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

Sponsor:	Tolerx Inc.
Collaborator:	Juvenile Diabetes Research Foundation
Information provided by:	Tolerx Inc.
ClinicalTrials.gov Identifier:	NCT00678886

Purpose

The purpose of this study 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.

DEFEND-1 is now closed to enrollment.

DEFEND-2 will begin early in 2010. It is very similar to DEFEND-1 and will again require subjects with new onset type 1 diabetes. Please check back here for more details.

In the meantime, established and new onset type 1 diabetes patients in North America are welcome to consider the TTEDD study:

http://www.clinicaltrials.gov/ct2/show/NCT00451321?term=TTEDD&rank=1

Condition	Intervention	Phase
Type 1 Diabetes Mellitus	Biological: otelixizumab Biological: placebo	Phase III

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

Resource links provided by NLM:

MedlinePlus related topics: Diabetes Diabetes Medicines Diabetes Type 1

Drug Information available for: Immunoglobulins Globulin, Immune

U.S. FDA Resources

Further study details as provided by Tolerx Inc.:

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 Months 6, 12, 18, and 24 ] [ Designated as safety issue: Yes ]

Estimated Enrollment:	240
Study Start Date:	May 2008
Estimated Primary Completion Date:	December 2010 (Final data collection date for primary outcome measure)

Arms	Assigned Interventions
1: Experimental otelixizumab	Biological: otelixizumab infusion
2: Placebo Comparator	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.
Dosing Visits: 8 outpatient visits on consecutive days, each lasting about 4-6 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, glucose monitors and PDAs to record insulin will be provided to all study subjects for the duration fo the study. Frequent glycemic monitoring will occur through lab testing and blood glucose self-monitoring to help facilitate tight glycemic control in all subjects.

Eligibility

Ages Eligible for Study:	12 Years to 45 Years
Genders Eligible for Study:	Both
Accepts Healthy Volunteers:	No

Criteria

Inclusion Criteria:

Ages 12-45
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.
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: NCT00678886

Show 123 Study Locations

Sponsors and Collaborators

Tolerx Inc.

Juvenile Diabetes Research Foundation

More Information

Additional Information:

Website containing information on Tolerx This link exits the ClinicalTrials.gov site

Website containing information on DEFEND study 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.

Responsible Party:	Tolerx, Inc. ( Kathleen Osborn/Clinical Study Manager )
ClinicalTrials.gov Identifier:	NCT00678886 History of Changes
Obsolete Identifiers:	NCT00893022
Other Study ID Numbers:	TRX4006
Study First Received:	May 13, 2008
Last Updated:	August 31, 2010
Health Authority:	United States: Food and Drug Administration; Canada: Health Canada; Denmark: Danish Medicines Agency; Finland: Finnish Medicines Agency; Germany: Paul-Ehrlich-Institut; Italy: Ministry of Health; Spain: Spanish Medicines and Health product Agency; Sweden: Medical Products Agency; United Kingdom: Medicines and Healthcare Products Regulatory Agency

Keywords provided by Tolerx Inc.:

Type 1 diabetes
new onset type 1 diabetes
juvenile diabetes
T1DM
Type l 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

ClinicalTrials.gov processed this record on August 31, 2010