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

Purpose

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:

Genetics Home Reference related topics: type 1 diabetes

MedlinePlus related topics: Diabetes Diabetes Medicines Diabetes Type 1

U.S. FDA Resources

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 otelixizumab	Biological: Otelixizumab infusion Other Names: ChAglyCD3 TRX4 monoclonal antibody anti-CD3
Placebo Comparator: placebo placebo	Biological: Placebo Infusion

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.

Eligibility

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

Criteria

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 ClinicalTrials.gov identifier: NCT01123083

Show 122 Study Locations

Sponsors and Collaborators

GlaxoSmithKline

Juvenile Diabetes Research Foundation

Investigators

Study Director:

GSK Clinical Trials

GlaxoSmithKline

More Information

Additional Information:

Website containing information regarding the DEFEND-2 trial This link exits the ClinicalTrials.gov site

Publications:

Keymeulen B, Vandemeulebroucke E, Ziegler AG, Mathieu C, Kaufman L, Hale G, Gorus F, Goldman M, Walter M, Candon S, Schandene L, Crenier L, De Block C, Seigneurin JM, De Pauw P, Pierard D, Weets I, Rebello P, Bird P, Berrie E, Frewin M, Waldmann H, Bach JF, Pipeleers D, Chatenoud L. Insulin needs after CD3-antibody therapy in new-onset type 1 diabetes. N Engl J Med. 2005 Jun 23;352(25):2598-608.

You S, Candon S, Kuhn C, Bach JF, Chatenoud L. CD3 antibodies as unique tools to restore self-tolerance in established autoimmunity their mode of action and clinical application in type 1 diabetes. Adv Immunol. 2008;100:13-37. Review. No abstract available.

Keymeulen B, Walter M, Mathieu C, Kaufman L, Gorus F, Hilbrands R, Vandemeulebroucke E, Van de Velde U, Crenier L, De Block C, Candon S, Waldmann H, Ziegler AG, Chatenoud L, Pipeleers D. Four-year metabolic outcome of a randomised controlled CD3-antibody trial in recent-onset type 1 diabetic patients depends on their age and baseline residual beta cell mass. Diabetologia. 2010 Apr;53(4):614-23. Epub 2010 Jan 14.

Responsible Party:	GlaxoSmithKline
ClinicalTrials.gov 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
T1DM
Type 1 diabetes

Additional relevant MeSH terms:

Diabetes Mellitus, Type 1
Diabetes Mellitus
Glucose Metabolism Disorders
Metabolic Diseases
Endocrine System Diseases
Autoimmune Diseases

Immune System Diseases
Antibodies, Monoclonal
Immunologic Factors
Physiological Effects of Drugs
Pharmacologic Actions

ClinicalTrials.gov processed this record on June 18, 2013