Trial of Otelixizumab for Adolescents and Adults With Newly Diagnosed Type 1 Diabetes Mellitus (Autoimmune): DEFEND-2

Durable-Response Therapy Evaluation For Early- or New-Onset Type 1 Diabetes

DEFEND-2 is a Phase 3 confirmatory study for the Phase 3 DEFEND-1 study. The study objective is to find out if an 8-day series of otelixizumab infusions leads to greater improvement in insulin secretion as compared with placebo. Insulin secretion will be assessed using mixed meal-stimulated C-peptide.

Subjects will be assigned to receive either otelixizumab or placebo at a ratio of 2:1 (2/3 otelixizumab, 1/3 placebo). These study agents will be administered as an addition to insulin, diet, and other standard of care treatments.

The following visits are required:

• Screening Visits: 2 to 3 appointments will be conducted to determine eligibility. At 2 of these visits participants will drink a liquid meal and have blood tests done over the post-meal period. Participants will also be required to wear a continuous glucose monitor for a short period of time.
• Dosing Visits: 8 outpatient visits on consecutive days, each lasting about 2-4 hours.
• Follow-up Visits: weekly for the first month, then every 2 weeks for 3 months, followed by monthly visits through 1 year. There will be 3 visits in the second year.
• The total duration of the study is 2 years.
• Glucose test strips and glucose monitors will be provided to participants for the duration of the study. Frequent glycemic monitoring will occur through lab testing and blood glucose self-monitoring to help facilitate tight glycemic control in all subjects. Subjects will be asked to intermittently record their insulin doses using a telephone or web based system and continuous glucose monitoring will be performed every 6 months.

Inclusion Criteria:

• Ages 12-17
• Diagnosis of diabetes mellitus, consistent with ADA criteria
• No more than 90 days between diagnosis and administration of study compounds
• Requires insulin for type 1 diabetes mellitus, or has required insulin at some time between diagnosis and administration of study compounds. In Canada, has to be using insulin at the time of dosing.
• Stimulated C-peptide level greater than 0.20 nmol/L and less than or equal to 3.50 nmol/L
• Positive for one or more of the autoantibodies typically associated with T1DM: antibody to glutamic acid decarboxylase (anti-GAD); antibody to protein tyrosine phosphatase-like protein (anti-IA-2); zinc transporter autoantibodies (ZNT8); insulin autoantibodies (IAA). A subject who is positive for insulin autoantibodies (IAA) and negative for the other autoantibodies will only be eligible if the subject has used insulin for less than 7 days total.

Exclusion Criteria:

•Other, significant medical conditions based on the study doctor's evaluation