Anti-CD3 mAb Treatment of Recent Onset Type 1 Diabetes

This study is ongoing, but not recruiting participants.

Sponsor:

Collaborators:

National Institute of Diabetes and Digestive and Kidney Diseases (NIDDK)

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

History of Changes

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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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

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Other Adverse Events

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More Information

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Certain Agreements:

All Principal Investigators ARE employed by the organization sponsoring the study.

Limitations and Caveats

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
No text entered.

Results Point of Contact:

Name/Title: Kevan Herold, MD
Organization: Yale University
phone: 203-785-6507
e-mail: Kevan.Herold@yale.edu

Publications:

Herold KC, Hagopian W, Auger JA, Poumian-Ruiz E, Taylor L, Donaldson D, Gitelman SE, Harlan DM, Xu D, Zivin RA, Bluestone JA. Anti-CD3 monoclonal antibody in new-onset type 1 diabetes mellitus. N Engl J Med. 2002 May 30;346(22):1692-8.

Herold KC, Gitelman SE, Masharani U, Hagopian W, Bisikirska B, Donaldson D, Rother K, Diamond B, Harlan DM, Bluestone JA. A single course of anti-CD3 monoclonal antibody hOKT3gamma1(Ala-Ala) results in improvement in C-peptide responses and clinical parameters for at least 2 years after onset of type 1 diabetes. Diabetes. 2005 Jun;54(6):1763-9.

Responsible Party:	Kevan Herold, Yale University
ClinicalTrials.gov Identifier:	NCT00378508 History of Changes
Other Study ID Numbers:	Delay-Study 5, R01DK57846
Study First Received:	September 18, 2006
Results First Received:	September 4, 2012
Last Updated:	October 31, 2012
Health Authority:	United States: Food and Drug Administration

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