Study to Evaluate the Safety and Efficacy of the GGTA1 KO Thymokidney in Patients With ESRD

NCT07224763 | Recruiting Phase 1 DMC FDA Drug

• 1 other identifier: GPT-KF-101
• Study Type: interventional
• Target: 50
• Locations: 1 country
• Sites: 1

Brief Summary

The purpose of this study is to evaluate the safety and efficacy of the GGTA1 KO Thymokidney in patients with end-stage renal disease (ESRD) who are either not eligible for conventional allogeneic kidney transplantation (Group 1) or are on an Organ Procurement and Transplantation Network (OPTN) kidney transplant waitlist, but are more likely to die or go untransplanted within 5 years than receive a kidney transplant (Group 2). The study consists of xenotransplantation followed by a 24-week Post-transplant Follow-up Period (Part A) to evaluate the efficacy and safety objectives followed by a Long-term Follow-up Period (Part B) to evaluate participant survival, GGTA1 KO Thymokidney survival, and screening for zoonotic infections. Part B will continue for the lifetime of the participant or for 52 weeks following nephrectomy, if required.

Conditions

ESRD (End-Stage Renal Disease); Kidney Transplantation; Xenotransplantation

Keywords

End-stage renal disease; ESRD; Xenotransplantation; GGTA1 KO Thymokidney

Outcome Measures

Primary Outcomes (16)

• Survival Rate of Patients with ESRD Receiving the GGTA1 KO Thymokidney at 24 Weeks Post Transplant

  Participant survival rate at 24 weeks post transplant.

  Day 0 (day of xenotransplantation) to 24 weeks post transplant

• Survival Rate of the GGTA1 KO Thymokidney at 24 Weeks Post Transplant

  GGTA1 KO Thymokidney survival rate at 24 weeks post transplant. GGTA1 KO Thymokidney failure is defined as GGTA1 KO Thymokidney nephrectomy.

  Day 0 (day of xenotransplantation) to 24 weeks post transplant

• Survival Time of Participants Receiving the GGTA1 KO Thymokidney

  Participant survival post transplant. Participant survival is defined as time from xenotransplantation to death for any cause.

  Day 0 (day of xenotransplantation) until death for any cause, assessed at least every 24 weeks after transplantation while the participant is alive, up to 50 years

• Survival Time of the GGTA1 KO Thymokidney (Overall Survival)

  Overall survival of the GGTA1 KO Thymokidney post transplant. Overall survival time of the GGTA1 KO Thymokidney is defined as time from xenotransplantation to GGTA1 KO Thymokidney nephrectomy or death, whichever occurs first.

  Day 0 (day of xenotransplantation) until start of chronic dialysis, nephrectomy, or death, whichever occurs first, assessed at least every 24 weeks after transplantation while the participant is alive and the thymokidney is functional, up to 50 years

• Survival Time of the GGTA1 KO Thymokidney (Death-censored Survival)

  Death-censored survival GGTA1 KO Thymokidney. Death-censored survival time of the GGTA1 KO Thymokidney is defined as time from xenotransplantation to GGTA1 KO Thymokidney nephrectomy censored for death.

  Day 0 (day of xenotransplantation) until start of chronic dialysis, nephrectomy, or death, whichever occurs first, assessed at least every 24 weeks after transplantation while the participant is alive and the thymokidney is functional, up to 50 years

• GGTA1 KO Thymokidney Function Post Transplant (Endogenous GFR)

  Endogenous measured GFR (24-hour urine creatinine clearance) at 24 weeks post transplant.

  At 24 weeks post transplant

• GGTA1 KO Thymokidney Function Post Transplant (Exogenous GFR)

  Exogenous measured GFR (nuclear medicine GFR) at 24 weeks post transplant.

  At 24 weeks post transplant

• GGTA1 KO Thymokidney Function Post Transplant (Proliferative Responsiveness)

  Proliferative responsiveness to source GGTA1 KO Pig versus third-party pig as measured by mixed lymphocyte reaction from baseline to 24 weeks post transplant.

  At 24 weeks post transplant

• Quality of Life in Participants Receiving the GGTA1 KO Thymokidney by EuroQol 5-Dimension 5-Level (EQ-5D-5L)

  Change in the EQ-5D-5L from baseline to 24 weeks post transplant. The EQ-5D-5L questionnaire assesses health-related quality of life across 5 categories (Mobility, Self-Care, Usual Activities, Pain/Discomfort, and Anxiety/Depression). Each category has 5 levels, ranging from 1 (no problems) to 5 (extreme problems or inability to perform the activity). Higher scores indicate a worse health outcome (more mobility issues, greater pain, more anxiety, etc).

  Baseline to 24 weeks post transplant

• Quality of Life in Participants Receiving the GGTA1 KO Thymokidney by Standardized Outcomes in Nephrology Life Participant (SONG-LP)

  Change in SONG-LP from baseline to 24 weeks post transplant. The SONG-LP assesses participation in different life activities over the past month. The minimum score (worst outcome) is 4 (if all responses are "1" - Never) and the maximum score (best outcome) is 20 (if all responses are "5" - Always). Higher scores indicate a better health outcome (greater ability to participate in activities).

  Baseline to 24 weeks post transplant

• Quality of Life in Participants Receiving the GGTA1 KO Thymokidney by Kidney Transplant Questionnaire (KTQ)

  Change in KTQ from baseline to 24 weeks post transplant. Each question in the KTQ is scored on a 1 to 7 scale with: 1 = worst outcome (eg, "A very great deal of trouble or distress" / "All of the time") and 7 = best outcome (eg, "No trouble or distress" / "None of the time"). Higher scores indicate a better outcome, meaning less distress, fewer symptoms, and better well-being.

  Baseline to 24 weeks post transplant

• Quality of Life in Participants Receiving the GGTA1 KO Thymokidney by Patient Global Impression of Change (PGI-C)

  PGI-C at 24 weeks post transplant. The PGI-C assesses a patient's perception of improvement or worsening over time. The minimum score (best outcome) is 1 ("Very Much Improved") and the maximum score (worst outcome) is 7 ("Very Much Worse"). Higher scores indicate a worse health outcome (greater worsening).

  At 24 weeks post transplant

• Incidence of Treatment-Emergent Adverse Events (Safety of the GGTA1 KO Thymokidney)

  Incidence of adverse events and serious adverse events; all-cause mortality.

  Baseline until last visit, assessed at least every 24 weeks after transplantation while the participant is alive and the thymokidney is functional, up to 50 years, or for 1 year after nephrectomy if required

• Incidence of Proteinuria

  Incidence of proteinuria from Day 0.

  Day 0 (day of xenotransplantation) until last visit, assessed at least every 24 weeks after transplantation while the participant is alive and the thymokidney is functional, up to 50 years, or for 1 year after nephrectomy if required

• Incidence of Zoonotic Infection

  Incidence of zoonotic infection from Day 0.

  Day 0 (day of xenotransplantation) until last visit, assessed at least every 24 weeks after transplantation while the participant is alive and the thymokidney is functional, up to 50 years, or for 1 year after nephrectomy if required

• Incidence of Opportunistic Infection

  Incidence of opportunistic infection from Day 0.

  Day 0 (day of xenotransplantation) until last visit, assessed at least every 24 weeks after transplantation while the participant is alive and the thymokidney is functional, up to 50 years, or for 1 year after nephrectomy if required

Study Arms (1)

GGTA1 KO Thymokidney

EXPERIMENTAL

Participants will receive GGTA1 KO Thymokidney

Biological: GGTA1 KO Thymokidney

Interventions

GGTA1 KO Thymokidney BIOLOGICAL

Porcine kidney containing an intentional genomic alteration and thymic tissue autograft for xenotransplantation

GGTA1 KO Thymokidney

Eligibility Criteria

• Age: 40 Years - 70 Years
• Sex: all
• Healthy Volunteers: No
• Age Groups: Adult (18-64), Older Adult (65+)

You may qualify if:

• Provide voluntarily informed consent to participate in the study and for lifetime follow-up.
• Have a diagnosis of ESRD at the time of informed consent.
• Hemodialysis dependent for a minimum of 6 months and has a functioning arterial-venous fistula/graft or permanent catheter at the time of informed consent.
• to 70 years of age at the time of informed consent, or 40 to \<50 years of age with a calculated panel reactive antibody (cPRA) of ≥99.9%.
• Evidence of thymic involution on chest computed tomography (CT) scan with a thymic region of interest score of ≤1.
• Live within 3 hours travel time of the xenotransplant center.
• Female participants must be postmenopausal or permanently sterilized (eg, hysterectomy, bilateral oophorectomy, or bilateral salpingectomy). Male participants must agree to the use of a highly effective method of birth control, if the possibility of conception exists.
• Negative xeno-crossmatch at Screening and pre-transplant.
• Estimated Post Transplant Survival Calculator score \>20%.(https://optn.transplant.hrsa.gov/data/allocation-calculators/epts-calculator/).
• Body mass index ≤35 kg/m2.
• Have completed or have initiated and plan to complete (meningococcal A, C, W, Y and meningococcal B vaccine series only) Centers for Disease Control and Prevention-recommended courses of age- and risk-factor-appropriate vaccinations.
• Seropositive (immunoglobulin G) for cytomegalovirus and Epstein-Barr virus.
• \. Ineligible for conventional allogeneic kidney transplantation due to medical reason(s) for any of the following:
• Ineligible for a living donor transplant.
• Ineligible for an OPTN kidney transplant waitlist (reason for ineligibility will be collected).

You may not qualify if:

• Need for multiple organ transplants.
• Severe medical co-morbidities including, but not limited to:
• Chronic liver disease.
• Advanced cardiovascular disease.
• Severe peripheral vascular disease that limits technical ability to transplant the GGTA1 KO Thymokidney.
• Severe neurologic diseases or conditions that would preclude meaningful recovery or informed consent.
• Oral steroid-dependent airway disorder or chronic pulmonary disease or requires chronic, intermittent, or continuous supplemental oxygen.
• Pulmonary hypertension.
• Uncontrolled diabetes or sequelae of diabetes mellitus including severe non-proliferative diabetic retinopathy.
• Severe neurogenic bladder that requires intermittent catheterization.
• ESRD due to hereditary or structural kidney disease.
• Active or recently treated malignancy at the time of informed consent.
• Non-renal cause of hematological disorders associated with anemia (eg, thalassemia and sickle disease).
• Cannot discontinue chronic anticoagulation therapy (low-dose daily aspirin is permissible).
• History of major psychiatric disorders with psychiatric hospitalization and/or suicidal ideation within 5 years of informed consent.

Sponsors & Collaborators

• United Therapeutics: lead

Study Sites (1)

New York University Langone Health

New York, New York, 10016, United States

RECRUITING

MeSH Terms

Conditions

Renal Insufficiency, Chronic; Kidney Failure, Chronic

Condition Hierarchy (Ancestors)

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

Central Study Contacts

United Therapeutics Global Medical Information

CONTACT

919-485-8350; clinicaltrials@unither.com

Study Design

• Study Type: interventional
• Phase: phase 1
• Allocation: NA
• Masking: NONE
• Purpose: TREATMENT
• Intervention Model: SINGLE GROUP
• Sponsor Type: INDUSTRY
• Responsible Party: SPONSOR

Model Details: This single group study will enroll participants simultaneously from either of 2 patient populations: (1) participants that are ineligible for conventional allogeneic kidney transplantation due to medical reason(s) or (2) participants on an OPTN kidney transplant waitlist that are more likely to die or go untransplanted within 5 years than receive a kidney transplant.

Study Record Dates

• First Submitted: November 4, 2025
• First Posted: November 5, 2025
• Study Start: March 1, 2026
• Primary Completion (Estimated): March 1, 2029
• Study Completion (Estimated): March 1, 2076
• Last Updated: December 2, 2025

Record last verified: 2025-11

Data Sharing

• IPD Sharing: Will not share

Locations

US (1)