Now Available for Public Comment: Notice of Proposed Rulemaking (NPRM) for FDAAA 801 and NIH Draft Reporting Policy for NIH-Funded Trials

Anti-CD3 mAb Treatment of Recent Onset Type 1 Diabetes

The recruitment status of this study is unknown because the information has not been verified recently.
Verified October 2012 by Yale University.
Recruitment status was  Active, not recruiting
Sponsor:
Collaborators:
Juvenile Diabetes Research Foundation
Information provided by (Responsible Party):
Kevan Herold, Yale University
ClinicalTrials.gov Identifier:
NCT00378508
First received: September 18, 2006
Last updated: October 31, 2012
Last verified: October 2012
Results First Received: September 4, 2012  
Study Type: Interventional
Study Design: Allocation: Randomized;   Endpoint Classification: Safety/Efficacy Study;   Intervention Model: Parallel Assignment;   Masking: Double Blind (Subject, Caregiver, Investigator);   Primary Purpose: Treatment
Condition: Type 1 Diabetes Mellitus
Interventions: Drug: mAb hOKT3gamma1(Ala-Ala), Teplizumab
Drug: Placebo Arm

  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
Subjects were recruited from 4 clinical sites and were eligible if they were between the ages of 8-30 and diagnosed with Type 1 Diabetes for at least 4 months, but not more than 12 months prior to enrollment.

Pre-Assignment Details
Significant events and approaches for the overall study following participant enrollment, but prior to group assignment
No text entered.

Reporting Groups
  Description
Saline Infusions (Placebo) The course of normal saline infusion comprises daily doses of 51 µg/m2, 103 µg/m2, 207 µg/m2, 413 µg/m2, and 10 of 826 µg/m2 over a 14 day treatment period.
Teplizumab Infusion (Active) The course of teplizumab infusion comprises daily doses of 51 µg/m2, 103 µg/m2, 207 µg/m2, 413 µg/m2, and 10 of 826 µg/m2 over a 14 day treatment period.

Participant Flow:   Overall Study
    Saline Infusions (Placebo)     Teplizumab Infusion (Active)  
STARTED     29     34  
Randomized     29     34  
Received Intervention/Placebo     28     31  
COMPLETED     27     31  
NOT COMPLETED     2     3  
Withdrawal by Subject                 1                 3  
Lost to Follow-up                 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
Saline Infusions (Placebo) The course of normal saline infusion comprises daily doses of 51 µg/m2, 103 µg/m2, 207 µg/m2, 413 µg/m2, and 10 of 826 µg/m2 over a 14 day treatment period.
Teplizumab Infusions (Active) The course of teplizumab infusion comprises daily doses of 51 µg/m2, 103 µg/m2, 207 µg/m2, 413 µg/m2, and 10 of 826 µg/m2 over a 14 day treatment period.
Total Total of all reporting groups

Baseline Measures
    Saline Infusions (Placebo)     Teplizumab Infusions (Active)     Total  
Number of Participants  
[units: participants]
  27     31     58  
Age, Customized  
[units: participants]
     
<15 years     20     18     38  
>=15 years     7     13     20  
Gender, Customized  
[units: participants]
     
Female     10     15     25  
Male     17     16     33  



  Outcome Measures
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1.  Primary:   C-peptide Area Under the Curve (AUC) Response to a Mixed Meal Tolerance Test (MMTT) at 12 Months   [ Time Frame: At month 12 post-treatment ]

Measure Type Primary
Measure Title C-peptide Area Under the Curve (AUC) Response to a Mixed Meal Tolerance Test (MMTT) at 12 Months
Measure Description

C-peptide secretory response was calculated as ln[(Area Under the Curve of the C-peptide from the 240 minute MMTT/240 +1]

For presentation, the C-peptide data were converted to the AUC as pmol/ml. This is adjusted for baseline.

Time Frame At month 12 post-treatment  
Safety Issue No  

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.
This endpoint was compared in the modified intent to treat population which included all subjects with at least one post-randomization mixed meal tolerance test (MMTT)

Reporting Groups
  Description
Teplizumab Infusions (Active) The course of teplizumab infusion comprises daily doses of 51 µg/m2, 103 µg/m2, 207 µg/m2, 413 µg/m2, and 10 of 826 µg/m2 over a 14 day treatment period.
Saline Infusions (Placebo) The course of normal saline infusion comprises daily doses of 51 µg/m2, 103 µg/m2, 207 µg/m2, 413 µg/m2, and 10 of 826 µg/m2 over a 14 day treatment period.

Measured Values
    Teplizumab Infusions (Active)     Saline Infusions (Placebo)  
Number of Participants Analyzed  
[units: participants]
  31     27  
C-peptide Area Under the Curve (AUC) Response to a Mixed Meal Tolerance Test (MMTT) at 12 Months  
[units: pmol/ml]
Least Squares Mean ( 95% Confidence Interval )
  0.451  
  ( 0.4 to 0.505 )  
  0.371  
  ( 0.319 to 0.424 )  

No statistical analysis provided for C-peptide Area Under the Curve (AUC) Response to a Mixed Meal Tolerance Test (MMTT) at 12 Months



2.  Primary:   C-peptide Area Under the Curve (AUC) Response to a Mixed Meal Tolerance Test (MMTT) at Baseline   [ Time Frame: At Baseline (before treatment) ]

Measure Type Primary
Measure Title C-peptide Area Under the Curve (AUC) Response to a Mixed Meal Tolerance Test (MMTT) at Baseline
Measure Description

C-peptide secretory response was calculated as ln[(Area Under the Curve of the C-peptide from the 240 minute MMTT/240 +1]

For presentation, the C-peptide data were converted to the AUC as pmol/ml. This baseline data was used to adjust for the C-peptide AUC primary endpoint measure at 12 months.

Time Frame At Baseline (before treatment)  
Safety Issue No  

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.
This endpoint was compared in the modified intent to treat population which included all subjects with at least one post-randomization mixed meal tolerance test (MMTT)

Reporting Groups
  Description
Teplizumab Infusions (Active) The course of teplizumab infusion comprises daily doses of 51 µg/m2, 103 µg/m2, 207 µg/m2, 413 µg/m2, and 10 of 826 µg/m2 over a 14 day treatment period.
Saline Infusions (Placebo) The course of normal saline infusion comprises daily doses of 51 µg/m2, 103 µg/m2, 207 µg/m2, 413 µg/m2, and 10 of 826 µg/m2 over a 14 day treatment period.

Measured Values
    Teplizumab Infusions (Active)     Saline Infusions (Placebo)  
Number of Participants Analyzed  
[units: participants]
  31     27  
C-peptide Area Under the Curve (AUC) Response to a Mixed Meal Tolerance Test (MMTT) at Baseline  
[units: pmol/ml]
Least Squares Mean ( 95% Confidence Interval )
  0.593  
  ( 0.493 to 0.699 )  
  0.554  
  ( 0.417 to 0.705 )  

No statistical analysis provided for C-peptide Area Under the Curve (AUC) Response to a Mixed Meal Tolerance Test (MMTT) at Baseline



3.  Secondary:   Hemoglobin A1c   [ Time Frame: At 12 months post-treatment ]

Measure Type Secondary
Measure Title Hemoglobin A1c
Measure Description No text entered.
Time Frame At 12 months post-treatment  
Safety Issue No  

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
Teplizumab Infusions (Active) The course of teplizumab infusion comprises daily doses of 51 µg/m2, 103 µg/m2, 207 µg/m2, 413 µg/m2, and 10 of 826 µg/m2 over a 14 day treatment period.
Saline Infusions (Placebo) The course of normal saline infusion comprises daily doses of 51 µg/m2, 103 µg/m2, 207 µg/m2, 413 µg/m2, and 10 of 826 µg/m2 over a 14 day treatment period.

Measured Values
    Teplizumab Infusions (Active)     Saline Infusions (Placebo)  
Number of Participants Analyzed  
[units: participants]
  31     27  
Hemoglobin A1c  
[units: percentage of hemogloblin A1c]
Least Squares Mean ( 95% Confidence Interval )
  6.85  
  ( 6.47 to 7.23 )  
  7.35  
  ( 6.87 to 7.83 )  

No statistical analysis provided for Hemoglobin A1c



4.  Secondary:   Average Insulin Use Over 12 Months   [ Time Frame: After 12 months post-treatment ]

Measure Type Secondary
Measure Title Average Insulin Use Over 12 Months
Measure Description No text entered.
Time Frame After 12 months post-treatment  
Safety Issue No  

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.
This endpoint was compared in the modified intent to treat population which included all subjects with at least one post-randomization mixed meal tolerance test (MMTT)

Reporting Groups
  Description
Teplizumab Infusions (Active) The course of teplizumab infusion comprises daily doses of 51 µg/m2, 103 µg/m2, 207 µg/m2, 413 µg/m2, and 10 of 826 µg/m2 over a 14 day treatment period.
Saline Infusion (Placebo) The course of normal saline infusion comprises daily doses of 51 µg/m2, 103 µg/m2, 207 µg/m2, 413 µg/m2, and 10 of 826 µg/m2 over a 14 day treatment period.

Measured Values
    Teplizumab Infusions (Active)     Saline Infusion (Placebo)  
Number of Participants Analyzed  
[units: participants]
  31     27  
Average Insulin Use Over 12 Months  
[units: U/kg/d]
Least Squares Mean ( 95% Confidence Interval )
  0.475  
  ( 0.428 to 0.521 )  
  0.574  
  ( 0.0526 to 0.622 )  

No statistical analysis provided for Average Insulin Use Over 12 Months



5.  Secondary:   Baseline Insulin Use   [ Time Frame: At baseline (before treatment) ]

Measure Type Secondary
Measure Title Baseline Insulin Use
Measure Description No text entered.
Time Frame At baseline (before treatment)  
Safety Issue No  

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.
This endpoint was compared in the modified intent to treat population which included all subjects with at least one post-randomization mixed meal tolerance test (MMTT)

Reporting Groups
  Description
Teplizumab Infusions (Active) The course of teplizumab infusion comprises daily doses of 51 µg/m2, 103 µg/m2, 207 µg/m2, 413 µg/m2, and 10 of 826 µg/m2 over a 14 day treatment period.
Saline Infusion (Placebo) The course of normal saline infusion comprises daily doses of 51 µg/m2, 103 µg/m2, 207 µg/m2, 413 µg/m2, and 10 of 826 µg/m2 over a 14 day treatment period.

Measured Values
    Teplizumab Infusions (Active)     Saline Infusion (Placebo)  
Number of Participants Analyzed  
[units: participants]
  31     27  
Baseline Insulin Use  
[units: U/kg/d]
Least Squares Mean ( 95% Confidence Interval )
  0.405  
  ( 0.354 to 0.456 )  
  0.386  
  ( 0.308 to 0.464 )  

No statistical analysis provided for Baseline Insulin Use



6.  Secondary:   Baseline Hemoglobin A1c   [ Time Frame: At baseline (before treatment) ]

Measure Type Secondary
Measure Title Baseline Hemoglobin A1c
Measure Description No text entered.
Time Frame At baseline (before treatment)  
Safety Issue No  

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
Teplizumab Infusions (Active) The course of teplizumab infusion comprises daily doses of 51 µg/m2, 103 µg/m2, 207 µg/m2, 413 µg/m2, and 10 of 826 µg/m2 over a 14 day treatment period.
Saline Infusions (Placebo) The course of normal saline infusion comprises daily doses of 51 µg/m2, 103 µg/m2, 207 µg/m2, 413 µg/m2, and 10 of 826 µg/m2 over a 14 day treatment period.

Measured Values
    Teplizumab Infusions (Active)     Saline Infusions (Placebo)  
Number of Participants Analyzed  
[units: participants]
  31     27  
Baseline Hemoglobin A1c  
[units: percentage of hemoglobin A1c]
Least Squares Mean ( 95% Confidence Interval )
  6.32  
  ( 6.04 to 6.60 )  
  7.1  
  ( 6.66 to 7.64 )  

No statistical analysis provided for Baseline Hemoglobin A1c




  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