RecruitingPhase 1Phase 2NCT06052436

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


Sponsor

Hospital General Universitario Gregorio Marañon

Enrollment

24 participants

Start Date

Jun 27, 2023

Study Type

INTERVENTIONAL

Conditions

Summary

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.


Eligibility

Min Age: 18 YearsMax Age: 65 Years

Inclusion Criteria6

  • Patient over 18 to 65 years of age
  • Patient Informed and non-opposed to the research by his medical doctor during hospitalization
  • Patient with clinical, radiological, gasometric and immunological criteria defined as:
  • Acute respiratory failure secondary to acute lung injury of noncardiogenic cause
  • Pulmonary abnormalities compatible with bilateral alveoloinsterstitial infiltrates by chest imaging (radiograph or scan)
  • 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 Criteria17

  • Pregnancy or breast feeding
  • Body mass index >35
  • Patients not expected to survive 48 hours after enrolment based on clinical assessment
  • Patients with an extracorporeal respiratory support
  • Neutropenia (absolute neutrophil count <1000/uL)
  • Thrombocytopenia (absolute neutrophil count <50000/uL)
  • Positive serology for HBV, HCV, or HIV at Screening
  • Life expectancy of less than 6 months due to other pathologies
  • History of significant underlying pulmonary disease requiring oxygen therapy prior to inclusion.
  • Patients with a history of autoimmune diseases
  • Patients with a history of hematopoietic neoplasia or oncology disease
  • Patients with a history of hematopoietic or solid organ transplant
  • Patients with a congenital or induced immunodeficiency
  • Patients received thymoglobulin, basiliximab or any anti-T-cell therapies within 6 moths prior to the screening visit
  • Patients received other cell therapy in the last 12 months
  • Patients received intravenous immunoglobulin (IVIg) within 5 moths prior to the screening visit
  • 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

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Interventions

BIOLOGICALAllogeneic thyTreg 5.000.000

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

BIOLOGICALAllogeneic 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

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NCT06052436


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