Investigative Autologous Cell Trials in DKD

In Mississippi, a state with a disproportionately high prevalence of diabetic kidney disease (DKD), fewer than 10% of patients at high risk receive adequate testing. DKD is associated with adverse outcomes and costs and creates a significant burden on the state’s health care system.

During a poster session at the NKF Spring Clinical Meetings 2023, Davis Rippee and colleagues reported on two novel investigative autologous cell trials underway in Mississippi that have the potential to improve renal function and delay initiation of dialysis. The poster was titled Novel Renal Autologous Cell Therapy (REACT) for Chronic Kidney Disease With Diabetes (DKD): Investigative Trial Experience in Mississippi.

The two FDA-approved phase 2 trials are being conducted in Tupelo with Nephrology & Hypertension Associates, Ltd.,  and North Mississippi Medical Center. Participants with DKD and estimated glomerular filtration rate (eGFR) 20 to 50 mL/min/1.73 m² receive outpatient percutaneous kidney biopsy. The biopsy undergoes ex vivo culture expansion of selected renal cells that are formulated, returned to North Mississippi Medical Center, and reinjected into the kidney cortex with computed tomography guidance.

In the first trial (NCT02836574), 83 patients were randomized to receive either two injections 6 months apart into the biopsied kidney or standard of care for 12 months followed by two REACT injections in the same protocol. In the second trial (NCT05018416), 50 patients will be randomized into two treatment cohorts. Patients in cohort 1 will receive two REACT injections 3 months apart, one in each kidney. Patients in cohort 2 will receive one injection and following attainment of a predefined trigger (decline in eGFR of ≥20% or >30% decrease in urine albumin-creatinine ratio >30 mg/g) will receive a second injection in the contralateral kidney.

The follow-up period for both trials is 18 months post injections. Outcomes of interest include safety and change in kidney function as measured by eGFR.

Preliminary evidence has demonstrated preservation of kidney function as measured by eGFR compared with baseline (P=.015), and favorable impact on albuminuria. The potential to delay time to kidney failure supported FDA and European Medicines Agency regulatory allowance of two global phase 3 REACT trials.

“Cell-based therapies have the potential to effect nephron structure and function by preserving, stabilizing, or improving DKD progression and comorbidities. Current phase 2/3 trials will determine efficacy, safety, renal dosing, and time to treatment with bilateral kidney injections,” the researchers said.

Source: Rippee D, Wooldridge T, Dossabhoy N, et al. Novel renal autologous cell therapy (REACT) for chronic kidney disease with diabetes (DKD): investigative trial experience in Mississippi. Poster #247. Abstract of a poster presented at the National Kidney Foundation Spring Clinical Meetings 2023; April 11-15, 2023; Austin Texas.