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

NCT ID: NCT01030861

Last Updated: 2020-08-05

Basic Information

• Recruitment Status: COMPLETED
• Clinical Phase: PHASE2
• Total Enrollment: 76 participants
• Study Classification: INTERVENTIONAL
• Study Start Date: 2010-08-31
• Study Completion Date: 2019-06-30

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.

Conditions

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

Study Design

• Allocation Method: RANDOMIZED
• Intervention Model: PARALLEL
• Primary Study Purpose: TREATMENT
• Blinding Strategy: QUADRUPLE

Study Groups

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.

Group Type: ACTIVE_COMPARATOR

Teplizumab

Intervention Type: DRUG

intravenous infusions

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.

Group Type: PLACEBO_COMPARATOR

Placebo infusion

Intervention Type: DRUG

Placebo for Teplizumab

Interventions

Teplizumab

intravenous infusions

Intervention Type: DRUG

Placebo infusion

Placebo for Teplizumab

Intervention Type: DRUG

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

• Minimum Eligible Age: 8 Years
• Maximum Eligible Age: 45 Years
• Eligible Sex: ALL
• Accepts Healthy Volunteers: No

Sponsors

National Institute of Allergy and Infectious Diseases (NIAID)

NIH

Sponsor Role: collaborator

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

NIH

Sponsor Role: collaborator

National Center for Research Resources (NCRR)

NIH

Sponsor Role: collaborator

Juvenile Diabetes Research Foundation

OTHER

Sponsor Role: collaborator

American Diabetes Association

OTHER

Sponsor Role: collaborator

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

NIH

Sponsor Role: lead

Responsible Party

Responsibility Role: SPONSOR

Principal Investigators

Carla J Greenbaum, MD

Role: STUDY_CHAIR

Type 1 Diabetes TrialNet

Locations

University of California in San Francisco

San Francisco, California, United States

University of California-San Francisco

San Francisco, California, United States

Stanford University

Stanford, California, United States

Barbara Davis Center for Childhood Diabetes/ University of Colorado

Denver, Colorado, United States

Yale University School of Medicine

New Haven, Connecticut, United States

University of Florida

Gainesville, Florida, United States

University of Miami

Miami, Florida, United States

University of South Florida

Tampa, Florida, United States

Indiana University

Indianapolis, Indiana, United States

University of Minnesota

Minneapolis, Minnesota, United States

The Children's Mercy Hospital

Kansas City, Missouri, United States

Columbia University

New York, New York, United States

University of Pittsburgh

Pittsburgh, Pennsylvania, United States

Vanderbilt University

Nashville, Tennessee, United States

University of Texas

Dallas, Texas, United States

Baylor College of Medicine

Houston, Texas, United States

Benaroya Research Institute

Seattle, Washington, United States

The Hospital for Sick Children

Toronto, Ontario, Canada

Forschergruppe Diabetes

Munich, , Germany

Countries

United States; Canada; Germany

References

Ajmal N, Bogart MC, Khan P, Max-Harry IM, Healy AM, Nunemaker CS. Identifying Promising Immunomodulators for Type 1 Diabetes (T1D) and Islet Transplantation. J Diabetes Res. 2024 Dec 20;2024:5151171. doi: 10.1155/jdr/5151171. eCollection 2024.

Reference Type: DERIVED

PMID: 39735417 (View on PubMed)

Lledo-Delgado A, Preston-Hurlburt P, Currie S, Clark P, Linsley PS, Long SA, Liu C, Koroleva G, Martins AJ, Tsang JS, Herold KC. Teplizumab induces persistent changes in the antigen-specific repertoire in individuals at risk for type 1 diabetes. J Clin Invest. 2024 Aug 13;134(18):e177492. doi: 10.1172/JCI177492.

Reference Type: DERIVED

PMID: 39137044 (View on PubMed)

Novograd J, Frishman WH. Teplizumab Therapy to Delay the Onset of Type 1 Diabetes. Cardiol Rev. 2024 Nov-Dec 01;32(6):572-576. doi: 10.1097/CRD.0000000000000563. Epub 2023 May 9.

Reference Type: DERIVED

PMID: 37158990 (View on PubMed)

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.

Reference Type: DERIVED

PMID: 35713929 (View on PubMed)

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.

Reference Type: DERIVED

PMID: 31180194 (View on PubMed)

Provided Documents

Document Type: Study Protocol

View Document

Document Type: Statistical Analysis Plan

View Document

Related Links

https://www.diabetestrialnet.org/publicationsdatabase/Article

Type 1 Diabetes TrialNet

Other Identifiers

UC4DK106993

Identifier Type: NIH

Identifier Source: secondary_id

View Link

TrialNet - tep (IND)

Identifier Type: -

Identifier Source: org_study_id