Study to Evaluate the Safety and Efficacy of the 10 GE Xenokidney in Patients With ESRD

EXPAND: A Prospective Study to Evaluate the Safety and Efficacy of the 10 GE Xenokidney in Patients With End-stage Renal Disease (ESRD)

The purpose of this study is to evaluate the safety and efficacy of the 10 GE Xenokidney in patients with 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, 10 GE Xenokidney survival, and screening for zoonotic infections. Part B will continue for the lifetime of the participant.

This is a Phase 1/2/3, multicenter, open-label, safety and efficacy study of the 10 GE Xenokidney in patients with ESRD. The study will be comprised of the following:

• A Screening Period up to 52 weeks.
• Part A consists of the 10 GE Xenokidney transplantation followed by a 24-week Post-transplant Follow-up Period, including the evaluation of all study endpoints and safety assessments.
• Part B is a Long-term Follow-up Period that extends for the lifetime of participants who received the 10 GE Xenokidney, including but not limited to documentation of participant survival, 10 GE Xenokidney survival, and screening for zoonotic infections.

There will be 2 groups of participants enrolled in the study. Group 1 will be participants deemed ineligible for conventional allogeneic kidney transplantation due to medical reason(s). Group 2 will be participants on an OPTN kidney transplant waitlist but are more likely to die or go untransplanted within 5 years than receive a kidney transplant.

Inclusion Criteria for all Participants (Groups 1 and 2):

1. Provide voluntarily informed consent to participate in the study and for lifetime follow up.
2. Have a diagnosis of ESRD at the time of informed consent.
3. 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.
4. 50 to 70 years of age at the time of informed consent, or 40 to <50 years of a age with a calculated panel reactive antibody (cPRA) of ≥99.9%.
5. Live withing 3 hours travel time of the xenotransplant center.
6. 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.
7. Negative xeno-crossmatch at Screening and pre-transplant.
8. Estimated Post Transplant Survival Calculator score >20% (https://optn.transplant.hrsa.gov/data/allocation-calculators/epts-calculator/).
9. Body mass index ≤35 kg/m2.
10. 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.
11. Seropositive (immunoglobulin G) for cytomegalovirus and Epstein-Barr virus.

Additional Inclusion Criteria for Group 1:

1. Ineligible for conventional allogeneic kidney transplantation due to medical reason(s) for any of the following:

1. Ineligible for a living donor transplant.
2. Ineligible for an OPTN kidney transplant waitlist (reason for ineligibility will be collected).
3. Delisted from OPTN kidney transplant waitlist (reason for delisting will be collected).

Additional Inclusion Criteria for Group 2:

1. On an OPTN kidney transplant waitlist (active or inactive status).
2. No approved living kidney donors.
3. More likely to die or go untransplanted within 5 years than receive a kidney transplant as measured by the Kidney Transplant Decision Aid at the time of informed consent (select United States for "Choose your state" field and National average for "Choose your transplant program" field; https://www.srtr.org/tools/kidney-transplant-decision-aid/).

Exclusion Criteria (pertain to all participants in Groups 1 and 2):

1. Need for multiple organ transplants.

2. Severe medical co-morbidities including, but not limited to:

   1. Chronic liver disease.
   2. Advanced cardiovascular disease.
   3. Severe peripheral vascular disease that limits technical ability to transplant the 10 GE Xenokidney.
   4. Severe neurologic diseases or conditions that would preclude meaningful recovery or informed consent.
   5. Oral steroid-dependent airway disorder or chronic pulmonary disease or requires chronic, intermittent or continuous supplemental oxygen.
   6. Pulmonary hypertension.
   7. Uncontrolled diabetes or sequelae of diabetes mellitus including severe non-proliferative diabetic retinopathy.
   8. Severe neurogenic bladder that requires intermittent catheterization.

3. ESRD due to hereditary or structural kidney disease.

4. Active or recently treated malignancy at the time of informed consent.

5. Non-renal cause of hematological disorders associated with anemia (eg, thalassemia and sickle disease).

6. Cannot discontinue chronic anticoagulation therapy (low-dose daily aspirin is permissible).

7. History of major psychiatric disorders with a psychiatric hospitalization and/or suicidal ideation within 5 years of informed consent.

8. Being treated for active tuberculosis (TB), have received prophylaxis for positive FDA-approved interferon-gamma release assay, or test positive for TB by FDA-approved interferon-gamma release assay test during Screening.

9. Nucleic acid test (NAT) positive for hepatitis B virus and/or hepatitis C virus, hepatitis B surface antibody (anti HBs) titer <10 mIU/mL unless the participant is determined to be a nonresponder to hepatitis B vaccination (a nonresponder is defined as having an anti-HBs titer <10 mIU/mL after having completed both the standard vaccine series and a fourth booster dose and/or second standard vaccine series), and/or positive for human immunodeficiency virus (HIV; HIV-1 and HIV-2 antibody and/or NAT).

10. Not able to independently perform activities of daily life.

11. Have a history of medical noncompliance that may preclude adherence to the demands and requirements of xenotransplantation (eg, history of substance use disorder (SUD) within 1 year of informed consent, lack of social support, untreated psychological conditions).