Autologous Neo-Kidney Augment (NKA) in Patients With Type 2 Diabetes and Chronic Kidney Disease (CKD)

A Phase II, Open-Label Safety and Efficacy Study of an Autologous Neo-Kidney Augment (NKA) in Patients With Type 2 Diabetes and Chronic Kidney Disease (RMTX-CL001). NKA is made from expanded autologous selected renal cells (SRC) obtained from the patient's kidney biopsy. All enrolled subjects will be treated with up to two injections of NKA at least 6 months apart.

A Phase II, Open-Label Safety and Efficacy Study of an Autologous Neo-Kidney Augment (NKA) in Patients With Type 2 Diabetes and Chronic Kidney Disease (RMTX-CL001). This is a Multi-center, prospective, open-label, single-group study. NKA is made from expanded autologous selected renal cells (SRC) obtained from the patient's kidney biopsy. To manufacture NKA, kidney biopsy tissue from each enrolled patient will be sent to RegenMedTX, LLC, where renal cells will be expanded and SRC selected. SRC will be formulated in a gelatin based hydrogel at a concentration of 100 x 106 cells/mL, packaged in a 10 mL syringe, and shipped to the clinical site for use. All enrolled subjects will be treated with up to two injections of NKA at least 6 months apart. Up to 30 subjects undergoing NKA injection will be enrolled into the study. Patients who have received a single injection of NKA under previous research protocols may enroll in this clinical trial to receive a single additional implantation. Patients who have never received an NKA injection may enroll in this clinical trial for up to a total of two (2) NKA injections, temporally spaced at least 6 months apart. All biopsies are to be taken from a single kidney, and all NKA injections are to be given into the kidney that was biopsied.

Patients who complete screening procedures satisfying all I/E criteria will be enrolled into the study immediately prior to the injection. Patients who do not meet all criteria before injection will be considered screen failures. Once a patient has been injected, the patient will have completed treatment and every effort should be made to ensure the patient completes all follow-up visits. Injection dates for the first 3 patients receiving their second NKA injection will be staggered by a minimum of 3 week intervals to allow for assessment of acute adverse events and other safety parameters by a Data Safety Monitoring Board (DSMB). At the completion of the follow-up visits, patients will continue in a long-term observational follow-up period. Patients will be followed for a total of 36 months following the last NKA injection under this protocol, whether the first or second injection.

Eligibility Criteria:
Inclusion Criteria:

1. Males and females, age 30 - 70 years.
2. Patients with type 2 diabetes mellitus (T2DM).
3. Patients with diabetic nephropathy as the underlying cause of their renal disease.
4. If not previously implanted with NKA, CKD defined as a GFR of 20 - 50 mL/min/1.73m2 inclusive. Ifs previously treated with a single NKA implantation, eGFR 15 to 60 mL/min may also enroll.
5. Microalbuminuria (urinary albumin-creatinine ratio (UACR) ≥ 30 mg/g or urine albumin excretion ≥ 30 mg/day on 24 hour urine collection) not explained by an alternative diagnosis.
6. Systolic blood pressure between 105 and 140 mmHg (inclusive) and diastolic blood pressure ≤90 mmHg.
7. Treatment with angiotensin inhibitor (ACEI) or angiotensin blocker (ARB) initiated at least 8 weeks prior to enrollment. Treatment must be stable for the 6 weeks prior to implant. Patients intolerant of ACEI or ARBs may be included if stable BP is within acceptable limits.
8. Minimum of 2 measurements of eGFR or serum creatinine (sCr) at least 3 months apart and within 12 months before Screening, to define the rate of progression of CKD.
9. Willing and able to refrain from use of non-steroidal drugs (NSAIDs) (including aspirin), clopidogrel, fish oil, dipyridamole, prasugrel, or platelet inhibitors for 7 days before and after both biopsy and implant.
10. Willing and able to cooperate with all aspects of the study.
11. Willing and able to give signed informed consent.

Exclusion Criteria:

1. Type 1 diabetes mellitus (DM).
2. History of renal transplant.
3. HbA1c \> 10% at Screening.
4. Hemoglobin levels \< 9 g/dL prior to implant.
5. Known allergy to kanamycin or structurally similar aminoglycoside antibiotics.
6. Abnormal coagulation status as measured by partial thromboplastin time (APTT), international normalized ratio (INR), and/or platelet count at Screening.
7. Not a good candidate for the implantation procedure (based on the assessment of the investigator or operator) including patients who are morbidly obese, have BMI \> 45, have excessive fat surrounding the kidney, or who are otherwise at risk for serious complications.
8. Clinically significant infection requiring parenteral antibiotics within 6 weeks of implantation.
9. Patients with small kidneys (average size \< 9 cm) or only one kidney, as assessed by MRI or renal US within 1 year of screening.
10. Patients with acute kidney injury or a rapid decline in renal function within 3 months prior to implantation.
11. Patients with renal tumors, polycystic kidney disease, renal cysts or other anatomic abnormalities that would interfere with implantation procedure (e.g., cysts in the pathway of the injection for implantation), hydronephrosis, skin infection over proposed implantation sites, or evidence of a urinary tract infection.
12. Female subjects who are pregnant, lactating (breast feeding) or planning a pregnancy during the course of the study, or who are of child bearing potential and not using a highly effective method of birth control (including sexual abstinence). Subjects must be willing to continue birth control methods throughout the course of the study.
13. History of cancer within the past 3 years (excluding non-melanoma skin cancer and carcinoma in situ of the cervix).
14. Life expectancy of less than 2 years.
15. Any contraindication or known anaphylactic or severe systemic reaction to either human blood products or materials of animal (bovine, porcine) origin or anesthetic agents.
16. Positive for Human Immunodeficiency Virus (HIV), Hepatitis B Virus (HBV), or Hepatitis C Virus (HCV) assessed at the Screening Visit.
17. Subjects requiring treatment for tuberculosis (TB) in the past 3 years.
18. Immunocompromised subjects or patients receiving systemic immunosuppressive agents (including patients treated for chronic glomerulonephritis) within 3 months of implantation.
19. Subjects with uncontrolled diabetes (defined as metabolically unstable by the PI), or with incapacitating cardiac and/or pulmonary disorders.
20. History of active alcohol and/or drug abuse that in the investigator's assessment would impair the subject's ability to comply with the protocol.
21. Patients with elevated transaminases (ALT or AST \> 3.0 x ULN) at Screening.
22. Patients with bleeding disorders that would, in the opinion of the Investigator, interfere with the performance of study procedures; patients taking coumarins (e.g. Warfarin) or other anticoagulants (e.g. enoxaparin or direct thrombin inhibitors).
23. Any circumstance in which the investigator deems participation in the study is not in the subject's best interest.
24. Use of any investigational product within 3 months of the implantation without receiving prior written consent of the Medical Monitor.