Multicenter, Phase 1/2 Pilot Study of Safety and Efficacy Assessment of Tegoprubart and Calcineurin Inhibitors- Free Immunosuppression Therapy for Pancreatic Islet Transplantation in Patients With T1DM and Chronic Kidney Disease
Single arm- subject treated with Tegoprubart and everolimus. The purpose of this research is to gather information on the safety and effectiveness of investigational regimen containing 2 experimental components: * An investigational drug called Tegoprubart and * Human pancreatic islet cells Both Tegoprubart and human pancreatic islet cells are considered investigational because they are not approved for use in the United States by the Food and Drug Administration (FDA). Participation in this research will last about 5 years. Assess safety, tolerability, and efficacy of transplanted islet cells and immunomodulation with Tegoprubart in combination with anti-thymocyte globulin (ATG), etanercept and with everolimus in adults with brittle T1D and chronic kidney disease (stage 2-3a).
• Subjects 18-70 years of age.
• A diagnosis of T1D ≥5 years with onset of disease at \<40 years of age.
• Ability to provide informed consent.
• Able to comply with study procedures, including the requirement to utilize continuous glucose monitoring (CGM).
• Involvement in appropriate diabetes management in accordance with the standard of care, using an insulin pump or multiple daily injection (MDI) insulin therapy and, unable to achieve acceptable metabolic control because of the occurrence of unexplained SHEs.
• HbA1c level 6.5% to 9.5% inclusive.
• Absence of stimulated C-peptide (\<0.3 ng/mL) in response to a mixed- meal tolerance test (MMTT).
• Chronic kidney disease stage 1, 2 or 3a
• Impaired awareness of hypoglycemia based on:
‣ IAH (HypoA-Q Impaired Awareness Subscale ≥12) and at least one level 3 SHE during the last year or
⁃ IAH and time-below-range (\<70 mg/dl) ≥4% with level 2 hypoglycemia (\<54 mg/dl) ≥1% (in Diabetes Care, Jan 2025, Patrick Choudhary) or
⁃ Clarke Score \>4 or
⁃ Recurrent SHE defined by two or more level 3 SHEs in the year prior to screening
⁃ If female, must be surgically sterile or postmenopausal. Women of childbearing potential may be enrolled if a pregnancy test is negative at screening/baseline. Women of childbearing potential and men with partners that are of childbearing potential must agree to use 2 forms of highly effective methods of contraception from Screening, throughout the study, and while receiving immunosuppressive therapy for the functioning graft after the conclusion of the study. Contraception use must continue for 90 days after the last administration of the study drug (see Appendix 5). Male participants must refrain from donating sperm for the duration of the study and agree to not donate sperm for 90 days after last administration of the study drug.