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

Primary Purpose

Autoantibody Positive, Non-diabetic Relatives at Risk for Type 1 Diabetes, High Risk

Status
Completed
Phase
Phase 2
Locations
International
Study Type
Interventional
Intervention
Teplizumab
Placebo infusion
Sponsored by
National Institute of Diabetes and Digestive and Kidney Diseases (NIDDK)
About
Eligibility
Locations
Arms
Outcomes
Full info

About this trial

This is an interventional treatment trial for Autoantibody Positive focused on measuring type 1 diabetes, pre-diabetic, autoantibody positive, at risk for type 1 diabetes, glucose intolerance, relatives of people with type 1 diabetes

Eligibility Criteria

8 Years - 45 Years (Child, Adult)All SexesDoes not accept healthy volunteers

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

Sites / Locations

  • University of California in San Francisco
  • University of California-San Francisco
  • Stanford University
  • Barbara Davis Center for Childhood Diabetes/ University of Colorado
  • Yale University School of Medicine
  • University of Florida
  • University of Miami
  • University of South Florida
  • Indiana University
  • University of Minnesota
  • The Children's Mercy Hospital
  • Columbia University
  • University of Pittsburgh
  • Vanderbilt University
  • University of Texas
  • Baylor College of Medicine
  • Benaroya Research Institute
  • The Hospital for Sick Children
  • Forschergruppe Diabetes

Arms of the Study

Arm 1

Arm 2

Arm Type

Active Comparator

Placebo Comparator

Arm Label

teplizumab

Placebo infusion

Arm Description

Intravenous infusions of teplizumab given for 14 consecutive days. Each infusion takes about 30 minutes and is followed by a 2 hour observation period.

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.

Outcomes

Primary Outcome Measures

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.

Secondary Outcome Measures

Number of Participants With Adverse Events
Adverse events categorized and graded via CTCAE.

Full Information

First Posted
December 11, 2009
Last Updated
July 21, 2020
Sponsor
National Institute of Diabetes and Digestive and Kidney Diseases (NIDDK)
Collaborators
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
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1. Study Identification

Unique Protocol Identification Number
NCT01030861
Brief Title
Teplizumab for Prevention of Type 1 Diabetes In Relatives "At-Risk"
Official Title
AntiCD3 Mab (Teplizumab) For Prevention of Diabetes In Relatives At-Risk for Type 1 Diabetes Mellitus
Study Type
Interventional

2. Study Status

Record Verification Date
July 2020
Overall Recruitment Status
Completed
Study Start Date
August 2010 (Actual)
Primary Completion Date
November 2018 (Actual)
Study Completion Date
June 2019 (Actual)

3. Sponsor/Collaborators

Responsible Party, by Official Title
Sponsor
Name of the Sponsor
National Institute of Diabetes and Digestive and Kidney Diseases (NIDDK)
Collaborators
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

4. Oversight

Data Monitoring Committee
Yes

5. Study Description

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.

6. Conditions and Keywords

Primary Disease or Condition Being Studied in the Trial, or the Focus of the Study
Autoantibody Positive, Non-diabetic Relatives at Risk for Type 1 Diabetes, High Risk, Impaired Glucose Tolerance
Keywords
type 1 diabetes, pre-diabetic, autoantibody positive, at risk for type 1 diabetes, glucose intolerance, relatives of people with type 1 diabetes

7. Study Design

Primary Purpose
Treatment
Study Phase
Phase 2
Interventional Study Model
Parallel Assignment
Masking
ParticipantCare ProviderInvestigatorOutcomes Assessor
Allocation
Randomized
Enrollment
76 (Actual)

8. Arms, Groups, and Interventions

Arm Title
teplizumab
Arm Type
Active Comparator
Arm Description
Intravenous infusions of teplizumab given for 14 consecutive days. Each infusion takes about 30 minutes and is followed by a 2 hour observation period.
Arm Title
Placebo infusion
Arm Type
Placebo Comparator
Arm Description
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.
Intervention Type
Drug
Intervention Name(s)
Teplizumab
Intervention Description
intravenous infusions
Intervention Type
Drug
Intervention Name(s)
Placebo infusion
Intervention Description
Placebo for Teplizumab
Primary Outcome Measure Information:
Title
Rate of New Diabetes Per Year
Description
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.
Time Frame
During follow-up, median 745 days, range 74 to 2683
Secondary Outcome Measure Information:
Title
Number of Participants With Adverse Events
Description
Adverse events categorized and graded via CTCAE.
Time Frame
Baseline Visit to Diagnosis of Type 1 Diabetes median 745 days, range 74 to 2683

10. Eligibility

Sex
All
Minimum Age & Unit of Time
8 Years
Maximum Age & Unit of Time
45 Years
Accepts Healthy Volunteers
No
Eligibility 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, 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
Overall Study Officials:
First Name & Middle Initial & Last Name & Degree
Carla J Greenbaum, MD
Organizational Affiliation
Type 1 Diabetes TrialNet
Official's Role
Study Chair
Facility Information:
Facility Name
University of California in San Francisco
City
San Francisco
State/Province
California
ZIP/Postal Code
94143
Country
United States
Facility Name
University of California-San Francisco
City
San Francisco
State/Province
California
ZIP/Postal Code
94143
Country
United States
Facility Name
Stanford University
City
Stanford
State/Province
California
ZIP/Postal Code
94305
Country
United States
Facility Name
Barbara Davis Center for Childhood Diabetes/ University of Colorado
City
Denver
State/Province
Colorado
ZIP/Postal Code
80045
Country
United States
Facility Name
Yale University School of Medicine
City
New Haven
State/Province
Connecticut
ZIP/Postal Code
06519
Country
United States
Facility Name
University of Florida
City
Gainesville
State/Province
Florida
ZIP/Postal Code
32610
Country
United States
Facility Name
University of Miami
City
Miami
State/Province
Florida
ZIP/Postal Code
33136
Country
United States
Facility Name
University of South Florida
City
Tampa
State/Province
Florida
ZIP/Postal Code
33612
Country
United States
Facility Name
Indiana University
City
Indianapolis
State/Province
Indiana
ZIP/Postal Code
46202
Country
United States
Facility Name
University of Minnesota
City
Minneapolis
State/Province
Minnesota
ZIP/Postal Code
55455
Country
United States
Facility Name
The Children's Mercy Hospital
City
Kansas City
State/Province
Missouri
ZIP/Postal Code
64108
Country
United States
Facility Name
Columbia University
City
New York
State/Province
New York
ZIP/Postal Code
10032
Country
United States
Facility Name
University of Pittsburgh
City
Pittsburgh
State/Province
Pennsylvania
ZIP/Postal Code
15201
Country
United States
Facility Name
Vanderbilt University
City
Nashville
State/Province
Tennessee
ZIP/Postal Code
37232
Country
United States
Facility Name
University of Texas
City
Dallas
State/Province
Texas
ZIP/Postal Code
75390-9072
Country
United States
Facility Name
Baylor College of Medicine
City
Houston
State/Province
Texas
ZIP/Postal Code
77030
Country
United States
Facility Name
Benaroya Research Institute
City
Seattle
State/Province
Washington
ZIP/Postal Code
982101
Country
United States
Facility Name
The Hospital for Sick Children
City
Toronto
State/Province
Ontario
ZIP/Postal Code
MSG-1X8
Country
Canada
Facility Name
Forschergruppe Diabetes
City
Munich
Country
Germany

12. IPD Sharing Statement

Plan to Share IPD
Yes
IPD Sharing Plan Description
Data are available at the National Institute of Diabetes and Digestive and Kidney Diseases (NIDDK) Central Repository: https://repository.niddk.nih.gov/studies/tn10-anti-cd3-prevention/?query=trialnet%20Teplizumab
IPD Sharing URL
https://repository.niddk.nih.gov/studies/tn10-anti-cd3-prevention/?query=trialnet%20Teplizumab
Citations:
PubMed Identifier
35713929
Citation
Leung SS, Borg DJ, McCarthy DA, Boursalian TE, Cracraft J, Zhuang A, Fotheringham AK, Flemming N, Watkins T, Miles JJ, Groop PH, Scheijen JL, Schalkwijk CG, Steptoe RJ, Radford KJ, Knip M, Forbes JM. Soluble RAGE Prevents Type 1 Diabetes Expanding Functional Regulatory T Cells. Diabetes. 2022 Sep 1;71(9):1994-2008. doi: 10.2337/db22-0177.
Results Reference
derived
PubMed Identifier
31180194
Citation
Herold KC, Bundy BN, Long SA, Bluestone JA, DiMeglio LA, Dufort MJ, Gitelman SE, Gottlieb PA, Krischer JP, Linsley PS, Marks JB, Moore W, Moran A, Rodriguez H, Russell WE, Schatz D, Skyler JS, Tsalikian E, Wherrett DK, Ziegler AG, Greenbaum CJ; Type 1 Diabetes TrialNet Study Group. An Anti-CD3 Antibody, Teplizumab, in Relatives at Risk for Type 1 Diabetes. N Engl J Med. 2019 Aug 15;381(7):603-613. doi: 10.1056/NEJMoa1902226. Epub 2019 Jun 9. Erratum In: N Engl J Med. 2020 Feb 6;382(6):586.
Results Reference
derived
Links:
URL
https://www.diabetestrialnet.org/publicationsdatabase/Article
Description
Type 1 Diabetes TrialNet

Learn more about this trial

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

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