NCT01030861

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.

Trial Health

90
On Track

Trial Health Score

Automated assessment based on enrollment pace, timeline, and geographic reach

Enrollment
76

participants targeted

Target at P50-P75 for phase_2

Timeline
Completed

Started Aug 2010

Longer than P75 for phase_2

Geographic Reach
3 countries

19 active sites

Status
completed

Health score is calculated from publicly available data and should be used for screening purposes only.

Trial Relationships

Click on a node to explore related trials.

Study Timeline

Key milestones and dates

First Submitted

Initial submission to the registry

December 11, 2009

Completed
3 days until next milestone

First Posted

Study publicly available on registry

December 14, 2009

Completed
8 months until next milestone

Study Start

First participant enrolled

August 1, 2010

Completed
8.3 years until next milestone

Primary Completion

Last participant's last visit for primary outcome

November 1, 2018

Completed
7 months until next milestone

Study Completion

Last participant's last visit for all outcomes

June 1, 2019

Completed
1.2 years until next milestone

Results Posted

Study results publicly available

August 5, 2020

Completed
Last Updated

August 5, 2020

Status Verified

July 1, 2020

Enrollment Period

8.3 years

First QC Date

December 11, 2009

Results QC Date

July 2, 2020

Last Update Submit

July 21, 2020

Conditions

Autoantibody PositiveNon-diabetic Relatives at Risk for Type 1 DiabetesHigh RiskImpaired Glucose Tolerance

Keywords

type 1 diabetespre-diabeticautoantibody positiveat risk for type 1 diabetesglucose intolerancerelatives of people with type 1 diabetes

Outcome Measures

Primary Outcomes (1)

  • 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.

    During follow-up, median 745 days, range 74 to 2683

Secondary Outcomes (1)

  • Number of Participants With Adverse Events

    Baseline Visit to Diagnosis of Type 1 Diabetes median 745 days, range 74 to 2683

Study Arms (2)

teplizumab

ACTIVE COMPARATOR

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

Placebo infusion

PLACEBO COMPARATOR

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: Placebo infusion

Interventions

TeplizumabDRUG

intravenous infusions

teplizumab
Placebo infusionDRUG

Placebo for Teplizumab

Placebo infusion

Eligibility Criteria

Age8 Years - 45 Years
Sexall
Healthy VolunteersNo
Age GroupsChild (0-17), Adult (18-64)

You may qualify if:

  • 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

You may not qualify if:

  • 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

Contact the study team to confirm eligibility.

Sponsors & Collaborators

Study Sites (19)

University of California in San Francisco

San Francisco, California, 94143, United States

Location

University of California-San Francisco

San Francisco, California, 94143, United States

Location

Stanford University

Stanford, California, 94305, United States

Location

Barbara Davis Center for Childhood Diabetes/ University of Colorado

Denver, Colorado, 80045, United States

Location

Yale University School of Medicine

New Haven, Connecticut, 06519, United States

Location

University of Florida

Gainesville, Florida, 32610, United States

Location

University of Miami

Miami, Florida, 33136, United States

Location

University of South Florida

Tampa, Florida, 33612, United States

Location

Indiana University

Indianapolis, Indiana, 46202, United States

Location

University of Minnesota

Minneapolis, Minnesota, 55455, United States

Location

The Children's Mercy Hospital

Kansas City, Missouri, 64108, United States

Location

Columbia University

New York, New York, 10032, United States

Location

University of Pittsburgh

Pittsburgh, Pennsylvania, 15201, United States

Location

Vanderbilt University

Nashville, Tennessee, 37232, United States

Location

University of Texas

Dallas, Texas, 75390-9072, United States

Location

Baylor College of Medicine

Houston, Texas, 77030, United States

Location

Benaroya Research Institute

Seattle, Washington, 982101, United States

Location

The Hospital for Sick Children

Toronto, Ontario, MSG-1X8, Canada

Location

Forschergruppe Diabetes

Munich, Germany

Location

Related Publications (5)

  • 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.

    PMID: 39735417DERIVED

  • 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.

    PMID: 39137044DERIVED

  • 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.

    PMID: 37158990DERIVED

  • 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.

    PMID: 35713929DERIVED

  • 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.

    PMID: 31180194DERIVED

Related Links

MeSH Terms

Conditions

Glucose IntoleranceDiabetes Mellitus, Type 1

Interventions

teplizumab

Condition Hierarchy (Ancestors)

HyperglycemiaGlucose Metabolism DisordersMetabolic DiseasesNutritional and Metabolic DiseasesDiabetes MellitusEndocrine System DiseasesAutoimmune DiseasesImmune System Diseases

Results Point of Contact

Title
Carla Greenbaum, MD
Organization
Benaroya Research Institute
cjgreen@benaroyaresearch.org
206-342-6933

Study Officials

  • Carla J Greenbaum, MD

    Type 1 Diabetes TrialNet

    STUDY CHAIR

Publication Agreements

PI is Sponsor Employee
No
Restrictive Agreement
No

Study Design

Study Type
interventional
Phase
phase 2
Allocation
RANDOMIZED
Masking
QUADRUPLE
Who Masked
PARTICIPANT, CARE PROVIDER, INVESTIGATOR, OUTCOMES ASSESSOR
Purpose
TREATMENT
Intervention Model
PARALLEL
Sponsor Type
NIH
Responsible Party
SPONSOR

Study Record Dates

First Submitted

December 11, 2009

First Posted

December 14, 2009

Study Start

August 1, 2010

Primary Completion

November 1, 2018

Study Completion

June 1, 2019

Last Updated

August 5, 2020

Results First Posted

August 5, 2020

Record last verified: 2020-07

Data Sharing

IPD Sharing
Will share

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

More information

Locations

CA(1)DE(1)US(17)