Covid19Phase 1/2COVID-19EXONCT04491240
Evaluation of Safety and Efficiency of Method of Exosome Inhalation in SARS-CoV-2 Associated Pneumonia.
A Phase 1/2 study testing EXO 1 inhalation and EXO 2 inhalation in people with Covid19 and SARS-CoV-2 PNEUMONIA, run by State-Financed Health Facility "Samara Regional Medical Center Dinasty" at 1 site in Russia.
Trial summary
Coronavirus is an acute viral disease with prevailing upper respiratory tract infections caused by the RNA-containing virus of the genus Betacoronavirus of the Coronaviridae family. Most patients with severe COVID-19 develop pneumonia in the first week of the disease. Read more about this study
- Who is it for?
- Ages 18 to 65 years
- Conditions the study is for
- Covid19, SARS-CoV-2 PNEUMONIA, COVID-19
- What is being tested?
- EXO 1 inhalation and EXO 2 inhalation
- Could I receive a placebo?
- Yes, some participants may receive a placebo
- How many people
- 30 participants
- Where
- 1 siteRussia
- Study dates
- 20 Jul 2020to 20 Oct 2020
- Phase
- Phase 1/2
- Are there results?
- Yes, posted in the registrySummary in the doctors' view
Key requirements
Who can take part, as listed by the sponsor. Only the study team can confirm whether you are eligible, so take this list to your doctor.
- Ages 18 to 65 years
- All sexes
- No healthy volunteers
- Adult, Older adult
Who may be able to join
- Ability to understand the study objectives and risks and provide signed and dated informed consent;
- Confirmed COVID-19 infection (by PCR or antibody test);
- Pneumonia requiring hospitalization, and oxygen saturation of <94% indoors or a need for auxiliary oxygen. The confirmed volume of lung damage by CT: not less than 30% and not more than 80%;
- ability to proceed with inhalation by self;
Who cannot join
- Severe respiratory failure at the time of screening due to COVID-19 pneumonia;
- Known to undergo medical resuscitation for 14 days before randomization;
- Any serious medical condition or deviation of the clinical laboratory parameter that, in the opinion of the researcher, prevents safe participation and completion of the study by the participant Confirmed uncontrolled active bacterial, fungal, viral or other infection (other than SARS-CoV-2).
- According to the researcher, the progression to death is inevitable and will occur within the next 24 hours, regardless of the therapy.
- The life expectancy of fewer than 28 days, taking into account a medical condition already existing that cannot be corrected, e.g. participants with the following conditions or suspicions: polyorganic insufficiency, poorly controlled neoplasms, terminal stage heart disease, cardiopulmonary cardiac arrest that required cardiopulmonary resuscitation, or electrical activity not accompanied by a pulse, or asystole within the last 30 days, terminal stage liver disease, terminal stage liver disease, or liver disease;
- Pregnancy or breastfeeding;
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- Liver function failure (Class C for Child-Pugh), detected within 24 hours at screening (local laboratory);
- Absolute neutrophil count (ANC) <500 cells/µL at screening (local laboratory);
- Platelet count <50000 cells/µL at screening (based on laboratory data);
- Creatinine level ≥ 1.5 from the upper limit;
- Uncontrolled or untreated arrhythmia with clinical manifestations, myocardial infarction within the last 6 weeks or congestive heart failure (NYHA Degrees 3 or 4);
- Respiratory failure in the last 6 months or home use of oxygen in severe chronic respiratory disease (COPD);
- Quadriplegia;
- Primary immunodeficiency, tuberculosis, progressive multifocal leukoencephalopathy, aspergillosis or other invasive mold/fungal infection in anamnesis, or internal or bone marrow transplantation for 6 months before randomization;
- Known infection with hepatitis B or C viruses requiring therapy;
Trial locations and contacts
1 site in 1 country.
About this study
Official title: The Protocol of Evaluation of Safety and Efficiency of Method of Exosome Inhalation in SARS-CoV-2 Associated Two-Sided Pneumonia
Coronavirus is an acute viral disease with prevailing upper respiratory tract infections caused by the RNA-containing virus of the genus Betacoronavirus of the Coronaviridae family. Most patients with severe COVID-19 develop pneumonia in the first week of the disease. As the infection progresses, the infiltration increases, and the affected areas increases. Excessive and uncontrolled immune system response with rapidly developing fatal cytokine storm plays the main role in the pathogenesis of acute respiratory distress syndrome (ARDS) due to SARS-CoV-2 infection.
According to available data, exosomes can regulate inflammation and regenerative processes due to the change in the concentration of anti-inflammatory cytokines and switch the immune cell to regenerative secretome. Inhalation of exosomes may reduce inflammation and damage to the lung tissue and stimulate the regenerative processes.
This protocol has been developed based on the literature, information about the ongoing tests NCT04276987 (A Pilot Clinical Study on Inhalation of Mesenchymal Stem Cells Exosomes Treating Severe Novel Coronavirus Pneumonia) and NCT04384445 (Organicell Flow for Patients With COVID-19), Patent No 271036826 of 2019. "A method for obtaining and concentrating microRNA-containing exosomal multi-potent mesenchymal-stromal cells for use in cosmetic and pharmaceutical products to stimulate regenerative processes and slow down aging.
Read the detailed description
COVID-19 is an infectious disease caused by the most recently discovered coronavirus. This new virus and disease were unknown before the outbreak began in Wuhan, China, in December 2019. COVID-19 is now a pandemic affecting many countries worldwide. Globally, as of 1:09 pm CEST, 27 July 2020, there have been 16 096 741 confirmed cases of COVID-19, including 646 384 deaths, reported to WHO.
The main and rapidly achievable target of SARS-CoV-2 is lung type II alveolar cells (AT2), which determines the development of diffuse alveolar damage. In the pathogenesis of ARDS due to COVID-19, the main role is played by an over-response of the immune system with rapidly developing severe life-threatening cytokine release syndrome (cytokine storm). Cytokine release syndrome threatens the emergence and progression of ARDS. The key components of the pathogenesis of ARDS also include disruption of cell cytotoxicity mechanisms, excessive activation of cytotoxic lymphocytes and macrophages with a massive release of proinflammatory cytokines (FNO-α, IL-1, IL-2, IL-6, IL-8, IL-10), granulocytic colony-stimulating factor, monocytic chemoattractive protein 1), and inflammatory markers (CRP, serum ferritin), infiltration of internal organs and tissues by activated T-lymphocytes and macrophages, resulting in a hyperinflammatory reaction. Such severe lesions can lead to death or severe lung damage, including long rehabilitation after discharge.
Experimental studies have demonstrated that mesenchymal stem cells (MSCs) may significantly reduce lung inflammation and pathological impairment resulting from different types of lung injury. Many researchers connect the anti-inflammatory effect of MSC with their secretome which includes MSC derived exosomes. It is highly likely that MSC exosomes have the same therapeutic effect on inoculation pneumonia as MSCs themselves. Moreover, exosomes show a strong effect of regenerative stimulation on different wounds so the regenerative effect can be extended on patients with COVID-19 pneumonia.
The purpose of this protocol is to explore the safety and efficiency of aerosol inhalation of the exosomes in the treatment of severe patients hospitalized with novel coronavirus pneumonia (NCP).
- Conditions
- Covid19, SARS-CoV-2 PNEUMONIA, COVID-19
- Being tested
- EXO 1 inhalation, EXO 2 inhalation, Placebo inhalation
- Keywords
- Covid-19, SARS-CoV-2, exosomes, MSC
- Medical subject headings
- COVID-19
What participants receive
What participants receive. In a randomised study each person is assigned to one group by chance.
EXO 1 inhalationDrug
Twice a day during 10 days inhalation of 3 ml special solution contained 0.5-2x10^10 of nanoparticles (exosomes) of the first type.
EXO 2 inhalationDrug
Twice a day during 10 days inhalation of 3 ml special solution contained 0.5-2x10^10 of nanoparticles (exosomes) of the second type.
Placebo inhalationDrug
Twice a day during 10 days inhalation of 3 ml special solution free of nanoparticles (exosomes).
| Study group | Role | What they receive |
|---|---|---|
| EXO-1 | Experimental | Participants (n=10) in this group will receive standard therapy and exosomes of the first type. Receives: Drug: EXO 1 inhalation |
| EXO-2 | Experimental | Participants (n=10) in this group will receive standard therapy and exosomes of the second type. Receives: Drug: EXO 2 inhalation |
| Placebo | Placebo comparator | Participants (n=10) in this group will receive standard therapy and inhalation placebo solution. Receives: Drug: Placebo inhalation |
What is being measured
The primary outcome is the main question the study is designed to answer.
Number of Participants With Non-serious and Serious Adverse Events During Trial
Safety assessment such as adverse events will be registered. Adverse events will be monitored during all trial
Measured: 30 days after clinic discharge
Number of Participants With Non-serious and Serious Adverse During Inhalation Procedure
Safety assessments such as adverse events during the inhalation procedures will be registered.
Measured: after each inhalation during 10 days
Secondary outcomes (4)
Time to Clinical Recovery (TTCR)
Measure and compare time to clinical recovery compared to placebo. Time to clinical recovery calculated by the number of days the patient has hospitalized.
Measured: from first inhalation until discharge from the clinic, up to 30 days
SpO2 Concentration
The concentration of SpO2 by Pulse oximetry device during procedures in the groups. The measure was done before and after each inhalation (total 4 measures per day). The intraday SpO2 data of all patients in groups was calculated as Median with Inter-Quartile Range and presented in the table by days.
Measured: 10 days during inhalation
C-reactive Protein
Blood biochemistry C reactive protein level in serum.
Measured: At the begining of inhalation (day 1) and on next day of last inhalation (day 11)
Lactic Acid Dehydrogenase (LDH)
Lactic Acid Dehydrogenase (LDH) level in serum
Measured: At the beginning of inhalation (day 1) and on next day of last inhalation (day 11)
Timeline
From the start of the study to its completion; the mark is today. Estimated dates are the sponsor’s plan.
- First posted29 Jul 2020
- Study start20 Jul 2020
- Primary completion1 Oct 2020
- Study completion20 Oct 2020
Resources
- Official record on ClinicalTrials.govThe registry entry this page is built from, with its full change history.
- Posted resultsParticipant flow, outcome measures and adverse events reported by the sponsor.
- Other trials for Covid19Studies of the same condition, open and under way.
- What the trial phases meanHow a treatment moves from first tests in people to approval.
More details
For doctors and researchers: how the study is designed, who runs it, and its registry IDs.
Study design
- Study type
- Interventional
- Phase
- Phase 1/2
- Primary purpose
- Other
- Allocation
- Randomised
- Intervention model
- Parallel groups
- Model description
- The trial has three groups, each with 10 subjects (n=30). All eligible study subjects will be randomized, double-blinded, to either the two treatment groups or placebo group.
- Masking
- Double blind
- Who is masked
- Participant, Care provider
- Enrolment
- 30 participants (actual)
Sponsor and investigators
- Lead sponsor
- State-Financed Health Facility "Samara Regional Medical Center Dinasty"
- Sponsor type
- University, hospital or other
- Collaborators
- Samara State Medical University, Samara Regional Clinical Hospital V.D. Seredavin
- Responsible party
- Sponsor
IDs, dates and publications
- ClinicalTrials.gov ID
- NCT04491240
- Sponsor's protocol ID
- COVID-19 EXO
- Acronym
- COVID-19EXO
- Status last verified
- Oct 2020
- First submitted
- 27 Jul 2020
- Last updated
- 4 Nov 2020
- Results posted
- Yes, on ClinicalTrials.gov
- Data monitoring committee
- No
- FDA-regulated drug
- No
- FDA-regulated device
- No
Study at a glance
From the registry record, last updated by the sponsor on 4 Nov 2020. Recruitment status is as the sponsor reported it: confirm with the study team.
- Official title
- The Protocol of Evaluation of Safety and Efficiency of Method of Exosome Inhalation in SARS-CoV-2 Associated Two-Sided Pneumonia
- ClinicalTrials.gov ID
- NCT04491240
- Acronym / sponsor ID
- COVID-19EXO / COVID-19 EXO
- Conditions
- Covid19, SARS-CoV-2 PNEUMONIA, COVID-19
- Keywords
- Covid-19, SARS-CoV-2, exosomes, MSC
- Phase
- Phase 1/2
- Study type
- Interventional
- Recruitment status
- Completed
- Enrolment
- 30 participants (actual)
- Lead sponsor
- State-Financed Health Facility "Samara Regional Medical Center Dinasty"University, hospital or other
- Collaborators
- Samara State Medical University, Samara Regional Clinical Hospital V.D. Seredavin
- Study start
- 20 Jul 2020 (actual)
- Primary completion
- 1 Oct 2020 (actual)
- Study completion
- 20 Oct 2020 (actual)
- First posted
- 29 Jul 2020 (actual)
- Results
- Posted 4 Nov 2020
Clinical summary
The research question as the sponsor registered it. This describes what the study plans to test, not what it found.
Coronavirus is an acute viral disease with prevailing upper respiratory tract infections caused by the RNA-containing virus of the genus Betacoronavirus of the Coronaviridae family. Most patients with severe COVID-19 develop pneumonia in the first week of the disease. As the infection progresses, the infiltration increases, and the affected areas increases. Excessive and uncontrolled immune system response with rapidly developing fatal cytokine storm plays the main role in the pathogenesis of acute respiratory distress syndrome (ARDS) due to SARS-CoV-2 infection.
According to available data, exosomes can regulate inflammation and regenerative processes due to the change in the concentration of anti-inflammatory cytokines and switch the immune cell to regenerative secretome. Inhalation of exosomes may reduce inflammation and damage to the lung tissue and stimulate the regenerative processes.
This protocol has been developed based on the literature, information about the ongoing tests NCT04276987 (A Pilot Clinical Study on Inhalation of Mesenchymal Stem Cells Exosomes Treating Severe Novel Coronavirus Pneumonia) and NCT04384445 (Organicell Flow for Patients With COVID-19), Patent No 271036826 of 2019. "A method for obtaining and concentrating microRNA-containing exosomal multi-potent mesenchymal-stromal cells for use in cosmetic and pharmaceutical products to stimulate regenerative processes and slow down aging.
Detailed description
COVID-19 is an infectious disease caused by the most recently discovered coronavirus. This new virus and disease were unknown before the outbreak began in Wuhan, China, in December 2019. COVID-19 is now a pandemic affecting many countries worldwide. Globally, as of 1:09 pm CEST, 27 July 2020, there have been 16 096 741 confirmed cases of COVID-19, including 646 384 deaths, reported to WHO.
The main and rapidly achievable target of SARS-CoV-2 is lung type II alveolar cells (AT2), which determines the development of diffuse alveolar damage. In the pathogenesis of ARDS due to COVID-19, the main role is played by an over-response of the immune system with rapidly developing severe life-threatening cytokine release syndrome (cytokine storm). Cytokine release syndrome threatens the emergence and progression of ARDS. The key components of the pathogenesis of ARDS also include disruption of cell cytotoxicity mechanisms, excessive activation of cytotoxic lymphocytes and macrophages with a massive release of proinflammatory cytokines (FNO-α, IL-1, IL-2, IL-6, IL-8, IL-10), granulocytic colony-stimulating factor, monocytic chemoattractive protein 1), and inflammatory markers (CRP, serum ferritin), infiltration of internal organs and tissues by activated T-lymphocytes and macrophages, resulting in a hyperinflammatory reaction. Such severe lesions can lead to death or severe lung damage, including long rehabilitation after discharge.
Experimental studies have demonstrated that mesenchymal stem cells (MSCs) may significantly reduce lung inflammation and pathological impairment resulting from different types of lung injury. Many researchers connect the anti-inflammatory effect of MSC with their secretome which includes MSC derived exosomes. It is highly likely that MSC exosomes have the same therapeutic effect on inoculation pneumonia as MSCs themselves. Moreover, exosomes show a strong effect of regenerative stimulation on different wounds so the regenerative effect can be extended on patients with COVID-19 pneumonia.
The purpose of this protocol is to explore the safety and efficiency of aerosol inhalation of the exosomes in the treatment of severe patients hospitalized with novel coronavirus pneumonia (NCP).
Study design
- Primary purpose
- Other
- Allocation
- Randomised
- Intervention model
- Parallel groups
- Masking
- Double blind (participant, care provider)
- Number of arms
- 3
- Model description
- The trial has three groups, each with 10 subjects (n=30). All eligible study subjects will be randomized, double-blinded, to either the two treatment groups or placebo group.
| Arm | Type | Receives |
|---|---|---|
| EXO-1 | Experimental | Drug: EXO 1 inhalationParticipants (n=10) in this group will receive standard therapy and exosomes of the first type. |
| EXO-2 | Experimental | Drug: EXO 2 inhalationParticipants (n=10) in this group will receive standard therapy and exosomes of the second type. |
| Placebo | Placebo comparator | Drug: Placebo inhalationParticipants (n=10) in this group will receive standard therapy and inhalation placebo solution. |
Who may qualify
- Ages
- 18 to 65 years
- Sex
- All
- Healthy volunteers
- Not accepted
- Age groups
- Adult, Older adult
Key inclusion criteria (4 listed)
- Ability to understand the study objectives and risks and provide signed and dated informed consent;
- Confirmed COVID-19 infection (by PCR or antibody test);
- Pneumonia requiring hospitalization, and oxygen saturation of <94% indoors or a need for auxiliary oxygen. The confirmed volume of lung damage by CT: not less than 30% and not more than 80%;
- ability to proceed with inhalation by self;
Key exclusion criteria (15 listed)
- Severe respiratory failure at the time of screening due to COVID-19 pneumonia;
- Known to undergo medical resuscitation for 14 days before randomization;
- Any serious medical condition or deviation of the clinical laboratory parameter that, in the opinion of the researcher, prevents safe participation and completion of the study by the participant Confirmed uncontrolled active bacterial, fungal, viral or other infection (other than SARS-CoV-2).
- According to the researcher, the progression to death is inevitable and will occur within the next 24 hours, regardless of the therapy.
- The life expectancy of fewer than 28 days, taking into account a medical condition already existing that cannot be corrected, e.g. participants with the following conditions or suspicions: polyorganic insufficiency, poorly controlled neoplasms, terminal stage heart disease, cardiopulmonary cardiac arrest that required cardiopulmonary resuscitation, or electrical activity not accompanied by a pulse, or asystole within the last 30 days, terminal stage liver disease, terminal stage liver disease, or liver disease;
Eligibility is decided by the study team after screening; this overview does not establish that a patient qualifies. Full inclusion and exclusion criteria.
Interventions
| Intervention | Type | Arms |
|---|---|---|
| EXO 1 inhalationTwice a day during 10 days inhalation of 3 ml special solution contained 0.5-2x10^10 of nanoparticles (exosomes) of the first type. | Drug | EXO-1 |
| EXO 2 inhalationTwice a day during 10 days inhalation of 3 ml special solution contained 0.5-2x10^10 of nanoparticles (exosomes) of the second type. | Drug | EXO-2 |
| Placebo inhalationTwice a day during 10 days inhalation of 3 ml special solution free of nanoparticles (exosomes). | Drug | Placebo |
Primary outcome
Number of Participants With Non-serious and Serious Adverse Events During Trial
Time frame: 30 days after clinic discharge
Safety assessment such as adverse events will be registered. Adverse events will be monitored during all trial
Number of Participants With Non-serious and Serious Adverse During Inhalation Procedure
Time frame: after each inhalation during 10 days
Safety assessments such as adverse events during the inhalation procedures will be registered.
4 secondary outcomes
Time to Clinical Recovery (TTCR)
Time frame: from first inhalation until discharge from the clinic, up to 30 days
SpO2 Concentration
Time frame: 10 days during inhalation
C-reactive Protein
Time frame: At the begining of inhalation (day 1) and on next day of last inhalation (day 11)
Lactic Acid Dehydrogenase (LDH)
Time frame: At the beginning of inhalation (day 1) and on next day of last inhalation (day 11)
Results and safety
Loading the posted results from ClinicalTrials.gov…
Research links
- Official record on ClinicalTrials.govLast updated by the sponsor 4 Nov 2020.
- Posted resultsParticipant flow, baseline, all outcome measures and adverse events.
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Referral and contact
AzTrials does not enrol participants or take referrals. Contact the study team or a site listed below; they decide who can take part. This study is not recruiting at the moment.
The record lists no contact. Use the official record to reach the sponsor.
1 site in 1 country: see every site and its status.
Questions about this trial
What is this clinical trial studying?
A Phase 1/2 study testing EXO 1 inhalation and EXO 2 inhalation in people with Covid19 and SARS-CoV-2 PNEUMONIA, run by State-Financed Health Facility "Samara Regional Medical Center Dinasty" at 1 site in Russia.
The full registered description is in the About this study section and the official record.
Who may be eligible to take part?
The sponsor lists 4 inclusion and 15 exclusion criteria. Eligibility is decided by the study team after screening, so read the full criteria and contact a listed site.
Is this clinical trial currently recruiting?
The record says: finished, as of the sponsor's last update on 4 Nov 2020. Status can change between updates, so confirm with the study contact before making plans.
Where is the study taking place?
The record lists 1 site in Russia. Whether a site is taking part right now should be confirmed with that site. See every site.
What are the possible benefits and risks?
They depend on the study and the treatment, and no study can promise a benefit. Some participants in this study may receive a placebo. The study team explains the known risks during informed consent, before anyone joins; the record itself does not list them.
What does this combined phase mean?
Phase 1 studies test a treatment in a small group of people for the first time or in a new way, mainly to check safety and find the right dose.
Phase 2 studies give the treatment to a larger group to see whether it has the intended effect and to keep checking safety.
Not every study follows the same path, and some studies (observational studies, device studies) have no phase.
Are results available for this study?
Yes. Results are posted in the registry (first posted 4 Nov 2020). A summary is in the For doctors view, and the full results are on ClinicalTrials.gov.
How can a doctor refer a patient or contact the research team?
The record lists no contact. The official record names the sponsor, who can be asked directly. AzTrials does not enrol participants or take referrals.
What does the primary outcome measure?
Number of Participants With Non-serious and Serious Adverse Events During Trial (time frame: 30 days after clinic discharge). The study lists 2 primary outcomes in all. It is what the study was designed to measure, not a finding.
Where can I read the original study information?
Does a listing mean the treatment is approved or proven to work?
No. A listing means the study is registered. It does not show that the treatment is safe, works, or is approved by a regulator.
How often is this information updated?
AzTrials copies changed records from ClinicalTrials.gov every night and reloads the whole registry every week. The sponsor last updated this record on 4 Nov 2020.