#3696 THE PROACT 2 PHASE 3 STUDY DESIGN: A RANDOMIZED CONTROLLED STUDY OF REACT IN PARTICIPANTS WITH TYPE 2 DIABETES AND CHRONIC KIDNEY DISEASE

Abstract

Abstract Background and Aims The global burden of chronic kidney disease (CKD) is estimated at 850 million people worldwide, with diabetic kidney disease (DKD) being the main cause. Existing medical therapies may delay the deterioration of kidney function; however, many patients continue to progress to kidney failure. REACT (Renal Autologous Cell Therapy), a cell-based advanced therapy, is being developed to decrease the risk of CKD progression. REACT is composed of selected renal cells (SRC), isolated from a participant's own kidney, which are involved in the process of kidney repair and regeneration. Preclinical studies in multiple animal models of DKD have demonstrated that SRC injected directly into the kidney cortex produced a regenerative response improving overall kidney function and histology. Encouraging early clinical results from phase 2 studies with REACT resulted in RMAT (Regenerative Medicine Advanced Therapy) designation by the Food and Drug Administration in the USA. Method Description of therapy - REACT is derived from the participant's kidney tissue obtained by percutaneous biopsy in an outpatient setting. Renal cells are culture expanded ex vivo, and SRC are isolated. SRC are cryopreserved at a concentration of 100 × 106 cells/mL and shipped to the clinical site approximately 12 weeks after the biopsy. REACT will be percutaneously reinjected by specially trained interventional proceduralists utilizing CT guidance and a non-cutting 25-gauge needle inserted into the kidney cortex. A single REACT dose will be injected into each kidney, approximately 3 months apart. Participants - The study will enroll 600 participants from approximately 250 global sites (including 38 sites in the EU)) with up to 60 months of follow-up. Patients aged 30-80 years with type 2 diabetes who have an estimated glomerular filtration rate (eGFR) of 20-50 mL/min/1.73 m2, and urine albumin-to-creatinine ratio (UACR) 300-5000 mg/g will be eligible. Participants will be randomized 1:1 to REACT or sham biopsy/injection in a single blind manner. Standard-of care therapies including renin angiotensin system inhibitors and sodium glucose cotransporter inhibitors may be given as per local guidance. Results Study Endpoints - The primary endpoint for proact 2 is the time from first injection to the earliest of ≥40% eGFR decline, eGFR < 15 mL/min/1.73m2 sustained for 30 days, initiation of chronic dialysis or kidney transplantation, or cardiovascular or renal death. proact 2 is an endpoint driven trial with 80% power to detect a hazard ratio of 0.6 for the primary outcome. Key secondary outcomes will include time to these individual components as well as annualized change in eGFR and change from baseline in UACR. Conclusion proact 2 is a global Phase 3 randomized controlled trial that will evaluate the safety and efficacy of REACT on major kidney disease endpoints, among participants with type 2 diabetes and moderate-severe CKD. This trial is part of a comprehensive phase 3 development program with an estimated start date of June 2023. REACT, a novel autologous cell therapy composed of SRC, has the potential to directly improve kidney function with a goal to prevent kidney failure.