RecruitingPhase 2NCT06552169

REgulatory T Cell Therapy to Achieve Immunosuppression REduction

The RETIRE Trial: A Randomized Phase 2 Trial of Adoptive Therapy With Treg Adoptive Cell Transfer (TRACT) To Prevent Rejection in Living Donor Kidney Transplant Recipients

Sponsor

Singulera Therapeutics Inc.

Enrollment

34 participants

Start Date

Jun 13, 2025

Study Type

INTERVENTIONAL

Conditions

Kidney Transplantation

Summary

The goal of this multi-national, multi-center, open-label, randomized Phase 2 trial is to determine the safety and efficacy of administering expanded regulatory T cells (TRK-001) to prevent allograft rejection in living donor renal transplant recipients. Enrolled subjects will be randomized to one of 2 study arms: Arm 1 subjects will receive standard of care immunosuppression Arm 2 subjects will receive initial standard of care (SOC) immunosuppression and a single infusion of TRK-001. Three months after the transplant, Arm 2 subjects may be able to begin reducing their immunosuppression medication to a 1-drug regimen. The primary outcome measures of trial are to evaluate several components indicating immunologic problems with the transplanted organ at 1-year post-transplant and to evaluate the ability for the study subjects given TRK-001 to wean to a 1-drug immunosuppression regimen. All enrolled subjects will be followed for 5 years post-transplant.

Eligibility

Min Age: 18 YearsMax Age: 65 Years

Inclusion Criteria9

Males or females aged 18-65 years as of the date of informed consent who will undergo a single organ, living donor kidney transplant.
Donor aged 18-65 years as of the date of organ donation. A certain degree of HLA matching between the donor and the recipient is not required.
Blood type compatibility between recipient and donor must be established as follows.
Recipient A to Donor A or O; Recipient B to Donor B or O; Recipient AB to Donor A, B, AB, or O; Recipient O to Donor O.
No prior organ transplant of any kind.
Women of childbearing potential must agree to use a medically acceptable method of contraception throughout the trial. A list of the medically acceptable methods of contraception are listed in the informed consent document.
Male patients must agree to use birth control following the initiation of standard-of-care immunosuppression and for a minimum of 6 months following kidney transplant.
Subjects (recipients) must be able to understand the consent form and give written informed consent prior to any trial procedure.
If donor informed consent is required by IRB/IEC, donor must be able to understand the consent form and give written informed consent prior to any trial procedure. Note: Donor informed consent is required for donors participating in the research assay collections.

Exclusion Criteria35

Known sensitivity or contraindication to thymoglobulin, everolimus, sirolimus, or tacrolimus or other immunosuppression medication prescribed.
Subjects with a positive crossmatch by virtual cross matching or complement-dependent cytotoxicity (CDC) cross matching or flow cytometry cross matching (FCXM).
Subjects with PRA \>80% per SOC pre-transplant assessment. PRA must be repeated prior to transplant if patient receives a blood product transfusion after the initial assessment.
Subjects with current or historic donor specific antibodies.
Body Mass Index (BMI) of \< 16 kg/m2 or \> 38 kg/m2 per SOC pre-transplant evaluation.
Subjects who are pregnant or nursing mothers.
Subjects whose life expectancy is severely limited by diseases other than renal disease, per judgement of an investigator.
Ongoing active drug or alcohol substance abuse, per judgement of an investigator.
Major ongoing psychiatric illness or recent history of noncompliance with current medical therapy, per judgement of an investigator.
Significant cardiovascular disease (e.g.):
Significant non-correctable coronary artery disease, per judgement of an investigator
Ejection fraction below 30% per SOC echocardiogram if an echocardiogram is performed for an individual subject as part of their pre-transplant evaluation
History of recent (\< 12 months) myocardial infarction at time of informed consent
History of recent (within 3 months) vascular intervention(s) for coronary artery disease at the time of informed consent
Documented arrhythmias that require a pacemaker or medical therapy for control.
Subjects who require use of chronic anticoagulation medications. Use of anti-platelet medications will be allowed in absence of a documented arrhythmia.
Malignancy within 3 years, excluding non-melanoma skin cancers such as basal cell carcinoma and squamous cell carcinoma.
Serologic evidence of active infection with HCV, HIV or HBV per SOC pre-transplant evaluation. Historical data within three months of transplant are acceptable.
Subjects with a total white blood cell count \< 4,000/mm3; platelet count \< 50,000/mm3; triglyceride \> 400 mg/dL; total cholesterol \> 300 mg/dL, prothrombin time \<8.4 seconds or \>15.7 seconds, activated partial thromboplastin time \<21.6 or \> 42.3 seconds, fibrinogen \<177 mg/dL or \>598 mg/dL, and INR \<0.64 or \>1.4.
Subjects with underlying renal disease etiologies with high risk of disease recurrence such as primary focal segmental glomerulosclerosis and others per investigator discretion.
Subjects requiring the use of chronic immunosuppressive medication to control an underlying renal disease, or a disease with extrarenal manifestations (i.e., inflammatory bowel disease). Subjects requiring chronic or intermittent use of inhaled corticosteroids for respiratory conditions will be allowed.
Diabetic subjects with an HbA1c of \>8%.
Subjects with an active infection considered clinically significant by an investigator that has not resolved prior to transplant.
Subjects with an active infection considered clinically significant by an investigator that has not resolved prior to leukapheresis.
Subjects with PRA \>80%, if repeated after SOC pre-transplant assessment. (PRA must be repeated prior to leukapheresis if patient receives a blood product transfusion after the initial assessment).
Subjects who are pregnant or nursing.
Subjects who received an investigational drug within 30 days prior to leukapheresis.
Subjects who received anti-T cell therapy within 30 days prior to leukapheresis.
Subjects who do not meet pre-leukapheresis clearance parameters per institutional practices or per investigator discretion.
Subjects with an active infection considered clinically significant by the investigator that has not resolved prior to planned Treg infusion.
Subjects with a new, clinically significant medical condition that, per investigator opinion, would impact the ability to safely administer TRK-001.
Subjects who experience a rejection episode of the kidney graft prior to the planned Treg infusion.
Subjects who are pregnant or nursing. Women who are of childbearing potential must have a negative urine or serum pregnancy test before infusion of TRK-001.
Subjects who received an investigational drug within 30 days prior to infusion.
Subjects who received anti-T cell therapy within 30 days prior to infusion.

Interventions

DRUGArm 1: SOC (mTOR + CNI)

Subjects randomized to Arm 1 will remain on standard dual-immunosuppression therapy (CNI and mTOR) throughout the trial.

BIOLOGICALArm 2A: TRACT/MONO mTOR

All subjects will be prescribed standard of care (SOC) immunosuppressive agents. Subjects randomized to Arm 2 will be maintained on the prescribed SOC immunosuppression (tacrolimus + sirolimus or everolimus) and have a single intravenous infusion of autologous, expanded Tregs (TRK-001) at Day +53 to +67 post-transplant. At Month 3 post-transplant, Arm 2 subjects will be further randomized to receive either: * Arm 2A: mTOR monotherapy or * Arm 2B: CNI monotherapy. These subjects will transition to the assigned 1-drug immunosuppression regimen beginning at Month 3 post-transplant. Weaning must be completed by 12 months post-transplant. Subjects in Arm 2 will undergo leukapheresis to collect peripheral blood mononuclear cells required for the cellular product.

BIOLOGICALArm 2B: TRACT/MONO CNI