hOKT3γ1 (Ala-Ala) Combined With Sirolimus and Delayed Tacrolimus in Type 1 Diabetic Islet Allograft Recipients
The collective effects of two-layer pancreas preservation, pretransplant islet culture, day -2 pretransplant immunosuppression, and induction immunosuppression with the FcR-nonbinding anti-CD3 monoclonal antibody hOKT3γ1 (Ala-Ala)to facilitate diabetes reversal after single-donor islet transplantation.
Type 1 Diabetes
Drug: Allogeneic Islets of Langerhans
Drug: hOKT3γ1 (Ala-Ala)
|Study Design:||Allocation: Non-Randomized
Endpoint Classification: Safety/Efficacy Study
Intervention Model: Single Group Assignment
Masking: Open Label
Primary Purpose: Treatment
|Official Title:||hOKT3γ1 (Ala-Ala) Combined With Sirolimus and Delayed Tacrolimus in Type 1 Diabetic Islet Allograft Recipients|
- Safety, tolerability, immune activity, and pharmacokinetics of hOKT3γ1 (Ala-Ala) antibody induction therapy for the prevention of autoimmune destruction and rejection of allogeneic islet transplants as measured by:
- -Physical examination
- -Vital signs
- -Body weight
- -Adverse events
- -Laboratory and diagnostic safety assessments included complete blood counts with differential and platelets, circulating T cell phenotypes, and serum chemistry.
- -Immune activity and pharmacokinetic assessments included hOKT3γ1 (Ala-Ala) level and half-life, monoclonal antibody coating and modulation of CD3 on peripheral blood T cells, and anti-hOKT3γ1 (Ala-Ala) antibody responses.
- Efficacy of hOKT3γ1 (Ala-Ala) antibody induction therapy for the prevention of autoimmune destruction and rejection of islet transplants as defined by:
- -Proportion of subjects with full islet graft function (insulin independence and HbA1c <7%);
- -Proportion of subjects with partial islet graft function (insulin dependence, basal or arginine-stimulated C-peptide levels of greater or equal to 0.5 ng/ml and HbA1c <7%);
- -Proportion of subjects with slet graft loss will be defined as a return to insulin therapy for >30 days, absence of basal and arginine-stimulated C-peptide, re-transplantation, or patient death;
|Study Start Date:||April 2000|
|Study Completion Date:||January 2004|
|Primary Completion Date:||January 2004 (Final data collection date for primary outcome measure)|
This is an open-label, one-year follow-up study of type 1 diabetic islet allograft recipients who receive FcR non-binding OKT3 antibody hOKT3γ1 (Ala-Ala) plus sirolimus induction immunotherapy combined with sirolimus and delayed tacrolimus maintenance immunosuppression. Six subjects were transplanted.
The premise behind the proposal is that hOKT3γ1(Ala-Ala) corrects the imbalance between autoreactive and regulatory T cells and consequently prevents autoimmune destruction of transplanted islets. To prevent allorejection, hOKT3γ1(Ala-Ala)was combined with sirolimus and delayed tacrolimus. Additionally, the safety and efficacy of the maintenance immunosuppressive regimen of sirolimus combined with tacrolimus was monitored.
|United States, Minnesota|
|Universtiy of Minnesota|
|Minneapolis, Minnesota, United States, 55455|
|Principal Investigator:||Bernhard J. Hering, M.D.||University of Minnesota - Clinical and Translational Science Institute|