Regulatory T Cell Therapy for Kidney Transplants

(RETIRE Trial)

Recruiting at 4 trial locations

Overseen By Charlie Sun

Age: 18+

Sex: Any

Trial Phase: Phase 2

Sponsor: Tract Therapeutics, Inc.

Must be taking: Immunosuppressants

Must not be taking: Anticoagulants, Anti-T cell therapy

Disqualifiers: Active infection, Cardiovascular disease, Malignancy, others

No Placebo Group All trial participants will receive the active study treatment (no placebo)

Prior Safety Data This treatment has passed at least one previous human trial

Compensation: Varies

Number of Visits: Unknown

Duration: 3 months

34 Participants Needed

Trial Summary

What is the purpose of this trial?

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.

Will I have to stop taking my current medications?

The trial does not specify if you need to stop taking your current medications. However, if you are on chronic immunosuppressive medication for an underlying renal disease, you may not be eligible to participate.

What data supports the effectiveness of the treatment TRK-001 for kidney transplants?

Research shows that regulatory T cell (Treg) therapy, similar to TRK-001, has been effective in animal studies and early human trials for improving kidney transplant outcomes by reducing the need for immunosuppressive drugs and preventing chronic immune injury. ^{1 2 3 4 5}

Is regulatory T cell therapy safe for kidney transplant patients?

Regulatory T cell therapy has been shown to be safe in initial clinical trials for kidney transplant patients, with no serious side effects, infections, or rejection events reported up to two years after treatment. ^{1 2 3 6 7}

How is the treatment TRK-001 different from other treatments for kidney transplants?

TRK-001 is unique because it uses the patient's own regulatory T cells (Tregs) to help reduce the need for traditional immunosuppressive drugs, which often have harmful side effects. This approach aims to promote long-term acceptance of the kidney transplant by enhancing the body's natural ability to prevent immune rejection. ^{1 2 3 4 7}

Eligibility Criteria

This trial is for living donor kidney transplant recipients. Participants must be eligible for a transplant and willing to follow the study procedures. Those with certain medical conditions, previous organ transplants, or who are unable to reduce immunosuppression drugs may not qualify.

Inclusion Criteria

My blood type matches the donor's as required.

I have not had an organ transplant.

Subjects must understand and provide written informed consent prior to any trial procedure

Exclusion Criteria

I am allergic or react badly to certain medications.

Major psychiatric illness or noncompliance with medical therapy

Positive flow cytometric crossmatch

Timeline

Screening

Participants are screened for eligibility to participate in the trial

2-4 weeks

Treatment

Participants receive standard of care immunosuppression or TRK-001 infusion with initial SOC immunosuppression

3 months

Multiple visits for monitoring and infusion

Weaning to Monotherapy

Arm 2 subjects begin reducing immunosuppression to a 1-drug regimen if criteria are met

9 months

Follow-up

Participants are monitored for safety and effectiveness after treatment

24 months

Long-term Surveillance

Participants are monitored for long-term outcomes including malignancy, metabolic anomalies, and quality of life

36 months

Treatment Details

Interventions

• TRK-001

Trial Overview The trial tests if TRK-001 regulatory T cells can prevent organ rejection post-transplant. Patients will either receive standard care or standard care plus TRK-001, with some potentially reducing their medication after three months.

Participant Groups

Group I: Arm 2B: TRACT/MONO CNI Experimental Treatment 1 Intervention

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.

Group II: Arm 2A: TRACT/MONO mTOR Experimental Treatment 1 Intervention

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.

Group III: Arm 1: Standard of Care (SOC) Active Control 1 Intervention

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.

Who Is Running the Clinical Trial?

Tract Therapeutics, Inc.

Lead Sponsor

Trials

1

Recruited

30+

Taiwan Bio Therapeutics Inc.

Industry Sponsor

Trials

4

Recruited

130+

PhiBio Therapeutics Inc

Industry Sponsor

Trials

1

Recruited

30+

Findings from Research

Tr1 cell-enriched lymphocytes can be generated from patients on dialysis awaiting kidney transplantation, but using total peripheral blood mononuclear cells (PBMCs) resulted in a low anergic phenotype, making them unsuitable for clinical use.

In contrast, using purified CD4(+) T cells from these patients produced a highly anergic donor-specific product, indicating that tailoring the generation protocol to the patients' immune profiles can enhance the efficacy of this therapy.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Generation of Donor-specific T Regulatory Type 1 Cells From Patients on Dialysis for Cell Therapy After Kidney Transplantation. Petrelli, A., Tresoldi, E., Mfarrej, BG., et al.[2015]

References

1. United States pubmed.ncbi.nlm.nih.gov

Generation of Donor-specific T Regulatory Type 1 Cells From Patients on Dialysis for Cell Therapy After Kidney Transplantation. [2015]

2. Netherlands pubmed.ncbi.nlm.nih.gov

Isolation, expansion and functional assessment of CD4+CD25+FoxP3+ regulatory T cells and Tr1 cells from uremic patients awaiting kidney transplantation. [2011]

3. England pubmed.ncbi.nlm.nih.gov

Transplantation Without Overimmunosuppression (TWO) study protocol: a phase 2b randomised controlled single-centre trial of regulatory T cell therapy to facilitate immunosuppression reduction in living donor kidney transplant recipients. [2022]

4. Switzerland pubmed.ncbi.nlm.nih.gov

Antigen Specific Regulatory T Cells in Kidney Transplantation and Other Tolerance Settings. [2021]

5. Turkey pubmed.ncbi.nlm.nih.gov

T-regulatory cells in chronic rejection versus stable grafts. [2015]

6. England pubmed.ncbi.nlm.nih.gov

A Phase I Clinical Trial with Ex Vivo Expanded Recipient Regulatory T cells in Living Donor Kidney Transplants. [2019]

7. United States pubmed.ncbi.nlm.nih.gov

Cell Therapy in Kidney Transplantation: Focus on Regulatory T Cells. [2021]