Last updated: 11/07/2018 09:35:40
Trial of Otelixizumab for Adults with Newly Diagnosed Type 1 Diabetes Mellitus (autoimmune): DEFEND-1DEFEND-1
EudraCT ID
EU CT Number
Not applicable
Trial status
Completed
Completed
Trial overview
Official title: Durable-Response Therapy Evaluation For Early or New-Onset Type 1 Diabetes - DEFEND
Trial description: 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 infusion. 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 physician determined 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
Primary purpose:
Treatment
Trial design:
Parallel Assignment
Masking:
Double (Participant, Investigator)
Allocation:
Randomized
Primary outcomes:
Change from Baseline in 2-hour mixed meal stimulated C-peptide Area under curve [AUC] (normalized for 120-minute time interval) at month 12
Timeframe: Baseline (0-120 minutes on Day 1) and Month 12 (0-120 minutes)
Secondary outcomes:
Number of participants who were responders for (glycosylated hemoglobin) HbA1c/Insulin Use Response at Week 12 and Months 6 and 12
Timeframe: Week 12 and Months 6 and 12
Mean daily insulin use at Week 12 and Months 6 and 12.
Timeframe: Week 12 and Months 6 and 12.
HbA1c level at Week 12 and Months 6 and 12
Timeframe: Week 12 and Months 6 and 12
Number of hypoglycemic events defined by hypoglycemic event categories from Baseline upto month 12
Timeframe: Upto Month 12
Number of participants with hypoglycemic events defined by hypoglycemic event categories from Baseline upto month 12
Timeframe: Upto Month 12
Number of hypoglycemic excursions (<=70 mg/dL) with most complete glucose at Week 12 and Months 6 and 12.
Timeframe: Week 12 and Months 6 and 12.
Magnitude of Greatest hypoglycemic excursions with most complete glucose at Week 12 and Months 6 and 12.
Timeframe: Week 12 and Months 6 and 12.
Number of participants with hypoglycemic excursions with most complete glucose at Week 12 and Months 6 and 12
Timeframe: Week 12 and Months 6 and 12
Number of hyperglycemic excursions with most complete glucose at Week 12 and Months 6 and 12.
Timeframe: Week 12 and Months 6 and 12
Magnitude of Greatest hyperglycemic excursions with most complete glucose at Week 12 and Months 6 and 12.
Timeframe: Week 12 and Months 6 and 12.
Number of participants with hyperglycemic excursions with most complete glucose at Week 12 and Months 6 and 12
Timeframe: Week 12 and Months 6 and 12
Change from Baseline in average daily risk range (ADRR) at Week 12 and Months 6 and 12.
Timeframe: Baseline (Day 1) and Week 12, Months 6 and 12.
Composite Rank Summary for HbA1c and Exogenous Insulin Use at month 6 and month 12
Timeframe: Month 6 and 12
Composite Rank Summary for C-Peptide AUC, HbA1c and Exogenous Insulin Use at month 6 and month 12
Timeframe: Month 6 and 12
Change from Baseline in level of cytokines Interleukin (IL-6), IL-10 and Tumor necrosis factor-alpha (TNF-a) at Day 1, Day 4, Day 8
Timeframe: Day 1, Day 4, Day 8
Percent change from Baseline in circulating peripheral lymphocytes CD4+CD25+FoxP3+ T Cells and CD4+CD25hiFoxP3+ T Cells in Type 1 Diabetes Mellitus (TIDM) up to month 12
Timeframe: Baseline (pre-dose on Day 1) and up to 12 Months
Percent change from Baseline in cell-bound otelixizumab on CD4+ T cells at Day 1, Day 4, Day 8
Timeframe: Baseline (pre-dose on Day 1), Day 4 and Day 8
Percent change from Baseline in CD3/TCR saturation on CD4+ T cells and CD8+ T cells at Day 1, Day 4, Day 8
Timeframe: Baseline (Pre-dose Day 1), Day 4, Day 8
Percent change from Baseline in CD3/TCR modulation on CD4+ T cells and CD8+ T cells at Day 1, Day 4, Day 8
Timeframe: Baseline (Pre-dose Day 1), Day 4, Day 8
Interventions:
Biological/vaccine: otelixizumab infusion plus physician determined standard of care
Biological/vaccine: placebo infusion plus physician determined standard of care
Enrollment:
272
Observational study model:
Not applicable
Primary completion date:
2012-31-01
Time perspective:
Not applicable
Clinical 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. doi: 10.1016/S0065-2776(08)00802-X. Review.
Ronnie Aronson, Peter A. Gottlieb, Jens S. Christiansen, Thomas W. Donner, Emanuele Bosi, Bruce W. Bode, and Paolo Pozzilli, for the DEFEND Investigator Group.Low-Dose Otelixizumab Anti-CD3 Monoclonal Antibody DEFEND-1 Study: Results of the Randomized Phase III Study in Recent-Onset Human Type 1 Diabetes.Diabetes Care.2014;37(10):2746-54
Medical condition
Diabetes Mellitus, Type 1
Product
otelixizumab
Collaborators
Juvenile Diabetes Research Foundation (JDRF)
Study date(s)
July 2008 to Invalid Date
Type
Interventional
Phase
3
Participation criteria
Sex
Female & Male
Age
12 - 45 years
Accepts healthy volunteers
No
- _Ages 12-45
- _Diagnosis of diabetes mellitus, consistent with ADA criteria
- _Other, significant medical conditions based on the study doctor's evaluation
Inclusion and exclusion 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
Trial location(s)
Location
GSK Investigational Site
Durham, North Carolina, United States, 27713
Status
Terminated/Withdrawn
Location
GSK Investigational Site
Boca Raton, Florida, United States, 33486
Status
Terminated/Withdrawn
Location
GSK Investigational Site
Santa Ana, California, United States, 92705
Status
Terminated/Withdrawn
Location
GSK Investigational Site
Columbus, Ohio, United States, 43205
Status
Terminated/Withdrawn
Location
GSK Investigational Site
Calgary, Alberta, Canada, T2H 2G4
Status
Terminated/Withdrawn
Location
GSK Investigational Site
Dallas, Texas, United States, 75231
Status
Terminated/Withdrawn
Location
GSK Investigational Site
Smiths Falls, Ontario, Canada, K7A 4W8
Status
Terminated/Withdrawn
Location
GSK Investigational Site
Costa Mesa, California, United States, 92626
Status
Terminated/Withdrawn
Location
GSK Investigational Site
Nashville, Tennessee, United States, 37212
Status
Terminated/Withdrawn
Location
GSK Investigational Site
Orlando, Florida, United States, 32835
Status
Terminated/Withdrawn
Location
GSK Investigational Site
Orlando, Florida, United States, 32803
Status
Terminated/Withdrawn
Location
GSK Investigational Site
Tacoma, Washington, United States, 98405
Status
Terminated/Withdrawn
Location
GSK Investigational Site
New York, New York, United States, 10032
Status
Terminated/Withdrawn
Location
GSK Investigational Site
Miami, Florida, United States, 33169
Status
Terminated/Withdrawn
Location
GSK Investigational Site
Atlanta, Georgia, United States, 30342
Status
Terminated/Withdrawn
Location
GSK Investigational Site
Jupiter, Florida, United States, 33458
Status
Terminated/Withdrawn
Location
GSK Investigational Site
Gulfport, Mississippi, United States, 39501
Status
Terminated/Withdrawn
Location
GSK Investigational Site
Miami, Florida, United States, 33136
Status
Terminated/Withdrawn
Location
GSK Investigational Site
Topeka, Kansas, United States, 66606
Status
Terminated/Withdrawn
Location
GSK Investigational Site
Walnut Creek, California, United States, 94598
Status
Terminated/Withdrawn
Location
GSK Investigational Site
Trinity, Florida, United States, 34655
Status
Terminated/Withdrawn
Location
GSK Investigational Site
Rapid City, South Dakota, United States, 57701
Status
Terminated/Withdrawn
Location
GSK Investigational Site
Mineola, New York, United States, 11501
Status
Terminated/Withdrawn
Location
GSK Investigational Site
Idaho Falls, Idaho, United States, 83404-7542
Status
Terminated/Withdrawn
Location
GSK Investigational Site
Tulsa, Oklahoma, United States, 74136-8303
Status
Terminated/Withdrawn
Location
GSK Investigational Site
Washington, District of Columbia, United States, 20037
Status
Terminated/Withdrawn
Location
GSK Investigational Site
Atlanta, Georgia, United States, 30309
Status
Terminated/Withdrawn
Location
GSK Investigational Site
Los Angeles, California, United States, 90033
Status
Terminated/Withdrawn
Location
GSK Investigational Site
Indianapolis, Indiana, United States, 46260
Status
Terminated/Withdrawn
Location
GSK Investigational Site
Monserrato, Sardegna, Italy, 09042
Status
Terminated/Withdrawn
Location
GSK Investigational Site
Detroit, Michigan, United States, 48201
Status
Terminated/Withdrawn
Location
GSK Investigational Site
Kansas City, Missouri, United States, 64106
Status
Terminated/Withdrawn
Location
GSK Investigational Site
Orange, California, United States, 92868
Status
Terminated/Withdrawn
Location
GSK Investigational Site
Ogden, Utah, United States, 84403
Status
Terminated/Withdrawn
Location
GSK Investigational Site
Portland, Oregon, United States, 97210
Status
Terminated/Withdrawn
Location
GSK Investigational Site
Bristol, United Kingdom, BS2 8HW
Status
Terminated/Withdrawn
Location
GSK Investigational Site
Langhorne, Pennsylvania, United States, 19047
Status
Terminated/Withdrawn
Location
GSK Investigational Site
Philadelphia, Pennsylvania, United States, 19140
Status
Terminated/Withdrawn
Location
GSK Investigational Site
Chicago, Illinois, United States, 60612
Status
Terminated/Withdrawn
Location
GSK Investigational Site
Torrance, California, United States, 90502
Status
Terminated/Withdrawn
Location
GSK Investigational Site
Aurora, Colorado, United States, 80045
Status
Terminated/Withdrawn
Location
GSK Investigational Site
Bad Lauterberg, Niedersachsen, Germany, 37431
Status
Terminated/Withdrawn
Location
GSK Investigational Site
Columbia, Missouri, United States, 65212
Status
Terminated/Withdrawn
Location
GSK Investigational Site
Boise, Idaho, United States, 83702
Status
Terminated/Withdrawn
Location
GSK Investigational Site
Bad Nauheim, Hessen, Germany, 61231
Status
Terminated/Withdrawn
Location
GSK Investigational Site
Worcester, Massachusetts, United States, 01655-0002
Status
Terminated/Withdrawn
Location
GSK Investigational Site
Newcastle upon Tyne, United Kingdom, NE1 4LP
Status
Terminated/Withdrawn
Location
GSK Investigational Site
Rochester, New York, United States, 14642
Status
Terminated/Withdrawn
Location
GSK Investigational Site
Riverside, California, United States, 92506
Status
Terminated/Withdrawn
Location
GSK Investigational Site
Honolulu, Hawaii, United States, 96813
Status
Terminated/Withdrawn
Location
GSK Investigational Site
Columbus, Ohio, United States, 43210
Status
Terminated/Withdrawn
Location
GSK Investigational Site
Tarrasa, Barcelona, Spain, 08221
Status
Terminated/Withdrawn
Location
GSK Investigational Site
Winter Park, Florida, United States, 32789
Status
Terminated/Withdrawn
Location
GSK Investigational Site
Buffalo, New York, United States, 14209
Status
Terminated/Withdrawn
Location
GSK Investigational Site
Baltimore, Maryland, United States, 21201
Status
Terminated/Withdrawn
Location
GSK Investigational Site
San Antonio, Texas, United States, 78229
Status
Terminated/Withdrawn
Location
GSK Investigational Site
Heidelberg, Baden-Wuerttemberg, Germany, 69120
Status
Terminated/Withdrawn
Location
GSK Investigational Site
Houston, Texas, United States, 77030
Status
Terminated/Withdrawn
Location
GSK Investigational Site
Hurst, Texas, United States, 76054
Status
Terminated/Withdrawn
Location
GSK Investigational Site
Pointe-Claire, Québec, Canada, H9R 3J1
Status
Terminated/Withdrawn
Location
GSK Investigational Site
Pembroke Pines, Florida, United States, 33024
Status
Terminated/Withdrawn
Location
GSK Investigational Site
Little Rock, Arkansas, United States, 72205
Status
Terminated/Withdrawn
Location
GSK Investigational Site
Dayton, Ohio, United States, 45415-2560
Status
Terminated/Withdrawn
Location
GSK Investigational Site
Chicago, Illinois, United States, 60637
Status
Terminated/Withdrawn
Location
GSK Investigational Site
Kalamazoo, Michigan, United States, 49048
Status
Terminated/Withdrawn
Location
GSK Investigational Site
Charleston, South Carolina, United States, 29425-6240
Status
Terminated/Withdrawn
Location
GSK Investigational Site
Eugene, Oregon, United States, 97401
Status
Terminated/Withdrawn
Location
GSK Investigational Site
Mentor, Ohio, United States, 44060
Status
Terminated/Withdrawn
Location
GSK Investigational Site
Omaha, Nebraska, United States, 68131
Status
Terminated/Withdrawn
Location
GSK Investigational Site
Dallas, Texas, United States, 75390
Status
Terminated/Withdrawn
Location
GSK Investigational Site
Neptune, New Jersey, United States, 07753
Status
Terminated/Withdrawn
Location
GSK Investigational Site
Blackburn, United Kingdom, BB2 3HH
Status
Terminated/Withdrawn
Location
GSK Investigational Site
Oakville, Ontario, Canada, L6H 3P1
Status
Terminated/Withdrawn
Location
GSK Investigational Site
Toronto, Ontario, Canada, M4G 3E8
Status
Terminated/Withdrawn
Location
GSK Investigational Site
Memphis, Tennessee, United States, 38119
Status
Terminated/Withdrawn
Location
GSK Investigational Site
Montreal, Québec, Canada, H2W 1T8
Status
Terminated/Withdrawn
Location
GSK Investigational Site
Schertz, Texas, United States, 782154
Status
Terminated/Withdrawn
Location
GSK Investigational Site
Birmingham, Alabama, United States, 35294
Status
Terminated/Withdrawn
Location
GSK Investigational Site
St. Louis, Missouri, United States, 63110
Status
Terminated/Withdrawn
Location
GSK Investigational Site
Bath, Somerset, United Kingdom, BA1 3NG
Status
Terminated/Withdrawn
Location
GSK Investigational Site
Chattanooga, Tennessee, United States, 37403
Status
Terminated/Withdrawn
Location
GSK Investigational Site
London, London, United Kingdom, SE1 9RT
Status
Terminated/Withdrawn
Location
GSK Investigational Site
Baltimore, Kansas, United States, 21287
Status
Terminated/Withdrawn
Study documents
Clinical study report
Available language(s): English
Scientific result summary
Available language(s): English
If you wish to request for full study report, please contact - [email protected]
Results overview
Results posted on ClinicalTrials.gov
Recruitment status
Completed
Actual primary completion date
2012-31-01
Actual study completion date
Not applicable
Plain language summaries
Plain language summaries of clinical trial results for Phase 2-4 clinical trials that were initiated on or after January 2022 will be posted by GSK within one year following study completion.
Additional information about the trial
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Additional information
Website containing information on DEFEND study
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