NCT00672204

Raptiva and Sirolimus in Islet Transplantation for Type 1 Diabetes

Efalizumab (Raptiva) Combined With Sirolimus in Type 1 Diabetic Islet Allograft Recipients

• Status: Terminated
• Phase: Phase 1 / Phase 2
• Study type: Interventional
• Enrollment: 23 (actual)
• Sponsor: University of Minnesota · Academic / Other
• Sex: All
• Age: 18 Years – 65 Years
• Healthy volunteers: Not accepted

Summary

The primary objective of this protocol is to test the safety and efficacy of a treatment regimen consisting of maintenance therapy with efalizumab and sirolimus for 1 year followed by withdrawal of efalizumab and maintenance therapy with sirolimus, for the prevention of the destruction and rejection of islet transplants in type 1 diabetic recipients. Genentech, the manufacturer of efalizumab voluntarily withdrew the drug from the U.S. market in April of 2009. Previously transplanted subjects have been transitioned to alternative immunosuppressives and no new subjects will be transplanted under this protocol.

Detailed description

The purpose of this study is to improve the applicability of islet transplantation for treatment of type 1 diabetes utilizing a novel immunosuppressive regimen centered on the use of adhesion molecule blockade with an anti-LFA-1 antibody (efalizumab). The lymphocyte-function associated antigen-1 (LFA-1) adhesion molecule is expressed on multiple cellular populations including T cells, B cells, and NK cells and is important in facilitating cell migration and homing. In addition, interaction of LFA-1 with its ligand ICAM-1 on antigen presenting cells provides a powerful costimulatory signal for T cell activation. Animal models using anti-LFA-1 antibodies have shown impressive prolongation of vascularized and cellular allograft survival. These potent immunosuppressive properties have also been documented in several clinical trials with efalizumab, a humanized IgG1 monoclonal antibody directed against LFA-1. The drug was found to be safe, well tolerated, and efficacious in treating moderate to severe psoriasis. More recently, a multicenter trial employing efalizumab in conjunction with prednisone, sirolimus and cyclosporine maintenance immunosuppression in recipients of kidney allografts showed an acceptable safety profile when used at a dose of 0.5mg/kg/week and excellent rejection-free graft survival over the first 6 months after transplant. This study represents the first clinical trial that applies adhesion molecule blockade with efalizumab to prevent the immune response against pancreatic islets in the setting of type 1 diabetes mellitus, with the long-term goal of immunosuppression withdrawal. Genentech, the manufacturer of efalizumab voluntarily withdrew the drug from the U.S. market in April of 2009. Previously transplanted subjects have been transitioned to alternative immunosuppressives and no new subjects will be transplanted under this protocol.

Conditions

• Type 1 Diabetes Mellitus
• Hypoglycemia

Interventions

Type	Name	Description
BIOLOGICAL	Allogeneic islets of Langerhans transplant	Up to 3 intraportal infusions of cadaveric pancreatic islets of Langerhans. Each infusion to contain at least 5,000 islet equivalents/kg body weight.
DRUG	Raptiva	Treatment Day -1 pretransplant to Treatment Day 90 after tx.: 1.0 mg/kg/wk SQ; Treatment Day 91 to Treatment Day 365: 0.5 mg/kg/wk SQ;
DRUG	Sirolimus	Initial dose 0.1 mg/kg PO on day -2, followed by 0.05 mg/kg daily, whole blood 24-hour trough adjusted to target 3-15 ng/ml as tolerated
DRUG	anti-thymocyte globulin	2.0 mg/kg on days -2, and -1 IV

Timeline

• Start date: 2007-11-01
• Primary completion: 2010-12-01
• Completion: 2012-08-01
• First posted: 2008-05-06
• Last updated: 2017-10-25
• Results posted: 2013-03-27

Locations

1 site across 1 country: United States