Aims: Phase III DEFEND-2 investigated whether otelixizumab (3.1 mg over 8 days) preserved C-peptide secretion in patients with new-onset Type 1 diabetes, focusing on adolescents (12-17 years).
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 month 12. Enrolment was suspended in April 2011 following negative efficacy results from DEFEND-1. DEFEND-2 terminated early after 12 months' efficacy and safety follow-up.
Results: Change from baseline C-peptide was not significantly different [∆ = -0.09 nmol/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: NCT 00763451.
Trial registration: ClinicalTrials.gov NCT00763451.
© 2013 The Authors. Diabetic Medicine © 2013 Diabetes UK.