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

This study has been completed.
Sponsor:
ClinicalTrials.gov Identifier:
NCT00678886
First Posted: May 16, 2008
Last Update Posted: October 3, 2017
The safety and scientific validity of this study is the responsibility of the study sponsor and investigators. Listing a study does not mean it has been evaluated by the U.S. Federal Government. Read our disclaimer for details.
Collaborator:
Juvenile Diabetes Research Foundation
Information provided by (Responsible Party):
GlaxoSmithKline
Results First Submitted: July 19, 2017  
Study Type: Interventional
Study Design: Allocation: Randomized;   Intervention Model: Parallel Assignment;   Masking: Double (Participant, Investigator);   Primary Purpose: Treatment
Condition: Diabetes Mellitus, Type 1
Interventions: Biological: otelixizumab infusion plus physician determined standard of care
Biological: placebo infusion plus physician determined standard of care

  Participant Flow
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Recruitment Details
Key information relevant to the recruitment process for the overall study, such as dates of the recruitment period and locations
This study was conducted at 85 centers in 9 countries namely Canada (4), Germany (3), Denmark (1), Spain (5), Finland (2), United Kingdom (4), Italy (8), Sweden (11) and United States of America (47) from 29 July 2008 to 31 January 2012. A total of 240 participants with new-onset Type 1 diabetes mellitus (NOT1DM) were planned to be enrolled.

Pre-Assignment Details
Significant events and approaches for the overall study following participant enrollment, but prior to group assignment
Participants were screened for a period of 35 days and a total of 272 participants were randomized in the study.

Reporting Groups
  Description
Adolescent (Placebo) Eligible adolescent participants received matching placebo to Otelixizumab administered as intravenous (IV) infusions, with each infusion given over a 30-minute period. Participants received a series of 8 infusions, 1 infusion per Day over 8 consecutive days. Participants were followed-up for 24 months after the last dose.
Adolescent (Otelixizumab) Eligible adolescent participants received Otelixizumab administered as IV infusions, with each infusion given over a 30-minute period. Participants received a series of 8 infusions as first dose (Day 1 of 0.1 milligram [mg], second dose (Day 2 of 0.2 mg), third dose (Day 3 of 0.3 mg), fourth, fifth, sixth, seventh and eight dose (on Days 4,5,6,7,8 of 0.5 mg per Day) 1 infusion per Day over 8 consecutive days . The total amount of Otelixizumab administered was 3.1 mg. Participants were followed-up for 24 months after the last dose.
Adult (Placebo) Eligible adult participants received matching placebo to Otelixizumab administered as IV infusions, with each infusion given over a 30-minute period. Participants received a series of 8 infusions, 1 infusion per day over 8 consecutive Days. Participants were followed-up for 24 months after the last dose.
Adult (Otelixizumab) Eligible adult participants received Otelixizumab administered as IV infusions, with each infusion given over a 30-minute period. Participants received a series of 8 infusions as first dose (Day 1 of 0.1 mg), second dose (Day 2 of 0.2 mg), third dose (Day 3 of 0.3 mg), fourth, fifth, sixth, seventh and eight dose (on Days 4,5,6,7,8 of 0.5 mg per Day) 1 infusion per Day over 8 consecutive days . The total amount of Otelixizumab administered was 3.1 mg. Participants were followed-up for 24 months after the last dose.

Participant Flow:   Overall Study
    Adolescent (Placebo)   Adolescent (Otelixizumab)   Adult (Placebo)   Adult (Otelixizumab)
STARTED   10   19   81   162 
COMPLETED   10   19   72   153 
NOT COMPLETED   0   0   9   9 
Withdrawal by Subject                0                0                4                6 
Physician Decision                0                0                1                1 
Lost to Follow-up                0                0                3                2 
Other                0                0                1                0 



  Baseline Characteristics
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Population Description
Explanation of how the number of participants for analysis was determined. Includes whether analysis was per protocol, intention to treat, or another method. Also provides relevant details such as imputation technique, as appropriate.
No text entered.

Reporting Groups
  Description
Placebo Eligible participants received matching placebo to Otelixizumab administered as IV infusions, with each infusion given over a 30-minute period. Participants received a series of 8 infusions, 1 infusion per Day over 8 consecutive days. Participants were followed-up for 24 months after the last dose.
Otelixizumab Eligible participants received Otelixizumab administered as IV infusions, with each infusion given over a 30-minute period. Participants received a series of 8 infusions as first dose (Day 1 of 0.1 mg, second dose (Day 2 of 0.2 mg), third dose (Day 3 of 0.3 mg), fourth, fifth, sixth, seventh and eight dose (on Days 4,5,6,7,8 of 0.5 mg per Day) 1 infusion per Day over 8 consecutive days . The total amount of Otelixizumab administered was 3.1 mg. Participants were followed-up for 24 months after the last dose.
Total Total of all reporting groups

Baseline Measures
   Placebo   Otelixizumab   Total 
Overall Participants Analyzed 
[Units: Participants]
 91   181   272 
Age 
[Units: Years]
Mean (Standard Deviation)
 25.2  (7.13)   24.7  (6.54)   24.9  (6.73) 
Sex: Female, Male 
[Units: Participants]
Count of Participants
     
Female      31  34.1%      64  35.4%      95  34.9% 
Male      60  65.9%      117  64.6%      177  65.1% 
Race (NIH/OMB) 
[Units: Participants]
Count of Participants
     
American Indian or Alaska Native      0   0.0%      1   0.6%      1   0.4% 
Asian      2   2.2%      1   0.6%      3   1.1% 
Native Hawaiian or Other Pacific Islander      0   0.0%      0   0.0%      0   0.0% 
Black or African American      2   2.2%      6   3.3%      8   2.9% 
White      85  93.4%      169  93.4%      254  93.4% 
More than one race      2   2.2%      4   2.2%      6   2.2% 
Unknown or Not Reported      0   0.0%      0   0.0%      0   0.0% 


  Outcome Measures
  Show All Outcome Measures

1.  Primary:   Change From Baseline in 2-hour Mixed Meal Stimulated C-peptide Area Under Curve [AUC] (Normalized for 120-minute Time Interval) at Month 12   [ Time Frame: Baseline (0-120 minutes on Day 1) and Month 12 (0-120 minutes) ]

2.  Secondary:   Number of Participants Who Were Responders for (Glycosylated Hemoglobin) HbA1c/Insulin Use Response at Week 12 and Months 6 and 12   [ Time Frame: Week 12 and Months 6 and 12 ]

3.  Secondary:   Mean Daily Insulin Use at Week 12 and Months 6 and 12.   [ Time Frame: Week 12 and Months 6 and 12. ]

4.  Secondary:   HbA1c Level at Week 12 and Months 6 and 12   [ Time Frame: Week 12 and Months 6 and 12 ]

5.  Secondary:   Number of Hypoglycemic Events Defined by Hypoglycemic Event Categories From Baseline Upto Month 12   [ Time Frame: Upto Month 12 ]

6.  Secondary:   Number of Participants With Hypoglycemic Events Defined by Hypoglycemic Event Categories From Baseline Upto Month 12   [ Time Frame: Upto Month 12 ]

7.  Secondary:   Number of Hypoglycemic Excursions (<=70 mg/dL) With Most Complete Glucose at Week 12 and Months 6 and 12.   [ Time Frame: Week 12 and Months 6 and 12. ]

8.  Secondary:   Magnitude of Greatest Hypoglycemic Excursions With Most Complete Glucose at Week 12 and Months 6 and 12.   [ Time Frame: Week 12 and Months 6 and 12. ]

9.  Secondary:   Number of Participants With Hypoglycemic Excursions With Most Complete Glucose at Week 12 and Months 6 and 12   [ Time Frame: Week 12 and Months 6 and 12 ]

10.  Secondary:   Number of Hyperglycemic Excursions With Most Complete Glucose at Week 12 and Months 6 and 12.   [ Time Frame: Week 12 and Months 6 and 12 ]

11.  Secondary:   Magnitude of Greatest Hyperglycemic Excursions With Most Complete Glucose at Week 12 and Months 6 and 12.   [ Time Frame: Week 12 and Months 6 and 12. ]

12.  Secondary:   Number of Participants With Hyperglycemic Excursions With Most Complete Glucose at Week 12 and Months 6 and 12   [ Time Frame: Week 12 and Months 6 and 12 ]

13.  Secondary:   Change From Baseline in Average Daily Risk Range (ADRR) at Week 12 and Months 6 and 12.   [ Time Frame: Baseline (Day 1) and Week 12, Months 6 and 12. ]

14.  Secondary:   Composite Rank Summary for HbA1c and Exogenous Insulin Use at Month 6 and Month 12   [ Time Frame: Month 6 and 12 ]

15.  Secondary:   Composite Rank Summary for C-Peptide AUC, HbA1c and Exogenous Insulin Use at Month 6 and Month 12   [ Time Frame: Month 6 and 12 ]

16.  Secondary:   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   [ Time Frame: Day 1, Day 4, Day 8 ]

17.  Secondary:   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   [ Time Frame: Baseline (pre-dose on Day 1) and up to 12 Months ]

18.  Secondary:   Percent Change From Baseline in Cell-bound Otelixizumab on CD4+ T Cells at Day 1, Day 4, Day 8   [ Time Frame: Baseline (pre-dose on Day 1), Day 4 and Day 8 ]

19.  Secondary:   Percent Change From Baseline in CD3/TCR Saturation on CD4+ T Cells and CD8+ T Cells at Day 1, Day 4, Day 8   [ Time Frame: Baseline (Pre-dose Day 1), Day 4, Day 8 ]

20.  Secondary:   Percent Change From Baseline in CD3/TCR Modulation on CD4+ T Cells and CD8+ T Cells at Day 1, Day 4, Day 8   [ Time Frame: Baseline (Pre-dose Day 1), Day 4, Day 8 ]


  Serious Adverse Events


  Other Adverse Events


  Limitations and Caveats
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Limitations of the study, such as early termination leading to small numbers of participants analyzed and technical problems with measurement leading to unreliable or uninterpretable data
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  More Information
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Certain Agreements:  
Principal Investigators are NOT employed by the organization sponsoring the study.
There IS an agreement between Principal Investigators and the Sponsor (or its agents) that restricts the PI's rights to discuss or publish trial results after the trial is completed.
The agreement is:
unchecked The only disclosure restriction on the PI is that the sponsor can review results communications prior to public release and can embargo communications regarding trial results for a period that is less than or equal to 60 days. The sponsor cannot require changes to the communication and cannot extend the embargo.
unchecked The only disclosure restriction on the PI is that the sponsor can review results communications prior to public release and can embargo communications regarding trial results for a period that is more than 60 days but less than or equal to 180 days. The sponsor cannot require changes to the communication and cannot extend the embargo.


Results Point of Contact:  
Name/Title: GSK Response Center
Organization: GlaxoSmithKline
phone: 866-435-7343


Publications:

Responsible Party: GlaxoSmithKline
ClinicalTrials.gov Identifier: NCT00678886     History of Changes
Obsolete Identifiers: NCT00893022
Other Study ID Numbers: 115495
TRX4006 ( Other Identifier: Tolerx )
First Submitted: May 13, 2008
First Posted: May 16, 2008
Results First Submitted: July 19, 2017
Results First Posted: October 3, 2017
Last Update Posted: October 3, 2017