An Exploratory Study of Itolizumab on the Preservation of Beta Cell Function in Adults with Recent-Onset Type 1 Diabetes

Abstract

We conducted a phase I-IIa, randomized, monocentric, double-blind, placebo-controlled clinical trial to evaluate the safety and impact of the combination treatment of Itolizumab and insulin on preserving beta cell function in adults with recent-onset type 1 diabetes. Twelve patients were randomly assigned to three treatment groups, each receiving a different Itolizumab dose (0.4/0.8/1.6 mg/kg body weight, respectively) and a placebo group. All patients received concomitant intensive multiple-dose insulin therapy. Endogenous insulin secretion was assessed by the measurement of C-peptide during the mixed-meal tolerance test. No serious adverse events were reported. No changes in the total daily insulin doses, glycated hemoglobin levels, and stimulated C-peptide were observed between the Itolizumab and placebo groups at 52 weeks. A significant decrease in stimulated C-peptide was observed during the follow-up period (p = 0.012). One subject treated with 1.6 mg of Itolizumab showed a marked increase in the levels of stimulated C-peptide three years after completion of the trial. Taken together, this is the first study to demonstrate that combination treatment with Itolizumab and insulin is safe in humans and does not affect the residual function of beta cells up to 52 weeks. The findings from our study show preliminary evidence that high doses of Itolizumab could potentially arrest the loss of beta cell function in the long term. Further studies with a longer follow-up and larger numbers of patients are envisaged to assess the effect with high dose Itolizumab.

Keywords: C-peptide; Itolizumab; human trials; insulin; type 1 diabetes.

Figure 1

Description of eligible, enrolled, and participating patients in the study. T1D: newly diagnosed T1D patients; anti-HBs: hepatitis B surface antibody; MMTT: mixed-meal tolerance test. The 52-week study period was divided into three stages. During the first stage (week 0–8), Itolizumab was administered through the intravenous route, once a week (dose 0.4 and 0.8 mg/kg/day), or every two weeks (dose 1.6 mg/kg/day). During the second stage (week 9–24), Itolizumab was administered through the intravenous route every four weeks. At the third stage, all patients received insulin up to 28 weeks after the last Itolizumab administration (week 25–52).

Figure 2

Area under the curve (AUC-CP) for mixed-meal tolerance test (MMTT)-stimulated C-peptide in five patients at three years after completion of the trial.