REgulatory T Cell Therapy to Achieve Immunosuppression REduction

NCT06552169 | Recruiting Phase 2 DMC FDA Drug

• 1 other identifier: TRACT-KD-101
• Study Type: interventional
• Target: 34
• Locations: 2 countries
• Sites: 7

Brief 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.

Conditions

Kidney Transplantation

Keywords

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

Outcome Measures

Primary Outcomes (5)

• 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 Outcomes (15)

• Successful maintenance of monotherapy (Arm 2)

  Month 24 Post-transplant

• Development of de novo donor-specific antibodies

  To Month 60 Post-transplant

• Biopsy-proven acute rejection

  To Month 60 Post-transplant

• Biopsy-proven subclinical rejection

  To Month 60 Post-transplant

• Development of significant (2+) interstitial fibrosis/tubular atrophy

  To Month 60 Post-transplant

Study Arms (3)

Arm 1: Standard of Care (SOC)

ACTIVE COMPARATOR

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)

Arm 2A: TRACT/MONO mTOR

EXPERIMENTAL

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

Arm 2B: TRACT/MONO CNI

EXPERIMENTAL

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

Interventions

Arm 1: SOC (mTOR + CNI) DRUG

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

Also known as: sirolimus or everolimus + tacrolimus

Arm 1: Standard of Care (SOC)

Arm 2A: TRACT/MONO mTOR BIOLOGICAL

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.

Also known as: TRK-001 + sirolimus or everolimus

Arm 2A: TRACT/MONO mTOR

Arm 2B: TRACT/MONO CNI BIOLOGICAL

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.

Also known as: TRK-001 + tacrolimus

Arm 2B: TRACT/MONO CNI

Eligibility Criteria

• Age: 18 Years - 65 Years
• Sex: all
• Healthy Volunteers: No
• Age Groups: Adult (18-64), Older Adult (65+)

You may qualify if:

• 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.

You may not qualify if:

• 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.

Sponsors & Collaborators

• Singulera Therapeutics Inc.: lead
• Taiwan Bio Therapeutics Inc.: collaborator

Study Sites (7)

Mayo Clinic in Arizona

Phoenix, Arizona, 85054, United States

RECRUITING

Northwestern Memorial Hospital

Chicago, Illinois, 60611, United States

RECRUITING

Mayo Clinic in Minnesota

Rochester, Minnesota, 55905, United States

RECRUITING

Taichung Veterans General Hospital

Taichung, 407219, Taiwan

RECRUITING

National Cheng Kung University Hospital

Tainan, 704, Taiwan

NOT YET RECRUITING

National Taiwan University Hospital

Taipei, 100229, Taiwan

RECRUITING

Chang Gung Medical Foundation Hospital

Taoyuan District, 333, Taiwan

RECRUITING

MeSH Terms

Conditions

Kidney Failure, Chronic

Interventions

cni protein, Drosophila; Sirolimus; Everolimus; Tacrolimus

Condition Hierarchy (Ancestors)

Renal Insufficiency, Chronic; Renal Insufficiency; Kidney Diseases; Urologic Diseases; Female Urogenital Diseases; Female Urogenital Diseases and Pregnancy Complications; Urogenital Diseases; Male Urogenital Diseases; Chronic Disease; Disease Attributes; Pathologic Processes; Pathological Conditions, Signs and Symptoms

Intervention Hierarchy (Ancestors)

Macrolides; Lactones; Organic Chemicals

Central Study Contacts

Susan B Murray

CONTACT

+1-312-219-4670; susan.murray@singulera-tx.com

Erwin Teng

CONTACT

+886-931-392700; erwin.teng@twbio-thera.com

Study Design

• Study Type: interventional
• Phase: phase 2
• Allocation: RANDOMIZED
• Masking: NONE
• Purpose: PREVENTION
• Intervention Model: PARALLEL
• Sponsor Type: INDUSTRY
• Responsible Party: SPONSOR

Study Record Dates

• First Submitted: July 26, 2024
• First Posted: August 13, 2024
• Study Start: June 13, 2025
• Primary Completion (Estimated): December 1, 2027
• Study Completion (Estimated): December 1, 2031
• Last Updated: April 27, 2026

Record last verified: 2026-04

Locations

TW (4); US (3)