Adverse events related to drug lot

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.

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.

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.

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.