This multi-center randomized controlled trial will assess the safety and efficacy of ATG followed by either adalimumab or verapamil in preserving insulin secretion 2 years from randomization in persons aged 9 to \<21 with recent-onset stage 3 T1D.
Recent-onset stage 3 T1D diagnosed by standard ADA criteria, with the ability to be randomized within 6 months from the date of T1D diagnosis and within 37 days of Screening Visit.
At least one positive T1D auto-antibody.
If clearly positive (≥20% above local lab's ULN) at screening, repeat antibody testing for central lab is not required.
Insulin auto-antibodies are only considered if exogenous insulin use is <10 days when blood is drawn.
Prior treatment with ATG or known allergy to ATG or rabbit-derived products.
Immunodeficient or have clinically significant chronic lymphopenia: Leukopenia (<3,000 leukocytes /μL), neutropenia (<1,500 neutrophils/μL), lymphopenia (<800 lymphocytes/μL).
Thrombocytopenia (<100,000 platelets/μL) or anemia (hemoglobin < 10g/dL).
Leukocytosis (>14,000/μL)
Parallel
Anti-thymocyte globulin (ATG)
DrugATG (brand name Thymoglobulin) a polyclonal T cell antibody preparation. The first dose (0.5 mg/kg) will be infused on day 0, during a period of 6 hours. The second dose (2 mg/kg) will be given on day 1, over a period of 4 to 6 hours.
verapamil extended-release capsule
DrugDaily oral (pill) administration at 60, 120, 240 or 360 mg based on weight and ECG findings.
Adalimumab
Drug40 mg administered subcutaneously every other week beginning 6 weeks after the last dose of ATG until the 156-week visit.
Stimulated C-peptide AUC
The primary outcome is the C-peptide in response to a 2-hour MMTT at week 104. This is measured as the area under the stimulated C-peptide curve (AUC). AUC is computed using a trapezoidal rule, which is a weighted sum of the C-peptide values over 120 minutes.
Severe Adverse Events
Prevalence of SAE of grade 3 or above, that may be attributable to study medications at all follow-up time points.
Adverse Events
Number and severity of AEs.
Severe Hypoglycemia
Rate of severe hypoglycemia, defined as an event requiring assistance of another person due to altered consciousness and another person to actively administer carbohydrate, glucagon, or other resuscitative actions.
Diabetic ketoacidosis (DKA)
Number of DKA events (rate assessed if sufficient events)
Click on the lead sponsor to view all of their trials.
City of Hope Medical Center
Lead sponsor
Jaeb Center for Health Research
Collaborator
