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

P. Ambery, T. W. Donner, N. Biswas, J. Donaldson, J. Parkin, C. M. Dayan

Research output: Contribution to journalArticlepeer-review

Abstract

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 [{increment} = -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.

Original languageEnglish (US)
Pages (from-to)399-402
Number of pages4
JournalDiabetic Medicine
Volume31
Issue number4
DOIs
StatePublished - 2014

ASJC Scopus subject areas

  • Internal Medicine
  • Endocrinology, Diabetes and Metabolism
  • Endocrinology

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