Treatment With hOKT3gamma1(Ala-Ala) in T1DM

Diabetes Mellitus, Type 1 Clinical Trial

Official title:

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

Clinical Trial Details — Status: Terminated

Administrative data

• NCT number: NCT00806572
• Other study ID #: DAIT ITN007AI
• Secondary ID: NDB01
• Status: Terminated
• Phase: Phase 2
• First received: December 9, 2008
• Last updated: February 6, 2017
• Start date: May 2002
• Est. completion date: August 2007

Study information

• Verified date: February 2017
• Source: National Institute of Allergy and Infectious Diseases (NIAID)
• Contact: n/a
• Is FDA regulated: No
• Study type: Interventional

Clinical Trial Summary

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.

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.

Recruitment information / eligibility

• Status: Terminated
• Enrollment: 10
• Est. completion date: August 2007
• Est. primary completion date: July 2004
• Accepts healthy volunteers: No
• Gender: All
• Age group: 7 Years to 30 Years

Eligibility

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.

Related Conditions & MeSH terms

• Diabetes Mellitus
• Diabetes Mellitus, Type 1

Intervention

Drug:
• hOKT3gamma1(Ala-Ala)
3 cycles, six months apart, each consisting of 12 daily infusions with 455-1818ug/m2 hOKT3g1(Ala-Ala)

Locations

Country	Name	City	State
United States	Naomie Berrie Diabetes Center, Columbia University	New York	New York
United States	University of California San Francisco	San Francisco	California
United States	Benaroya Research Institute	Seattle	Washington

Sponsors (2)

Lead Sponsor	Collaborator
National Institute of Allergy and Infectious Diseases (NIAID)	Immune Tolerance Network (ITN)

Country where clinical trial is conducted

United States, 

References & Publications (1)

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 sin — View Citation

Outcome

Type	Measure	Description	Time frame	Safety issue
Primary	4-hour C-peptide AUC		24 months
Secondary	Insulin usage		throughout study

External Links

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