Teplizumab for Prevention of Type 1 Diabetes In Relatives "At-Risk"

Impaired Glucose Tolerance Clinical Trial

Official title:

AntiCD3 Mab (Teplizumab) For Prevention of Diabetes In Relatives At-Risk for Type 1 Diabetes Mellitus

Clinical Trial Details — Status: Completed

Administrative data

• NCT number: NCT01030861
• Other study ID #: TrialNet - tep (IND)
• Secondary ID: UC4DK106993
• Status: Completed
• Phase: Phase 2
• Start date: August 2010
• Est. completion date: June 2019

Study information

• Verified date: July 2020
• Source: National Institute of Diabetes and Digestive and Kidney Diseases (NIDDK)
• Contact: n/a
• Is FDA regulated: No
• Study type: Interventional

Clinical Trial Summary

The study will determine whether the anti-CD3 monoclonal antibody, teplizumab, can help to prevent or delay the onset of type 1 diabetes (T1D) in relatives determined to be at very high risk for developing the disease. Teplizumab has been studied in new onset type 1 diabetes for testing of efficacy and safety in previous studies; other studies are currently in progress. The results of previous studies indicate that teplizumab reduces the loss of insulin production during the first year after diagnosis in individuals with type 1 diabetes. The purpose of this study is to determine if teplizumab can interdict the immune process that causes the destruction of insulin secreting beta cells in the pancreas during the "pre-diabetic" state and thereby prevent or delay the onset of type 1 diabetes.

Description:

The study plans to enroll approximately 71 subjects between the ages of 8-45 years, over 2-3 years. The study is projected to last between 4-6 years, depending upon rate of enrollment and number of subjects who develop diabetes.

The main study objective is to determine whether intervention with teplizumab will prevent or delay the development of type 1 diabetes in high risk autoantibody positive non-diabetic relatives of individuals with T1D. Secondary outcomes are to include analyses of C-peptide and other measures from Oral Glucose Tolerance Testing (OGTT), safety, tolerability, and other mechanistic outcomes will be assessed during the study.

Recruitment information / eligibility

• Status: Completed
• Enrollment: 76
• Est. completion date: June 2019
• Est. primary completion date: November 2018
• Accepts healthy volunteers: No
• Gender: All
• Age group: 8 Years to 45 Years

Eligibility

Inclusion Criteria:

• Between ages of 8-45 years

• Have a relative with type 1 diabetes

• If first degree relative must be 8-45 years old (brother, sister, parent, offspring)

• If second degree relative must be between 8-20 years old (niece, nephew, aunt, uncle, grandchild, cousin)

• Abnormal glucose tolerance by OGTT confirmed with 7 weeks of baseline visit [fasting blood glucose greater than 110mg/dL or and less than 126 mg/dL OR 2 hour glucose greater or equal to 140 mg/dL and less than 200 mg/dL OR 30, 60, or 90 minute value on OGTT greater than or equal to 200 mg/dL]

• Presence of at least two confirmed diabetes autoantibodies

Exclusion Criteria:

• type 1 diabetes previously diagnosed or detected at screening [fasting glucose greater or equal to 126 mg/dL or 2 hour glucose greater or equal to 200 mg/dL]

• abnormalities in blood counts, liver enzymes, international normalised ratio (INR),

• positive purified protein derivative (PPD) test

• vaccination with live virus within 6 weeks of randomization

• evidence of acute infection based on laboratory testing or clinical evidence

• serological evidence of past current or past HIV , hepatitis B, or hepatitis C infection

• Be currently pregnant or lactating

• Prior treatment with study drug

• Prior treatment with other monoclonal antibody in past one year

Related Conditions & MeSH terms

• Autoantibody Positive
• Diabetes Mellitus
• Diabetes Mellitus, Type 1
• Glucose Intolerance
• High Risk
• Impaired Glucose Tolerance
• Non-diabetic Relatives at Risk for Type 1 Diabetes

Intervention

Drug:
• Teplizumab
intravenous infusions
• Placebo infusion
Placebo for Teplizumab

Locations

Country	Name	City	State
Canada	The Hospital for Sick Children	Toronto	Ontario
Germany	Forschergruppe Diabetes	Munich
United States	University of Texas	Dallas	Texas
United States	Barbara Davis Center for Childhood Diabetes/ University of Colorado	Denver	Colorado
United States	University of Florida	Gainesville	Florida
United States	Baylor College of Medicine	Houston	Texas
United States	Indiana University	Indianapolis	Indiana
United States	The Children's Mercy Hospital	Kansas City	Missouri
United States	University of Miami	Miami	Florida
United States	University of Minnesota	Minneapolis	Minnesota
United States	Vanderbilt University	Nashville	Tennessee
United States	Yale University School of Medicine	New Haven	Connecticut
United States	Columbia University	New York	New York
United States	University of Pittsburgh	Pittsburgh	Pennsylvania
United States	University of California in San Francisco	San Francisco	California
United States	University of California-San Francisco	San Francisco	California
United States	Benaroya Research Institute	Seattle	Washington
United States	Stanford University	Stanford	California
United States	University of South Florida	Tampa	Florida

Sponsors (6)

Lead Sponsor	Collaborator
National Institute of Diabetes and Digestive and Kidney Diseases (NIDDK)	American Diabetes Association, Eunice Kennedy Shriver National Institute of Child Health and Human Development (NICHD), Juvenile Diabetes Research Foundation, National Center for Research Resources (NCRR), National Institute of Allergy and Infectious Diseases (NIAID)

Countries where clinical trial is conducted

United States,  Canada,  Germany, 

Outcome

Type	Measure	Description	Time frame	Safety issue
Primary	Rate of New Diabetes Per Year	Rate at which criteria are met for diabetes onset as defined by the American Diabetes Association (ADA) based on glucose testing or the presence of unequivocal hyperglycemia with acute metabolic decompensation.	During follow-up, median 745 days, range 74 to 2683
Secondary	Number of Participants With Adverse Events	Adverse events categorized and graded via CTCAE.	Baseline Visit to Diagnosis of Type 1 Diabetes median 745 days, range 74 to 2683

External Links

•   Type 1 Diabetes TrialNet