome

Keywords

Cytokines; Chemokines; COVID-19; SARS-CoV-2; Immune modulation

Outcome Measures

Primary Outcomes (6)

• Change 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.

  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.

  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.

  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.

  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.

  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.

  Baseline and day 11 or discharge, whichever comes first.

Secondary Outcomes (2)

• Median change from baseline to day 56 in World Health Organization (WHO) Scale Assessment of COVID-19 Symptom Severity

  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

  Day 1 (baseline) of ventilator and/or oxygen use until ventilator and/or oxygen use is discontinued

Study Arms (2)

non-ICU hospitalized

EXPERIMENTAL

Patients who are hospitalized at study enrollment but are not being treated in the ICU

Drug: EOM613

ICU hospitalized

EXPERIMENTAL

Patients who, at study enrollment, are being treated in the hospital ICU

Drug: EOM613

Interventions

EOM613 DRUG

peptide nucleic acid (PNA)

ICU hospitalized; non-ICU hospitalized

Eligibility Criteria

• Age: 18 Years - 84 Years
• Sex: all
• Healthy Volunteers: No
• Age Groups: Adult (18-64), Older Adult (65+)

You may qualify if:

• 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
• 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
• 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

You may not qualify if:

• 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
• 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

Sponsors & Collaborators

• EOM Pharmaceuticals: lead

Study Sites (4)

Oswaldo Cruz

Manguinhos, Rio de Janeiro, 21040-900, Brazil

RECRUITING

Hospital de Amor

Barretos, São Paulo, 14784-400, Brazil

RECRUITING

Hospital Municipal de Barueri

Barueri, São Paulo, Brazil

RECRUITING

Casa De Saúde

Boqueirão, São Paulo, Brazil

RECRUITING

Related Publications (16)

• Advanced Viral Research Corp. (ADVR). ADVR reports AVR118 inhibits inflammatory arthritis in animal model and in rheumatoid arthritis patients in human clinical trial. ADVR press release, PR Newswire, December 3, 2003.

  BACKGROUND

• Chasen M, Bhargava R, Hirschman SZ, Taraporewala I. Phase II study of OHR/AVR118 in anorexia- cachexia. Abstract of poster presentation at the 7th Cachexia conference, Kobe/Osaka, Japan, December 9-11, 2013. J Cachexia Sarcopenia Muscle 2013;4(4):335-6.

  BACKGROUND

• Chasen M, Hirschman SZ, Bhargava R. Phase II study of the novel peptide-nucleic acid OHR118 in the management of cancer-related anorexia/cachexia. J Am Med Dir Assoc. 2011 Jan;12(1):62-7. doi: 10.1016/j.jamda.2010.02.012. Epub 2010 May 15.

  PMID: 21194662 BACKGROUND

• COVID-19 Treatment Guidelines, Interleukin-6 Inhibitors. National Institutes of Health. https://www.covid19treatmentguidelines.nih.gov/therapies/immunomodulators/interleukin-6-inhibitors/. Updated April 21, 2021. Accessed August 24, 2021.

  BACKGROUND

• Diao L, Meibohm B. Pharmacokinetics and pharmacokinetic-pharmacodynamic correlations of therapeutic peptides. Clin Pharmacokinet. 2013 Oct;52(10):855-68. doi: 10.1007/s40262-013-0079-0.

  PMID: 23719681 BACKGROUND

• D'Olimpio JT, Chasen MR, Sharma R, Diego M, Gullo V, MacDonald N. Phase II study of AVR118 in the management of cancer-related anorexia/cachexia. Doi: 10.1200/jco.2009.27.15_suppl.e20631 (abstract presentation). Journal of Clinical Oncology 2009; 27, No. 15_suppl., e20631-e20631.

  BACKGROUND

• D'Olimpio JT, Hirschman SZ, Shtemer Z, Didiego M. Anti-cachectic effects of a novel peptide nucleic acid: Preliminary results of a phase I/II clinical trial. Doi: 10.1200/jco.2004.22.90140.8087 (abstract presentation). Journal of Clinical Oncology. July 15, 2004; 22, no. 14_suppl 8087-8087.

  BACKGROUND

• Friedland B. In vitro antiviral activity of a peptide-nucleic acid solution against the human immunodeficiency virus and influenza A virus. J R Soc Health. 1991 Oct;111(5):170-1. doi: 10.1177/146642409111100505.

  PMID: 1724467 BACKGROUND

• Hirschman SZ, Chen CW. Peptide nucleic acids stimulate gamma interferon and inhibit the replication of the human immunodeficiency virus. J Investig Med. 1996 Aug;44(6):347-51.

  PMID: 8795297 BACKGROUND

• Hirschman SZ. Activation of human monocytes/macrophages by OHR/AVR118 promotes both pro-and anti-inflammatory phenotypes. Available: https://www.scirp.org/journal/PaperInformation.aspx?paperID=42617. Accessed August 24, 2021. Adv Bioscience Biotechnology. 2014, 5:161-168.

  BACKGROUND

• Hojyo S, Uchida M, Tanaka K, Hasebe R, Tanaka Y, Murakami M, Hirano T. How COVID-19 induces cytokine storm with high mortality. Inflamm Regen. 2020 Oct 1;40:37. doi: 10.1186/s41232-020-00146-3. eCollection 2020.

  PMID: 33014208 BACKGROUND

• Lazzarino DA, Diego M, Musi E, Hirschman SZ, Alexander RJ. CXCR4 and CCR5 expression by H9 T-cells is downregulated by a peptide-nucleic acid immunomodulator. Immunol Lett. 2000 Nov 1;74(3):189-95. doi: 10.1016/s0165-2478(00)00258-3.

  PMID: 11064099 BACKGROUND

• Lazzarino DA, de Diego M, Hirschman SZ, Zhang KY, Shaikh S, Musi E, Liaw L, Alexander RJ. IL-8 and MCP-1 secretion is enhanced by the peptide-nucleic acid immunomodulator, Product R, in U937 cells and primary human monocytes. Cytokine. 2001 May 21;14(4):234-9. doi: 10.1006/cyto.2001.0867.

  PMID: 11448124 BACKGROUND

• Levett PN, Hirschman SZ, Roach TC, Broome H, Alexander RJ, Fraser HS. Randomized, placebo-controlled trial of product R, a peptide-nucleic acid immunomodulator, in the treatment of adults infected with HIV. HIV Clin Trials. 2002 Jul-Aug;3(4):272-8. doi: 10.1310/N34A-653T-ABF5-8Q1R.

  PMID: 12187500 BACKGROUND

• Scherger S, Henao-Martinez A, Franco-Paredes C, Shapiro L. Rethinking interleukin-6 blockade for treatment of COVID-19. Med Hypotheses. 2020 Nov;144:110053. doi: 10.1016/j.mehy.2020.110053. Epub 2020 Jun 27.

  PMID: 32758889 BACKGROUND

• Alexander R.J., Meyer K.A., Camposano E., Lazzarino D.A., De Diego M. Product R induces differentiation of the human myelocytic leukemia cell line HL-60. American Association for Cancer Research Special Conference (Proteases, Extracellular Matrix and Cancer). Hilton Head Island, SC, USA, 2002.

  BACKGROUND

MeSH Terms

Conditions

COVID-19

Interventions

EOM613

Condition Hierarchy (Ancestors)

Pneumonia, Viral; Pneumonia; Respiratory Tract Infections; Infections; Virus Diseases; Coronavirus Infections; Coronaviridae Infections; Nidovirales Infections; RNA Virus Infections; Lung Diseases; Respiratory Tract Diseases

Study Officials

• Irach Taraporewala, PhD

  CEO and Director, EOM Pharma

  STUDY CHAIR

• Frank L Douglas, PhD, MD

  Scientific Advisor & Chair of Scientific Advisory Board, EOM Pharma

  STUDY DIRECTOR

• Florentino Cardoso Filho, MD, PhD

  Physician, Casa de Saude Hospital, Campinas, SP

  PRINCIPAL INVESTIGATOR

Central Study Contacts

Melina Szkelnik-Sidi, BS

CONTACT

+ 55 11 98258-6261; melina.sidi@azidusbrasil.com.br

Study Design

• Study Type: interventional
• Phase: phase 1
• Allocation: NON RANDOMIZED
• Masking: NONE
• Purpose: TREATMENT
• Intervention Model: PARALLEL
• Sponsor Type: INDUSTRY
• Responsible Party: SPONSOR

Model Details: Open label study will include 2 cohorts, non-ICU hospitalized and ICU hospitalized patients

Study Record Dates

• First Submitted: August 25, 2021
• First Posted: January 28, 2022
• Study Start: August 9, 2021
• Primary Completion: February 28, 2022
• Study Completion: March 30, 2022
• Last Updated: January 28, 2022

Record last verified: 2022-01

Data Sharing

• IPD Sharing: Will not share

Locations

BR (4)