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. Issue 4 (6th December 2013)

• Record Type: Journal Article
• Authors: Ambery, P.; Donner, T. W.; Biswas, N.; Donaldson, J.; Parkin, J.; Dayan, C. M.
• Is Part Of: Diabetic medicine. Volume 31:Issue 4(2014:Apr.)
• Page Start: 399
• Page End: 402
• Publication Date: 2013-12-06
• Subjects: Diabetes -- Periodicals; 616.462
• DOI: 10.1111/dme.12361
• Languages: English
• ISSNs: 0742-3071

Abstract

<abstract abstract-type="main" id="dme12361-abs-0001"> <title>Abstract</title> <sec id="dme12361-sec-0001" sec-type="section"> <title>Aims</title> <p>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).</p> </sec> <sec id="dme12361-sec-0002" sec-type="section"> <title>Methods</title> <p>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.</p> </sec> <sec id="dme12361-sec-0003" sec-type="section"> <title>Results</title> <p>Change from baseline C‐peptide was not significantly different [∆ = –0.09 nmol/l (95% CI –0.17 to 0; <italic>P </italic>= 0.051)]. No differential C‐peptide effect was seen for otelixizumab in adolescents and more adverse events were reported.</p> </sec> <sec id="dme12361-sec-0004" sec-type="section"> <title>Conclusions</title> <p>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.</p> <p> <bold>Clinical Trials Registry No:</bold> NCT 00763451</p> </sec> </abstract>