Anti-CD3 mAb Treatment of Recent Onset Type 1 Diabetes

Type 1 Diabetes Mellitus Clinical Trial

Official title:

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

Clinical Trial Details — Status: Completed

Administrative data

• NCT number: NCT00378508
• Other study ID #: Delay-Study 5
• Secondary ID: R01DK057846
• Status: Completed
• Phase: Phase 2
• Start date: September 2006
• Est. completion date: August 2013

Study information

• Verified date: August 2021
• Source: Yale University
• Contact: n/a
• Is FDA regulated: No
• Study type: Interventional

Clinical Trial 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.

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.

Recruitment information / eligibility

• Status: Completed
• Enrollment: 63
• Est. completion date: August 2013
• Est. primary completion date: August 2011
• Accepts healthy volunteers: No
• Gender: All
• Age group: 8 Years to 30 Years

Eligibility

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

Related Conditions & MeSH terms

• Diabetes Mellitus
• Diabetes Mellitus, Type 1
• Type 1 Diabetes Mellitus

Intervention

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.
• Placebo Arm

Locations

Country	Name	City	State
United States	Barbara Davis Diabetes Center	Aurora	Colorado
United States	Yale University	New Haven	Connecticut
United States	Children's Hospital of Philadelphia (CHOP)	Philadelphia	Pennsylvania
United States	University of California at San Francisco	San Francisco	California

Sponsors (3)

Lead Sponsor	Collaborator
Yale University	Juvenile Diabetes Research Foundation, National Institute of Diabetes and Digestive and Kidney Diseases (NIDDK)

Country where clinical trial is conducted

United States, 

References & Publications (2)

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. — View Citation

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. — View Citation

Outcome

Type	Measure	Description	Time frame	Safety issue
Primary	C-peptide Area Under the Curve (AUC) Response to a Mixed Meal Tolerance Test (MMTT) at 12 Months	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.	At month 12 post-treatment
Primary	C-peptide Area Under the Curve (AUC) Response to a Mixed Meal Tolerance Test (MMTT) at Baseline	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.	At Baseline (before treatment)
Secondary	Hemoglobin A1c		At 12 months post-treatment
Secondary	Average Insulin Use Over 12 Months		After 12 months post-treatment
Secondary	Baseline Insulin Use		At baseline (before treatment)
Secondary	Baseline Hemoglobin A1c		At baseline (before treatment)