RENAL12: Can Renal Autologous Cell Therapy (REACT) Delay Dialysis and Renal Transplantation in Chronic Kidney Disease with Type 2 Diabetes? The proact 1 and 2 Phase 3 Trial Design

Introduction: REACT is being developed to preserve renal function and delay or prevent ESRD. REACT is composed of bioactive selected renal cells (SRCs), isolated from a participant’s kidney, which participate in kidney repair and regeneration. Preclinical studies have demonstrated that SRCs injected directly into the kidney cortex produced a regenerative response improving kidney function and structure. Description of therapy REACT is derived from a standard kidney biopsy in an outpatient setting. SRCs are expanded ex vivo, cryopreserved, and shipped to the clinical site approximately 12 weeks later. REACT is percutaneously injected into the kidney cortex utilizing CT guidance in each kidney, 3 months apart. Participants proact 1 and proact will enroll 1200 pts from ~150 sites in the US and ~25 other countries with up to 60 months of follow-up, aged 30-80 years with type 2 diabetes who have an eGFR of 20-50 mL/min/1.73 m2, and UACR 300-5000 mg/g. Eligible participants will be randomized 1:1 to REACT or sham biopsy/injection in a single blind manner. Standard-of-care therapies including RAASi, SGLT2i, and MRAs are given per local guidance. Study Endpoints Time-to-event primary composite endpoint from first injection to the earliest of >≥40% eGFR decline, eGFR < 15 mL/min/1.73m2 sustained for 30 days, initiation of chronic dialysis, kidney transplantation, cardiovascular or renal death. Conclusion:proact 1 and 2 are global phase 3 randomized controlled trials evaluating the safety and efficacy of REACT on major kidney disease endpoints, among participants with type 2 diabetes and Stage 3a/4 CKD. REACT, a novel cell therapy comprised of SRCs, has the potential to directly preserve kidney function with a goal to prevent kidney failure.