306-OR: Modified Approach for Improved Islet Allotransplantation into Prevascularized Sernova Cell Pouch Device: Preliminary Results of the Phase I/II Clinical Trial at University of Chicago

Abstract

Introduction: After the pilot study demonstrated safety of the Sernova Cell Pouch (SCP) , we modified islet transplantation (ITx) conditions for improved engraftment in the SCP. Methods: SCPs were implanted in the abdominal anterior rectus sheath of 7 patients with T1DM and problematic hypoglycemia. Immunosuppression was initiated 1 month after SCP implantation and a marginal dose ITx of highly purified islets 1 month later. A second ITx was scheduled 6 to 12 months later. Sentinel SCPs are explanted for histopathology 3 months after ITx. Graft function is monitored by blood glucose (BG) , C-peptide and insulin usage. Results: Seven patients underwent 27 study-related surgeries with wound infection in 2 (7.4%) patients after SCP implantation. One patient discontinued following device excision and the second patient’s infection resolved. SCPs are well tolerated with implant durations exceeding 35 months. Three patients received two ITx into SCPs, resulting in new, measurable islet function documented by detectable levels of stimulated C-peptide. A supplemental, single intraportal ITx was sufficient for the first two patients to achieve ongoing insulin independence and freedom from severe hypoglycemic events for over 22 and 4 months with HbA1c 5.4 and 5.5%, respectively. The third patient discontinued insulin support 2 months after a single supplemental intraportal ITx and presented normal blood glucose control during MMTT on post-transplant day 75 with fasting and peak values of 97 and 142mg/ml, respectively, serum C-peptide of 1. and 3.39 ng/ml and HbA1c of 5.8%. The other three patients on study are progressing as planned. All have received SCP implants and at least one ITx. Conclusion: ITx with SCP demonstrates long-term safety and efficacy in an early subset of trial patients. Ongoing results for transplanted SCPs have led to procedural adjustments to further optimize clinical outcomes. Disclosure P.J.Bachul: None. L.H.Philipson: Advisory Panel; Nevro Corp., Research Support; Dompé, Novo Nordisk, provention BIo. R.Barth: None. J.Fung: n/a. P.Witkowski: Advisory Panel; Sernova, Corp., Vertex Pharmaceuticals Incorporated. A.Perez-gutierrez: None. B.Juengel: None. K.Golab: None. L.Basto: None. L.Perea: None. L.Wang: None. M.Tibudan: None. C.Thomas: None.