Anti-CD3 mAb Treatment of Recent Onset Type 1 Diabetes

• ClinicalTrials.gov Identifier: NCT00378508
• Recruitment Status: Completed
• First Posted: September 20, 2006
• Results First Posted: October 31, 2012
• Last Update Posted: August 2, 2016
• Sponsor: Yale University
• Collaborators: National Institute of Diabetes and Digestive and Kidney Diseases (NIDDK); Juvenile Diabetes Research Foundation
• Information provided by (Responsible Party): Yale University

Tracking Information

• First Submitted Date: September 18, 2006
• First Posted Date: September 20, 2006
• Results First Submitted Date: September 4, 2012
• Results First Posted Date: October 31, 2012
• Last Update Posted Date: August 2, 2016
• Study Start Date: September 2006
• Actual Primary Completion Date: August 2011 (Final data collection date for primary outcome measure)

Current Primary Outcome Measures (submitted: October 1, 2012)

• C-peptide Area Under the Curve (AUC) Response to a Mixed Meal Tolerance Test (MMTT) at 12 Months [ Time Frame: At month 12 post-treatment ]
  C-peptide secretory response was calculated as ln[(Area Under the Curve of the C-peptide from the 240 minute MMTT/240 +1] For presentation, the C-peptide data were converted to the AUC as pmol/ml. This is adjusted for baseline.
• C-peptide Area Under the Curve (AUC) Response to a Mixed Meal Tolerance Test (MMTT) at Baseline [ Time Frame: At Baseline (before treatment) ]
  C-peptide secretory response was calculated as ln[(Area Under the Curve of the C-peptide from the 240 minute MMTT/240 +1] For presentation, the C-peptide data were converted to the AUC as pmol/ml. This baseline data was used to adjust for the C-peptide AUC primary endpoint measure at 12 months.

• Original Primary Outcome Measures (submitted: September 18, 2006): C-peptide response to a mixed meal tolerance test

Current Secondary Outcome Measures (submitted: October 1, 2012)

• Hemoglobin A1c [ Time Frame: At 12 months post-treatment ]
• Average Insulin Use Over 12 Months [ Time Frame: After 12 months post-treatment ]
• Baseline Insulin Use [ Time Frame: At baseline (before treatment) ]
• Baseline Hemoglobin A1c [ Time Frame: At baseline (before treatment) ]

Original Secondary Outcome Measures (submitted: September 18, 2006)

• Hemoglobin A1c
• insulin usage

• Current Other Pre-specified Outcome Measures: Not Provided
• Original Other Pre-specified Outcome Measures: Not Provided

Descriptive Information

• Brief Title: Anti-CD3 mAb Treatment of Recent Onset Type 1 Diabetes
• Official Title: Phase II Trial of hOKT3gamma1(Ala-Ala) Teplizumab for Treatment of Patients With Recent Onset Type 1 Diabetes
• Brief Summary: This is a randomized placebo controlled study to test whether a single 14 course of treatment with the anti-CD3 monoclonal antibody, hOKT3gamma1(Ala-Ala),Teplizumab will prevent the loss of insulin secretory capacity in individuals with Type 1 diabetes of 4 - 12 months duration since diagnosis.
• Detailed Description: The study design is a double blind placebo controlled trial that will enroll subjects between the ages of 8 - 30 who have had the diagnosis of Type 1 diabetes made 4 - 12 months prior to enrollment. A single 14 course of treatment with mAb hOKT3gamma1(Ala-Ala), Teplizumab will be given. The primary endpoint is the C-peptide response to a mixed meal at 12 months. A total of 60 subjects will be enrolled (30 in the drug treatment and 30 in the placebo groups) at 4 study sites: Yale University,the University of California at San Francisco, Children's Hospital of Philadelphia, and the Barbara Davis Diabetes Center.
• Study Type: Interventional
• Study Phase: Phase 2
• Study Design: Allocation: Randomized; Intervention Model: Parallel Assignment; Masking: Triple (Participant, Care Provider, Investigator); Primary Purpose: Treatment
• Condition: Type 1 Diabetes Mellitus

Intervention

• Drug: mAb hOKT3gamma1(Ala-Ala), Teplizumab
  This is a randomized, two-arm, double blind placebo controlled phase II trial in which 60 participants with recent-onset T1DM are randomized at a 1:1 ratio to receive Teplizumab or placebo over a 14 day treatment period. The course of Teplizumab comprises daily doses of 51 µg/m2, 103 µg/m2, 207 µg/m2, 413 µg/m2, and 10 of 826 µg/m2.
  Other Name: mAb hOKT3gamma1(Ala-Ala), MGA031, Teplizumab
• Drug: Placebo Arm

Study Arms

• Experimental: 1
  The course of Teplizumab comprises daily doses of 51 µg/m2, 103 µg/m2, 207 µg/m2, 413 µg/m2, and 10 of 826 µg/m2 over a 14 day treatment period.
  Intervention: Drug: mAb hOKT3gamma1(Ala-Ala), Teplizumab
• Placebo Comparator: 2
  Normal saline infusion
  Intervention: Drug: Placebo Arm

Publications *

• Herold KC, Hagopian W, Auger JA, Poumian-Ruiz E, Taylor L, Donaldson D, Gitelman SE, Harlan DM, Xu D, Zivin RA, Bluestone JA. Anti-CD3 monoclonal antibody in new-onset type 1 diabetes mellitus. N Engl J Med. 2002 May 30;346(22):1692-8.
• Herold KC, Gitelman SE, Masharani U, Hagopian W, Bisikirska B, Donaldson D, Rother K, Diamond B, Harlan DM, Bluestone JA. A single course of anti-CD3 monoclonal antibody hOKT3gamma1(Ala-Ala) results in improvement in C-peptide responses and clinical parameters for at least 2 years after onset of type 1 diabetes. Diabetes. 2005 Jun;54(6):1763-9.
• Sherr JL, Ghazi T, Wurtz A, Rink L, Herold KC. Characterization of residual β cell function in long-standing type 1 diabetes. Diabetes Metab Res Rev. 2014 Feb;30(2):154-62. doi: 10.1002/dmrr.2478.
• Lebastchi J, Deng S, Lebastchi AH, Beshar I, Gitelman S, Willi S, Gottlieb P, Akirav EM, Bluestone JA, Herold KC. Immune therapy and β-cell death in type 1 diabetes. Diabetes. 2013 May;62(5):1676-80. doi: 10.2337/db12-1207. Epub 2013 Feb 19.
• Herold KC, Gitelman SE, Willi SM, Gottlieb PA, Waldron-Lynch F, Devine L, Sherr J, Rosenthal SM, Adi S, Jalaludin MY, Michels AW, Dziura J, Bluestone JA. Teplizumab treatment may improve C-peptide responses in participants with type 1 diabetes after the new-onset period: a randomised controlled trial. Diabetologia. 2013 Feb;56(2):391-400. doi: 10.1007/s00125-012-2753-4. Epub 2012 Oct 21.

Recruitment Information

• Recruitment Status: Completed
• Actual Enrollment (submitted: October 31, 2012): 63
• Original Enrollment (submitted: September 18, 2006): 60
• Actual Study Completion Date: August 2013
• Actual Primary Completion Date: August 2011 (Final data collection date for primary outcome measure)

Eligibility Criteria

Inclusion Criteria:

• age 8 - 30,
• duration of diabetes 4 - 12 months,
• weight greater than 27.5 kg,
• stimulated C-peptide >= 0.2 pmol/ml

Exclusion Criteria:

• asthma,
• history of hepatitis C, hepatitis B, HIV

Sex/Gender

• Sexes Eligible for Study: All

• Ages: 8 Years to 30 Years (Child, Adult)
• Accepts Healthy Volunteers: No
• Contacts: Contact information is only displayed when the study is recruiting subjects
• Listed Location Countries: United States

Administrative Information

• NCT Number: NCT00378508
• Other Study ID Numbers: Delay-Study 5; R01DK057846 ( U.S. NIH Grant/Contract )
• Has Data Monitoring Committee: Yes
• U.S. FDA-regulated Product: Not Provided
• IPD Sharing Statement: Not Provided
• Responsible Party: Yale University
• Study Sponsor: Yale University

Collaborators

• National Institute of Diabetes and Digestive and Kidney Diseases (NIDDK)
• Juvenile Diabetes Research Foundation

Investigators

• Principal Investigator: Kevan C Herold; Yale University
• Principal Investigator: Jeffrey A Bluestone, PhD; University of California at San Francisco

• PRS Account: Yale University
• Verification Date: July 2016