Regulatory T Cell Therapy for Kidney Transplants

(RETIRE Trial)

Recruiting at 5 trial locations

Overseen By Erwin Teng

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

What You Need to Know Before You Apply

What is the purpose of this trial?

This trial tests a new therapy, TRK-001 (a regulatory T cell therapy), to determine its effectiveness for individuals who have received a kidney from a living donor. The goal is to assess whether TRK-001 can safely reduce the need for other medications typically required to prevent kidney rejection. Participants will be divided into two groups: one will continue with the usual medications, while the other will receive TRK-001 and may gradually reduce their medication load. This trial may suit those with an upcoming living donor kidney transplant who have not previously undergone a transplant. Researchers will monitor participants for five years to track any issues and evaluate the treatment's effectiveness. As a Phase 2 trial, this research focuses on measuring the treatment's effectiveness in an initial, smaller group of people.

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.

Is there any evidence suggesting that this trial's treatments are likely to be safe?

Research shows that TRK-001 is generally safe for individuals who have undergone a kidney transplant. In earlier studies, patients receiving TRK-001 experienced no major issues during the infusion. No serious side effects related to the treatment were reported during or after the infusion. These patients also maintained good kidney function over the long term, with no signs of organ rejection two years post-transplant.

Although researchers continue to study this treatment, these results suggest that TRK-001 is well-tolerated. However, like any medical treatment, risks may still exist. The current trial aims to explore these risks further and ensure the treatment's safety and effectiveness. ^{1 2 3 4 5}

Why are researchers excited about this trial's treatment?

Unlike the standard of care for kidney transplants, which typically involves a combination of immunosuppressive drugs like tacrolimus and sirolimus or everolimus, TRK-001 offers an innovative approach by using expanded regulatory T cells (Tregs). Researchers are excited because TRK-001 targets the immune system more precisely, potentially reducing the risk of organ rejection while minimizing the side effects associated with broad-spectrum immunosuppression. Additionally, the treatment allows for a more personalized regimen, as patients in the experimental arms can transition to a single-drug protocol, possibly enhancing long-term transplant success and quality of life.

What evidence suggests that TRK-001 could be an effective treatment for preventing kidney transplant rejection?

Research shows that a treatment called TRK-001, which participants in this trial may receive, could benefit kidney transplant patients. Studies have found that this treatment can improve long-term kidney function and reduce the need for many other immune-suppressing medications. This therapy calms the body's immune response to the new kidney, helping to prevent rejection. Earlier trials demonstrated that this treatment is safe and well-tolerated by patients. Overall, TRK-001 may help patients rely less on traditional drugs while maintaining the health of their transplanted kidney. ^{1 5 6 7 8}

Are You a Good Fit for This Trial?

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

Positive flow cytometric crossmatch

Pregnant or nursing mothers

Major psychiatric illness or noncompliance with medical therapy

Timeline for a Trial Participant

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

What Are the Treatments Tested in This Trial?

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.

How Is the Trial Designed?

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+

Singulera Therapeutics Inc.

Lead Sponsor

Taiwan Bio Therapeutics Inc.

Industry Sponsor

Trials

4

Recruited

130+

PhiBio Therapeutics Inc

Industry Sponsor

Trials

1

Recruited

30+

Published Research Related to This Trial

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]

Citations

1. nature.com nature.com/articles/s41598-018-25574-7

A Phase I Clinical Trial with Ex Vivo Expanded Recipient ... Overall, these results demonstrated that infusion up to 5 × 109 polyclonally expanded recipient Tregs into renal transplant patients is safe.

2. pmc.ncbi.nlm.nih.gov pmc.ncbi.nlm.nih.gov/articles/PMC12189525/

Regulatory T Cell in Kidney Transplant - PubMed Central - NIH Treg therapy holds significant promise in kidney transplantation by reducing reliance on long-term immunosuppressive drugs and promoting immune tolerance. ...

3. sciencedirect.com sciencedirect.com/science/article/pii/S2666634024004550

Article Regulatory T cell therapy is associated with distinct ... In the current study, the authors show that renal transplant patients receiving Treg therapy had excellent long-term kidney function with no ...

4. frontiersin.org frontiersin.org/journals/immunology/articles/10.3389/fimmu.2021.717594/full

Antigen Specific Regulatory T Cells in Kidney ... Clinically, polyclonal human Tregs have been shown to be safe to infuse in kidney transplant patients in the multi-centre One Study (18) and the safety of this ...

5. clinicaltrials.gov clinicaltrials.gov/study/NCT02088931

Study Details | NCT02088931 | Treg Adoptive Therapy for ... The purpose of this study is to test the safety of the experimental therapy of a single infusion of Regulatory T cells (Tregs).

6. clinicaltrials.gov clinicaltrials.gov/study/NCT06552169

Study Details | NCT06552169 | REgulatory T Cell Therapy ... ... safety and efficacy of administering expanded regulatory T cells (TRK-001) to prevent allograft rejection in living donor renal transplant recipients.

7. pmc.ncbi.nlm.nih.gov pmc.ncbi.nlm.nih.gov/articles/PMC7613119/

Feasibility, long-term safety, and immune monitoring of ... Nineteen patients received standard immunosuppression (Reference cohort). Primary outcomes were rejection-free and patient survival. Patient and transplant ...

8. amjtransplant.org amjtransplant.org/article/S1600-6135(25)01881-7/fulltext

Treg Therapy to Minimize Immunosuppression (IS) in ... TRK-001 was shown to be safe with no infusion-related SAEs and no biopsy-confirmed rejection 2 years post-Tx. Importantly, an increase in Tregs in peripheral ...