Abstract

Objective - This randomized, four-arm, placebo-controlled dose-ranging phase-2 trial was conducted to determine whether repeated subcutaneous injections of the altered peptide ligand, NBI-6024, designed to inhibit autoreactive T-cells, improves beta cell function in patients with recently diagnosed type 1 diabetes.

Research, Design and Methods - One hundred eighty-eight patients, aged 10-35 years with recently diagnosed type 1 diabetes were randomized for a treatment consisting in the subcutaneous administration of placebo or 1 mg, 0.5 mg or 0.1 mg of NBI-6024 at baseline, week 2 and 4 and then monthly until month 24. Fasting, peak and AUC C-peptide concentrations during a 2-hour mixed meal tolerance test were measured at 3-monthly intervals during treatment. Immune function parameters (islet antibodies, CD4 and CD( T cells) were also studied.

Results The mean peak C-peptide at 24 months after study entry showed no significant difference between the groups treated with 0.1 mg (0.59 pmol/mL), 0.5 mg (0.57 pmol/mL), and 1.0 mg NBI-6024 (0.48 pmol/mL), and the placebo group (0.54 pmol/mL). Fasting, stimulated peak and AUC C-peptide concentrations declined linearly in all groups by approximately 60% over the 24 month treatment period. The average daily insulin needs at month 24 values were also comparable between the 4 groups. No treatment related changes in islet antibodies and T cell numbers were observed.

Conclusions Treatment with altered peptide ligand NBI-6024 at repeated doses of 0.1, 0.5 or 1.0 mg did not improve or maintain beta cell function.