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

Phase 1

Withdrawn

• Conditions: Autoimmune Diseases
• Interventions: Drug: Efalizumab

• Registration Number: NCT00777400
• Lead Sponsor: University of California, San Francisco

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.

Detailed Description

The objective of this pilot trial is to determine whether the conversion from calcineurin inhibitors (CNI) and mycophenolate mofetil (MMF) to efalizumab and sirolimus is associated with an increase in T regulatory cells and does not result in an increase in acute rejection following conversion. CNIs are associated with progressive nephrotoxicity, increased cardiovascular risk factor as well as an inhibitory effect on T regulatory cells.

PRIMARY OBJECTIVE:

To determine if the combination of efalizumab and sirolimus results in a significant increase in T regulatory cells. A hundred percent increase in T regulatory cells will be determined to be an important biologic effect of the combination of efalizumab and sirolimus.

SECONDARY OBJECTIVES:

To assess the feasibility of the conversion from CNI/MMF to efalizumab/sirolimus and to determine that this combination is safe and effective

To determine if there is an increase in FoxP3 mRNA in the urine of converted patients. Urine FoxP3 is believed to correlate with T regs in the kidney.

Study Timeline

• Study First Submitted: 2008-10-20
• Study First Submitted QC: 2008-10-21
• Study First Posted: 2008-10-22
• Study Start: 2008-12
• Primary Completion: 2009-04
• Study Completion: 2009-04
• Status Verified: 2013-05
• Last Update Submitted: 2013-05-13
• Last Update Posted: 2013-05-14

Recruitment & Eligibility

• Status: WITHDRAWN
• Sex: All
• Target Recruitment: Not specified

Inclusion Criteria

• 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
• Hematocrit >30% at the time of inclusion, platelet count >100,000 and WBC ≥ 3.0
• 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.

Exclusion Criteria

• 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

Study & Design

• Study Type: INTERVENTIONAL
• Study Design: SINGLE_GROUP

Arm && Interventions

Group	Intervention	Description
1	Efalizumab	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.

Primary Outcome Measures

Name	Time	Method
To determine if the combination of efalizumab and sirolimus results in a significant increase in T regulatory cells.	Month 6

Secondary Outcome Measures

Name	Time	Method
The successful conversion from CNI to non-CNI regimen without increasing the rejection rate by more than 20%.	6 Months

Trial Locations

Locations (1)

University of California, San Francisco; 🇺🇸 San Francisco, California, United States