Clinical trial NCT01030861: 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
Overall status: COMPLETED
Phase: PHASE2
Conditions: 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
Lead sponsor: National Institute of Diabetes and Digestive and Kidney Diseases (NIDDK)
Sponsor class: NIH
Collaborators: name: National Institute of Allergy and Infectious Diseases (NIAID)
name: Eunice Kennedy Shriver National Institute of Child Health and Human Development (NICHD)
name: National Center for Research Resources (NCRR)
name: Juvenile Diabetes Research Foundation
name: American Diabetes Association
First posted: 2009-12-14
Enrollment: 76
Sex: ALL
Minimum age (years): 8
Maximum age (years): 45
Standard ages: CHILD
ADULT
Accepts healthy volunteers: no
Allocation: RANDOMIZED
Intervention model: PARALLEL
Primary purpose: TREATMENT

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.

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

Primary outcomes:
measure: Rate of New Diabetes Per Year
timeFrame: During follow-up, median 745 days, range 74 to 2683
Secondary outcomes:
measure: Number of Participants With Adverse Events
timeFrame: Baseline Visit to Diagnosis of Type 1 Diabetes median 745 days, range 74 to 2683
Other outcomes:
Locations:
city: San Francisco
country: United States
facility: University of California in San Francisco
state: California
city: San Francisco
country: United States
facility: University of California-San Francisco
state: California
city: Stanford
country: United States
facility: Stanford University
state: California
city: Denver
country: United States
facility: Barbara Davis Center for Childhood Diabetes/ University of Colorado
state: Colorado
city: New Haven
country: United States
facility: Yale University School of Medicine
state: Connecticut
city: Gainesville
country: United States
facility: University of Florida
state: Florida
city: Miami
country: United States
facility: University of Miami
state: Florida
city: Tampa
country: United States
facility: University of South Florida
state: Florida
city: Indianapolis
country: United States
facility: Indiana University
state: Indiana
city: Minneapolis
country: United States
facility: University of Minnesota
state: Minnesota
city: Kansas City
country: United States
facility: The Children's Mercy Hospital
state: Missouri
city: New York
country: United States
facility: Columbia University
state: New York
city: Pittsburgh
country: United States
facility: University of Pittsburgh
state: Pennsylvania
city: Nashville
country: United States
facility: Vanderbilt University
state: Tennessee
city: Dallas
country: United States
facility: University of Texas
state: Texas
city: Houston
country: United States
facility: Baylor College of Medicine
state: Texas
city: Seattle
country: United States
facility: Benaroya Research Institute
state: Washington
city: Toronto
country: Canada
facility: The Hospital for Sick Children
state: Ontario
city: Munich
country: Germany
facility: Forschergruppe Diabetes
Study officials:
affiliation: Type 1 Diabetes TrialNet
name: Carla J Greenbaum, MD
role: STUDY_CHAIR
References:
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.
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.