| Outcome Measures: |
Primary: Acceptable T cell phenotype signature by the change from baseline in the Programmed Cell Death 1 (PD1) during the first 12 weeks., Evaluating four siplizumab dosing regimens for induction of a T cell phenotype signature based on the 20% increase or greater from baseline in PD1. The primary analysis will identify siplizumab doses with acceptable safety profiles and favorable changes in the T cell phenotype in each age cohort. The primary assessments will be made during the first 12 weeks with an interim analysis for futility after the 5th per protocol participant (PP) per dosing arm reaches Week 12 in each age cohort., From week 0 (baseline) to week 12|Acceptable T cell phenotype signature by the change from baseline in the T cell immunoreceptor with Ig and ITIM domains (TIGIT) during the first 12 weeks., Evaluating four siplizumab dosing regimens for induction of a T cell phenotype signature based on the 20% increase or greater from baseline in TIGIT. The primary analysis will identify siplizumab doses with acceptable safety profiles and favorable changes in the T cell phenotype in each age cohort. The primary assessments will be made during the first 12 weeks with an interim analysis for futility after 5 PP per dosing arm reach Week 12 in each age cohort., From week 0 (baseline) to week 12|Acceptable T cell phenotype signature by the change from Baseline in the frequency within circulating cluster of differentiation 4 (CD4) Tem cells during the first 12 weeks., Evaluating four siplizumab dosing regimens for induction of a T cell phenotype signature based on the 20% increase or greater from baseline in frequency on CD4 Tem. The primary analysis will identify siplizumab doses with acceptable safety profiles and favorable changes in the T cell phenotype in each age cohort. The primary assessments will be made during the first 12 weeks with an interim analysis for futility after 5 PP per dosing arm reaches Week 12 in each age cohort., From week 0 (baseline) to week 12|Acceptable T cell phenotype signature by the change from baseline in the CD4 Treg/Tem ratio, Evaluating four siplizumab dosing regimens for induction of a T cell phenotype signature based on the 75% increase or greater from baseline in the Treg/Tem ratio, From week 0 (baseline) to week 12 | Secondary: Frequency of Adverse Events (AEs) in all siplizumab dosing arms, AE will include any untoward medical occurrence associated with siplizumab administration or any study-mandated procedure, From week 0 to week 52|Mixed Meal Tolerance Test (MMTT)-stimulated mean 2-hour C-peptide AUC, The mean 2-hour C-peptide AUC, measured in nmol/L, is computed by dividing the total AUC by 120 minutes, At Week 12, 24, 36, 52|Insulin use (U/kg/day), Measured as U/kg body weight/day; participants should record the type and amount of insulin they have used during the 5-day period immediately preceding the beginning of treatment, middle of treatment, end of treatment, and at all follow-up visits, At Weeks 12, 24, 36 and 52.
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| Locations: |
University of Alabama at Birmingham: Division of Endocrinology, Diabetes and Metabolism, Birmingham, Alabama, 35294, United States|UCSF School of Medicine: UCSF Diabetes Clinic, San Francisco, California, 94143, United States|Stanford School of Medicine: Department of Pediatrics, Division of Pediatric Endocrinology and Diabetes, Stanford, California, 94305, United States|University of Colorado School of Medicine: Barbara Davis Center for Diabetes, Aurora, Colorado, 80045, United States|University of Florida: Diabetes Center of Excellence, Gainesville, Florida, 32608, United States|University of Miami Miller School of Medicine: Diabetes Research Institute, Miami, Florida, 33136, United States|University of South Florida: Diabetes Center, Tampa, Florida, 33612, United States|Emory University School of Medicine: Emory & Children's Pediatric Research Center, Division of Endocrinology & Diabetes, Atlanta, Georgia, 30307, United States|The University of Chicago: Duchossois Center for Academic Medicine-Hyde Park, Chicago, Illinois, 60637, United States|Indiana University Medical Center: Riley Hospital for Children, Department of Pediatric Endocrinology & Diabetology, Indianapolis, Indiana, 46202, United States|University of Iowa Children's Hospital: Department of Pediatrics, Pediatric Endocrinology and Diabetes, Iowa City, Iowa, 52242, United States|Joslin Diabetes Center: Joslin Clinic, Boston, Massachusetts, 02215, United States|University of Minnesota Medical School: Division of Pediatric Endocrinology and Diabetes, Minneapolis, Minnesota, 55454, United States|Children's Mercy Hospitals and Clinics: Section of Pediatric Endocrinology and Diabetes, Kansas City, Missouri, 64108, United States|University at Buffalo, Department of Pediatrics: Division of Endocrinology and Diabetes, Buffalo, New York, 14203, United States|Columbia University Medical Center: Naomi Berrie Diabetes Center, New York, New York, 10032, United States|Children's Hospital of Philadelphia: Diabetes Center for Children, Philadelphia, Pennsylvania, 19104, United States|University of Texas Southwestern Medical Center: Department of Internal Medicine, Division of Endocrinology, Dallas, Texas, 75390, United States|Benaroya Research Institute at Virginia Mason: Diabetes Research Program, Seattle, Washington, 98101, United States
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