Autoimmune DiseasesPhase 1/2NCT00777400
Pilot Trial to Assess Effect of CNI Conversion of Efalizumab on T Reg Cells
A Phase 1/2 study testing Efalizumab in people with Autoimmune Diseases, run by University of California, San Francisco at 1 site in United States.
Trial 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… Read more about this study
- Who is it for?
- Ages 18 to 70 years
- Conditions the study is for
- Autoimmune Diseases
- What is being tested?
- Efalizumab
- Could I receive a placebo?
- No, everyone receives an active treatment
- How many people
- 0 participants
- Where
- 1 siteUnited States
- Study dates
- Dec 2008to Apr 2009
- Phase
- Phase 1/2
- Are there results?
- None posted in the registry
Key requirements
Who can take part, as listed by the sponsor. Only the study team can confirm whether you are eligible, so take this list to your doctor.
- Ages 18 to 70 years
- All sexes
- No healthy volunteers
- Adult, Older adult
Who may be able to join
- 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
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- 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.
Who cannot join
- 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
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- 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
Trial locations and contacts
1 site in 1 country.
United States1 site
University of California, San Francisco
San Francisco, California, 94143
About this study
Official title: A Pilot Trial to Assess the Effect of CNI Conversion to Efalizumab in T Regulatory Cells in Renal Transplantation
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.
Read the 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.
- Conditions
- Autoimmune Diseases
- Being tested
- Efalizumab
- Keywords
- Kidney transplant, T regulatory cells, Efalizumab, Rejection, Safely convert renal transplant from mycophenolate mofetil and Calcineurin inhibitor to efalizumab and sirolimus
- Medical subject headings
- Autoimmune Diseases, Rejection, Psychology
What participants receive
What participants receive. In a randomised study each person is assigned to one group by chance.
EfalizumabDrug
1 mg/kg of efalizumab administered sub q once weekly
| Study group | Role | What they receive |
|---|---|---|
| 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. Receives: Drug: Efalizumab |
What is being measured
The primary outcome is the main question the study is designed to answer.
To determine if the combination of efalizumab and sirolimus results in a significant increase in T regulatory cells.
Measured: Month 6
Secondary outcomes (1)
The successful conversion from CNI to non-CNI regimen without increasing the rejection rate by more than 20%.
Measured: 6 Months
Timeline
From the start of the study to its completion; the mark is today. Estimated dates are the sponsor’s plan.
- First posted22 Oct 2008 (estimated)
- Study startDec 2008
- Primary completionApr 2009
- Study completionApr 2009
Why it stopped: New safety information reported in the post-marketing setting with efalizumab for treatment of chronic plaque psoriasis and trial conduct feasibility issues.
Resources
- Official record on ClinicalTrials.govThe registry entry this page is built from, with its full change history.
- Publications (3)Papers the sponsor has linked to this study.
- Other trials for Autoimmune DiseasesStudies of the same condition, open and under way.
- More trials run by University of California, San FranciscoThe sponsor's other registered studies.
- What the trial phases meanHow a treatment moves from first tests in people to approval.
More details
For doctors and researchers: how the study is designed, who runs it, and its registry IDs.
Study design
- Study type
- Interventional
- Phase
- Phase 1/2
- Allocation
- Non-randomised
- Intervention model
- Single group
- Masking
- None (open label)
- Enrolment
- 0 participants (actual)
Sponsor and investigators
- Lead sponsor
- University of California, San Francisco
- Sponsor type
- University, hospital or other
- Collaborators
- Genentech, Inc.
- Responsible party
- Sponsor
- Investigators
- Flavio Vincenti, M.D., Principal investigator, University of California, San Francisco
IDs, dates and publications
- ClinicalTrials.gov ID
- NCT00777400
- Sponsor's protocol ID
- ACD4520 Efalizumab
- Other IDs
- ACD4520
- Status last verified
- May 2013
- First submitted
- 20 Oct 2008
- Last updated
- 14 May 2013
- Results posted
- No
- Data monitoring committee
- Yes
Publications
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.
PubMed 14668458Meier-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.
PubMed 14961990Vincenti 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.
PubMed 17564637
Study at a glance
From the registry record, last updated by the sponsor on 14 May 2013. Recruitment status is as the sponsor reported it: confirm with the study team.
- Official title
- A Pilot Trial to Assess the Effect of CNI Conversion to Efalizumab in T Regulatory Cells in Renal Transplantation
- ClinicalTrials.gov ID
- NCT00777400
- Acronym / sponsor ID
- ACD4520 Efalizumab
- 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
- Phase
- Phase 1/2
- Study type
- Interventional
- Recruitment status
- WithdrawnReason stopped: New safety information reported in the post-marketing setting with efalizumab for treatment of chronic plaque psoriasis and trial conduct feasibility issues.
- Enrolment
- 0 participants (actual)
- Lead sponsor
- University of California, San FranciscoUniversity, hospital or other
- Collaborators
- Genentech, Inc.
- Study start
- Dec 2008
- Primary completion
- Apr 2009 (actual)
- Study completion
- Apr 2009 (actual)
- First posted
- 22 Oct 2008 (estimated)
- Results
- Not posted in the source record
Clinical summary
The research question as the sponsor registered it. This describes what the study plans to test, not what it found.
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 design
- Allocation
- Non-randomised
- Intervention model
- Single group
- Masking
- None (open label)
- Number of arms
- 1
| Arm | Type | Receives |
|---|---|---|
| 1 | Experimental | Drug: EfalizumabEfalizumab 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. |
Who may qualify
- Ages
- 18 to 70 years
- Sex
- All
- Healthy volunteers
- Not accepted
- Age groups
- Adult, Older adult
Key inclusion criteria (9 listed)
- 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
Key exclusion criteria (11 listed)
- 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
Eligibility is decided by the study team after screening; this overview does not establish that a patient qualifies. Full inclusion and exclusion criteria.
Interventions
| Intervention | Type | Arms |
|---|---|---|
| Efalizumab1 mg/kg of efalizumab administered sub q once weekly | Drug | 1 |
Primary outcome
To determine if the combination of efalizumab and sirolimus results in a significant increase in T regulatory cells.
Time frame: Month 6
1 secondary outcome
The successful conversion from CNI to non-CNI regimen without increasing the rejection rate by more than 20%.
Time frame: 6 Months
Results and safety
The study was withdrawn before enrolling participants, so there are no results.
Research links
- Official record on ClinicalTrials.govLast updated by the sponsor 14 May 2013.
- Results publication: PubMed 14668458Nankivell 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.
- Results publication: PubMed 14961990Meier-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.
- Results publication: PubMed 17564637Vincenti 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.
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Referral and contact
AzTrials does not enrol participants or take referrals. Contact the study team or a site listed below; they decide who can take part. This study is not recruiting at the moment.
Flavio Vincenti, M.D. principal investigator
University of California, San Francisco
1 site in 1 country: see every site and its status.
Questions about this trial
What is this clinical trial studying?
A Phase 1/2 study testing Efalizumab in people with Autoimmune Diseases, run by University of California, San Francisco at 1 site in United States.
The full registered description is in the About this study section and the official record.
Who may be eligible to take part?
The sponsor lists 9 inclusion and 11 exclusion criteria. Eligibility is decided by the study team after screening, so read the full criteria and contact a listed site.
Is this clinical trial currently recruiting?
The record says: withdrawn, as of the sponsor's last update on 14 May 2013. Status can change between updates, so confirm with the study contact before making plans.
Where is the study taking place?
The record lists 1 site in United States. Whether a site is taking part right now should be confirmed with that site. See every site.
What are the possible benefits and risks?
They depend on the study and the treatment, and no study can promise a benefit. The study team explains the known risks during informed consent, before anyone joins; the record itself does not list them.
What does this combined phase mean?
Phase 1 studies test a treatment in a small group of people for the first time or in a new way, mainly to check safety and find the right dose.
Phase 2 studies give the treatment to a larger group to see whether it has the intended effect and to keep checking safety.
Not every study follows the same path, and some studies (observational studies, device studies) have no phase.
Are results available for this study?
The study was withdrawn before enrolling participants, so there are no results.
How can a doctor refer a patient or contact the research team?
The record lists no contact. The official record names the sponsor, who can be asked directly. AzTrials does not enrol participants or take referrals.
What does the primary outcome measure?
To determine if the combination of efalizumab and sirolimus results in a significant increase in T regulatory cells. (time frame: Month 6). It is what the study was designed to measure, not a finding.
Where can I read the original study information?
On the ClinicalTrials.gov record for NCT00777400, which also lists 3 linked publications.
Does a listing mean the treatment is approved or proven to work?
No. A listing means the study is registered. It does not show that the treatment is safe, works, or is approved by a regulator.
How often is this information updated?
AzTrials copies changed records from ClinicalTrials.gov every night and reloads the whole registry every week. The sponsor last updated this record on 14 May 2013.