Autoimmunity-blocking Antibody for Tolerance in Recently Diagnosed Type 1 Diabetes (AbATE)

This study has been completed.
Sponsor:
Collaborator:
Immune Tolerance Network (ITN)
Information provided by (Responsible Party):
National Institute of Allergy and Infectious Diseases (NIAID)
ClinicalTrials.gov Identifier:
NCT00129259
First received: August 9, 2005
Last updated: June 4, 2014
Last verified: June 2014
Results First Received: June 21, 2013  
Study Type: Interventional
Study Design: Allocation: Randomized;   Endpoint Classification: Efficacy Study;   Intervention Model: Parallel Assignment;   Masking: Open Label;   Primary Purpose: Treatment
Condition: Diabetes Mellitus, Type 1
Interventions: Biological: Anti-CD3 mAb
Other: Diabetes Standard of Care Treatment
Dietary Supplement: Iron supplementation

  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
Seven centers randomized 83 subjects between September 2005 and March 2009. Seventy-seven subjects are in the intent-to-treat (ITT) population. Those not in the ITT population did not have a baseline visit and were not included in the participant flow portion of the results section.

Pre-Assignment Details
Significant events and approaches for the overall study following participant enrollment, but prior to group assignment
At a screening visit, subjects underwent procedures to establish that all inclusion criteria were met and none of the exclusion criteria were met. All subjects or guardians provided written informed consent at screening.

Reporting Groups
  Description
Anti-CD3 mAb Plus Diabetes Standard of Care Treatment

Other name: mAb hOKT3gamma1(Ala-Ala), Teplizumab, MGA031. Subjects received 1.) a 14-day course of anti-CD3 monoclonal antibody (mAb) intravenously (IV) comprised of daily doses of 51 µg/m2, 103 µg/m2, 207 µg/m2, 413 µg/m2, and 10 days of 826 µg/m2 [Cycle 1] and, when eligible per protocol, receipt of a second 14-day course after a 12-month interval (at month 13)[Cycle 2]. Note: Prior to May 2007, the course of IV daily doses of anti-CD3 mAb were: 57 µg/m2, 115 µg/m2, 230 µg/m2, 460 µg/m2, and 10 days of 919 µg/m2 and, when eligible per protocol, a second course after a 12-month interval (at month 13). 2.) and intensive diabetes standard of care treatment/management under the care of a physician: dietary counseling, insulin dosing and multiple consultations during the course of the trial with the clinical diabetes management team.

Iron supplementation was initiated status post treatment randomization.

Diabetes Standard of Care Treatment

Subjects received intensive diabetes standard of care treatment/management under the care of a physician: dietary counseling, insulin dosing and multiple consultations during the course of the trial with the clinical diabetes management team.

Iron supplementation was initiated status post treatment randomization.


Participant Flow:   Overall Study
    Anti-CD3 mAb Plus Diabetes Standard of Care Treatment     Diabetes Standard of Care Treatment  
STARTED     52 [1]   25 [1]
Received All or Part of Cycle 1     52     0  
Received All or Part of Cycle 2     40     0  
COMPLETED     49     22  
NOT COMPLETED     3     3  
Lost to Follow-up                 1                 1  
Withdrawal by Subject                 2                 1  
Only available minimal phone assessments                 0                 1  
[1] Subjects not in the Intent-to-treat group did not have a baseline visit and are not included here



  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.
Intent-to-treat

Reporting Groups
  Description
Anti-CD3 mAb Plus Diabetes Standard of Care Treatment Other name: mAb hOKT3gamma1(Ala-Ala), Teplizumab, MGA031. Subjects received 1.) a 14-day course of anti-CD3 monoclonal antibody (mAb) intravenously (IV) comprised of daily doses of 51 µg/m2, 103 µg/m2, 207 µg/m2, 413 µg/m2, and 10 days of 826 µg/m2 [Cycle 1] and, when eligible per protocol, receipt of a second 14-day course after a 12-month interval (at month 13)[Cycle 2]. Note: Prior to May 2007, the course of IV daily doses of anti-CD3 mAb were: 57 µg/m2, 115 µg/m2, 230 µg/m2, 460 µg/m2, and 10 days of 919 µg/m2 and, when eligible per protocol, a second course after a 12-month interval (at month 13). 2.) and intensive diabetes standard of care treatment/management under the care of a physician: dietary counseling, insulin dosing and multiple consultations during the course of the trial with the clinical diabetes management team.
Diabetes Standard of Care Treatment Subjects received intensive diabetes standard of care treatment/management under the care of a physician: dietary counseling, insulin dosing and multiple consultations during the course of the trial with the clinical diabetes management team.
Total Total of all reporting groups

Baseline Measures
    Anti-CD3 mAb Plus Diabetes Standard of Care Treatment     Diabetes Standard of Care Treatment     Total  
Number of Participants  
[units: participants]
  52     25     77  
Age  
[units: years]
Mean ± Standard Deviation
  12.7  ± 4.9     12.3  ± 4.1     12.5  ± 4.6  
Age, Customized  
[units: participants]
     
8-12     34     15     49  
13-17     14     9     23  
18-30     4     1     5  
Gender  
[units: participants]
     
Female     24     9     33  
Male     28     16     44  
Region of Enrollment  
[units: participants]
     
United States     52     25     77  
C-peptide Area Under the Curve (AUC) Response to a Mixed Meal Tolerance Test (MMTT) at Baseline [1]
[units: pmol/mL]
Mean ± Standard Deviation
  0.72  ± 0.29     0.67  ± 0.28     0.70  ± 0.29  
Hemoglobin A1c at Baseline (Pre-treatment) [2]
[units: Percentage (%)]
Mean ± Standard Deviation
  7.4  ± 0.99     7.7  ± 1.23     7.5  ± 1.07  
Average Total Daily Insulin Dose Per Body Weight at Baseline (Pre-treatment) [3]
[units: Units of Insulin/kilogram/day (U/kg/day)]
Mean ± Standard Deviation
  0.39  ± 0.26     0.39  ± 0.17     0.39  ± 0.23  
[1] C-peptide AUC is computed using the trapezoidal rule and dividing by the interval of time from the 4 hour Mixed Meal Tolerance Test (MMTT) where assessments are taken every 30 minutes after initial assessments 15 minutes apart. A higher C-peptide AUC is desirable as detectable C-peptide is a marker for the ability of the pancreas to produce insulin in response to a MMTT.
[2] Glycosylated hemoglobin (HbA1c) is a measure of the average plasma glucose concentration over prolonged periods of time. (Normal :< 5.7%; pre-diabetes: 5.7% -6.4%; diabetes: 6.5% or higher).
[3] This measure is computed using the subject’s average amount of exogenous insulin taken per day for the 3 days prior to the visit. (Formula: Total daily insulin dose=total daily insulin requirement (in units of insulin) multiplied by total body weight in kilograms).



  Outcome Measures
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1.  Primary:   Change in Mean C-peptide Area Under the Curve (AUC) Response to a Mixed Meal Tolerance Test (MMTT)   [ Time Frame: Baseline (Pre-treatment), Month 24 ]

2.  Secondary:   Change in HbA1c   [ Time Frame: Baseline (Pre-treatment), Month 24 ]

3.  Secondary:   Change in Average Total Insulin Dose Per Body Weight   [ Time Frame: Baseline (Pre-treatment), Month 24 ]


  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 NOT 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.


Results Point of Contact:  
Name/Title: Associate Director, Clinical Research Operations Program
Organization: DAIT/NIAID
phone: 301-594-7669
e-mail: DAITClinicalTrialsGov@niaid.nih.gov


Publications of Results:
Other Publications:
Publications automatically indexed to this study:

Responsible Party: National Institute of Allergy and Infectious Diseases (NIAID)
ClinicalTrials.gov Identifier: NCT00129259     History of Changes
Other Study ID Numbers: DAIT ITN027AI
Study First Received: August 9, 2005
Results First Received: June 21, 2013
Last Updated: June 4, 2014
Health Authority: United States: Food and Drug Administration
United States: Institutional Review Board