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

This study has been completed.
Juvenile Diabetes Research Foundation
Information provided by (Responsible Party):
GlaxoSmithKline Identifier:
First received: May 11, 2010
Last updated: December 13, 2012
Last verified: December 2012

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.

Condition Intervention Phase
Diabetes Mellitus, Type 1
Biological: Otelixizumab
Biological: Placebo
Phase 3

Study Type: Interventional
Study Design: Allocation: Randomized
Endpoint Classification: Efficacy Study
Intervention Model: Parallel Assignment
Masking: Double Blind (Subject, Investigator)
Primary Purpose: Treatment
Official Title: DEFEND 2: Durable-Response Therapy Evaluation ForEarly- or New-Onset Type 1 Diabetes

Resource links provided by NLM:

Further study details as provided by GlaxoSmithKline:

Primary Outcome Measures:
  • Amount of C-peptide (a protein that shows how much insulin the body is producing) during a mixed meal stimulation test. [ Time Frame: at 12 months ] [ Designated as safety issue: No ]

Secondary Outcome Measures:
  • Average daily insulin use, HbA1c (a measurement of blood glucose control), and incidence of abnormal blood glucose levels. [ Time Frame: at Week 12, Months 6, 12, 18, and 24 ] [ Designated as safety issue: No ]

Enrollment: 179
Study Start Date: May 2010
Study Completion Date: March 2012
Primary Completion Date: March 2012 (Final data collection date for primary outcome measure)
Arms Assigned Interventions
Experimental: otelixizumab
Biological: Otelixizumab
Other Names:
  • ChAglyCD3
  • TRX4
  • monoclonal antibody
  • anti-CD3
Placebo Comparator: placebo
Biological: Placebo

Detailed Description:

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.

Ages Eligible for Study:   12 Years to 17 Years
Genders Eligible for Study:   Both
Accepts Healthy Volunteers:   No

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

  Contacts and Locations
Please refer to this study by its identifier: NCT01123083

  Show 122 Study Locations
Sponsors and Collaborators
Juvenile Diabetes Research Foundation
Study Director: GSK Clinical Trials GlaxoSmithKline
  More Information

Additional Information:
Responsible Party: GlaxoSmithKline Identifier: NCT01123083     History of Changes
Other Study ID Numbers: 115494, TRX4018
Study First Received: May 11, 2010
Last Updated: December 13, 2012
Health Authority: Netherlands: Central Committee on Research inv. Human Subjects
Spain: Spanish Medicines and Health product Agency
United Kingdom: Medicines and Healthcare Products Regulatory Agency
Finland: Finnish Medicines Agency
Belgium: Belgian Federal Agency for Medicinal and Health Products
Italy: Ministry of Health
Canada: Health Canada
Denmark: Danish Medicines Agency
Germany: Paul-Ehrlich-Institut
Sweden: Medical Products Agency
United States: Food and Drug Administration

Keywords provided by GlaxoSmithKline:
new onset type 1 diabetes
juvenile diabetes
Type 1 diabetes

Additional relevant MeSH terms:
Diabetes Mellitus
Diabetes Mellitus, Type 1
Glucose Metabolism Disorders
Metabolic Diseases
Endocrine System Diseases
Autoimmune Diseases
Immune System Diseases
Antibodies, Monoclonal
Immunologic Factors
Physiological Effects of Drugs
Pharmacologic Actions processed this record on April 14, 2014