Efficacy and safety of low-dose otelixizumab anti-CD3 monoclonal antibody in preserving C-peptide secretion in adolescent type 1 diabetes: DEFEND-2, a randomized, placebo-controlled, double-blind, multi-centre study

Aims PhaseIII DEFEND-2 investigated whether otelixizumab (3.1mg over 8days) preserved C-peptide secretion in patients with new-onset Type1 diabetes, focusing on adolescents (12-17years). Methods One hundred and seventy-nine patients (54 adolescents) were randomized to otelixizumab or placebo. The primary endpoint was change in 2-h mixed-meal-stimulated C-peptide area under the curve at month12. Enrolment was suspended in April 2011 following negative efficacy results from DEFEND-1. DEFEND-2 terminated early after 12months' efficacy and safety follow-up. Results Change from baseline C-peptide was not significantly different [ increment =-0.09nmol/l (95%CI -0.17 to 0; P=0.051)]. No differential C-peptide effect was seen for otelixizumab in adolescents and more adverse events were reported. Conclusions Efficacy and tolerability of otelixizumab was similar to DEFEND-1. The 3.1-mg dose was non-efficacious in adults and adolescents. Further investigation of the mechanism of action seen at higher doses and therapeutic window is required. Clinical Trials Registry No: NCT00763451