RECRUITINGPhase 1 / Phase 2INTERVENTIONAL

Cell Therapy With Treg Cells Obtained From Thymic Tissue (thyTreg) to Control the Immune Hyperactivation Associated With COVID-19 and/or Acute Respiratory Distress Syndrome (THYTECH2)

Open Phase I/IIa Clinical Trial to Evaluate the Safety and Efficacy of Allogenic Administration of Treg Cells Obtained From Thymic Tissue (thyTreg) to Control The Immune Hyperactivation Associated With COVID-19 and/or Acute Respiratory Distress Syndrome

About This Trial

The investigators developed a GMP protocol to isolate Treg cells from thymic tissue (thyTreg). The thyTreg cells are being evaluated in a Phase I/II clinical trial to evaluate the safety and efficacy of the adoptive transfer of autologous thyTreg to prevent rejection in heart transplant children (NCT04924491), with preliminary results indicating the feasibility and safety of the therapy. In addition, thyTreg cells have shown low immunogenicity in the pre-clinical setting, indicating that allogeneic use of these thyTreg cells (allo-thyTreg) would have a low risk of adverse effects. These thyTreg cells could inhibit an excessive inflammation in SARS-CoV-2 infection, or ameliorate the immunological affection underlying Acute respiratory distress syndrome, improving life-threatening manifestations, restoring immune balance, and protecting affected tissues. This clinical trial is an open-label Sequential Parallel Group Phase I/II study to evaluate the safety and efficacy of allogeneic thymus derived Tregs (thyTreg) (thyTreg) in controlling the immune dysregulation associated with SARS-CoV-2 infection and/or Acute Respiratory Distress Syndrome.

Who May Be Eligible (Plain English)

Who May Qualify: 1. Patient over 18 to 65 years of age 2. Patient Informed and non-opposed to the research by his medical doctor during hospitalization 3. Patient with clinical, radiological, gasometric and immunological criteria defined as: 1. Acute respiratory failure secondary to acute lung injury of noncardiogenic cause 2. Pulmonary abnormalities compatible with bilateral alveoloinsterstitial infiltrates by chest imaging (radiograph or scan) 3. PaO2/FiO2≤ 300 Presence of at least one of the following markers of inflammation: IL6 \> 40 pg/ml or ferritin \>300 ng/ml or CRP \>3 mg/dl or increasing over the last 24 hours Who Should NOT Join This Trial: 1. Pregnancy or breast feeding 2. Body mass index \>35 3. Patients not expected to survive 48 hours after enrolment based on clinical assessment 4. Patients with an extracorporeal respiratory support 5. Neutropenia (absolute neutrophil count \<1000/uL) 6. Thrombocytopenia (absolute neutrophil count \<50000/uL) 7. Positive serology for HBV, HCV, or HIV at Screening 8. Life expectancy of less than 6 months due to other pathologies 9. History of significant underlying pulmonary disease requiring oxygen therapy prior to inclusion. 10. Patients with a history of autoimmune conditions (where your immune system attacks your own body)s 11. Patients with a history of hematopoietic neoplasia or oncology disease 12. Patients with a history of hematopoietic or solid organ transplant 13. Patients with a congenital or induced weakened immune system 14. Patients received thymoglobulin, basiliximab or any anti-T-cell therapies within 6 moths prior to the screening visit 15. Patients received other cell therapy in the last 12 months 16. Patients received intravenous immunoglobulin (IVIg) within 5 moths prior to the screening visit 17. Patients who have participated or is participating in a clinical research study evaluating COVID-19 or ARDS within 30 days prior to the screening visit Always talk to your doctor about whether this trial is right for you.

Original Eligibility Criteria

View original clinical language

Inclusion Criteria: 1. Patient over 18 to 65 years of age 2. Patient Informed and non-opposed to the research by his medical doctor during hospitalization 3. Patient with clinical, radiological, gasometric and immunological criteria defined as: 1. Acute respiratory failure secondary to acute lung injury of noncardiogenic cause 2. Pulmonary abnormalities compatible with bilateral alveoloinsterstitial infiltrates by chest imaging (radiograph or scan) 3. PaO2/FiO2≤ 300 Presence of at least one of the following markers of inflammation: IL6 \> 40 pg/ml or ferritin \>300 ng/ml or CRP \>3 mg/dl or increasing over the last 24 hours Exclusion Criteria: 1. Pregnancy or breast feeding 2. Body mass index \>35 3. Patients not expected to survive 48 hours after enrolment based on clinical assessment 4. Patients with an extracorporeal respiratory support 5. Neutropenia (absolute neutrophil count \<1000/uL) 6. Thrombocytopenia (absolute neutrophil count \<50000/uL) 7. Positive serology for HBV, HCV, or HIV at Screening 8. Life expectancy of less than 6 months due to other pathologies 9. History of significant underlying pulmonary disease requiring oxygen therapy prior to inclusion. 10. Patients with a history of autoimmune diseases 11. Patients with a history of hematopoietic neoplasia or oncology disease 12. Patients with a history of hematopoietic or solid organ transplant 13. Patients with a congenital or induced immunodeficiency 14. Patients received thymoglobulin, basiliximab or any anti-T-cell therapies within 6 moths prior to the screening visit 15. Patients received other cell therapy in the last 12 months 16. Patients received intravenous immunoglobulin (IVIg) within 5 moths prior to the screening visit 17. Patients who have participated or is participating in a clinical research study evaluating COVID-19 or ARDS within 30 days prior to the screening visit

Treatments Being Tested

BIOLOGICAL

Allogeneic thyTreg 5.000.000

Treg lymphocytic cells, differentiated, allogeneic, of thymic tissue, expanded and stimulated with Interleukin (IL-) 2 (thyTreg)

BIOLOGICAL

Allogeneic thyTreg 10.000.000

Treg lymphocytic cells, differentiated, allogeneic, of thymic tissue, expanded and stimulated with Interleukin (IL-) 2 (thyTreg)

Locations (1)

Hospital General Universitario Gregorio Marañon

Madrid, Madrid, Spain