This subproject is one of many research subprojects utilizing theresources provided by a Center grant funded by NIH/NCRR. The subproject andinvestigator (PI) may have received primary funding from another NIH source,and thus could be represented in other CRISP entries. The institution listed isfor the Center, which is not necessarily the institution for the investigator.We propose a multicenter, randomized, two-arm, open-label phase II trial in which 81 participants within 6 weeks of diagnosis with T1DM are randomly assigned at a 2:1 ratio to receive hOKT3 1 (Ala-Ala) plus standard diabetes management or standard diabetes management alone. Participants assigned to receive hOKT3 1 (Ala-Ala) will be given a 14-day course at study entry and may, if eligible, be given a second course at 13 months. Total study duration is approximately 4 years (a 2-year accrual and a 2-year follow-up). Immunologic testing may occur for up to 5 years post study initiation as outlined in the protocol. Both groups will undergo the MMTT stimulated C-peptide test and have blood collected for mechanistic studies on the same schedule. Diabetes-related objectives are to assess whether the drug has prolonged clinical efficacy and to assess the effect of hOKT3?1 (Ala-Ala) on selected secondary clinical outcomes. Safety and pharmacokinetics objectives include to determine the pharmacokinetics and mechanism of action for hOKT3?1 (Ala-Ala) and to gain additional information about the safety of hOKT3?1 (Ala-Ala). Mechanistic studies are aimed at determining how the drug alters general and diabetes-specific immune responses and determining the mechanism of action for hOKT3?1 (Ala-Ala) in maintenance of ?-cell function.
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