Regulatory T-cell therapy to reduce immunosuppression after a living-donor kidney transplant

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

This trial will test whether a single infusion of a patient's expanded regulatory T cells (TRK-001) after a living-donor kidney transplant lets people safely reduce their long-term anti-rejection medications.

Quick facts

• Phase: Phase 2
• Study type: Interventional
• Enrollment: 34 (estimated)
• Ages: 18 Years to 65 Years
• Sex: All
• Sponsor: Singulera Therapeutics Inc. (Industry-sponsored)
• Locations: 7 sites (Phoenix, Arizona and 6 other locations)
• Trial ID: NCT06552169 on ClinicalTrials.gov

What this trial studies

This randomized, open-label Phase 2 trial enrolls adults receiving a living-donor kidney transplant and compares standard immunosuppression alone versus standard care plus one infusion of autologous expanded regulatory T cells (TRK-001). Participants assigned to TRK-001 will start with standard immunosuppression and may begin weaning to a one-drug regimen three months after transplant, with a further randomization to either mTOR or CNI monotherapy within the TRK arm. Primary outcomes include immunologic indicators of graft problems at one year and the ability to maintain monotherapy, and all subjects will be followed for five years. Approximately 34 participants will be enrolled across multiple U.S. transplant centers.

Who should consider this trial

Good fit: Adults aged 18–65 with end-stage kidney disease scheduled for a living-donor kidney transplant who have no prior organ transplant and meet blood-type compatibility and contraception requirements.

Not a fit: People receiving deceased-donor kidneys, those outside the 18–65 age range, patients with prior organ transplants, or those with incompatible blood types or unwilling to undergo cell therapy may not be eligible or likely to benefit.

Why it matters

Potential benefit: If successful, this approach could allow some transplant recipients to reduce or simplify lifelong immunosuppression, lowering drug side effects and infection risk.

How similar studies have performed: Early-phase trials of regulatory T cell therapies in transplantation and autoimmune diseases have shown safety and some promising signals for reducing rejection, but randomized evidence is still limited.

Eligibility criteria

Inclusion Criteria

All inclusion criteria must be met prior to randomization.

1. Males or females aged 18-65 years as of the date of informed consent who will undergo a single organ, living donor kidney transplant.
2. 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.
3. 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.
4. No prior organ transplant of any kind.
5. 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.
6. 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.
7. Subjects (recipients) must be able to understand the consent form and give written informed consent prior to any trial procedure.
8. 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 Criteria Based on SOC Pre-Transplant Evaluation

The following exclusion criteria must be determined prior to randomization per SOC pre-transplant evaluation.

1. Known sensitivity or contraindication to thymoglobulin, everolimus, sirolimus, or tacrolimus or other immunosuppression medication prescribed.
2. Subjects with a positive crossmatch by virtual cross matching or complement-dependent cytotoxicity (CDC) cross matching or flow cytometry cross matching (FCXM).
3. 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.
4. Subjects with current or historic donor specific antibodies.
5. Body Mass Index (BMI) of \< 16 kg/m2 or \> 38 kg/m2 per SOC pre-transplant evaluation.
6. Subjects who are pregnant or nursing mothers.
7. Subjects whose life expectancy is severely limited by diseases other than renal disease, per judgement of an investigator.
8. Ongoing active drug or alcohol substance abuse, per judgement of an investigator.
9. Major ongoing psychiatric illness or recent history of noncompliance with current medical therapy, per judgement of an investigator.
10. 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.
11. Subjects who require use of chronic anticoagulation medications. Use of anti-platelet medications will be allowed in absence of a documented arrhythmia.
12. Malignancy within 3 years, excluding non-melanoma skin cancers such as basal cell carcinoma and squamous cell carcinoma.
13. Serologic evidence of active infection with HCV, HIV or HBV per SOC pre-transplant evaluation. Historical data within three months of transplant are acceptable.
14. 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.
15. Subjects with underlying renal disease etiologies with high risk of disease recurrence such as primary focal segmental glomerulosclerosis and others per investigator discretion.
16. 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.
17. Diabetic subjects with an HbA1c of \>8%.

    The following exclusion criteria must be determined prior to transplant per SOC pre-transplant evaluation.
18. Subjects with an active infection considered clinically significant by an investigator that has not resolved prior to transplant.

Exclusion Criteria Prior to Leukapheresis (Arm 2)

1. Subjects with an active infection considered clinically significant by an investigator that has not resolved prior to leukapheresis.
2. 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).
3. Subjects who are pregnant or nursing.
4. Subjects who received an investigational drug within 30 days prior to leukapheresis.
5. Subjects who received anti-T cell therapy within 30 days prior to leukapheresis.
6. Subjects who do not meet pre-leukapheresis clearance parameters per institutional practices or per investigator discretion.

Exclusion Criteria Prior to TRACT Cellular Product Infusion (Arm 2)

1. Subjects with an active infection considered clinically significant by the investigator that has not resolved prior to planned Treg infusion.
2. Subjects with a new, clinically significant medical condition that, per investigator opinion, would impact the ability to safely administer TRK-001.
3. Subjects who experience a rejection episode of the kidney graft prior to the planned Treg infusion.
4. 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.
5. Subjects who received an investigational drug within 30 days prior to infusion.
6. Subjects who received anti-T cell therapy within 30 days prior to infusion.

Where this trial is running

Phoenix, Arizona and 6 other locations

• Mayo Clinic in Arizona — Phoenix, Arizona, United States (Recruiting)
• Northwestern Memorial Hospital — Chicago, Illinois, United States (Recruiting)
• Mayo Clinic in Minnesota — Rochester, Minnesota, United States (Recruiting)
• Taichung Veterans General Hospital — Taichung, Taiwan (Recruiting)
• National Cheng Kung University Hospital — Tainan, Taiwan (Not_yet_recruiting)
• National Taiwan University Hospital — Taipei, Taiwan (Recruiting)
• Chang Gung Medical Foundation Hospital — Taoyuan, Taiwan (Recruiting)

Study contacts

• Study coordinator: Susan B Murray

Conditions Kidney Transplantation; Regulatory T cells; Treg adoptive cell transfer; Graft Rejection; Autologous cell therapy; End stage renal disease; Prevention of organ transplant rejection; Tregs