Pilot Trial to Assess Effect of CNI Conversion of Efalizu... | NCT00777400

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

NCT00777400

Sponsor

University of California, San Francisco

Status

Withdrawn

Last Update Posted

May 14, 2013Estimated

Enrollment

0Actual

Phase

Phase 1Phase 2

Conditions

Autoimmune Diseases

Interventions

Efalizumab

Countries

United States

Protocol Section

Identification Module Status Module Sponsor/Collaborators Module Oversight Module Description Module Conditions Module Design Module Arms/Interventions Module Outcomes Module Eligibility Module Contacts/Locations Module References Module IPD Sharing Statement Module

Results Section

Participant Flow Module Baseline Characteristics Module Outcome Measures Module Adverse Events Module More Info Module

Annotation Section

Annotation Module

Document Section

Large Document Module

Derived Section

Miscellaneous Info Module Condition Browse Module Intervention Browse Module

Protocol Section

Identification Module

NCT ID

Results Section

No data available

No data is available for this block.

Annotation Section

No data available

No data is available for this block.

Document Section

No data available

No data is available for this block.

Derived Section

Miscellaneous Info Module

Version Holder

ID	Type	Description	Link
ACD4520

Status Module

Record Verification Date

May 2013

Overall Recruitment Status or Expanded Access Status

Withdrawn

Last Known Status

Not provided

Delayed Posting

Not provided

Why Stopped

New safety information reported in the post-marketing setting with efalizumab for treatment of chronic plaque psoriasis and trial conduct feasibility issues.

Expanded Access Info

Start Date

Dec 2008

Primary Completion Date

Apr 2009Actual

Completion Date

Apr 2009Actual

First Submitted Date

Oct 20, 2008

First Submission Date that Met QC Criteria

Oct 21, 2008

First Posted Date

Oct 22, 2008Estimated

Results Waived

Not provided

Results First Submitted Date

Not provided

Results First Submitted that Met QC Criteria

Not provided

Results First Posted Date

Not provided

Certification/Extension (aka Delayed Results) First Submitted Date

Not provided

Certification/Extension First Submitted that Passed QC Review

Not provided

Certification/Extension First Posted Date

Not provided

Last Update Submitted Date

May 13, 2013

Last Update Posted Date

May 14, 2013Estimated

Name	Class
Genentech, Inc.	INDUSTRY

Oversight Module

Has Data Monitoring Committee (DMC)

Yes

Is FDA Regulated Drug

Not provided

Is FDA Regulated Device

Not provided

Is Unapproved Device

Not provided

Pediatric Postmarket Surveillance of a Device Product

Not provided

Product Exported from US

Not provided

FDAAA801 Violation

Not provided

Description Module

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.

Design Module

Study Type

Interventional

Number of References to an Expanded Access Study

Not provided

Expanded Access Types

Not provided

Patient Registry

Not provided

Target Follow-Up Duration

Not provided

Phases

Phase 1Phase 2

Interventional Study Design

Allocation

Biospecimen

No data available

No data is available for this block.

Enrollment

0Actual

Arms/Interventions Module

Arm Groups

Label	Type	Description	Intervention Names
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

Name	Type	Description	Arm Group Labels	Other Names
Efalizumab	Drug	1 mg/kg of efalizumab administered sub q once weekly	1

Outcomes Module

Primary Outcomes

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

Secondary Outcomes

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

Other Outcomes

Not provided

Eligibility Module

Eligibility Criteria

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

Accepts Healthy Volunteers

Sex

All

Sex/Gender Based

Not provided

Sex/Gender Description

Not provided

Minimum Age

18 Years

Maximum Age

70 Years

Standard Ages

AdultOlder Adult

Study Population

Not provided

Sampling Method

Not provided

Name	Affiliation	Role
Flavio Vincenti, M.D.	University of California, San Francisco	Principal Investigator

Facility	Status	City	State	ZIP	Country	Contacts
University of California, San Francisco		San Francisco	California	94143	United States

References Module

Citations

PubMed Identifier	Type	Citation	Retractions
14668458	Result	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.
14961990	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.

ID	Term
D001327	Autoimmune Diseases
D012059	Rejection, Psychology

ID	Term
D007154	Immune System Diseases
D012919	Social Behavior
D001519	Behavior