COVID-19 Specific T Cell Derived Exosomes (CSTC-Exo)

Aerosol Inhalation of the Exosomes Derived From Allogenic COVID-19 T Cell in the Treatment of Early Stage Novel Coronavirus Pneumonia

Severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) pandemic has caused mass mortality in the last 3 months that necessitates urgent development of new therapeutical agents. So far there is no effective anti-viral drug to reduce viral load that has critical importance to prevent progress into severe viral pneumonia and systemic hyper inflammation state. This project is to offer a biologic agent based on T cell derived exosomes. This is a novel approach using our proprietary protocols for drug development. This clinical trial is to test the safety and efficacy of this new agent following targeted delivery by metered dose inhaler. The project have received proper approvals from the Turkish Ministry of Health and Erciyes University, Kayseri Turkey. Turk-Patent Application Number: PCT/TR2020/050302

Study Overview

• Status: Unknown
• Conditions: Pneumonia; Corona Virus Infection
• Intervention / Treatment: Biological: COVID-19 Specific T Cell derived exosomes (CSTC-Exo)

Detailed Description

The Covid-19 disease due to infection with severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) has affected millions people and caused thousands of mortality in the world over the last 3 months. Clinically, COVID-19 presents with a wide range of disease severity ranging from asymptomatic or very mild flu-like symptoms to very severe acute respiratory syndrome and multi-organ failure. The severity of COVID-19 correlates with escalating levels of systemic inflammation that eventually leads to hyperinflammatory stage resembling macrophage activation syndrome and death. Therefore, early intervention is essential to prevent progress into respiratory failure that requires reduction of viral load.

The virus-specific T-cells (VSTs) are body's natural immune defense against various disease-causing viruses. Donor originated COVID-19 specific T-cells (CSTC) are in vitro activated and expanded by exposing to viral peptide fragments in the presence of natural immune stimulant proteins called cytokines. These COVID-19 specific fragment peptides activate specific T-cells and stimulate the secretion of potent mediators including IFN gamma in forms of exosomes. We propose treatment of COVID-19 patients -who are at early stages of pulmonary disease- with CSTC-exomes to control disease progression. This biological agent offers universal application without a need for HLA match. Furthermore, exosomes are suitable as "off the shelf product" that allows dose titration for personalized treatment.

The purpose of this single arm open labeled, combined interventional (phase I/II trials) clinical trial is to explore the safety and efficiency of inhaled CSTC-exomes in the treatment of early stage novel coronavirus (NCV) pneumonia.

• Study Type: Interventional
• Enrollment (Anticipated): 60
• Phase: Phase 1

Contacts and Locations

Study Locations

• Turkey
  • Melikgazi
    • Kayseri, Melikgazi, Turkey, 38039
      • GENKOK

Participation Criteria

Eligibility Criteria

• Ages Eligible for Study: 18 years to 75 years (Adult, Older Adult)
• Accepts Healthy Volunteers: No
• Genders Eligible for Study: All

Description

Inclusion Criteria:

1. Willingness of study participant to accept this treatment arm, and signed informed consent;
2. Male or female, aged at 18 years (including) to 75 years old;
3. Confirmation of SARS-CoV-2 infection by reverse-transcription polymerase chain reaction (RT-PCR) from respiratory tract or blood specimens;
4. Patients with confirmed novel coronavirus pneumonia per imaging and clinical findings;

5. Diagnostic criteria of "Early Stage NCV Pneumonia " includes:

   1. Respiratory rate (RR) ≥ 30 times/min
   2. Pulse oxygen saturation (SpO2) at rest ≤ 93%
   3. Oxygenation Index: (PaO2/FiO2: ≥ 100mmHg and ≤ 300mmHg)

Exclusion Criteria:

1. The patients showing finding of late severe pneumonia (PaO2/FiO2: < 100mmHg) with systemic hyperinflammation, shock, and multi organ involvement
2. Allergic or hypersensitive to any of the ingredients;
3. Pneumonia caused by bacteria, mycoplasma, chlamydia, legionella, fungi or other viruses;
4. History of severe chronic respiratory disease and requirement for long-term oxygen therapy
5. Liver disease (such as child Pugh score ≥ grade C, AST more than 5 times of the upper limit of normal
6. Obstructive HABP/VABP induced by lung cancer or other known causes;
7. History of long-term use of immunosuppressive agents;
8. Incapable of understanding study protocol;
9. History of deep venous thrombosis or pulmonary embolism within the last 3 years;
10. Undergoing ECMO or high-frequency oscillatory ventilation support.
11. HIV, hepatitis virus, or syphilis infection;
12. Period of pregnancy or lactation, or planned pregnancy within 6 months;
13. Any condition of unsuitable for the study determined by investigators;
14. Morbid obesity and /or hypertension

Study Plan

How is the study designed?

Design Details

• Primary Purpose: Supportive Care
• Allocation: N/A
• Interventional Model: Single Group Assignment
• Masking: None (Open Label)

Number of Arms

1

Arms and Interventions

Participant Group / Arm

Intervention / Treatment

Experimental: COVID-19 STCs -Exo therapy; In addition to the best available treatment, participants will receive inhaler COVID-19 STCs -Exo therapy *. Biological: Inhaler CSTH-Exo treatment will be applied daily x 5 times (2.0 x 108 nano vesicle / 3 ml; on day 1 to day 5). * If the improvement contribution is observed in the parameters, this application period could be extended

Biological: COVID-19 Specific T Cell derived exosomes (CSTC-Exo); The virus-specific T-cells (VSTs) are body's natural immune defense against various disease-causing viruses. Donor originated COVID-19 specific T-cells (CSTC) are in vitro activated and expanded by exposing to viral peptide fragments in the presence of natural immune stimulant proteins called cytokines. These Covid-19 specific fragment peptides activate specific T-cells and stimulate the secretion of potent mediators including IFN gamma in forms of exosomes. We propose treatment of Covid-19 patients -who are at early stages of pulmonary disease- with CSTC-exomes to control disease progression.

What is the study measuring?

Primary Outcome Measures

Outcome Measure	Measure Description	Time Frame
Adverse reaction (AE) and severe AE (SAE)	Safety Assessment	28 days
Efficacy Assessment	Time to Clinical Recovery (TTCR)	28 days
The Rate of Recovery Without Mechanical Ventilator	Efficacy Assessment	28 days

Collaborators and Investigators

• Sponsor: TC Erciyes University
• Investigators: Principal Investigator: Mustafa Cetin, Prof, TC Erciyes University

Study record dates

Study Major Dates

• Study Start (Actual): May 1, 2020
• Primary Completion (Anticipated): September 30, 2020
• Study Completion (Anticipated): May 31, 2021

Study Registration Dates

• First Submitted: May 12, 2020
• First Submitted That Met QC Criteria: May 14, 2020
• First Posted (Actual): May 15, 2020

Study Record Updates

• Last Update Posted (Actual): May 15, 2020
• Last Update Submitted That Met QC Criteria: May 14, 2020
• Last Verified: May 1, 2020

More Information

Terms related to this study

• Keywords: COVID-19; Cell therapy; Exosome; Corona virus; Pnemonia; Virus specific T cell
• Additional Relevant MeSH Terms: Coronaviridae Infections; Nidovirales Infections; RNA Virus Infections; Virus Diseases; Infections; Respiratory Tract Infections; Respiratory Tract Diseases; Pneumonia, Viral; Lung Diseases; COVID-19; Coronavirus Infections; Pneumonia
• Other Study ID Numbers: EruCovid2020

Plan for Individual participant data (IPD)

• Plan to Share Individual Participant Data (IPD)?: Undecided

Drug and device information, study documents

• Studies a U.S. FDA-regulated drug product: No
• Studies a U.S. FDA-regulated device product: No
• product manufactured in and exported from the U.S.: Yes