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

Phase 2

Completed

Conditions: Autoantibody Positive
Impaired Glucose Tolerance
Non-diabetic Relatives at Risk for Type 1 Diabetes
High Risk

Lead Sponsor: National Institute of Diabetes and Digestive and Kidney Diseases (NIDDK)

Brief 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.

Detailed 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 & 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

Arm && Interventions

Group	Intervention	Description
Placebo infusion	Placebo infusion	Intravenous infusion of placebo (saline) will be given for 14 consecutive days. Infusions will take approximately 30 minutes and will be followed by a two hour observation period.
teplizumab	Teplizumab	Intravenous infusions of teplizumab given for 14 consecutive days. Each infusion takes about 30 minutes and is followed by a 2 hour observation period.

Primary Outcome Measures

Name	Time	Method
Rate of New Diabetes Per Year	During follow-up, median 745 days, range 74 to 2683	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.

Secondary Outcome Measures

Name	Time	Method
Number of Participants With Adverse Events	Baseline Visit to Diagnosis of Type 1 Diabetes median 745 days, range 74 to 2683	Adverse events categorized and graded via CTCAE.

Locations (19): University of California in San Francisco
🇺🇸
San Francisco, California, United States
Barbara Davis Center for Childhood Diabetes/ University of Colorado
🇺🇸
Denver, Colorado, United States
Columbia University
🇺🇸
New York, New York, United States
The Children's Mercy Hospital
🇺🇸
Kansas City, Missouri, United States
Yale University School of Medicine
🇺🇸
New Haven, Connecticut, United States
University of Florida
🇺🇸
Gainesville, Florida, United States
Baylor College of Medicine
🇺🇸
Houston, Texas, United States
Vanderbilt University
🇺🇸
Nashville, Tennessee, United States
University of Texas
🇺🇸
Dallas, Texas, United States
The Hospital for Sick Children
🇨🇦
Toronto, Ontario, Canada
University of Minnesota
🇺🇸
Minneapolis, Minnesota, United States
Indiana University
🇺🇸
Indianapolis, Indiana, United States
University of South Florida
🇺🇸
Tampa, Florida, United States
Forschergruppe Diabetes
🇩🇪
Munich, Germany
Benaroya Research Institute
🇺🇸
Seattle, Washington, United States
University of Pittsburgh
🇺🇸
Pittsburgh, Pennsylvania, United States
Stanford University
🇺🇸
Stanford, California, United States
University of Miami
🇺🇸
Miami, Florida, United States
University of California-San Francisco
🇺🇸
San Francisco, California, United States