The study is a two-arm, multicenter, double-blinded clinical trial testing sequential therapy with rituximab-pvvr followed by abatacept versus rituximab-pvvr alone in new onset T1D. The primary objective is to test whether the C-peptide response to a 2-hour mixed meal tolerance test, will be improved in participants with new onset T1D who are treated with Abatacept after Rituximab-pvvr compared to those treated with Rituximab-pvvr and placebo 24 months after enrollment.
This is a two-arm, double-blind, multicenter clinical trial testing sequential therapy with rituximab-pvvr followed by abatacept versus rituximab-pvvr alone in individuals with new onset T1D to determine whether rituximab-pvvr followed by abatacept results in an improvement in the AUC C-Peptide during a MMTT compared to Rituximab-pvvr alone at 24 months. Additional aims will compare the safety, tolerability in the two treatment arms as well as other clinical metabolic measures: exogenous insulin use, hemoglobin A1c, time in range from continuous glucose monitors, and severe hypoglycemia. Exploratory studies will assess changes in immune markers.
Study Type
INTERVENTIONAL
Allocation
RANDOMIZED
Purpose
TREATMENT
Masking
TRIPLE
Enrollment
74
All participants will receive Rituximab-pvvr dosing from Week 1 to Week 4 of the trial. Rituximab-pvvr will be given by IV infusion over at least 3 hours, at a dose of 375mg/m2 on four visits each one week apart.
Participants in the active drug arm will receive initial Abatacept dosing at Week 16 of trial. Abatacept will be given by a subcutaneous (SC) formulation weekly for 20 months, and dosing be will determined according to weight: Up to 25 kg: 50 mg (0.4 mL); 25 to \<50 kg receive 87.5 mg (0.7 mL), and \> 50 kg receive 125 mg (1.0 mL).
Participants in the placebo arm will receive initial placebo injection at Week 16 of trial. Saline Placebo will be given by a subcutaneous (SC) formulation weekly for 20 months, and dosing volume be will determined according to weight to match active comparator: Up to 25 kg: 0.4 mL; 25 to \<50 kg receive 0.7 mL and \> 50 kg receive 1.0 mL.
Childrens Hospital of Orange County
Orange, California, United States
Stanford University
Palo Alto, California, United States
University of California San Francisco
San Francisco, California, United States
Barbara Davis Center for Childhood Diabetes
Aurora, Colorado, United States
Yale University
New Haven, Connecticut, United States
University of Florida
Gainesville, Florida, United States
University of Miami
Maimi, Florida, United States
Indiana University - Riley Hospital for Children
Indianapolis, Indiana, United States
The Children's Mercy Hospital
Kansas City, Kansas, United States
Joslin Diabetes Center
Boston, Massachusetts, United States
...and 9 more locations
C-Peptide Response to 2-hr MMTT at 24 months post-randomization
The primary objective is to test whether the C-peptide response to a 2-hour mixed meal tolerance test, will be improved in participants with new onset T1D who are treated with Abatacept after Rituximab compared to those participants treated with Rituximab and placebo 24 months after enrollment.
Time frame: 48-months from Day 0
C-peptide AUC Means
C-peptide AUC Mean at 0, 6, 12, 18, 24, 30, 36, 42 and 48 months using the ANCOVA model.
Time frame: Day 0 and every 6 months to trial end (up to 4 years)
Analysis of changes in immune responses to known diabetes antigens and a neoantigen over time by treatment group
Analysis of changes in immune responses to known diabetes antigens and a neoantigen. The investigators will compare the effects of drug treatments on the titers of autoantibodies: anti-insulin, anti-GAD65, anti-IA-2, anti-ZnT8. The investigators will also compare the effects of drug treatments on the response to Keyhole Limpet Hemocyanin (KLH) for which standardized immunological responses have been characterized.
Time frame: Day 0, month 2, 4, 5, 6, 12, 13, 18, 24, 25, 30, and 36
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