NCT00472082

Early Conversion From Tacrolimus to Efalizumab Maintenance Therapy in Kidney Transplant Recipients

An Open Label, Single-Center Pilot Study of Early Conversion From Tacrolimus to Efalizumab Maintenance Therapy in Primary Renal Transplant Recipients

• Status: Terminated
• Phase: Phase 1 / Phase 2
• Study type: Interventional
• Enrollment: 5 (actual)
• Sponsor: Emory University · Academic / Other
• Sex: All
• Age: 18 Years – 65 Years
• Healthy volunteers: Not accepted

Summary

The toxicity of calcineurin inhibitors(CNI)is a major factor limiting the success of renal transplantation. This protocol aims to replace the calcineurin inhibitor, tacrolimus, with efalizumab early after transplantation in patients with mild impairment of renal function in order to minimize the toxicities of CNI.

Detailed description

Over the last two decades there have been significant improvements in renal transplantation due in large part to the decreasing incidence of acute rejection (down to less than 20% for first renal transplants) with the use of calcineurin inhibitors (CNI) such as cyclosporin and tacrolimus. Though proven very effective anti-rejection medications their use is associated with adverse side effects, including high blood pressure, post transplant diabetes, and high cholesterol, predisposing risk factors for cardiovascular disease and cerebrovascular disease. Chronic use of these drugs has also waged limitations to the long term survival of transplanted kidneys and kidney recipients with an increase in the development of chronic allograft nephropathy (CAN). There is also an increased incidence of chronic renal failure in non renal transplant recipients receiving CNI based treatments. The mechanism of action for these reagents is known to be imprecise and science has sought to replace the current therapies in place with less toxic drugs more specific in their signaling pathway targets. In recent years cell surface proteins, restricted to cells of the immune system have been identified as mediators of the rejection response. The activation of T cells has been seen to activate an immune response correlated clinically with rejection. Integrins, specifically leukocyte function associated antigen LFA-1, are cell surface molecules which play a role in T-cell activation. LFA-1 is made up of two subunits, known as CD11 and CD18. Efalizumab is a humanized monoclonal antibody against the CD11 molecule. By binding to CD11 on T cells the system blocks the interaction between LFA-1 and ICAM-1, an intercellular adhesion molecule also necessary for T cell activation, thereby diminishing an immune response. The blockade formed does not deplete the T cells. There have been preliminary studies using efalizumab in combination with cyclosporine. A very low incidence of rejection was observed in all groups receiving efalizumab (7.8%). However 3 cases of post-transplant lymphoproliferative disease were seen in 38 patients. There have been no cases of lymphomas or lymphoproliferative disease reported in clinical trials evaluating efalizumab for the treatment of psoriasis, suggesting that the combination of efalizumab and cyclosporine may have resulted in over immunosuppression. As per standard of care, recipients of a kidney transplant at Emory are managed with a combination of the calcineurin inhibitor Prograf (tacrolimus), Cellcept (an antiproliferative agent) and Prednisone, a corticosteroid. For this study the investigators have chosen to substitute efalizumab in place of Prograf, after 3 months post transplant the period where the incidence of acute rejection is highest. Efalizumab, known by its trade name Raptiva, was approved by the FDA in October 2003 for the treatment of psoriasis. It is hypothesized that the conversion from Prograf to efalizumab will be associated with improved renal function and not associated with an increased risk of rejection. The investigators hope to address the challenges faced by recipients of transplanted kidneys in the long course of their transplanted organ's management with more favorable alternatives.

Conditions

• Kidney Transplantation
• Chronic Kidney Failure

Interventions

Type	Name	Description
DRUG	efalizumab	Administration of a test dose of efalizumab 0.7mg/kg will be administered at enrollment. Weekly subcutaneous injections of efalizumab 1mg/kg will begin with study visit 2 and continue for 1 year for this pilot study.

Timeline

• Start date: 2007-05-01
• Primary completion: 2009-04-01
• Completion: 2009-04-01
• First posted: 2007-05-11
• Last updated: 2014-01-27
• Results posted: 2012-12-06

Locations

1 site across 1 country: United States