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.
This protocol will enroll 60 participants between the ages of 4 and 34 with Stage 2 Type 1 diabetes. Oral glucose tolerance testing will be done at the screening, baseline visit (V0) and at 3, 6 and 12 months in the first year after study drug administration. Eligible study participants will be randomized to recieve either 2 doses of ATG over 2-3 days or 14 doses of teplizumab given once daily over 14 consecutive days. Safety labs will also be done during select study visits to monitor the participant's health. Once the treatment phase has been completed, participants will have 3 in-person study visits in year one of the study with interim contact to assess adverse events and symptoms of diabetes. After year one of the study, participants will continue in-person follow-up visits every 6 months until the last enrolled participant completes the 12-month visit or develops Stage 3 Type 1 diabetes, whichever occurs first. The total initial study duration is expected to last 3-4 years. There is a possibility the study will be extended after the initial study duration, dependent upon the primary outcome (DPTRS at the month 6 visit) and as determined by TrialNet. If the study extension is done, participants would be presented an additional consent form to opt into additional follow-up visits which would increase total time in study to about 9 years.
Study Type
INTERVENTIONAL
Allocation
RANDOMIZED
Purpose
PREVENTION
Masking
NONE
Enrollment
60
Thymoglobulin
Intravenous 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.
Barbara Davis Center
Aurora, Colorado, United States
RECRUITINGYale University
New Haven, Connecticut, United States
RECRUITINGUniversity of Florida
Gainesville, Florida, United States
RECRUITINGColumbia University
New York, New York, United States
RECRUITINGUniversity of Pittsburgh
Pittsburgh, Pennsylvania, United States
RECRUITINGBenaroya Research Institute
Seattle, Washington, United States
RECRUITINGChange 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
Time frame: 6 months after completion of study drug administration
Progression to Stage 3 T1D
Elapsed time from study drug administration to the development of diabetes or time of last contact among those randomized
Time frame: 6 months after study drug administration
OGTT glucose AUC
Mean area under the stimulated glucose curve (AUC) over the 2-hour oral glucose tolerance test.
Time frame: 6 months after study drug administration
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.
Time frame: 6 months after study drug administration
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.
Time frame: 6 months after study drug administration
OGTT C-peptide AUC
Mean area under the stimulated C-peptide curve (AUC) over the 2-hour oral glucose tolerance test
Time frame: 6 months after study drug administration
HbA1c
Measured as a percentage of total hemoglobin
Time frame: 6 months after study drug administration
Continuous Glucose Monitoring (CGM)
Measures of CGM glucose range and variability
Time frame: 6 months after study drug administration
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