Last updated: 11/07/2018 09:35:40

Trial of Otelixizumab for Adults with Newly Diagnosed Type 1 Diabetes Mellitus (autoimmune): DEFEND-1DEFEND-1

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GSK study ID
115495
See study documents
Clinicaltrials.gov ID
NCT00678886
See results summary
EudraCT ID
2008-002205-40
EU CT Number
Not applicable
Trial status
Study complete
Study complete
Overview
Eligibility
Locations
Study documents
Results summary
Plain language summaries
Additional information

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
    Primary completion date:
    2012-31-01
    Observational study model:
    Not applicable
    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
    Status
    Contact us
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    Location
    GSK Investigational Site
    Durham, North Carolina, United States, 27713
    Status
    Terminated/Withdrawn
    Contact us
    Location
    GSK Investigational Site
    Boca Raton, Florida, United States, 33486
    Status
    Terminated/Withdrawn
    Contact us
    Location
    GSK Investigational Site
    Santa Ana, California, United States, 92705
    Status
    Terminated/Withdrawn
    Contact us
    Location
    GSK Investigational Site
    Sant Joan, Spain, ´03550
    Status
    Terminated/Withdrawn
    Contact us
    Location
    GSK Investigational Site
    Columbus, Ohio, United States, 43205
    Status
    Terminated/Withdrawn
    Contact us
    Location
    GSK Investigational Site
    Calgary, Alberta, Canada, T2H 2G4
    Status
    Terminated/Withdrawn
    Contact us
    Showing 1 - 6 of 109 Results

    Study documents

    Clinical study report
    Available language(s): English
    Download document(s)
    Scientific result summary
    Available language(s): English
    Download document(s)

    If you wish to request for full study report, please contact - [email protected]

    Results overview

    Results posted on ClinicalTrials.gov

    Recruitment status
    Study complete
    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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    Access to clinical trial data by researchers
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