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
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.
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.
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
GENKOK
Kayseri, Melikgazi, Turkey
Mustafa Cetin, Prof, Principal Investigator
TC Erciyes University