TY - JOUR
T1 - Novel renal autologous cell therapy for type 2 diabetes mellitus chronic diabetic kidney disease
T2 - Clinical trial design
AU - Stavas, Joseph
AU - Gerber, David
AU - Coca, Steven G.
AU - Silva, Arnold L.
AU - Johns, Ashley
AU - Jain, Deepak
AU - Bertram, Tim
AU - De Ferris, Maria Díaz González
AU - Bakris, George
N1 - Publisher Copyright:
© 2022 The Author(s). Published by S. Karger AG, Basel.
PY - 2022
Y1 - 2022
N2 - Background: Cell therapies explore unmet clinical needs of patients with chronic kidney disease with the potential to alter the pathway toward end-stage kidney disease. We describe the design and baseline patient characteristics of a phase II multicenter clinical trial utilizing the novel renal autologous cell therapy (REACT), by direct kidney parenchymal injection via the percutaneous approach in adults with type 2 diabetic kidney disease (T2DKD), to delay or potentially avoid renal replacement therapy. Design: The study conducted a prospective, multicenter, randomized control, open-label, phase II clinical trial between an active treatment group (ATG) receiving REACT from the beginning of the trial and a contemporaneous deferred treatment group (DTG) receiving standard of care for 12 months before crossing over to receive REACT. Objectives: The objective of this study was to establish the safety and efficacy of 2 REACT injections with computed tomography guidance, into the renal cortex of patients with T2DKD administered 6 months apart, and to compare the longitudinal change in renal function between the ATG and the DTG. Setting: This was a multicenter study conducted in major US hospitals. Patients: We enrolled eighty-three adult patients with T2DKD, who have estimated glomerular filtration rates (eGFRs) between 20 and 50 mL/ min/1.73 m2. Methods: All patients undergo an image-guided percutaneous kidney biopsy to obtain epithelial phenotype selective renal cells isolated from the kidney tissue that is then expanded ex vivo over 4-6 weeks, resulting in the REACT biologic product. Patients are randomized 1:1 into the ATG or the DTG. Primary efficacy endpoints for both study groups include eGFR measurements at baseline and at 3-month intervals, through 24 months after the last REACT injection. Safety analyses include biopsy-related complications, REACT injection, and cellular-related adverse events. The study utilizes Good Clinical and Manufacturing Practices and a Data and Safety Monitoring Board. The sample size confers a statistical power of 80% to detect an eGFR change in the ATG compared to the DTG at 24 months with an α = 0.05. Limitations: Blinding cannot occur due to the intent to treat procedure, biopsy in both groups, and open trial design. Conclusion: This multicenter phase II randomized clinical trial is designed to determine the efficacy and safety of REACT in improving or stabilizing renal function among patients with T2DKD stages 3a-4.
AB - Background: Cell therapies explore unmet clinical needs of patients with chronic kidney disease with the potential to alter the pathway toward end-stage kidney disease. We describe the design and baseline patient characteristics of a phase II multicenter clinical trial utilizing the novel renal autologous cell therapy (REACT), by direct kidney parenchymal injection via the percutaneous approach in adults with type 2 diabetic kidney disease (T2DKD), to delay or potentially avoid renal replacement therapy. Design: The study conducted a prospective, multicenter, randomized control, open-label, phase II clinical trial between an active treatment group (ATG) receiving REACT from the beginning of the trial and a contemporaneous deferred treatment group (DTG) receiving standard of care for 12 months before crossing over to receive REACT. Objectives: The objective of this study was to establish the safety and efficacy of 2 REACT injections with computed tomography guidance, into the renal cortex of patients with T2DKD administered 6 months apart, and to compare the longitudinal change in renal function between the ATG and the DTG. Setting: This was a multicenter study conducted in major US hospitals. Patients: We enrolled eighty-three adult patients with T2DKD, who have estimated glomerular filtration rates (eGFRs) between 20 and 50 mL/ min/1.73 m2. Methods: All patients undergo an image-guided percutaneous kidney biopsy to obtain epithelial phenotype selective renal cells isolated from the kidney tissue that is then expanded ex vivo over 4-6 weeks, resulting in the REACT biologic product. Patients are randomized 1:1 into the ATG or the DTG. Primary efficacy endpoints for both study groups include eGFR measurements at baseline and at 3-month intervals, through 24 months after the last REACT injection. Safety analyses include biopsy-related complications, REACT injection, and cellular-related adverse events. The study utilizes Good Clinical and Manufacturing Practices and a Data and Safety Monitoring Board. The sample size confers a statistical power of 80% to detect an eGFR change in the ATG compared to the DTG at 24 months with an α = 0.05. Limitations: Blinding cannot occur due to the intent to treat procedure, biopsy in both groups, and open trial design. Conclusion: This multicenter phase II randomized clinical trial is designed to determine the efficacy and safety of REACT in improving or stabilizing renal function among patients with T2DKD stages 3a-4.
KW - Chronic kidney disease
KW - Diabetes-associated chronic kidney disease
KW - Diabetic nephropathy
KW - Neo-kidney augment
KW - Renal autologous cell therapy
KW - Renal outcomes
UR - http://www.scopus.com/inward/record.url?scp=85123987389&partnerID=8YFLogxK
U2 - 10.1159/000520231
DO - 10.1159/000520231
M3 - Article
C2 - 35034024
AN - SCOPUS:85123987389
SN - 0250-8095
VL - 53
SP - 50
EP - 58
JO - American Journal of Nephrology
JF - American Journal of Nephrology
IS - 1
ER -