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

Phase 1/Phase 2
18 Years
65 Years
Not Enrolling
Kidney Transplantation, Chronic Kidney Failure

Thank you

Trial Information

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

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.

Inclusion Criteria:

- Primary renal transplant recipients

- recipients of deceased donor or living donor transplant

- Age 18-65 years (inclusive)

- Male or female

- Within 3-9 month window post-transplantation

- No episodes of acute rejection prior to enrollment

- Mild impairment of renal function as defined by a calculated CrCl of 35-50 ml/min/m2

Exclusion Criteria:

- Subjects with any prior solid organ transplant (including kidney)

- Subjects with a history of panel-reactive antibodies greater than 20% or the
development of new anti-HLA antibodies after transplantation and prior to enrollment

- Subjects the Investigator deems to be at a relatively higher risk for acute rejection

- HLA-identical living donor pairs

- Evidence of infection with Hepatitis C (antibody positive or PCR positive), Hepatitis
B ( surface antigen positive), HIV

- Subjects with BK or CMV viremia prior to enrollment

- Multiple organ transplant recipients

- Subjects with underlying renal disease of focal segmental glomerulosclerosis,
membranoproliferative glomerulonephritis, hemolytic-uremic syndrome/thrombocytopenic
purpura syndrome (due to risk of rapid disease recurrence in the allograft

- EBV negative recipients

- Women who are pregnant or nursing

- Women of child bearing age unwilling or unable to use an acceptable method to avoid
pregnancy for the duration of the study and up to 8 weeks after last injection

- Patients not able to tolerate a dose of at least 500 mg of mycophenolate mofetil
twice daily

- Allergy to Iodine

Type of Study:


Study Design:

Endpoint Classification: Efficacy Study, Intervention Model: Single Group Assignment, Masking: Open Label, Primary Purpose: Treatment

Outcome Measure:

Efficacy Will be Determined by Change in Renal Function as Measured by Cold Iothalamate Glomerular Filtration Rate(GFR)3 Months After Enrollment, and Acute Rejection Episodes Within the First 6 Months Post Enrollment.

Outcome Time Frame:

6 months from conversion

Safety Issue:


Principal Investigator

Kenneth A Newell, MD, PhD

Investigator Role:

Principal Investigator

Investigator Affiliation:

Emory University


United States: Food and Drug Administration

Study ID:




Start Date:

May 2007

Completion Date:

April 2009

Related Keywords:

  • Kidney Transplantation
  • Chronic Kidney Failure
  • Immunosuppression
  • Renal Transplantation
  • Kidney Failure, Chronic
  • Renal Insufficiency



Emory UniversityAtlanta, Georgia  30322