Treatment With hOKT3gamma1(Ala-Ala) in T1DM

National Institute of Allergy and Infectious Diseases (NIAID)

Status and phase

Terminated

Phase 2

Conditions

Diabetes Mellitus, Type 1

Treatments

Drug: hOKT3gamma1(Ala-Ala)

Study type

Interventional

Funder types

NETWORK

NIH

Identifiers

NCT00806572

NDB01

DAIT ITN007AI

Details and patient eligibility

About

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.

Full 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.

Enrollment

10 patients

Sex

All

Ages

7 to 30 years old

Volunteers

No Healthy Volunteers

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.