Siplizumab in T1DM (DESIGNATE)
Type 1 Diabetes Mellitus
About this trial
This is an interventional treatment trial for Type 1 Diabetes Mellitus focused on measuring diabetic, Type 1 diabetes, T1DM, siplizumab
Eligibility Criteria
Inclusion Criteria:
- Ability to provide informed consent (parental permission and informed assent of minor, if applicable)
- Diagnosis of Type 1 Diabetes Mellitus (T1DM) within 18 months (550 days) of enrollment (V0)
Positive for at least one diabetes-related autoantibody including:
- Glutamate decarboxylase (GAD-65)
- Insulin, if obtained within 10 days of the onset of exogenous insulin therapy
- Insulinoma antigen-2 (IA-2)
- Zinc transporter-8 (ZnT8)
- Peak stimulated C-peptide level > 0.15 pmol/mL following a mixed- meal tolerance test (MMTT) conducted >= 21 days from diagnosis and within 37 days of enrollment (V0)
- Completion of a primary SARS-CoV-2 vaccination series, including any additional vaccine dose(s) for which the participant qualifies for, according to current The Centers for Disease Control and Prevention (CDC) recommendations and FDA approval(s) or emergency use authorization(s). If the participant requires administration of vaccine(s) to meet eligibility requirements, they must complete the vaccination series at least 2 weeks prior to enrollment (V0)
Exclusion Criteria:
- Use of investigational drugs within 24 weeks of participation with the exception of any vaccine for the prevention of SARS-CoV2 infection and emergency use authorization medications for treating SARS- CoV2
- Severe reaction or anaphylaxis to humanized monoclonal antibodies
- History of significant allergy (e.g. anaphylaxis) to milk or soy proteins
History of recent (within 180 days of V0) or ongoing uncontrolled bacterial, viral, fungal or other opportunistic infections, including:
- Human immunodeficiency virus (HIV)
- Current or prior infection with hepatitis B (HBV), as indicated by positive HBsAg or positive HBcAb
- Current or prior hepatitis C (HCV), unless treated with anti-viral therapy with achievement of a sustained virologic response (undetectable viral load 12 weeks after cessation of therapy)
- Positive Quantiferon-TB Gold or Quantiferon-TB Gold Plus tests. PPD or T-SPOT (R). TB may be substituted for the Quantiferon-TB Gold or Quantiferon-TB Gold Plus tests
- Active infection with Epstein-Barr virus (EBV) as detected by Polymerase Chain Reaction (PCR) or serology at the screening visit (V-1)
- Active infection with cytomegalovirus (CMV) as detected by PCR or serology at the screening visit (V-1)
- Positive molecular testing of SARS-CoV-2 within 21 days of V-1
Any of the following laboratory abnormalities within 37 days of enrollment (V0), confirmed by repeat tests at least 1 week apart:
- White blood count (WBC) < 3 x 10^3/µL
- CD4+ count below the lower limit of normal
- Platelet count <150,000 /µL
- Hemoglobin < 10 g/dL
- ALT >= 2x upper limit of normal (ULN) or
- AST >= 2x ULN
- Prior or current treatment that is known to alter the natural history of Type 1 Diabetes Mellitus (T1DM) or immunologic status, including high dose inhaled, extensive topical or systemic glucocorticoids
- Current or prior (within last 14 days of the V-1 mixed meal tolerance test (MMTT)) use of any medication known to influence glucose tolerance (e.g., atypical antipsychotics, diphenylhydantoin, thiazide, or other potassium- depleting diuretics, ß-adrenergic blockers, niacin)
- Current or prior (within the last 30 days of the V-1 MMTT) use of metformin, sulfonylureas, glinides, thiazolidinediones, exenatide, liraglutide, DPP-IV inhibitors or amylin
- Previous or current diagnosis of malignancy
- History of bone marrow transplantation, or autoimmune disease associated with lymphopenia
- History or diagnoses of other autoimmune diseases with the exception of stable thyroid or celiac disease
- History of significant cardiovascular disease
- Vaccination with a live attenuated vaccine (e.g., varicella, measles, mumps, rubella, coldattenuated intranasal influenza vaccine, bacillus Calmette- Guérin, and smallpox) within 30 days of V0
- Women of child-bearing potential who are unwilling to use a medically acceptable form of contraception from 14 days prior to V0 until study Week 52
- Women who are pregnant, lactating, or planning on pregnancy during the study
- Current, diagnosed mental illness (e.g. severe depression), current diagnosed or self-reported drug, or alcohol abuse that, in the opinion of the investigator, would interfere with the participant's ability to comply with study requirements
- Past or current medical problems or findings from physical examination or laboratory testing, which, in the opinion of the investigator, may pose additional risks from participation in the study, may interfere with the participant's ability to comply with study requirements or that may affect the quality or interpretation of the data obtained from the study
Sites / Locations
- University of Alabama at Birmingham: Division of Endocrinology, Diabetes and MetabolismRecruiting
- UCSF School of Medicine: UCSF Diabetes ClinicRecruiting
- Stanford School of Medicine: Department of Pediatrics, Division of Pediatric Endocrinology and DiabetesRecruiting
- University of Colorado School of Medicine: Barbara Davis Center for DiabetesRecruiting
- University of Florida: Diabetes Center of ExcellenceRecruiting
- University of Miami Miller School of Medicine: Diabetes Research InstituteRecruiting
- University of South Florida: Diabetes CenterRecruiting
- Emory University School of Medicine: Emory & Children's Pediatric Research Center, Division of Endocrinology & DiabetesRecruiting
- The University of Chicago: Duchossois Center for Academic Medicine-Hyde ParkRecruiting
- Indiana University Medical Center: Riley Hospital for Children, Department of Pediatric Endocrinology & DiabetologyRecruiting
- University of Iowa Children's Hospital: Department of Pediatrics, Pediatric Endocrinology and DiabetesRecruiting
- Joslin Diabetes Center: Joslin ClinicRecruiting
- University of Minnesota Medical School: Division of Pediatric Endocrinology and DiabetesRecruiting
- Children's Mercy Hospitals and Clinics: Section of Pediatric Endocrinology and Diabetes
- University at Buffalo, Department of Pediatrics: Division of Endocrinology and DiabetesRecruiting
- Columbia University Medical Center: Naomi Berrie Diabetes CenterRecruiting
- Children's Hospital of Philadelphia: Diabetes Center for ChildrenRecruiting
- Sanford Health, Sanford Research CenterRecruiting
- University of Texas Southwestern Medical Center: Department of Internal Medicine, Division of Endocrinology
- Benaroya Research Institute at Virginia Mason: Diabetes Research ProgramRecruiting
Arms of the Study
Arm 1
Arm 2
Arm 3
Arm 4
Arm 5
Arm 6
Arm 7
Arm 8
Experimental
Experimental
Experimental
Experimental
Experimental
Experimental
Experimental
Experimental
Adults with T1D 0.08 mg/kg SQ dose
Adults with T1D 0.12 mg/kg SQ dose
Adults with T1D 0.18 mg/kg SQ dose
Adults with T1D 0.22 mg/kg SQ dose
Children with T1D 0.08 mg/kg SQ dose
Children with T1D 0.12 mg/kg SQ dose
Children with T1D 0.18 mg/kg SQ dose
Children with T1D 0.22 mg/kg SQ dose
Cohort 1 Group1: 0.08 mg/kg SQ dose for a total of 12 weeks
Cohort 1 Group 2: 0.12 mg/kg SQ dose for a total of 12 weeks
Cohort 1 Group 3:0.18 mg/kg SQ dose for a total of 12 weeks
Cohort 1 Group 4: 0.22 mg/kg SQ dose for a total of 12 weeks
Cohort 2 Group 1:0.08 mg/kg SQ dose for a total of 12 weeks
Cohort 2 Group 2:0.12 mg/kg SQ dose for a total of 12 weeks
Cohort 2 Group 3: 0.18 mg/kg SQ dose for a total of 12 weeks
Cohort 2 Group 4: 0.22 mg/kg SQ dose for a total of 12 weeks