Autoimmunity-blocking Antibody for Tolerance in Recently Diagnosed Type 1 Diabetes (AbATE)

April 11, 2017 updated by: National Institute of Allergy and Infectious Diseases (NIAID)

Phase II Multiple-Dose Treatment of New Onset Type 1 Diabetes Mellitus With Anti-CD3 mAb

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.

Study Overview

Status

Completed

Conditions

Intervention / Treatment

Detailed Description

Type 1 diabetes is an autoimmune disease in which the immune system mistakenly attacks insulin-producing beta cells in the pancreas. Without these cells, the body cannot maintain proper blood glucose levels in response to daily activities, such as eating or exercise. Generally, at the time of type 1 diabetes diagnosis, 60% to 85% of the diabetic person's beta cells have already been destroyed. However, between 15% and 40% of these cells remain and are able to produce insulin. Treatment that slows the destruction of additional beta cells may be able to decrease a patient's reliance on insulin and improve their quality of life.

Anti-CD3 mAb is genetically engineered and directed against the CD3 antigen on T cells; this antibody selectively attacks the immune cells responsible for beta cell destruction. In a small exploratory clinical trial, patients with newly diagnosed type 1 diabetes who received a single, 2-week treatment with anti-CD3 mAb had preserved beta cell function and significantly lower insulin requirements than untreated patients for up to two years after therapy. This study will investigate whether a second course of anti-CD3 mAb administered one year after the first administration is able to prolong or improve the effects of the biologic in people who have recently diagnosed type 1 diabetes mellitus.

Participants will be randomly assigned to one of two groups. The Experimental Group will receive anti-CD3 mAb treatment plus Diabetes Standard of Care Treatment; the Active Comparator Group will receive Diabetes Standard of Care Treatment. The Experimental Group will be treated with the antibody for the first 14 days of the study and again one year later. These participants will be admitted to the hospital for the first 5 days of a treatment cycle. Participants who live within 1 hour of the hospital may receive the remainder of a treatment cycle as an outpatient, but those who live farther away will be hospitalized for 14 days. For the first treatment cycle, there will be study visits on the 3 consecutive days after the treatment cycle and at Months 1, 2, 3, 6, 9, and 12. For the second treatment cycle, there will be study visits on the 3 consecutive days after the treatment cycle and at Months 13, 16, 19, 21, and 24.The Active Comparator Group will have 12 study visits over two years.

At study entry, all participants will receive daily iron supplementation, either as ferrous sulfate or a multivitamin with iron. Participants will be followed for up to 2 years to assess their overall diabetes health and to capture laboratory measures of beta cell and immune system function. Medication history and adverse event assessment will occur at all visits. A physical exam, vital signs measurement, and blood collection will occur at most visits. Medical history and urine collection will occur at selected visits.

Study Type

Interventional

Enrollment (Actual)

83

Phase

  • Phase 2

Contacts and Locations

This section provides the contact details for those conducting the study, and information on where this study is being conducted.

Study Locations

  • United States
    • California
      • San Francisco, California, United States, 94143
        • The Diabetes Center at UCSF
    • Colorado
      • Denver, Colorado, United States, 80262
        • Barbara Davis Center for Childhood Diabetes
    • Connecticut
      • New Haven, Connecticut, United States, 06520
        • Yale University
    • Georgia
      • Augusta, Georgia, United States, 30912
        • Medical College of Georgia
    • New York
      • New York, New York, United States, 10032
        • Dept. of Medicine, Division of Endocrinology and the Naomi Berrie Diabetes Center/Columbia University
    • Washington
      • Seattle, Washington, United States, 98108
        • Benaroya Research Institute
      • Seattle, Washington, United States, 98122
        • Pacific Northwest Research Institute/University of Washington

Participation Criteria

Researchers look for people who fit a certain description, called eligibility criteria. Some examples of these criteria are a person's general health condition or prior treatments.

Eligibility Criteria

Ages Eligible for Study

6 years to 28 years (Child, Adult)

Accepts Healthy Volunteers

No

Genders Eligible for Study

All

Description

Inclusion Criteria:

  • 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

Exclusion Criteria:

  • 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

Study Plan

This section provides details of the study plan, including how the study is designed and what the study is measuring.

How is the study designed?

Design Details

  • Primary Purpose: Treatment
  • Allocation: Randomized
  • Interventional Model: Parallel Assignment
  • Masking: Single

Arms and Interventions

Participant Group / Arm
Intervention / Treatment
Experimental: Anti-CD3 mAb Plus Diabetes Standard of Care Treatment

Subjects 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.
Biological: Anti-CD3 mAb
Daily 14-day dose escalation course at study entry, with possible second course after 12-month interval
Other Names:
  • MGA031
  • mAb hOKT3gamma1(Ala-Ala)
  • teplizumab
Other: Diabetes Standard of Care Treatment
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.
Dietary supplement: Iron supplementation
Immediately following randomization, all participants regardless of arm allocation begin iron supplementation with either ferrous sulfate or multivitamin with iron.
Other Names:
  • Feosol
  • MVI
  • Fer-In-Sol
  • Fer-Iron
  • Ferolix
  • FeroSul
  • Irospan
Active Comparator: Diabetes Standard of Care Treatment

Subjects 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.
Other: Diabetes Standard of Care Treatment
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.
Dietary supplement: Iron supplementation
Immediately following randomization, all participants regardless of arm allocation begin iron supplementation with either ferrous sulfate or multivitamin with iron.
Other Names:
  • Feosol
  • MVI
  • Fer-In-Sol
  • Fer-Iron
  • Ferolix
  • FeroSul
  • Irospan

What is the study measuring?

Primary Outcome Measures

Outcome Measure
Measure Description
Time Frame
Change in Mean C-peptide Area Under the Curve (AUC) Response to a Mixed Meal Tolerance Test (MMTT)
Time Frame: Baseline (Pre-treatment), Month 24
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 Outcome Measures

Outcome Measure
Measure Description
Time Frame
Change in HbA1c
Time Frame: Baseline (Pre-treatment), Month 24
Glycosylated hemoglobin (HbA1c) is a measure of the average plasma glucose concentration over prolonged periods of time and measures the level of optimal management of underlying disease. (Normal :< 5.7%; pre-diabetes: 5.7% -6.4%; diabetes: 6.5% or higher).A decline in HbA1c from baseline to month 24 signifies an improvement in diabetic control. The goal of treatment: to maintain the HgA1c level as close to normal as possible without frequent occurrence of hypoglycemia.
Baseline (Pre-treatment), Month 24
Change in Average Total Insulin Dose Per Body Weight
Time Frame: Baseline (Pre-treatment), Month 24
This measure is computed using the average amount of exogenous insulin taken per day for the 3 days prior to the visit. The average insulin use is divided by the subject's weight in kilograms (kg). The need for lower dose(s) of prescribed exogenous insulin while maintaining optimal control of a subject's diabetes reflects improved management of the underlying disease.
Baseline (Pre-treatment), Month 24

Collaborators and Investigators

This is where you will find people and organizations involved with this study.

Sponsor

National Institute of Allergy and Infectious Diseases (NIAID)

Collaborators

Immune Tolerance Network (ITN)

Investigators

  • Principal Investigator: Kevan Herold, MD, Yale University

Publications and helpful links

The person responsible for entering information about the study voluntarily provides these publications. These may be about anything related to the study.

General Publications

Helpful Links

Study record dates

These dates track the progress of study record and summary results submissions to ClinicalTrials.gov. Study records and reported results are reviewed by the National Library of Medicine (NLM) to make sure they meet specific quality control standards before being posted on the public website.

Study Major Dates

Study Start

September 1, 2005

Primary Completion (Actual)

March 1, 2011

Study Completion (Actual)

March 1, 2011

Study Registration Dates

First Submitted

August 9, 2005

First Submitted That Met QC Criteria

August 9, 2005

First Posted (Estimate)

August 11, 2005

Study Record Updates

Last Update Posted (Actual)

May 22, 2017

Last Update Submitted That Met QC Criteria

April 11, 2017

Last Verified

April 1, 2017

More Information

Terms related to this study

Keywords

Additional Relevant MeSH Terms

Other Study ID Numbers

  • DAIT ITN027AI

Plan for Individual participant data (IPD)

Plan to Share Individual Participant Data (IPD)?

Yes

IPD Plan Description

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.

Study Data/Documents

  1. Individual Participant Data Set
    Information identifier: SDY524
    Information comments: ImmPort study identifier is SDY524.
  2. Study summary, -design (and protocol synopsis), adverse events, medications, demographics, lab tests, study files.
    Information identifier: SDY524
    Information comments: ImmPort study identifier is SDY524.
  3. Individual Participant Data Set
    Information identifier: AbaTE - ITN027AI
    Information comments: TrialShare is the Immune Tolerance Network (ITN) clinical trials research portal that makes data from their clinical trials publicly available without charge.
  4. Study overview and synopsis, -data and reports, -schedule of assessments, -participant flow diagram, -abstracts and manuscripts
    Information identifier: AbaTE-ITN027AI
    Information comments: TrialShare is the Immune Tolerance Network (ITN) clinical trials research portal that makes data from their clinical trials publicly available without charge.

This information was retrieved directly from the website clinicaltrials.gov without any changes. If you have any requests to change, remove or update your study details, please contact register@clinicaltrials.gov. As soon as a change is implemented on clinicaltrials.gov, this will be updated automatically on our website as well.

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