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

• ClinicalTrials.gov Identifier: NCT01030861
• Recruitment Status: Completed
• First Posted: December 14, 2009
• Results First Posted: August 5, 2020
• Last Update Posted: August 5, 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
• Information provided by (Responsible Party): National Institute of Diabetes and Digestive and Kidney Diseases (NIDDK)

Tracking Information

• First Submitted Date: December 11, 2009
• First Posted Date: December 14, 2009
• Results First Submitted Date: July 2, 2020
• Results First Posted Date: August 5, 2020
• Last Update Posted Date: August 5, 2020
• Actual Study Start Date: August 2010
• Actual Primary Completion Date: November 2018 (Final data collection date for primary outcome measure)

Current Primary Outcome Measures (submitted: July 21, 2020)

Rate of New Diabetes Per Year [ Time Frame: During follow-up, median 745 days, range 74 to 2683 ]

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.

• Original Primary Outcome Measures (submitted: December 11, 2009): 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) ]

Current Secondary Outcome Measures (submitted: July 21, 2020)

Number of Participants With Adverse Events [ Time Frame: Baseline Visit to Diagnosis of Type 1 Diabetes median 745 days, range 74 to 2683 ]

Adverse events categorized and graded via CTCAE.

• Original Secondary Outcome Measures (submitted: December 11, 2009): 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. ]
• Current Other Pre-specified Outcome Measures: Not Provided
• Original Other Pre-specified Outcome Measures: Not Provided

Descriptive Information

• 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
• 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.

• Study Type: Interventional
• Study Phase: Phase 2
• Study Design: Allocation: Randomized; Intervention Model: Parallel Assignment; Masking: Quadruple (Participant, Care Provider, Investigator, Outcomes Assessor); Primary Purpose: Treatment

Condition

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

Intervention

• Drug: Teplizumab
  intravenous infusions
• Drug: Placebo infusion
  Placebo for Teplizumab

Study Arms

• 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.
  Intervention: Drug: Teplizumab
• 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.
  Intervention: Drug: Placebo infusion

Publications *

• 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.
• 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.

Recruitment Information

• Recruitment Status: Completed
• Actual Enrollment (submitted: May 13, 2019): 76
• Original Estimated Enrollment (submitted: December 11, 2009): 170
• Actual Study Completion Date: June 2019
• Actual Primary Completion Date: November 2018 (Final data collection date for primary outcome measure)

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

Sex/Gender

• Sexes Eligible for Study: All

• Ages: 8 Years to 45 Years (Child, Adult)
• Accepts Healthy Volunteers: No
• Contacts: Contact information is only displayed when the study is recruiting subjects
• Listed Location Countries: Canada, Germany, United States

Administrative Information

• NCT Number: NCT01030861
• Other Study ID Numbers: TrialNet - tep (IND); UC4DK106993 ( U.S. NIH Grant/Contract )
• Has Data Monitoring Committee: Yes
• U.S. FDA-regulated Product: Not Provided

IPD Sharing Statement

• Plan to Share IPD: Yes
• 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
• URL: https://repository.niddk.nih.gov/studies/tn10-anti-cd3-prevention/?query=trialnet%20Teplizumab

• Current Responsible Party: National Institute of Diabetes and Digestive and Kidney Diseases (NIDDK)
• Original Responsible Party: Ellen Leschek, NIDDK/NIH
• Current Study Sponsor: National Institute of Diabetes and Digestive and Kidney Diseases (NIDDK)
• Original Study Sponsor: Same as current

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

Investigators

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

• PRS Account: National Institute of Diabetes and Digestive and Kidney Diseases (NIDDK)
• Verification Date: July 2020