REgulatory T Cell Therapy to Achieve Immunosuppression REduction (RETIRE)

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

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.

Study Overview

• Status: Recruiting
• Conditions: Kidney Transplantation
• Intervention / Treatment: Drug: Arm 1: SOC (mTOR + CNI); Biological: Arm 2A: TRACT/MONO mTOR; Biological: Arm 2B: TRACT/MONO CNI

Detailed Description

This is a prospective, multi-national, multi-center, open-label, randomized Phase 2 trial to determine the safety and efficacy of administering autologous expanded regulatory T cells (TRK-001) to prevent allograft rejection in living donor renal transplant recipients.

All subjects will be followed for 5 years post-transplant, comprising of a 2-year post-transplant follow-up period and a 3-year surveillance period.

Subjects with end-stage renal disease undergoing a living donor kidney transplant will be enrolled into the trial as follows:

Arm 1 SOC: Standard of care immunosuppression (N=14)

Arm 2 TRACT/MONO: TRK-001 and initial SOC immunosuppression weaned to monotherapy (N=20)

At Month 3 post-transplant, Arm 2 subjects will be further randomized prior to weaning to either mTOR or CNI monotherapy as follows:

Arm 2A: TRACT/MONO mTOR (N=10) or Arm 2B: TRACT/MONO CNI (N=10)

• Study Type: Interventional
• Enrollment (Estimated): 34
• Phase: Phase 2

Contacts and Locations

• Study Contact: Name: Erwin Teng; Phone Number: +886-931-392700; Email: erwin.teng@twbio-thera.com
• Study Contact Backup: Name: Susan B Murray; Phone Number: +1-312-219-4670; Email: susan.murray@singulera-tx.com

Study Locations

• Taiwan
  • Taichung, Taiwan, 407219
    • Recruiting
    • Taichung Veterans General Hospital
    • Principal Investigator: Cheng-Hsu Chen, MD, PhD
  • Tainan, Taiwan, 704
    • Not yet recruiting
    • National Cheng Kung University Hospital
    • Principal Investigator: Shen-Shin Chang, MD
  • Taipei, Taiwan, 100229
    • Recruiting
    • National Taiwan University Hospital
    • Principal Investigator: Chih-Yuan Lee, MD, PhD
  • Taoyuan District, Taiwan, 333
    • Recruiting
    • Chang Gung Medical Foundation Hospital
    • Principal Investigator: Huang-Yu Yang, MD, PhD
• United States
  • Arizona
    • Phoenix, Arizona, United States, 85054
      • Recruiting
      • Mayo Clinic in Arizona
      • Principal Investigator: Girish Mour, M.B.B.S.
  • Illinois
    • Chicago, Illinois, United States, 60611
      • Recruiting
      • Northwestern Memorial Hospital
      • Principal Investigator: M. Javeed Ansari, MD, MRCP
  • Minnesota
    • Rochester, Minnesota, United States, 55905
      • Recruiting
      • Mayo Clinic in Minnesota
      • Principal Investigator: Nikolaos Skartsis, M.D., Ph.D.

Participation Criteria

Eligibility Criteria

• Ages Eligible for Study: Adult; Older Adult
• Accepts Healthy Volunteers: No

Description

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.

Study Plan

How is the study designed?

Design Details

• Primary Purpose: Prevention
• Allocation: Randomized
• Interventional Model: Parallel Assignment
• Masking: None (Open Label)

Number of Arms

3

Arms and Interventions

Participant Group / Arm	Intervention / Treatment
Active Comparator: Arm 1: Standard of Care (SOC); Arm 1: SOC-Subjects randomized to Arm 1 will be followed on the prescribed 2-drug SOC immunosuppression throughout the trial. The study allowed SOC regimen is tacrolimus + sirolimus or everolimus.	Drug: Arm 1: SOC (mTOR + CNI); Subjects randomized to Arm 1 will remain on standard dual-immunosuppression therapy (CNI and mTOR) throughout the trial.; Other Names: sirolimus or everolimus + tacrolimus
Experimental: Arm 2A: TRACT/MONO mTOR; Arm 2: TRACT/MONO- At the beginning of the trial, subjects randomized to Arm 2 will be maintained on the prescribed 2-drug SOC immunosuppression and have a single infusion of expanded Tregs (TRK-001) at Day +53 to +67 following living donor kidney transplantation. At Month 3 post-transplant, Arm 2 TRACT/MONO subjects will be further randomized to either Arm 2A: TRACT/MONO mTOR or Arm 2B: TRACT/MONO CNI. Subjects randomized to Arm 2A: TRACT/MONO mTOR who have a normal biopsy and no de novo donor specific antibodies at Month 3 will begin weaning of tacrolimus and will remain on a 1-drug regimen with either everolimus or sirolimus until the end of the trial.	Biological: Arm 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.; Other Names: TRK-001 + sirolimus or everolimus
Experimental: Arm 2B: TRACT/MONO CNI; Arm 2: TRACT/MONO- At the beginning of the trial, subjects randomized to Arm 2 will be maintained on the prescribed 2-drug SOC immunosuppression and have a single infusion of expanded Tregs (TRK-001) at Day +53 to +67 following living donor kidney transplantation. At Month 3 post-transplant, Arm 2 TRACT/MONO subjects will be further randomized to either Arm 2A: TRACT/MONO mTOR or Arm 2B: TRACT/MONO CNI. Subjects randomized to Arm 2B: TRACT/MONO CNI who have a normal biopsy and no de novo donor specific antibodies at Month 3 will begin weaning of the mTOR medication and will remain on a 1-drug regimen with low dose tacrolimus until the end of the trial.	Biological: Arm 2B: TRACT/MONO CNI; 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.; Other Names: TRK-001 + tacrolimus

What is the study measuring?

Primary Outcome Measures

Outcome Measure	Measure Description	Time Frame
Development of de novo donor-specific antibodies	A primary outcome measure for this study is to evaluate a composite endpoint of immunologic events against the allograft, where a failure is defined as patient-experienced immunologic events including the development of de novo donor-specific antibodies.	Month 12 Post-transplant
Biopsy-proven acute rejection	A primary outcome measure for this study is to evaluate a composite endpoint of immunologic events against the allograft, where a failure is defined as patient-experienced immunologic events including biopsy-proven acute rejection.	Month 12 Post-transplant
Biopsy-proven subclinical rejection	A primary outcome measure for this study is to evaluate a composite endpoint of immunologic events against the allograft, where a failure is defined as patient-experienced immunologic events including biopsy-proven subclinical rejection.	Month 12 Post-transplant
Development of significant (2+) interstitial fibrosis/tubular atrophy	A primary outcome measure for this study is to evaluate a composite endpoint of immunologic events against the allograft, where a failure is defined as patient-experienced immunologic events including the development of significant (2+) interstitial fibrosis/tubular atrophy.	Month 12 Post-transplant
Successful taper to monotherapy (Arm 2)	A primary outcome measure for this study is to evaluate the ability for Arm 2 subjects to successfully taper to monotherapy by one-year post-transplant.	Month 12 Post-transplant

Secondary Outcome Measures

Outcome Measure	Measure Description	Time Frame
Successful maintenance of monotherapy (Arm 2)	A secondary outcome measure for this study is to evaluate the ability for Arm 2 subjects to successfully maintain monotherapy through two-years post-transplant.	Month 24 Post-transplant
Development of de novo donor-specific antibodies	A secondary outcome measure for this study is to evaluate overall and composite component-specific time to immunologic failure where a failure is defined as patient-experienced immunologic events including the development of de novo donor-specific antibodies.	To Month 60 Post-transplant
Biopsy-proven acute rejection	A secondary outcome measure for this study is to evaluate overall and composite component-specific time to immunologic failure where a failure is defined as patient-experienced immunologic events including biopsy-proven acute rejection.	To Month 60 Post-transplant
Biopsy-proven subclinical rejection	A secondary outcome measure for this study is to evaluate overall and composite component-specific time to immunologic failure where a failure is defined as patient-experienced immunologic events including biopsy-proven subclinical rejection.	To Month 60 Post-transplant
Development of significant (2+) interstitial fibrosis/tubular atrophy	A secondary outcome measure for this study is to evaluate overall and composite component-specific time to immunologic failure where a failure is defined as patient-experienced immunologic events including the development of significant (2+) interstitial fibrosis/tubular atrophy.	To Month 60 Post-transplant
Graft loss	A secondary outcome measure for the study is the incidence and timing of clinical outcomes, including graft loss. Graft loss is defined as 56 consecutive days of hemodialysis or re-transplantation.	To Month 60 Post-transplant
Malignancy	A secondary outcome measure for the study is the incidence and timing of clinical outcomes, including malignancy.	To Month 60 Post-transplant
Infections	A secondary outcome measure for the study is the incidence and timing of clinical outcomes, including infections (bacterial, viral, fungal).	To Month 60 Post-transplant
Metabolic anomalies	A secondary outcome measure for the study is the incidence and timing of clinical outcomes, including metabolic anomalies (e.g., diabetes mellitus, metabolic syndrome, hyperthyroidism, hypothyroidism).	To Month 60 Post-transplant
Biopsy-proven acute rejection	A secondary outcome measure for the study is to evaluate the incidence and timing of a composite endpoint of immunologic events against the allograft, where a failure is defined as patient-experienced immunologic event, including biopsy-proven acute rejection.	To Month 24 Post-transplant
Graft loss	A secondary outcome measure for the study is to evaluate the incidence and timing of a composite endpoint of immunologic events against the allograft, where a failure is defined as patient-experienced immunologic event, including graft loss. Graft loss is defined as 56 consecutive days of hemodialysis or re-transplantation.	To Month 24 Post-transplant
Death (all cause)	A secondary outcome measure for the study is to evaluate the incidence and timing of a composite endpoint of immunologic events against the allograft, where a failure is defined as patient- experienced immunologic event, including all cause death.	To Month 24 Post-transplant
Quality of Life Measures by using KDQOL-SF	The KDQOL-SF is an assessment tool designed for individuals with kidney disease to measure the impact of kidney disease and its treatment on a patient's quality of life.	To Month 60 Post-transplant
Quality of Life Measures by using EQ-5D-5L	The EQ-5D-5L is a standardized measurement tool to evaluate health status. The questionnaire has a descriptive section and a visual analog scale.	To Month 60 Post-transplant
Safety- Adverse Events	Incidence of adverse events	To Month 60 Post-transplant

Collaborators and Investigators

• Sponsor: Singulera Therapeutics Inc.
• Collaborators: Taiwan Bio Therapeutics Inc.

Study record dates

Study Major Dates

• Study Start (Actual): June 13, 2025
• Primary Completion (Estimated): December 1, 2027
• Study Completion (Estimated): December 1, 2031

Study Registration Dates

• First Submitted: July 26, 2024
• First Submitted That Met QC Criteria: August 11, 2024
• First Posted (Actual): August 13, 2024

Study Record Updates

• Last Update Posted (Actual): April 27, 2026
• Last Update Submitted That Met QC Criteria: April 22, 2026
• Last Verified: April 1, 2026

More Information

Terms related to this study

• Keywords: End stage renal disease; Kidney Transplantation; Tregs; Graft Rejection; Autologous cell therapy; Regulatory T cells; Treg adoptive cell transfer (TRACT); Prevention of organ transplant rejection; Reduced immunosuppression
• Additional Relevant MeSH Terms: Urogenital Diseases; Pathologic Processes; Male Urogenital Diseases; Kidney Diseases; Urologic Diseases; Female Urogenital Diseases; Female Urogenital Diseases and Pregnancy Complications; Chronic Disease; Disease Attributes; Renal Insufficiency; Renal Insufficiency, Chronic; Pathological Conditions, Signs and Symptoms; Kidney Failure, Chronic; Organic Chemicals; Macrolides; Lactones; Everolimus; Sirolimus; Tacrolimus; cni protein, Drosophila
• Other Study ID Numbers: TRACT-KD-101

Plan for Individual participant data (IPD)

• Plan to Share Individual Participant Data (IPD)?: UNDECIDED

Drug and device information, study documents

• Studies a U.S. FDA-regulated drug product: Yes
• Studies a U.S. FDA-regulated device product: No