Proact: A Study of REACT in Subjects With Type 2 Diabetes Mellitus and Chronic Kidney Disease

A Phase 3 Randomized Controlled Study of Renal Autologous Cell Therapy (REACT) in Subjects With Type 2 Diabetes and Chronic Kidney Disease (REGEN-006)

The purpose of this study is to assess the safety and efficacy of up to 2 REACT/rilparencel injections in participants with T2DM and CKD.

Randomized multi-center, blinded intervention, two cohort, study whereby eligible participants will be randomized 1:1, prior to kidney biopsy, to 1 of 2 cohorts. Cohort 1 participants will have scripted sham procedures that mimic the sounds and activities of biopsy, injection procedures, and evaluations as a control for Cohort 2 participants who will have a kidney biopsy followed with a rilparencel injection into the biopsied kidney, then, approximately 12 weeks later with a second rilparencel injection into the contralateral kidney. All participants will be followed until the global trial end date is declared.

Key Inclusion Criteria:

1. The participant is male or female, 30 to 80 years of age on the date of informed consent.
2. Documented diagnosis of type 2 diabetes mellitus (T2DM) and chronic kidney disease
3. Serum glycosylated hemoglobin (HbA1c) of 9.5% or lower at Screening.
4. Systolic blood pressure of ≤ 140 mm Hg and diastolic blood pressure of ≤ 90 mm Hg at Screening.
5. All participants should be strongly considered for treatment with sodium-glucose cotransporter 2 inhibitor (SGLT2i).
6. On a clinically relevant, maximally tolerated dose of an angiotensin converting-enzyme inhibitor (ACEI) OR an angiotensin receptor blocker (ARB), unless not tolerated or contraindicated.
7. Participant agrees and is able to refrain from using therapies that may increase bleeding risk for the specified pre-procedure and post-procedure durations.
8. Participant is willing and able to cooperate with all aspects of the protocol and provide signed informed consent.

Key Exclusion Criteria:

1. The participant has a history of type 1 diabetes mellitus.
2. The participant has a history of renal transplantation or other organ transplantation
3. The participant has any other known underlying cause of kidney disease
4. History of acute kidney injury or major surgery within 3 months prior to the Screening Visit.
5. Myocardial infarction, unstable angina, revascularization procedure or cerebrovascular accident within 12 weeks before randomization, or a revascularization procedure is planned during the trial.
6. Current or history of heart failure of New York Heart Association (NYHA) Class IV cardiac disease.
7. History of exclusionary malignancy within the past 3 years prior to Screening
8. Documented clinically significant liver disease, including acute or chronic hepatitis B or hepatitis C.
9. Known infection with HIV, active syphilis, or other unresolved active genitourinary infection, or active tuberculosis requiring treatment at Screening.
10. Immunocompromised condition or condition requiring chronic immunosuppressive agents, including individuals treated for chronic glomerulonephritis, within 3 months of signing ICF.
11. Has had a recent bleeding event or a known bleeding disorder(s) or increased risk of either thromboembolism or bleeding.
12. Kidney imaging reveals contraindications for undergoing biopsy or rilparencel injection
13. Maintained on any anticoagulant agents
14. History of anaphylactic or severe systemic reaction(s) to blood transfusions, Dextran 40, or bovine products, or contraindication(s) to above products due to medical reasons or participant preference.
15. History of severe systemic reaction(s) or any contraindication to local anesthetics or sedatives.
16. Use of an investigational product or device within 12 weeks prior to Randomization or previous treatment with rilparencel.
17. Participant's health status would, in the judgement of the Investigator, be jeopardized by participating in the study.