Autoimmunity-blocking Antibody for Tolerance in Recently Diagnosed Type 1 Diabetes
AbATE
Phase II Multiple-Dose Treatment of New Onset Type 1 Diabetes Mellitus With Anti-CD3 mAb
1 other identifier
interventional
83
1 country
7
Brief Summary
Anti-CD3 monoclonal antibody (a.k.a. hOKT3gamma1 \[Ala-Ala\],teplizumab, MGA031) is a humanized antibody that is commonly used to prevent organ rejection. The purpose of this study is determine whether anti-CD3 mAb treatment can halt the progression of newly diagnosed type 1 diabetes.
Trial Health
Trial Health Score
Automated assessment based on enrollment pace, timeline, and geographic reach
participants targeted
Target at P50-P75 for phase_2
Started Sep 2005
Longer than P75 for phase_2
7 active sites
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
August 9, 2005
CompletedFirst Posted
Study publicly available on registry
August 11, 2005
CompletedStudy Start
First participant enrolled
September 1, 2005
CompletedPrimary Completion
Last participant's last visit for primary outcome
March 1, 2011
CompletedStudy Completion
Last participant's last visit for all outcomes
March 1, 2011
CompletedResults Posted
Study results publicly available
September 16, 2013
CompletedMay 22, 2017
April 1, 2017
5.5 years
August 9, 2005
June 21, 2013
April 11, 2017
Conditions
Keywords
Outcome Measures
Primary Outcomes (1)
Change in Mean C-peptide Area Under the Curve (AUC) Response to a Mixed Meal Tolerance Test (MMTT)
C-peptide AUC is computed using the trapezoidal rule and dividing by the interval of time from the 4 hour Mixed Meal Tolerance Test (MMTT) where assessments are taken every 30 minutes after initial assessments 15 minutes apart. A higher C-peptide AUC is desirable as detectable C-peptide is a marker for the ability of the pancreas to produce insulin in response to a MMTT. The baseline data was used to adjust for the C-peptide AUC primary endpoint at 24 months. Missing month 24 C-peptide results are imputed using a conservative scenario.
Baseline (Pre-treatment), Month 24
Secondary Outcomes (2)
Change in HbA1c
Baseline (Pre-treatment), Month 24
Change in Average Total Insulin Dose Per Body Weight
Baseline (Pre-treatment), Month 24
Study Arms (2)
Anti-CD3 mAb Plus Diabetes Standard of Care Treatment
EXPERIMENTALSubjects receive 1.) a 14-day course of anti-CD3 monoclonal antibody (mAb) intravenously (IV) comprised of daily doses of 51 µg/m2, 103 µg/m2, 207 µg/m2, 413 µg/m2, and 10 days of 826 µg/m2 \[Cycle 1\] and, when eligible per protocol, receipt of a second 14-day course after a 12-month interval (at month 13)\[Cycle 2\]. Note: Prior to May 2007, the course of IV daily doses of anti-CD3 mAb were: 57 µg/m2, 115 µg/m2, 230 µg/m2, 460 µg/m2, and 10 days of 919 µg/m2 and, when eligible per protocol, a second course after a 12-month interval (at month 13). 2.) and intensive diabetes standard of care treatment/management under the care of a physician: dietary counseling, insulin dosing and multiple consultations during the course of the trial with the clinical diabetes management team. Iron supplementation initiated status post treatment randomization.
Diabetes Standard of Care Treatment
ACTIVE COMPARATORSubjects receive intensive diabetes standard of care treatment/management under the care of a physician: dietary counseling, insulin dosing and multiple consultations during the course of the trial with the clinical diabetes management team. Iron supplementation initiated status post treatment randomization.
Interventions
Daily 14-day dose escalation course at study entry, with possible second course after 12-month interval
Receipt of intensive diabetes standard of care treatment/management under the care of a physician: dietary counseling, insulin dosing and multiple consultations during the course of the trial with the clinical diabetes management team.
Immediately following randomization, all participants regardless of arm allocation begin iron supplementation with either ferrous sulfate or multivitamin with iron.
Eligibility Criteria
You may qualify if:
- Diagnosis of type 1 diabetes (according to American Diabetes Association \[ADA\] criteria) within the 8 weeks prior to study entry
- Weigh at least 25 kg (55 lbs)
- Insulin autoantibodies assessed within 10 days of any insulin use OR anti-glutamic acid decarboxylase (GAD) autoantibodies OR anti-ICA512/IA-2 autoantibodies
- Subjects or guardian(s) willing to provide informed consent
You may not qualify if:
- Prior participation in a clinical trial that could potentially affect diabetes condition or immunologic status
- Participation in another investigational clinical trial within the 6 weeks prior to study entry
- Pregnancy or breastfeeding
Contact the study team to confirm eligibility.
Sponsors & Collaborators
Study Sites (7)
The Diabetes Center at UCSF
San Francisco, California, 94143, United States
Barbara Davis Center for Childhood Diabetes
Denver, Colorado, 80262, United States
Yale University
New Haven, Connecticut, 06520, United States
Medical College of Georgia
Augusta, Georgia, 30912, United States
Dept. of Medicine, Division of Endocrinology and the Naomi Berrie Diabetes Center/Columbia University
New York, New York, 10032, United States
Benaroya Research Institute
Seattle, Washington, 98108, United States
Pacific Northwest Research Institute/University of Washington
Seattle, Washington, 98122, United States
Related Publications (7)
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. doi: 10.2337/diabetes.54.6.1763.
PMID: 15919798BACKGROUNDHerold 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. doi: 10.1056/NEJMoa012864.
PMID: 12037148BACKGROUNDHerold KC, Gitelman SE, Ehlers MR, Gottlieb PA, Greenbaum CJ, Hagopian W, Boyle KD, Keyes-Elstein L, Aggarwal S, Phippard D, Sayre PH, McNamara J, Bluestone JA; AbATE Study Team. Teplizumab (anti-CD3 mAb) treatment preserves C-peptide responses in patients with new-onset type 1 diabetes in a randomized controlled trial: metabolic and immunologic features at baseline identify a subgroup of responders. Diabetes. 2013 Nov;62(11):3766-74. doi: 10.2337/db13-0345. Epub 2013 Jul 8.
PMID: 23835333RESULTFlammer ER, Higdon LE, Sanda S, Garrett TJ, Ismail HM. Baseline Serum Metabolites as Predictors of Teplizumab Response in Individuals with Type 1 Diabetes. medRxiv [Preprint]. 2025 Dec 23:2025.12.22.25342822. doi: 10.64898/2025.12.22.25342822.
PMID: 41480032DERIVEDAjmal 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: 39735417DERIVEDBoyle KD, Keyes-Elstein L, Ehlers MR, McNamara J, Rigby MR, Gitelman SE, Weiner LJ, Much KL, Herold KC. Two- and Four-Hour Tests Differ in Capture of C-Peptide Responses to a Mixed Meal in Type 1 Diabetes. Diabetes Care. 2016 Jun;39(6):e76-8. doi: 10.2337/dc15-2077. Epub 2016 Apr 13. No abstract available.
PMID: 27208317DERIVEDSherr JL, Ghazi T, Wurtz A, Rink L, Herold KC. Characterization of residual beta cell function in long-standing type 1 diabetes. Diabetes Metab Res Rev. 2014 Feb;30(2):154-62. doi: 10.1002/dmrr.2478.
PMID: 24115337DERIVED
Related Links
MeSH Terms
Conditions
Interventions
Condition Hierarchy (Ancestors)
Intervention Hierarchy (Ancestors)
Results Point of Contact
- Title
- Director, Clinical Research Operations Program
- Organization
- DAIT/NIAID
Study Officials
- PRINCIPAL INVESTIGATOR
Kevan Herold, MD
Yale University
Publication Agreements
- PI is Sponsor Employee
- No
- Restrictive Agreement
- No
Study Design
- Study Type
- interventional
- Phase
- phase 2
- Allocation
- RANDOMIZED
- Masking
- SINGLE
- Who Masked
- OUTCOMES ASSESSOR
- Masking Details
- The staff at Northwest Lipid Research Laboratory were masked to the treatment assignment since they performed the mixed-meal tolerance test (MMTT) and the HgA1C assays. All study staff including the PI were masked to the results of the MMTT. They were notified of a detectable or undetectable fasting C-peptide result to assess for continuation to the next treatment cycle.
- Purpose
- TREATMENT
- Intervention Model
- PARALLEL
- Sponsor Type
- NIH
- Responsible Party
- SPONSOR
Study Record Dates
First Submitted
August 9, 2005
First Posted
August 11, 2005
Study Start
September 1, 2005
Primary Completion
March 1, 2011
Study Completion
March 1, 2011
Last Updated
May 22, 2017
Results First Posted
September 16, 2013
Record last verified: 2017-04
Data Sharing
- IPD Sharing
- Will share
Participant level data and additional relevant materials are available to the public in: 1.) the Immunology Database and Analysis Portal (ImmPort), a long-term archive of clinical and mechanistic data from Division of Allergy, Immunology, and Transplantation (DAIT)-funded grants and contracts that also provides data analysis tools available to researchers; and 2.) TrialShare, the Immune Tolerance Network (ITN) Clinical Trials Research Portal that makes data from the consortium's clinical trials publicly available.