Phase 3 Trial of Human Islet-after-Kidney Transplantation in Type 1 Diabetes.

Allogeneic islet transplantation offers a minimally invasive option for β-cell replacement in the treatment of type 1 diabetes (T1D). The CIT consortium trial of purified human pancreatic islets (PHPI) in patients with T1D after kidney transplantation (CIT06), a National Institutes of Health (NIH)-sponsored phase 3, prospective, open-label, single-arm pivotal trial of PHPI, was conducted in 24 patients with impaired awareness of hypoglycemia while receiving intensive insulin therapy (IIT). PHPI were manufactured using standardized processes. PHPI transplantation was effective with 62.5% of patients achieving the primary endpoint of freedom from severe hypoglycemic events (SHE) and HbA1c≤6.5% or reduced by ≥ 1 percentage point at 1-year post transplant. Median HbA1c declined from 8.1% before to 6.0% at 1-year and 6.3% at 2- and 3-years following transplantation (p<0.001 for all vs. baseline), with related improvements in hypoglycemia awareness and glucose variability. The improved metabolic control was associated with better health-related and diabetes-related quality-of-life. The procedure was safe and kidney allograft function remained stable after 3-years. These results add to evidence establishing allogeneic islet transplantation as a safe and effective treatment for patients with T1D and unstable glucose control despite intensive insulin treatment, supporting the indication for PHPI in the post renal transplant setting.