Pilot Trial to Assess Effect of CNI Conversion of Efalizumab on T Reg Cells

NCT00777400 | Withdrawn Phase 1 DMC

• 2 other identifiers: ACD4520 EfalizumabACD4520
• Study Type: interventional
• Target: N/A
• Locations: 1 country
• Sites: 1

Brief Summary

The purpose of this pilot trial is to determine whether a conversion from calcineurin inhibitors (CNI) and mycophenolate mofetil (MMF) to a regimen consisting of efalizumab and sirolimus is associated with an increase in T regulatory cells, white cells that control the immune system and can prevent autoimmune diseases like arthritis or rejection of foreign organs,and does not result in an increase in acute rejection.

Conditions

Autoimmune Diseases

Keywords

Kidney transplant; T regulatory cells; Efalizumab; Rejection; Safely convert renal transplant from mycophenolate mofetil and Calcineurin inhibitor to efalizumab and sirolimus

Outcome Measures

Primary Outcomes (1)

• To determine if the combination of efalizumab and sirolimus results in a significant increase in T regulatory cells.

  Month 6

Secondary Outcomes (1)

• The successful conversion from CNI to non-CNI regimen without increasing the rejection rate by more than 20%.

  6 Months

Study Arms (1)

1

EXPERIMENTAL

Efalizumab will be started on Day 0 until the end of the study at Week 24. At the end of the first week, after efalizumab is started, cyclosporine or tacrolimus will be decreased by 50% and at 2 weeks the dose of cyclosporine or tacrolimus will be completely discontinued. At 12 weeks Cellcept or myfortic will be discontinued and the patient will be converted to sirolimus for the remainder of the study.

Drug: Efalizumab

Interventions

Efalizumab DRUG

1 mg/kg of efalizumab administered sub q once weekly

1

Eligibility Criteria

• Age: 18 Years - 70 Years
• Sex: all
• Healthy Volunteers: No
• Age Groups: Adult (18-64), Older Adult (65+)

You may qualify if:

• Ability to provide written informed consent and comply with study assessments for the full duration of the study.
• Male or female, 18-70 years
• Recipients of primary renal transplants from living and deceased donors
• Stable renal function for 4 weeks prior to entry into the study
• No history of acute rejection
• Pretransplant negative crossmatch
• If a female of childbearing potential, a negative pregnancy test and commitment to the use of two forms of effective contraception (birth control) for the duration of the study are necessary.
• If a non-sterile male, commitment to the use of two forms of effective contraception (birth control) for the duration of the study is necessary.

You may not qualify if:

• Patients with known hypersensitivity to Raptiva® (efalizumab) or any of its components.
• Pregnant or lactating women
• Pretransplant PRA \>20%
• cGFR \< 35/ml/min
• \>500 mg protein as estimated by spot protein/creatinine ratio
• Recipients of other organ transplants
• Subject has a current malignancy or a history of malignancy, except non-metastatic basal or squamous cell carcinoma of the skin that has been treated successfully.
• Patients receiving experimental immunosuppressive agents
• Prior enrollment in the study
• Any other condition that the investigator believes would pose a significant hazard to the subject if the investigational therapy were initiated.
• Participation in another simultaneous medical investigation or trial

Sponsors & Collaborators

• University of California, San Francisco: lead
• Genentech, Inc.: collaborator

Study Sites (1)

University of California, San Francisco

San Francisco, California, 94143, United States

Location

Related Publications (3)

• Nankivell BJ, Borrows RJ, Fung CL, O'Connell PJ, Allen RD, Chapman JR. The natural history of chronic allograft nephropathy. N Engl J Med. 2003 Dec 11;349(24):2326-33. doi: 10.1056/NEJMoa020009.

  PMID: 14668458 RESULT

• Meier-Kriesche HU, Schold JD, Srinivas TR, Kaplan B. Lack of improvement in renal allograft survival despite a marked decrease in acute rejection rates over the most recent era. Am J Transplant. 2004 Mar;4(3):378-83. doi: 10.1111/j.1600-6143.2004.00332.x.

  PMID: 14961990 RESULT

• Vincenti F, Mendez R, Pescovitz M, Rajagopalan PR, Wilkinson AH, Butt K, Laskow D, Slakey DP, Lorber MI, Garg JP, Garovoy M. A phase I/II randomized open-label multicenter trial of efalizumab, a humanized anti-CD11a, anti-LFA-1 in renal transplantation. Am J Transplant. 2007 Jul;7(7):1770-7. doi: 10.1111/j.1600-6143.2007.01845.x.

  PMID: 17564637 RESULT

MeSH Terms

Conditions

Autoimmune Diseases; Rejection, Psychology

Interventions

efalizumab

Condition Hierarchy (Ancestors)

Immune System Diseases; Social Behavior; Behavior

Study Officials

• Flavio Vincenti, M.D.

  University of California, San Francisco

  PRINCIPAL INVESTIGATOR

Study Design

• Study Type: interventional
• Phase: phase 1
• Allocation: NON RANDOMIZED
• Masking: NONE
• Intervention Model: SINGLE GROUP
• Sponsor Type: OTHER
• Responsible Party: SPONSOR

Study Record Dates

• First Submitted: October 20, 2008
• First Posted: October 22, 2008
• Study Start: December 1, 2008
• Primary Completion: April 1, 2009
• Study Completion: April 1, 2009
• Last Updated: May 14, 2013

Record last verified: 2013-05

Locations

US (1)