Last updated: 11/07/2018 09:34:57

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

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GSK study ID
115494
See study documents
Clinicaltrials.gov ID
NCT01123083
See results summary
EudraCT ID
2010-018775-17
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
Trial description: 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.
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 (Day 1) and Month 12

Secondary outcomes:

Change from Baseline in 2 hour mixed meal-stimulated C-peptide AUC (normalized for 120-minute time interval) at Week 12 and 6 months

Timeframe: Baseline (Day 1) and Week 12, Month 6

Change from Baseline in stimulated C-Peptide Mean AUC at Week 12, Month 6, 12 and 18

Timeframe: Baseline (Day 1) and Week 12, Month 6, 12, 18

Number of participants with responder status

Timeframe: Month 3, 6 and 12

Change from Baseline in mean daily insulin use over 7 consecutive days during the 2 weeks prior to the assessment

Timeframe: Baseline (Day 1) and Month 3, 6, 12

Change from Baseline in HbA1c levels over 7 consecutive days during the 2 weeks prior to the assessment

Timeframe: Baseline (Day 1) and Month 3, 6, 12

Average number of Severe Hypoglycemic Events and Documented Symptomatic Hypoglycemic Events from Baseline to Month 12

Timeframe: Baseline (Day 1) and Month 12

Percentage of participants with change from Baseline in severe hypoglycemic events and documented symptomatic hypoglycemic events at Month 12

Timeframe: Baseline (Day 1) and Month 12

Composite Rank Sum: HbA1c and Exogenous Insulin Use at 6 and 12 months

Timeframe: Month 6 and 12

Composite Rank Sum: C-Peptide AUC, HbA1c and Exogenous Insulin Use at 6 and 12 months

Timeframe: Month 6 and 12

Interventions:
  • Biological/vaccine: Otelixizumab
  • Biological/vaccine: Placebo
    • Enrollment:
    179
    Primary completion date:
    2012-09-03
    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.
    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.
    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.
    Philip Ambery, Thomas W. Donner, Nandita Biswas, Jill Donaldson, Jackie Parkin, Colin M Dayan. Efficacy and Safety of Low-Dose Otelixizumab Anti-CD3 Monoclonal Antibody: The DEFEND-2 Study. Diabet Med. 2014;31(4):399-402.
    Medical condition
    Diabetes Mellitus, Type 1
    Product
    otelixizumab
    Collaborators
    GlaxoSmithKline, Juvenile Diabetes Research Foundation
    Study date(s)
    May 2010 to March 2012
    Type
    Interventional
    Phase
    3

    Participation criteria

    Sex
    Female & Male
    Age
    12 - 17 years
    Accepts healthy volunteers
    No
    • Ages 12-17
    • 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 12-17 •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

    Trial location(s)

    Location
    Status
    Contact us
    Contact us
    Location
    GSK Investigational Site
    Roma, Italy, 00155
    Status
    Study Complete
    Contact us

    Study documents

    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
    2012-09-03
    Actual study completion date
    2012-09-03

    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 regarding the DEFEND-2 trial
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