This is a 2-arm, multi-center, open label study to learn if ATG works the same or better than teplizumab in delaying or preventing Stage 3 Type 1 diabetes. Participants will be administered either 2 infusions of ATG or 14 infusions of teplizumab and will then be followed for at least 12-48 months after administration, depending on timepoint enrolled into the study. If the primary endpoint demonstrates a positive signal and as decided by TrialNet, there is potential for a study extention. This would extend follow-up visits for a possible study duration of about 9 years among the earliest enrollees of the initial study.
Willing to provide informed consent or have a parent or legal guardians provide informed consent when the participant is <18 years of age.
Aged ≥4 to <35 years
A history of at least two or more diabetes-related biochemical autoantibodies (mIAA, GADA, ICA, IA-2A, ZnT8A) present on the same sample. In the absence of other antibodies, ICA and GADA positivity alone will not suffice for eligibility in this trial.
Participants must meet ADA stage 2 T1D glycemic criteria* by TrialNet testing within 100 days of the baseline visit.
Immunodeficiency or clinically significant chronic lymphopenia: (Leukopenia (<3,000 leukocytes/μL), neutropenia (<1,500 neutrophils/μL), lymphopenia (<1000 lymphocytes/μL), thrombocytopenia (<150,000 platelets/μL).
Hemoglobin less than 13 g/dL for adult men and less than 11.5g/dL for adult females and less than 11 g/dL for participants under age 18.
Active signs or symptoms of acute or chronic infection at the time of the baseline visit including SARS-Cov-2.
Uncontrolled autoimmune thyroid disease and/or celiac disease (participants must be well controlled for the previous 6 months).
Parallel
Antithymocyte Globulin (ATG)
DrugThymoglobulin
Teplizumab
DrugIntravenous infusions of teplizumab given for 14 consecutive days. For participants ages 8-34 each infusion will take a minimum of 30 minutes. For participants ages 4-7 each infusion will take a minimum of 2 hours. Each infusion will also be followed by an observation period of at least 30 minutes.
Change in DPTRS at six months
DPTRS is calculated as DPTRS = (1.569 x log-BMI) - (0.056 x age) + (0.813 x glucose sum from 30 to 120 min /100) - (0.848 x C-peptide sum from 30 to 120 min/10) + (0.476 x log-fasting C-peptide), where the units are years for age, kg/m2 for BMI, mg/dl for glucose, ng/ml for C-peptide
Progression to Stage 3 T1D
Elapsed time from study drug administration to the development of diabetes or time of last contact among those randomized
OGTT glucose AUC
Mean area under the stimulated glucose curve (AUC) over the 2-hour oral glucose tolerance test.
M120 score
This is an aggregated score from multiple measurements calculated as follows: M120 = 0.448×(sex) + 0.631×(IA-2A) - 0.0302×(age) + 0.0605×(BMI) \+ 1.380×(HbA1c) + 0.0265×(120 min glucose) - 0.191×(120 min C-peptide), where the units for BMI, age, glucose, C-peptide and HbA1c are, respectively, kg/m2, years, mg/dl, ng/ml and percentage units. Sex was assigned a score of 1 for male and 2 for female, and IA-2A status assigned 0 for absent and 1 for present. Glucose is converted from mmol/l to mg/dl by multiplying by 18; C-peptide is converted from nmol/l to ng/ml by dividing by 3.00; and HbA1c is converted from mmol/mol to percentage units by adding 23.5 and then dividing by 10.93.
Index 60
This is an aggregated score from multiple measurements calculated as follows: Index60 = 0.3695×loge(fasting C-peptide) + 0.0165×(60 min glucose) - 0.3644×(60 min C-peptide), where the units for glucose and C-peptide are, respectively, mg/dl and ng/ml. Glucose is converted from mmol/l to mg/dl by multiplying by 18; C-peptide is converted from nmol/l to ng/ml by dividing by 3.00.
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