Anti-CD3 mAb Treatment of Recent Onset Type 1 Diabetes

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ClinicalTrials.gov Identifier: NCT00378508

Recruitment Status : Completed

First Posted : September 20, 2006

Results First Posted : October 31, 2012

Last Update Posted : August 2, 2016

Sponsor:

Collaborators:

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

Juvenile Diabetes Research Foundation

Information provided by (Responsible Party):

Yale University

Study Description

Brief Summary:

This is a randomized placebo controlled study to test whether a single 14 course of treatment with the anti-CD3 monoclonal antibody, hOKT3gamma1(Ala-Ala),Teplizumab will prevent the loss of insulin secretory capacity in individuals with Type 1 diabetes of 4 - 12 months duration since diagnosis.

Condition or disease	Intervention/treatment	Phase
Type 1 Diabetes Mellitus	Drug: mAb hOKT3gamma1(Ala-Ala), Teplizumab Drug: Placebo Arm	Phase 2

Detailed Description:

The study design is a double blind placebo controlled trial that will enroll subjects between the ages of 8 - 30 who have had the diagnosis of Type 1 diabetes made 4 - 12 months prior to enrollment. A single 14 course of treatment with mAb hOKT3gamma1(Ala-Ala), Teplizumab will be given. The primary endpoint is the C-peptide response to a mixed meal at 12 months. A total of 60 subjects will be enrolled (30 in the drug treatment and 30 in the placebo groups) at 4 study sites: Yale University,the University of California at San Francisco, Children's Hospital of Philadelphia, and the Barbara Davis Diabetes Center.

Study Design

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Study Type :	Interventional (Clinical Trial)
Actual Enrollment :	63 participants
Allocation:	Randomized
Intervention Model:	Parallel Assignment
Masking:	Triple (Participant, Care Provider, Investigator)
Primary Purpose:	Treatment
Official Title:	Phase II Trial of hOKT3gamma1(Ala-Ala) Teplizumab for Treatment of Patients With Recent Onset Type 1 Diabetes
Study Start Date :	September 2006
Actual Primary Completion Date :	August 2011
Actual Study Completion Date :	August 2013

Resource links provided by the National Library of Medicine

MedlinePlus Genetics related topics: Type 1 diabetes

MedlinePlus related topics: Diabetes Type 1

U.S. FDA Resources

Arms and Interventions

Arm	Intervention/treatment
Experimental: 1 The course of Teplizumab 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.	Drug: mAb hOKT3gamma1(Ala-Ala), Teplizumab This is a randomized, two-arm, double blind placebo controlled phase II trial in which 60 participants with recent-onset T1DM are randomized at a 1:1 ratio to receive Teplizumab or placebo over a 14 day treatment period. The course of Teplizumab comprises daily doses of 51 µg/m2, 103 µg/m2, 207 µg/m2, 413 µg/m2, and 10 of 826 µg/m2. Other Name: mAb hOKT3gamma1(Ala-Ala), MGA031, Teplizumab
Placebo Comparator: 2 Normal saline infusion	Drug: Placebo Arm

Arm

Intervention/treatment

Experimental: 1

The course of Teplizumab 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.

Drug: mAb hOKT3gamma1(Ala-Ala), Teplizumab

This is a randomized, two-arm, double blind placebo controlled phase II trial in which 60 participants with recent-onset T1DM are randomized at a 1:1 ratio to receive Teplizumab or placebo over a 14 day treatment period. The course of Teplizumab comprises daily doses of 51 µg/m2, 103 µg/m2, 207 µg/m2, 413 µg/m2, and 10 of 826 µg/m2.

Other Name: mAb hOKT3gamma1(Ala-Ala), MGA031, Teplizumab

Placebo Comparator: 2

Normal saline infusion

Drug: Placebo Arm

Outcome Measures

Primary Outcome Measures :

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

Secondary Outcome Measures :

Hemoglobin A1c [ Time Frame: At 12 months post-treatment ]
Average Insulin Use Over 12 Months [ Time Frame: After 12 months post-treatment ]
Baseline Insulin Use [ Time Frame: At baseline (before treatment) ]
Baseline Hemoglobin A1c [ Time Frame: At baseline (before treatment) ]

Eligibility Criteria

Information from the National Library of Medicine

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Ages Eligible for Study:	8 Years to 30 Years (Child, Adult)
Sexes Eligible for Study:	All
Accepts Healthy Volunteers:	No

Criteria

Inclusion Criteria:

age 8 - 30,
duration of diabetes 4 - 12 months,
weight greater than 27.5 kg,
stimulated C-peptide >= 0.2 pmol/ml

Exclusion Criteria:

asthma,
history of hepatitis C, hepatitis B, HIV

Contacts and Locations

Information from the National Library of Medicine

To learn more about this study, you or your doctor may contact the study research staff using the contact information provided by the sponsor.

Please refer to this study by its ClinicalTrials.gov identifier (NCT number): NCT00378508

Locations

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United States, California
University of California at San Francisco
San Francisco, California, United States, 94143
United States, Colorado
Barbara Davis Diabetes Center
Aurora, Colorado, United States, 80045
United States, Connecticut
Yale University
New Haven, Connecticut, United States, 06520
United States, Pennsylvania
Children's Hospital of Philadelphia (CHOP)
Philadelphia, Pennsylvania, United States, 10194

Sponsors and Collaborators

Yale University

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

Juvenile Diabetes Research Foundation

Investigators

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Principal Investigator:	Kevan C Herold	Yale University
Principal Investigator:	Jeffrey A Bluestone, PhD	University of California at San Francisco

More Information

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.

Publications automatically indexed to this study by ClinicalTrials.gov Identifier (NCT Number):

Sherr JL, Ghazi T, Wurtz A, Rink L, Herold KC. Characterization of residual β cell function in long-standing type 1 diabetes. Diabetes Metab Res Rev. 2014 Feb;30(2):154-62. doi: 10.1002/dmrr.2478.

Lebastchi J, Deng S, Lebastchi AH, Beshar I, Gitelman S, Willi S, Gottlieb P, Akirav EM, Bluestone JA, Herold KC. Immune therapy and β-cell death in type 1 diabetes. Diabetes. 2013 May;62(5):1676-80. doi: 10.2337/db12-1207. Epub 2013 Feb 19.

Herold KC, Gitelman SE, Willi SM, Gottlieb PA, Waldron-Lynch F, Devine L, Sherr J, Rosenthal SM, Adi S, Jalaludin MY, Michels AW, Dziura J, Bluestone JA. Teplizumab treatment may improve C-peptide responses in participants with type 1 diabetes after the new-onset period: a randomised controlled trial. Diabetologia. 2013 Feb;56(2):391-400. doi: 10.1007/s00125-012-2753-4. Epub 2012 Oct 21.

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Responsible Party:	Yale University
ClinicalTrials.gov Identifier:	NCT00378508
Other Study ID Numbers:	Delay-Study 5 R01DK057846 ( U.S. NIH Grant/Contract )
First Posted:	September 20, 2006 Key Record Dates
Results First Posted:	October 31, 2012
Last Update Posted:	August 2, 2016
Last Verified:	July 2016

Keywords provided by Yale University:


immune therapy autoimmunity insulin secretion diabetes mellitus

Additional relevant MeSH terms:

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Diabetes Mellitus Diabetes Mellitus, Type 1 Glucose Metabolism Disorders Metabolic Diseases	Endocrine System Diseases Autoimmune Diseases Immune System Diseases

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