A Randomized Clinical Trial of Kidney Autologous Cell Therapy in Diabetic Kidney Disease

Background: Despite new treatments to delay disease progression in patients with diabetes and chronic kidney disease (CKD), many patients continue to lose kidney function and progress to kidney failure. Additional therapeutic strategies, perhaps targeting multiple deleterious pathways, are necessary to preserve kidney function in patients with advanced CKD. Methods: A multi-center, randomized, Phase 2 clinical trial (NCT05018416) assessed rilparencel (an autologous cell therapy composed of cells obtained by kidney biopsy), in participants with diabetes and estimated glomerular filtration rate (eGFR) 20 – 50 mL/min/1.73 m 2 . Participants were randomized 1:1 to two cohorts. Cohort 1 received two rilparencel injections percutaneously into the kidney cortex, three months apart, one in each kidney. Cohort 2 received one injection and a second injection only upon a sustained decline in eGFR or increase in urinary albumin creatinine ratio. Participants were followed up to 18 months after their last injection. The primary efficacy endpoint was change in eGFR slope from the pre- injection period to the period after the last injection. The primary safety endpoint was the percentage of participants with procedure or rilparencel-related treatment emergent adverse events (TEAEs). Results: Fifty-three participants were randomized and 49 received at least one injection. In Cohort 1, annual eGFR slope (mL/min/1.73 m 2 /year) in the pre-injection period was -5.84 (standard error [SE] 1.07) versus -1.27 (SE 1.36) in the period after the last injection (difference 4.57 (95% confidence interval [CI] 1.95 to 7.18). In Cohort 2, annual eGFR slope in the pre-injection period was -3.40 (SE 0.81) versus -1.71 (SE 1.04) in the period after the last injection (difference 1.70 [95% CI -0.24 to 3.63]). No interactions were observed across multiple pre-defined baseline subgroups. Of 87 injections, procedure-related TEAEs occurred in 16 participants and rilparencel-related TEAEs occurred in six participants. No product-related serious adverse events and no procedure- or product-related deaths were reported. Conclusions: Bilateral kidney injection of rilparencel may preserve kidney function with an acceptable safety profile. A multi-center, Phase 3, randomized, sham-controlled study is ongoing.