Ladarixin, an inhibitor of IL ‐8 receptors CXCR1 and CXCR2 , in new‐onset type 1 diabetes: a multicenter, randomized, double‐blind, placebo‐controlled trial

To evaluate the ability of ladarixin, an inhibitor of the CXCR1/2 chemokine receptors (LDX, 400 mg b.i.d for 3 cycles of 14 days on/14 days off) to maintain C-peptide production in adult patients with newly diagnosed type 1 diabetes.A double-blind, randomized (2:1), placebo-controlled study was conducted in 45 males and 31 females (18-46 years) within 100 days from the first insulin administration. Primary end-point was the area under the curve for C-peptide in response to a 2-hour MMTT [AUC(0-120 min) ] at week 13+1. Secondary endpoints included C-peptide AUC(15-120 min) , HbA1c , daily insulin requirement, severe hypoglycaemic events (SHE), the proportion of subjects achieving HbA1c <7.0% without SHE or maintaining a residual beta cell function. Follow-up assessments were scheduled at weeks 13+1, 26+2 and 52+2.26/26 (100%, placebo) and 49/50 (98%, LDX) patients completed week 13. Mean change from baseline to week 13 in C-peptide AUC(0-120 min) was -0.144±0.449 nmol/L with placebo and 0.003±.322 nmol/L with LDX. The difference was not significant (0.149 nmol/L, 95% CI -0.04 to 0.33; p=0.122). The proportion of patients with HbA1c <7.0% without SHE was transiently (week 26) higher in LDX group (81% vs 54%, p=0.024). Otherwise, no significant secondary endpoint differences were noted. Transient metabolic benefit was seen at week 26 in favour of LDX group in the pre-specified subpopulation with fasting C-peptide < median value at screening.In newly diagnosed patients with type 1 diabetes, short-term LDX treatment had no appreciable effect on preserving residual beta-cell function. This article is protected by copyright. All rights reserved.