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

Study Description

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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.

Condition or disease	Intervention/treatment	Phase
Autoantibody Positive; Non-diabetic Relatives at Risk for Type 1 Diabetes; High Risk; Impaired Glucose Tolerance	Drug: Teplizumab	Phase 2

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.

Study Design

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Study Type :	Interventional (Clinical Trial)
Estimated Enrollment :	71 participants
Allocation:	Randomized
Intervention Model:	Parallel Assignment
Masking:	Quadruple (Participant, Care Provider, Investigator, Outcomes Assessor)
Primary Purpose:	Treatment
Official Title:	AntiCD3 Mab (Teplizumab) For Prevention of Diabetes In Relatives At-Risk for Type 1 Diabetes Mellitus
Study Start Date :	August 2010
Estimated Primary Completion Date :	January 2021
Estimated Study Completion Date :	January 2022

Arms and Interventions

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Arm	Intervention/treatment
Active Comparator: 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.	Drug: Teplizumab; intravenous infusions
Placebo Comparator: 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.	Drug: Teplizumab; intravenous infusions

Outcome Measures

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Primary Outcome Measures :

1. 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. [ Time Frame: Elapsed time from random treatment to development of type 1 diabetes (or time of last contact among those enrolled and determined to be eligible) ]

Secondary Outcome Measures :

1. effects on teplizumab based on age, gender, race/ethnicity,weight, BMI, immunologic, genetic , demographic, and lifestyle factors. [ Time Frame: Longitudinal analysis will take place over time until diagnosis of diabetes; some secondary outcome measures will be monitored longer such as metabolic and immunological markers. ]

Eligibility Criteria

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Ages Eligible for Study:	8 Years to 45 Years (Child, Adult)
Sexes Eligible for Study:	All
Accepts Healthy Volunteers:	No

Criteria

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, INR,

• positive 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

Contacts and Locations

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Locations

United States, California
University of California in San Francisco
San Francisco, California, United States, 94143
University of California-San Francisco
San Francisco, California, United States, 94143
Stanford University
Stanford, California, United States, 94305
United States, Colorado
Barbara Davis Center for Childhood Diabetes/ University of Colorado
Denver, Colorado, United States, 80045
United States, Connecticut
Yale University School of Medicine
New Haven, Connecticut, United States, 06519
United States, Florida
University of Florida
Gainesville, Florida, United States, 32610
University of Miami
Miami, Florida, United States, 33136
University of South Florida
Tampa, Florida, United States, 33612
United States, Indiana
Indiana University
Indianapolis, Indiana, United States, 46202
United States, Minnesota
University of Minnesota
Minneapolis, Minnesota, United States, 55455
United States, Missouri
The Children's Mercy Hospital
Kansas City, Missouri, United States, 64108
United States, New York
Columbia University
New York, New York, United States, 10032
United States, Pennsylvania
University of Pittsburgh
Pittsburgh, Pennsylvania, United States, 15201
United States, Tennessee
Vanderbilt University
Nashville, Tennessee, United States, 37232
United States, Texas
University of Texas
Dallas, Texas, United States, 75390-9072
Baylor College of Medicine
Houston, Texas, United States, 77030
United States, Washington
Benaroya Research Institute
Seattle, Washington, United States, 982101
Canada, Ontario
The Hospital for Sick Children
Toronto, Ontario, Canada, MSG-1X8
Germany
Forschergruppe Diabetes
Munich, Germany

Sponsors and Collaborators

National Institute of Diabetes and Digestive and Kidney Diseases (NIDDK)

National Institute of Allergy and Infectious Diseases (NIAID)

Eunice Kennedy Shriver National Institute of Child Health and Human Development (NICHD)

National Center for Research Resources (NCRR)

Juvenile Diabetes Research Foundation

American Diabetes Association

Investigators

Study Chair:	Carla J Greenbaum, MD	Type 1 Diabetes TrialNet

More Information

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Study Description Study Design Arms and Interventions Outcome Measures Eligibility Criteria Contacts and Locations More Information

Additional Information:

Type 1 Diabetes TrialNet 

Responsible Party:	National Institute of Diabetes and Digestive and Kidney Diseases (NIDDK)
ClinicalTrials.gov Identifier:	NCT01030861 History of Changes
Other Study ID Numbers:	TrialNet - tep (IND); UC4DK106993 ( U.S. NIH Grant/Contract )
First Posted:	December 14, 2009
Last Update Posted:	August 7, 2017
Last Verified:	August 2017

Keywords provided by National Institute of Diabetes and Digestive and Kidney Diseases (NIDDK):

type 1 diabetes; pre-diabetic; autoantibody positive	at risk for type 1 diabetes; glucose intolerance; relatives of people with type 1 diabetes

Additional relevant MeSH terms:

Diabetes Mellitus; Diabetes Mellitus, Type 1; Glucose Intolerance; Glucose Metabolism Disorders; Metabolic Diseases	Endocrine System Diseases; Autoimmune Diseases; Immune System Diseases; Hyperglycemia