#5734 RENAL AUTOLOGOUS CELL THERAPY (REACT™) FOR DIABETIC CHRONIC KIDNEY DISEASE: PHASE II TRIAL WITH BILATERAL CORTEX INJECTIONS AND RE-DOSING TRIGGERS

Abstract

Abstract Background and Aims Well-based therapies may repair diseased nephrons and stabilize and enhance kidney function to delay the onset of end-stage kidney disease and improve co-morbidities. REACT™ is a novel product formed of cryopreserved autologous homologous selected renal cells, undergoing phase III clinical trials for diabetic kidney disease (DKD). We describe an open label phase II study to evaluate how patients respond to REACT™ injections in both kidneys and a redosing trigger, as being evaluated in a Phase III blinded data trial (proact 1 & 2 trials). Method REGEN 007 is a multi-center Phase II, open label 1:1 randomized controlled trial enrolling up to 50 patients ages 30-80 years with DKD, who have an eGFR of 20 - 50 mL/min/1.73 m2. Each patient undergoes a percutaneous kidney biopsy and ex vivo culture expansion of their selected renal cells. Patients are then randomized to an arm where they receive two REACT™ injections, one in each kidney, three months apart if they meet inclusion criteria, or an arm with an initial single REACT™ dose in one kidney and a 2nd REACT™ dose in the contralateral kidney > 90 days apart, based on a sustained eGFR decline of ≥ 20%, and/or an increase in the urine albumin to creatinine ratio (UACR) from baseline of ≥ 30% and ≥ 30 mg/g. CT-guided bilateral percutaneous renal cortex injections of REACT™ are performed under conscious sedation. Trial design, inclusion and exclusion criteria can be found at the National Clinical Trial Registry (Trial number 05018416). Results Thirty-one of the targeted 50 participants have been enrolled with the following characteristics at screening: 64.0% males, 97.0% Non-Hispanic/Latino. Mean age 62.9 years, serum creatinine (sCr) 2.0 mg/dL ±0.50, Cystatin C 2.0 mg/L ±0.40, eGFR (sCr + Cystatin C) 31.2 ml/min/1.72m2 ±7.88, HgbA1C 7.4% ± 1.14, Hgb 12.9 g/dL ± 1.78, K+ 4.6 mEq/L ± 0.44, Bicarbonate 20.3 mEq/L ± 3.0, and a median UACR 662 mg/g [SD 705.8]. Percent baseline medications are: Angiotensin Converting Enzyme inhibitors 25.8, Angiotensin Converting Enzyme receptor Blockers 48.4, beta blockers 64.5, diuretics 64.4, glucose lowering agents 100, Sodium glucose Cotransporter 2 inhibitors 32.3, and platelet inhibitors 67.7. Efficacy endpoint is an eGFR slope improvement from first injection to 18 months after last injection. REACT™ and procedure related serious adverse events are expected to be commensurate with ongoing trials and standard of care Conclusion REACT™ cell-based therapy has the potential to effect nephron structure and function by stabilizing or improving DKD progression and its comorbidities. Current phase II and III trials are underway to determine efficacy, safety, renal function-dependent dosing, and time to treatment with bilateral kidney injections of REACT™.