Treatment With hOKT3gamma1(Ala-Ala) in T1DM

Phase II Multiple Dose Treatment of Type 1 Diabetes Mellitus With hOKT3gamma1(Ala-Ala)

This is a phase II study to examine the clinical and immunological effects of humanized FcR non-binding anti-CD3 mAb in participants with Type 1 diabetes mellitus (T1DM), and to develop this therapy to prevent the immune destruction leading to β cell loss.

Study Overview

• Status: Terminated
• Conditions: Diabetes Mellitus, Type 1
• Intervention / Treatment: Drug: hOKT3gamma1(Ala-Ala)

Detailed Description

This is a 2-arm, open-label phase II trial involving 0 or 3 cycles of treatment 6 months apart with hOKT3γ1 (Ala-Ala), over the first year of disease in participants with new onset T1DM. Each cycle consists of 12 daily doses of hOKT3γ1 (Ala-Ala).

Participants will be randomized in a ratio of 2:1 to either the experimental arm or the control arm and will be stratified by study site.

To be eligible, participants must be: male or female between 7-30 years of age, diagnosed with T1DM within the past 6 weeks, have a body weight ≥26 kg at the time of enrollment and have detectable anti-GAD, anti-ICA512/IA-2, or insulin autoantibodies (if the participant has been on insulin ≤10 days).

Participants randomized to the experimental group will start the first cycle of hOKT3γ1 (Ala-Ala) within 4-8 weeks of T1DM diagnosis. Each participant randomized to the experimental group will receive 3 cycles of drug treatment, separated by 6 months each. Each cycle consists of 12 days of drug treatment.

Both groups will undergo the Mixed Meal Stimulated C-Peptide Test and receive blood draws for mechanistic studies on the same schedule.

• Study Type: Interventional
• Enrollment (Actual): 10
• Phase: Phase 2

Contacts and Locations

Study Locations

• United States
  • California
    • San Francisco, California, United States, 94143
      • University of California San Francisco
  • New York
    • New York, New York, United States, 10032
      • Naomie Berrie Diabetes Center, Columbia University
  • Washington
    • Seattle, Washington, United States, 98101
      • Benaroya Research Institute

Participation Criteria

Eligibility Criteria

• Ages Eligible for Study: 7 years to 30 years (Child, Adult)
• Accepts Healthy Volunteers: No
• Genders Eligible for Study: All

Description

Inclusion Criteria:

• diagnosed with T1DM within the past 6 weeks
• have a body weight ≥26 kg at the time of enrollment
• have detectable anti-GAD, anti-ICA512/IA-2, or insulin autoantibodies (if the participant has been on insulin ≤10 days).

Exclusion Criteria:

• Pregnant or lactating females;
• Prior OKT3 treatment;
• Known hypersensitivity to murine products;
• Uncompensated heart failure or fluid overload, recent myocardial infarction;
• History of epilepsy, cancer, active infection, atopic disease, active Grave's disease, cystic fibrosis, sickle cell anemia, neuropathy, peripheral vascular disease, cerebrovascular disease, any concurrent autoimmune diseases, asthma;
• Any medical condition that in the opinion of the investigator will interfere with safe completion of the trial;
• Inability to give informed consent;
• Prior participation in a clinical trial that could potentially affect diabetes or immunologic status;
• Participation in a clinical trial within the last 6 weeks;
• HIV positive;
• Positive for Hepatitis B surface antigen or Anti-Hepatitis C antibody;
• Seropositivity for Toxoplasmosis (IgG);
• Lymphopenia (<1000 lymphocytes/microliter);
• Thrombocytopenia (<150,000/mm3 platelets);
• Anemia (Hgb < 10g/dL);
• Vaccination with a live virus within the past 6 weeks;
• Positive PPD skin test;
• Any infectious mononucleosis-like illness within the 3 months prior to enrollment;
• Serologic evidence of acute infection with EBV or CMV based on tests listed and as defined by the protocol.

Study Plan

How is the study designed?

Design Details

• Primary Purpose: Treatment
• Allocation: Randomized
• Interventional Model: Parallel Assignment
• Masking: None (Open Label)

Number of Arms

2

Arms and Interventions

Participant Group / Arm	Intervention / Treatment
No Intervention: Control
Experimental: Treatment	Drug: hOKT3gamma1(Ala-Ala); 3 cycles, six months apart, each consisting of 12 daily infusions with 455-1818ug/m2 hOKT3g1(Ala-Ala); Other Names: teplizumab

What is the study measuring?

Primary Outcome Measures

Outcome Measure	Time Frame
4-hour C-peptide AUC	24 months

Secondary Outcome Measures

Outcome Measure	Time Frame
Insulin usage	throughout study

Collaborators and Investigators

• Sponsor: National Institute of Allergy and Infectious Diseases (NIAID)
• Collaborators: Immune Tolerance Network (ITN)
• Investigators: Principal Investigator: Kevan C Herold, MD, Yale University

Publications and helpful links

General Publications

• Herold KC, Gitelman S, Greenbaum C, Puck J, Hagopian W, Gottlieb P, Sayre P, Bianchine P, Wong E, Seyfert-Margolis V, Bourcier K, Bluestone JA; Immune Tolerance Network ITN007AI Study Group. Treatment of patients with new onset Type 1 diabetes with a single course of anti-CD3 mAb Teplizumab preserves insulin production for up to 5 years. Clin Immunol. 2009 Aug;132(2):166-73. doi: 10.1016/j.clim.2009.04.007. Epub 2009 May 14.

Helpful Links

• National Institute of Allergy and Infectious Diseases (NIAID) website
• Division of Allergy, Immunology, and Transplantation (DAIT) website
• Immune Tolerance Network (ITN) website

Study record dates

Study Major Dates

• Study Start: May 1, 2002
• Primary Completion (Actual): July 1, 2004
• Study Completion (Actual): August 1, 2007

Study Registration Dates

• First Submitted: December 9, 2008
• First Submitted That Met QC Criteria: December 9, 2008
• First Posted (Estimate): December 11, 2008

Study Record Updates

• Last Update Posted (Estimate): February 8, 2017
• Last Update Submitted That Met QC Criteria: February 6, 2017
• Last Verified: February 1, 2017

More Information

Terms related to this study

• Keywords: Diabetes, juvenile diabetes, teplizumab
• Additional Relevant MeSH Terms: Glucose Metabolism Disorders; Metabolic Diseases; Immune System Diseases; Autoimmune Diseases; Endocrine System Diseases; Diabetes Mellitus; Diabetes Mellitus, Type 1
• Other Study ID Numbers: DAIT ITN007AI; NDB01

Plan for Individual participant data (IPD)

• Plan to Share Individual Participant Data (IPD)?: YES
• IPD Plan Description: Data access is provided to the public in 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 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: ITN007AI-NDB01
   Information comments: TrialShare is a portal developed by the Immune Tolerance Network (ITN) that makes data from the consortium's clinical trials publicly available without charge.Creating an account for ITN TrialShare is free and allows for searching studies of interest.
2. Study protocol synopsis, -navigator, -schedule of events,-data &reports, -specimens et al.
   Information identifier: ITN007AI-NDB01
   Information comments: TrialShare is a portal developed by the Immune Tolerance Network (ITN) that makes data from the consortium's clinical trials publicly available without charge.Creating an account for ITN TrialShare is free and allows for searching studies of interest.
3. Individual Participant Data Set
   Information identifier: SDY569
   Information comments: ImmPort study identifier is SDY569. ImmPort is a long-term archive of clinical and mechanistic data from DAIT-funded grants and contracts and is available to the Public.
4. Study summary, -design, -medications, -demographics, -lab tests, and -files.
   Information identifier: SDY569
   Information comments: ImmPort study identifier is SDY569. ImmPort is a long-term archive of clinical and mechanistic data from DAIT-funded grants and contracts and is available to the Public.