Efficacy and Safety of EXOSOME-MSC Therapy to Reduce Hyper-inflammation In Moderate COVID-19 Patients

NCT05216562 | Unknown Phase 2 DMC

• 2 other identifiers: DBL-EXO-MSC-COV-19-CT-01PPUK-RG.01.06.1.2.03.21.29
• Study Type: interventional
• Target: 60
• Locations: 1 country
• Sites: 3

Brief Summary

In COVID-19 infection caused by the Severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2), there is a dysregulation of the immune system response that causes cytokine storm syndrome. SARS-CoV-2 works like a hijacker (hackers), sabotaging communication between cells so that the immune system, like T-cells, kills not only infected cells but also healthy cells. This dysregulation results in hyper-inflammation which cause damage to organs, not just the lungs. This is the cause of the high mortality rate in COVID-19 patients. Exosomes are vesicles with a size of 30-100 nanometers originating from within cells that function to communicate with other cells. Exosomes are transport containers that contain bioactive cargo: such as proteins, genetic material, and various other molecules. These containers move from cells of origin, flowing through blood vessels or other body fluids to target cells. Exosomes penetrate the cell membrane and act on various organelles within the target cell. All cell types can produce exosomes. What differentiates them is the cargo they contain. The exosome produced by mesenchymal stem cells (MSCs) contains bioactive cargo derived from mesenchymal stem cells, such as anti-inflammatory cytokines, growth factors, messengerRNA (mRNA) and microRNA (miRNA). The target cells are immune system cells, infected cells and progenitor cells from infected organs. On target immune cells, the anti-inflammatory cytokines work as immunomodulators to relieve hyper-inflammation. In infected cells, the miRNAs work to prevent viral replication by inhibiting the expression of SARS-CoV-2 virus RNA (viral mRNA silencing and degrading). In lung progenitor cells and other infected organs, the growth factors work to stimulate protein synthesis processes that function for organ regeneration. This study is a multi-center, double-blind, randomized controlled trial (RCT) clinical trial with two arms: one intervention arm, and one control arm. The EXOSOME-MSC will be tested as adjuvant, on top of standard COVID-19 drugs. It will be injected to participants via intravenous route twice, in day-1 and day-7 of 14 days of study participation.

Conditions

SARS-CoV2 Infection

Keywords

Mesenchymal Stemcells - derived Exosomes; SARS-COV-2, COVID-19; Hyper-inflammation; Cytokine Storm

Outcome Measures

Primary Outcomes (1)

• Time to clinical improvement (days)

  Clinical improvement is fulfilled with score 1-3 of the scale 1. No hospitalization and no restrictions activity 2. Not hospitalized, with activity restrictions, oxygen requirements at home, or both 3. Hospitalized, does not require oxygen additional and no longer need maintenance ongoing medical treatment (used if hospitalization is extended for infection control or other reasons nonmedical) 4. Hospitalized, not requiring supplemental oxygen but requiring ongoing medical care (related to COVID-19 or other medical conditions) 5. hospitalized, requires supplemental oxygen 6. hospitalized, requiring noninvasive ventilation or use high flow oxygen device; 7. hospitalized, receiving mechanical ventilation invasive or extracorporeal membrane oxygenation (ECMO); 8. deaths.

  14 days

Secondary Outcomes (6)

• Increase in Lymphocytes counts

  14 days

• Decrease in D-dimer

  14 days

• Decrease in LDH level

  14 days

• Decrease in Ferritin concentration

  14 days

• Decrease in C-reactive protein

  14 days

Study Arms (2)

Intervention group

EXPERIMENTAL

Group participants who receive injection of EXOSOME-MSC as adjuvant

Drug: Exosome-MSC Intravenous injection; Drug: COVID-19 Standard Treatment

Control group

PLACEBO COMPARATOR

Group participants who receive injection of Placebo (NaCL) as adjuvant

Drug: Placebo Intravenous Injection; Drug: COVID-19 Standard Treatment

Interventions

Exosome-MSC Intravenous injection DRUG

Intravenous injection of Exosome-MSC

Also known as: Dermama Exosome-MSC

Intervention group

Placebo Intravenous Injection DRUG

Intravenous injection of Placebo

Also known as: Placebo

Control group

COVID-19 Standard Treatment DRUG

Specific drugs considered standard treatment for COVID-10 by each location may vary

Also known as: Drugs accepted as cures for COVID-19

Control group; Intervention group

Eligibility Criteria

• Age: 18 Years - 75 Years
• Sex: all
• Healthy Volunteers: No
• Age Groups: Adult (18-64), Older Adult (65+)

You may qualify if:

• Diagnosed with COVID-19 pneumonia confirmed by RT-PCR examination. Samples were obtained from nasopharyngeal swabs in patients with moderate
• There is evidence of changes in chest X-ray with a picture of COVID-19 pneumonia and/or CT-Scan of the thorax with a ground glass opacity picture
• Willing to participate in the study and sign the informed consent by the subject or family members.

You may not qualify if:

• Diagnosed with mild COVID-19 pneumonia
• Pregnant woman or positive pregnancy test
• The subject is participating in another clinical trial.
• Have a history of anaphylactic reactions, angioedema, or allergic reactions to antibiotics (penicillin and its derivatives) or other drugs.
• Have an autoimmune disease
• Have a history of malignancy
• Undergoing hemodialysis or peritoneal dialysis
• Recuring COVID-19 sufferers

Sponsors & Collaborators

• Dermama Bioteknologi Laboratorium: lead
• Kementerian Riset dan Teknologi / Badan Riset dan Inovasi Nasional, Indonesia: collaborator

Study Sites (3)

RSPAD Gatot Soebroto

Jakarta, DKI Jakarta, 10410, Indonesia

RECRUITING

RSUP Dr. M. Jamil

Padang, West Sumatra, 25171, Indonesia

RECRUITING

RSUP Dr. Sardjito

Yogyakarta, 55281, Indonesia

RECRUITING

MeSH Terms

Conditions

COVID-19; Cytokine Release Syndrome

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; Systemic Inflammatory Response Syndrome; Inflammation; Pathologic Processes; Pathological Conditions, Signs and Symptoms; Shock

Study Officials

• Indah H Kampono, Dr. Sp.DV

  Dermama

  STUDY CHAIR

• Bambang Darwono, Dr.Sp.OT

  Research Center for Chemistry, National Research and Innovation Agency of Indonesia

  PRINCIPAL INVESTIGATOR

Central Study Contacts

Bambang H Darwono, Dr.Sp.OT

CONTACT

+62 811-1180-21; bdarwono@hotmail.com

Indah H Kampono, Dr. Sp.DV

CONTACT

+62 811-2632-086; indahhidajati01@gmail.com

Study Design

• Study Type: interventional
• Phase: phase 2
• Allocation: RANDOMIZED
• Masking: TRIPLE
• Who Masked: PARTICIPANT, CARE PROVIDER, INVESTIGATOR
• Purpose: TREATMENT
• Intervention Model: PARALLEL
• Sponsor Type: INDUSTRY
• Responsible Party: PRINCIPAL INVESTIGATOR
• PI Title: Senior Clinical Consultant

Study Record Dates

• First Submitted: January 28, 2022
• First Posted: January 31, 2022
• Study Start: July 1, 2021
• Primary Completion: June 30, 2022
• Study Completion: December 30, 2022
• Last Updated: February 18, 2022

Record last verified: 2022-02

Data Sharing

• IPD Sharing: Will not share

Locations

ID (3)