Novel Autologous Dendritic Cell Therapy AVT001 for Type 1 Diabetes.

Background: CD8+ T regulatory (Treg) cells that recognize the nonclassical class 1b molecule Qa-1/human leukocyte antigen E (Q/E CD8+ Treg cells) are important in maintaining self-tolerance. We sought to investigate the role that these T cells play in type 1 diabetes (T1D) pathogenesis and whether an intervention targeting this mechanism may delay T1D progression.

Methods: We conducted a phase 1/2, randomized, double-blind, placebo-controlled trial of the autologous dendritic cell therapy AVT001 that included participants at least 16 years of age, within 1 year of T1D diagnosis, and with ex vivo evidence of a defect in Q/E CD8+ Treg function. Patients were randomly assigned in a 2:1 ratio to AVT001 or placebo, which was administered in three monthly intravenous infusions. The primary end point was safety; efficacy end points included changes from baseline in C-peptide area under the curve (AUC) during a 4-hour mixed meal, hemoglobin A1c (HbA1c), and insulin dose.

Results: Sixteen patients received AVT001, and nine received placebo. Similar rates and severity of adverse events were observed in both groups. None of the patients in the AVT001 group had serious adverse events through visit day 360. Compared with placebo, treatment with ATV001 was associated with less decline from baseline log-transformed C-peptide AUC (nmol/l), with the treatment effect between AVT001 and placebo at day 150 of 0.09 (95% confidence interval [CI], 0.03 to 0.15) and at day 360 of 0.10 (95% CI, 0.04 to 0.15). No clear differences in change in HbA1c and insulin dose from baseline were observed between groups. Estimated treatment effects of AVT001 versus placebo at day 360 were -0.17% (95% CI, -0.60 to 0.26%) for HbA1c and -0.06 U/kg/day (95% CI, -0.14 to 0.02) for daily insulin dose.

Conclusions: In this phase 1/2 trial, AVT001 did not result in dose-limiting adverse events. Potential signals of efficacy observed here warrant further evaluation in a fully powered trial. (Funded by Avotres Inc. and the Division of Diabetes, Endocrinology, and Metabolic Diseases; ClinicalTrials.gov number, NCT03895996.).