Cell Therapy with Treg Cells Obtained from Thymic Tissue (thyTreg) to Prevent Rejection in Heart Transplant Children (THYTECH)

Rafael Correa-Rocha

Status and phase: Enrolling; Phase 2; Phase 1

Conditions: Heart Transplantation

Treatments: Biological: Autologous thyTreg

Study type: Interventional

Funder types: Other

Identifiers

NCT04924491

2024-519845-30 (EudraCT Number)

THYTECH1-2018-005

2018-003574-28 (EudraCT Number)

Details and patient eligibility

About

The investigators developed a protocol to isolate Treg cells from thymic tissue (thyTreg) discarded in pediatric cardiac surgeries. After completing the pre-clinical studies, the investigators have initiated a phase I/II clinical trial to test the safety and efficacy of the adoptive transfer of autologous thyTreg to prevent rejection in heart transplant children.

Condition or disease: Heart Transplantation Intervention/treatment: Regulatory T Cell (Treg) Infusion

Full description

Current transplant practice is far from guaranteeing the life expectancy of patients, particularly if the patients are children. THYTECH aims to revolutionize the field of clinical immunology developing a new approach to govern the regulatory skills of immune system, preventing graft rejection and opening a new frontier in the treatment of immune diseases.

Transfer of regulatory T cells (Treg) has acquired growing interest in the race to achieve indefinite transplant survival. Up to now, the use of Treg therapy to prevent solid graft rejection in humans has demonstrated that this therapy is safe, but the clinical efficacy is limited. The small Treg numbers that can be purified from peripheral blood along with the low survival and limited suppressive capacity of differentiated Tregs obtained from adults have probably compromised the efficacy of this therapy.

The investigators have developed an innovative approach to overcome current barriers and make Treg transfer a reality equipped to achieve indefinite graft survival. The major innovation of THYTECH is the employment of thymic tissue, the site of Treg generation, as a new source of Tregs to obtain massive amounts of thymus-derived Tregs (thyTreg) with very high purity (>95% of CD 25+ Foxp3+ cells) and improved survival and suppressive capacities. The investigators are recruiting patients in a clinical trial transferring autologous Tregs in heart-transplanted children to prevent graft rejection.

Enrollment: 11 estimated patients

Sex: All

Ages: Under 2 years old

Volunteers: No Healthy Volunteers

Inclusion criteria

1. Patient under two years of age, who meets all the necessary requirements to undergo a heart transplant.
2. Patients without contraindication to immunosuppressive drugs.
3. Parents and/or guardians must be willing and able to understand the purpose and risks of the study and must sign the informed consent document

Exclusion criteria

1. Patients with DiGeorge Syndrome, since their thymic function is affected.
2. Human immunodeficiency virus positive serology
3. Epstein-Barr virus active infection
4. Patients hyperimmunized with cytotoxic anti-human leukocyte antigen antibodies
5. Patients with a history of previous malignancy
6. Patients who have participated in other intervention studies in the last month.
7. Patients who have received induction therapy with Basiliximab or Thymoglobulin.
8. Patients who have previously been thymectomized or transplanted.
9. Patients who have been diagnosed with severe autoimmune disease (celiac disease, autoimmune hypothyroidism, autoimmune diabetes)
10. Patients who will receive an asystole heart

Trial design

Primary purpose: Prevention

Allocation: Randomized

Interventional model: Parallel Assignment

Masking: None (Open label)

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11 participants in 2 patient groups

10.000.000 thyTreg /kg

Experimental group

Description:

Autologous thyTreg 10.000.000

Treatment:

Biological: Autologous thyTreg

20.000.000 thyTreg /kg

Experimental group

Description:

Autologous thyTreg 20.000.000

Treatment:

Biological: Autologous thyTreg