Investigating the safety, tolerability and immune modulation of a novel treatment for stage 3 type one diabetes and help preserve remaining beta cells.

ASITI-201 will be administered subcutaneously by a research nurse in a single-dose escalation and multiple dose, dose-ranging parallel group study in two parts. Part A: Three dose levels will be assessed in a single dose escalation study design Participants will be assigned to a dose level and s.c. site administration will be monitored. Dose Level 1 (4 active, 2 placebo) Dose Level 2 (4 active, 2 placebo) Dose Level 3 (4 active, 2 placebo) At each dose level two sentinel participants (1 active, 1 placebo) will be initially randomised. Dose Level 1 • Single 0.1 mL subcutaneous injection of ASITI-201 containing 0.5 µg/mL calcitriol and 13.8µg/mL proinsulin peptide, or approximately 0.7 ng/kg calcitriol and 0.020 µg/kg proinsulin peptide (4 patients); • Single 0.1 mL subcutaneous injection of placebo containing sterile 0.9% saline for injection (2 patients). Dose Level 2 • Single 0.2 mL subcutaneous injection of ASITI-201 containing 0.5 µg/mL calcitriol and 13.8 µg/mL proinsulin peptide, or approximately 1.4 ng/kg calcitriol and 0.04 µg/kg proinsulin peptide (4 patients); • Single 0.2 mL subcutaneous injection of placebo containing sterile 0.9% saline for injection (2 patients). Dose Level 3 • Single between 0.05 mL to 1 mL subcutaneous injection of ASITI-201 containing 0.5 µg/mL calcitriol and 13.8 µg/mL proinsulin peptide, or approximately 0.4 to 7.1 ng/kg calcitriol and 0.01 to 0.20 µg/kg proinsulin peptide (4 adult patients); • Single equivalent volume subcutaneous injection of placebo containing sterile 0.9% saline for injection (2 patients) Part B: Study participants will receive three administrations of IMP at weekly intervals (Day 1, Day 8, Day 15). There will be two patient cohorts and each of these groups will receive a different dose level of ASITI-201. Six patients in each cohort will receive subcutaneous ASITI-201 and 3 patients will receive placebo. Final dose selection will be based upon results from Parts A of the study with pre-defined selection criteria by the SMC and Dose Monitoring Team. Dose Group 1 (6 active, 3 placebo) Dose Group 2 (6 active, 3 placebo). The 2 dose levels to be tested in Part B will be based upon review of results in Part A. Subcutaneous site injection will be monitored.