Anti-CD3 mAb Treatment of Recent Onset Type 1 Diabetes

This study is ongoing, but not recruiting participants.
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
  Purpose

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 Intervention Phase
Type 1 Diabetes Mellitus
Drug: mAb hOKT3gamma1(Ala-Ala), Teplizumab
Drug: Placebo Arm
Phase 2

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
Official Title: Phase II Trial of hOKT3gamma1(Ala-Ala) Teplizumab for Treatment of Patients With Recent Onset Type 1 Diabetes

Resource links provided by NLM:


Further study details as provided by Yale University:

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 ] [ Designated as safety issue: No ]

    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) ] [ Designated as safety issue: No ]

    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 ] [ Designated as safety issue: No ]
  • Average Insulin Use Over 12 Months [ Time Frame: After 12 months post-treatment ] [ Designated as safety issue: No ]
  • Baseline Insulin Use [ Time Frame: At baseline (before treatment) ] [ Designated as safety issue: No ]
  • Baseline Hemoglobin A1c [ Time Frame: At baseline (before treatment) ] [ Designated as safety issue: No ]

Enrollment: 63
Study Start Date: September 2006
Estimated Study Completion Date: August 2013
Primary Completion Date: August 2011 (Final data collection date for primary outcome measure)
Arms Assigned Interventions
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

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.

  Eligibility

Ages Eligible for Study:   8 Years to 30 Years
Genders Eligible for Study:   Both
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
Choosing to participate in a study is an important personal decision. Talk with your doctor and family members or friends about deciding to join a study. To learn more about this study, you or your doctor may contact the study research staff using the Contacts provided below. For general information, see Learn About Clinical Studies.

Please refer to this study by its ClinicalTrials.gov identifier: NCT00378508

Locations
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
Juvenile Diabetes Research Foundation
Investigators
Principal Investigator: Kevan C Herold Yale University
Principal Investigator: Jeffrey A Bluestone, PhD University of California at San Francisco
  More Information

Publications:
Additional publications automatically indexed to this study by ClinicalTrials.gov Identifier (NCT Number):
Responsible Party: Kevan Herold, Professor, 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

Keywords provided by Yale University:
immune therapy
autoimmunity
insulin secretion
diabetes mellitus

Additional relevant MeSH terms:
Diabetes Mellitus
Diabetes Mellitus, Type 1
Glucose Metabolism Disorders
Metabolic Diseases
Endocrine System Diseases
Autoimmune Diseases
Immune System Diseases

ClinicalTrials.gov processed this record on July 31, 2014