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.
OBJECTIVE
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.
GlaxoSmithKline, Uxbridge, UK.
P
P
Ambery
T W
TW
Donner
N
N
Biswas
J
J
Donaldson
J
J
Parkin
C M
CM
Dayan
D000293:Adolescent; D000328:Adult; D061067:Antibodies, Monoclonal, Humanized / Q000627:therapeutic use*; D002096:C-Peptide / Q000378:metabolism*; D002648:Child; D003922:Diabetes Mellitus, Type 1 / Q000188:drug therapy*; D004311:Double-Blind Method; D057239:Early Termination of Clinical Trials; D005260:Female; D006801:Humans; D008297:Male; D016896:Treatment Outcome
D061067:Antibodies, Monoclonal, Humanized; D002096:C-Peptide; C550701:otelixizumab