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Efficacy and safety of low‐dose otelixizumab anti‐ CD 3 monoclonal antibody in preserving C‐peptide secretion in adolescent type 1 diabetes: DEFEND ‐2, a randomized, placebo‐controlled, double‐blind, multi‐centre study
Author(s) -
Ambery P.,
Donner T. W.,
Biswas N.,
Donaldson J.,
Parkin J.,
Dayan C. M.
Publication year - 2014
Publication title -
diabetic medicine
Language(s) - English
Resource type - Journals
SCImago Journal Rank - 1.474
H-Index - 145
eISSN - 1464-5491
pISSN - 0742-3071
DOI - 10.1111/dme.12361
Subject(s) - medicine , placebo , tolerability , randomized controlled trial , adverse effect , clinical endpoint , clinical trial , gastroenterology , pathology , alternative medicine
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