Evaluation of Safety and Efficiency of Method of Exosome Inhalation in SARS-CoV-2 Associated Pneumonia.

NCT04491240 | Completed Phase 1 Results

• 1 other identifier: COVID-19 EXO
• Study Type: interventional
• Target: 30
• Locations: 1 country
• Sites: 1

Brief 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. 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.

Conditions

COVID-19; SARS-CoV-2 PNEUMONIA

Keywords

Covid-19; SARS-CoV-2; exosomes; MSC

Outcome Measures

Primary Outcomes (2)

• 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

  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.

  after each inhalation during 10 days

Secondary Outcomes (4)

• Time to Clinical Recovery (TTCR)

  from first inhalation until discharge from the clinic, up to 30 days

• SpO2 Concentration

  10 days during inhalation

• C-reactive Protein

  At the begining of inhalation (day 1) and on next day of last inhalation (day 11)

• Lactic Acid Dehydrogenase (LDH)

  At the beginning of inhalation (day 1) and on next day of last inhalation (day 11)

Study Arms (3)

EXO-1

EXPERIMENTAL

Participants (n=10) in this group will receive standard therapy and exosomes of the first type.

Drug: EXO 1 inhalation

EXO-2

EXPERIMENTAL

Participants (n=10) in this group will receive standard therapy and exosomes of the second type.

Drug: EXO 2 inhalation

Placebo

PLACEBO COMPARATOR

Participants (n=10) in this group will receive standard therapy and inhalation placebo solution.

Drug: Placebo inhalation

Interventions

EXO 1 inhalation DRUG

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-1

EXO 2 inhalation DRUG

Twice a day during 10 days inhalation of 3 ml special solution contained 0.5-2x10\^10 of nanoparticles (exosomes) of the second type.

EXO-2

Placebo inhalation DRUG

Twice a day during 10 days inhalation of 3 ml special solution free of nanoparticles (exosomes).

Placebo

Eligibility Criteria

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

You may qualify if:

• 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;

You may not qualify if:

• 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;
• 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;

Sponsors & Collaborators

• State-Financed Health Facility "Samara Regional Medical Center Dinasty": lead
• Samara State Medical University: collaborator
• Samara Regional Clinical Hospital V.D. Seredavin: collaborator

Study Sites (1)

Medical Centre Dinasty

Samara, 443095, Russia

Location

MeSH Terms

Conditions

COVID-19

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

Results Point of Contact

• Title: Tyumina Olga
• Organization: MC Dinasty

centr123@bk.ru

+78462039808

Publication Agreements

• PI is Sponsor Employee: Yes
• Restrictive Agreement: No

Study Design

• Study Type: interventional
• Phase: phase 1
• Allocation: RANDOMIZED
• Masking: DOUBLE
• Who Masked: PARTICIPANT, CARE PROVIDER
• Masking Details: Two main groups will be provided with exosomes in a specially provided solution, the third group (control) will receive the same solution without exosomes. Due to exosomes are nanoparticles and requires special methods and devices to be detected the hospital staff and patients have no way to check which group receives exosomes.
• Purpose: OTHER
• Intervention Model: PARALLEL
• Sponsor Type: OTHER
• Responsible Party: SPONSOR

Model Details: 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.

Study Record Dates

• First Submitted: July 27, 2020
• First Posted: July 29, 2020
• Study Start: July 20, 2020
• Primary Completion: October 1, 2020
• Study Completion: October 20, 2020
• Last Updated: November 4, 2020
• Results First Posted: November 4, 2020

Record last verified: 2020-10

Locations

RU (1)