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

NCT ID: NCT05212532

Last Updated: 2022-01-28

Study Results

Results pending

The study team has not published outcome measurements, participant flow, or safety data for this trial yet. Check back later for updates.

Basic Information

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Recruitment Status

UNKNOWN

Clinical Phase

PHASE1

Total Enrollment

40 participants

Study Classification

INTERVENTIONAL

Study Start Date

2021-08-09

Study Completion Date

2022-03-30

Brief Summary

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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

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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.

Conditions

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

Study Design

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Allocation Method

NON_RANDOMIZED

Intervention Model

PARALLEL

Open label study will include 2 cohorts, non-ICU hospitalized and ICU hospitalized patients
Primary Study Purpose

TREATMENT

Blinding Strategy

NONE

Study Groups

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non-ICU hospitalized

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

Group Type EXPERIMENTAL

EOM613

Intervention Type DRUG

peptide nucleic acid (PNA)

ICU hospitalized

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

Group Type EXPERIMENTAL

EOM613

Intervention Type DRUG

peptide nucleic acid (PNA)

Interventions

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EOM613

peptide nucleic acid (PNA)

Intervention Type DRUG

Eligibility Criteria

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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

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
Minimum Eligible Age

18 Years

Maximum Eligible Age

84 Years

Eligible Sex

ALL

Accepts Healthy Volunteers

No

Sponsors

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EOM Pharmaceuticals

INDUSTRY

Sponsor Role lead

Responsible Party

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Responsibility Role SPONSOR

Principal Investigators

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Irach Taraporewala, PhD

Role: STUDY_CHAIR

CEO and Director, EOM Pharma

Frank L Douglas, PhD, MD

Role: STUDY_DIRECTOR

Scientific Advisor & Chair of Scientific Advisory Board, EOM Pharma

Florentino Cardoso Filho, MD, PhD

Role: PRINCIPAL_INVESTIGATOR

Physician, Casa de Saude Hospital, Campinas, SP

Locations

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Oswaldo Cruz

Manguinhos, Rio de Janeiro, Brazil

Site Status RECRUITING

Hospital de Amor

Barretos, São Paulo, Brazil

Site Status RECRUITING

Hospital Municipal de Barueri

Barueri, São Paulo, Brazil

Site Status RECRUITING

Casa De Saúde

Boqueirão, São Paulo, Brazil

Site Status RECRUITING

Countries

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Brazil

Central Contacts

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Melina Szkelnik-Sidi, BS

Role: CONTACT

+ 55 11 98258-6261

Facility Contacts

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Elie Fiss, MD, PhD

Role: primary

0xx21)2598-4242

Evelyn Cristina C Da Silva

Role: backup

0xx21)2598-4242

César Maurício, MD

Role: primary

Letícia Barbieri

Role: backup

Paulo Tierno

Role: primary

Marielle Nunes

Role: backup

Florentino Cardoso Filho, MD, PhD

Role: primary

+55 19 991232882

Jomenica do Livramento

Role: backup

13 3202 2500

References

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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.

Reference Type 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.

Reference Type 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.

Reference Type BACKGROUND
PMID: 21194662 (View on PubMed)

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.

Reference Type 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.

Reference Type BACKGROUND
PMID: 23719681 (View on PubMed)

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.

Reference Type 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.

Reference Type 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.

Reference Type BACKGROUND
PMID: 1724467 (View on PubMed)

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.

Reference Type BACKGROUND
PMID: 8795297 (View on PubMed)

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.

Reference Type 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.

Reference Type BACKGROUND
PMID: 33014208 (View on PubMed)

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.

Reference Type BACKGROUND
PMID: 11064099 (View on PubMed)

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.

Reference Type BACKGROUND
PMID: 11448124 (View on PubMed)

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.

Reference Type BACKGROUND
PMID: 12187500 (View on PubMed)

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.

Reference Type BACKGROUND
PMID: 32758889 (View on PubMed)

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.

Reference Type BACKGROUND

Other Identifiers

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CL-EOM613-001

Identifier Type: -

Identifier Source: org_study_id

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