Ladarixin, an inhibitor of the interleukin‐8 receptors CXCR1 and CXCR2, in new‐onset type 1 diabetes: A multicentre, randomized, double‐blind, placebo‐controlled trial

Aim To evaluate the ability of ladarixin (LDX, 400 mg twice-daily for three cycles of 14 days on/14 days off), an inhibitor of the CXCR1/2 chemokine receptors, to maintain C-peptide production in adult patients with newly diagnosed type 1 diabetes. Materials and Methods A double-blind, randomized (2:1), placebo-controlled study was conducted in 45 males and 31 females (aged 18-46 years) within 100 days of the first insulin administration. The primary endpoint was the area under the curve (AUC) for C-peptide in response to a 2-hour mixed meal tolerance test (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 less than 7.0% without SHE and maintaining a residual beta cell function. Follow-up assessments were scheduled at weeks 13 +/- 1, 26 +/- 2 and 52 +/- 2. Results In total, 26/26 (100%, placebo) and 49/50 (98%, LDX) patients completed week 13. The 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 = .122). At week 26, the proportion of patients with HbA1c less than 7.0% without SHE was transiently higher in the LDX group (81% vs. 54%, P = .024). Otherwise, no significant secondary endpoint differences were noted. Transient metabolic benefit was seen at week 26 in favour of the LDX group in the prespecified subpopulation with fasting C-peptide less than the median value at screening. Conclusions In newly diagnosed patients with type 1 diabetes, short-term LDX treatment had no appreciable effect on preserving residual beta cell function.