Anti-CD3 mAb Treatment of Recent Onset Type 1 Diabetes

Phase 2

Completed

• Conditions: Type 1 Diabetes Mellitus
• Interventions: Drug: mAb hOKT3gamma1(Ala-Ala), Teplizumab; Drug: Placebo Arm

• Registration Number: NCT00378508
• Lead Sponsor: Yale University

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.

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 Timeline

• Study Start: 2006-09
• Study First Submitted: 2006-09-18
• Study First Submitted QC: 2006-09-18
• Study First Posted: 2006-09-20
• Primary Completion: 2011-08
• Results First Submitted: 2012-09-04
• Results First Submitted QC: 2012-10-01
• Results First Posted: 2012-10-31
• Study Completion: 2013-08
• Status Verified: 2021-08
• Last Update Submitted: 2021-08-11
• Last Update Posted: 2021-08-13

Recruitment & Eligibility

• Status: COMPLETED
• Sex: All
• Target Recruitment: 63

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

Study & Design

• Study Type: INTERVENTIONAL
• Study Design: PARALLEL

Arm && Interventions

Group	Intervention	Description
1	mAb hOKT3gamma1(Ala-Ala), Teplizumab	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.
2	Placebo Arm	Normal saline infusion

Primary Outcome Measures

Name	Time	Method
C-peptide Area Under the Curve (AUC) Response to a Mixed Meal Tolerance Test (MMTT) at 12 Months	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	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

Name	Time	Method
Baseline Hemoglobin A1c	At baseline (before treatment)
Hemoglobin A1c	At 12 months post-treatment
Average Insulin Use Over 12 Months	After 12 months post-treatment
Baseline Insulin Use	At baseline (before treatment)

Trial Locations

Locations (4)

University of California at San Francisco; 🇺🇸 San Francisco, California, United States

Children's Hospital of Philadelphia (CHOP); 🇺🇸 Philadelphia, Pennsylvania, United States

Barbara Davis Diabetes Center; 🇺🇸 Aurora, Colorado, United States

Yale University; 🇺🇸 New Haven, Connecticut, United States