Kidney TransplantationPhase 1/2NCT00472082
Early Conversion From Tacrolimus to Efalizumab Maintenance Therapy in Kidney Transplant Recipients
A Phase 1/2 study testing efalizumab in people with Kidney Transplantation and Chronic Kidney Failure, run by Emory University at 1 site in United States.
Trial summary
The toxicity of calcineurin inhibitors(CNI)is a major factor limiting the success of renal transplantation. This protocol aims to replace the calcineurin inhibitor, tacrolimus, with efalizumab early after transplantation in patients with mild impairment of renal function in order to minimize the toxicities of CNI. Read more about this study
- Who is it for?
- Ages 18 to 65 years
- Conditions the study is for
- Kidney Transplantation, Chronic Kidney Failure
- What is being tested?
- efalizumab
- Type of treatment
- Injection or infusion
- Could I receive a placebo?
- No, everyone receives an active treatment
- How many people
- 5 participants
- Where
- 1 siteUnited States
- Study dates
- May 2007to Apr 2009
- Phase
- Phase 1/2
- Are there results?
- Yes, posted in the registrySummary in the doctors' view
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 65 years
- All sexes
- No healthy volunteers
- Adult, Older adult
Who may be able to join
- 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
Who cannot join
- 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
Show all 13Show fewer
- 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
Trial locations and contacts
1 site in 1 country.
About this study
Official title: An Open Label, Single-Center Pilot Study of Early Conversion From Tacrolimus to Efalizumab Maintenance Therapy in Primary Renal Transplant Recipients
The toxicity of calcineurin inhibitors(CNI)is a major factor limiting the success of renal transplantation. This protocol aims to replace the calcineurin inhibitor, tacrolimus, with efalizumab early after transplantation in patients with mild impairment of renal function in order to minimize the toxicities of CNI.
Read the detailed description
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.
- Conditions
- Kidney Transplantation, Chronic Kidney Failure
- Being tested
- efalizumab
- Keywords
- Immunosuppression, Renal Transplantation
- Medical subject headings
- Kidney Failure, Chronic
What participants receive
What participants receive. In a randomised study each person is assigned to one group by chance.
efalizumabDrug
Also called Raptiva is the brand name FDA approved for the treatment of psoriasis.
Administration of a test dose of efalizumab 0.7mg/kg will be administered at enrollment. Weekly subcutaneous injections of efalizumab 1mg/kg will begin with study visit 2 and continue for 1 year for this pilot study.
| Study group | Role | What they receive |
|---|---|---|
| 1 | Experimental | The study drug Efalizumab will be given as part of a triple drug regimen including mycophenolate mofetil and prednisone. A test dose of Efalizumab 0.7mg/kg will be given at the enrollment visit. Beginning with study visit 2, Efalizumab 1mg/kg will be administered subcutaneously by injection on a weekly basis for 1 year. Mycophenolate mofetil will be given at a dose of 2gm/day which is the same as the standard of care dose. If patient experiences drug toxicity with mycophenolate mofetil they may be reduced and resume a minimum of at least 1gram daily to continue in the study. Patients will be maintained at 10mg of prednisone daily, same as standard of care. Receives: Drug: efalizumab |
What is being measured
The primary outcome is the main question the study is designed to answer.
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.
Measured: 6 months from conversion
Secondary outcomes (1)
Safety, Including Incidence of Post- Transplant Infections, Malignancies, Morbidities, Hypertension, Glucose Intolerance, Serum Cholesterol and Triglycerides Profile Over Time, Development of New Anti-donor Antibodies.
Measured: 1 year
Timeline
From the start of the study to its completion; the mark is today. Estimated dates are the sponsor’s plan.
- First posted11 May 2007 (estimated)
- Study startMay 2007
- Primary completionApr 2009
- Study completionApr 2009
Why it stopped: This study was terminated at the request of the drug manufacturer.
Resources
- Official record on ClinicalTrials.govThe registry entry this page is built from, with its full change history.
- Posted resultsParticipant flow, outcome measures and adverse events reported by the sponsor.
- Other trials for Kidney TransplantationStudies of the same condition, open and under way.
- More trials run by Emory UniversityThe 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
- Primary purpose
- Treatment
- Allocation
- Not applicable
- Intervention model
- Single group
- Masking
- None (open label)
- Enrolment
- 5 participants (actual)
Sponsor and investigators
- Lead sponsor
- Emory University
- Sponsor type
- University, hospital or other
- Collaborators
- Genentech, Inc.
- Responsible party
- Principal investigator, Kenneth Newell, Emory University
- Investigators
- Kenneth A Newell, MD, PhD, Principal investigator, Emory University
IDs, dates and publications
- ClinicalTrials.gov ID
- NCT00472082
- Sponsor's protocol ID
- IRB00003005
- Other IDs
- ACD4056s
- Status last verified
- Dec 2013
- First submitted
- 10 May 2007
- Last updated
- 27 Jan 2014
- Results posted
- Yes, on ClinicalTrials.gov
- Data monitoring committee
- Yes
Study at a glance
From the registry record, last updated by the sponsor on 27 Jan 2014. Recruitment status is as the sponsor reported it: confirm with the study team.
- Official title
- An Open Label, Single-Center Pilot Study of Early Conversion From Tacrolimus to Efalizumab Maintenance Therapy in Primary Renal Transplant Recipients
- ClinicalTrials.gov ID
- NCT00472082
- Acronym / sponsor ID
- IRB00003005
- Conditions
- Kidney Transplantation, Chronic Kidney Failure
- Keywords
- Immunosuppression, Renal Transplantation
- Phase
- Phase 1/2
- Study type
- Interventional
- Recruitment status
- TerminatedReason stopped: This study was terminated at the request of the drug manufacturer.
- Enrolment
- 5 participants (actual)
- Lead sponsor
- Emory UniversityUniversity, hospital or other
- Collaborators
- Genentech, Inc.
- Study start
- May 2007
- Primary completion
- Apr 2009 (actual)
- Study completion
- Apr 2009 (actual)
- First posted
- 11 May 2007 (estimated)
- Results
- Posted 6 Dec 2012
Clinical summary
The research question as the sponsor registered it. This describes what the study plans to test, not what it found.
The toxicity of calcineurin inhibitors(CNI)is a major factor limiting the success of renal transplantation. This protocol aims to replace the calcineurin inhibitor, tacrolimus, with efalizumab early after transplantation in patients with mild impairment of renal function in order to minimize the toxicities of CNI.
Detailed description
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.
Study design
- Primary purpose
- Treatment
- Allocation
- Not applicable
- Intervention model
- Single group
- Masking
- None (open label)
- Number of arms
- 1
| Arm | Type | Receives |
|---|---|---|
| 1 | Experimental | Drug: efalizumabThe study drug Efalizumab will be given as part of a triple drug regimen including mycophenolate mofetil and prednisone. A test dose of Efalizumab 0.7mg/kg will be given at the enrollment visit. Beginning with study visit 2, Efalizumab 1mg/kg will be administered subcutaneously by injection on a weekly basis for 1 year. Mycophenolate mofetil will be given at a dose of 2gm/day which is the same as the standard of care dose. If patient experiences drug toxicity with mycophenolate mofetil they may be reduced and resume a minimum of at least 1gram daily to continue in the study. Patients will be maintained at 10mg of prednisone daily, same as standard of care. |
Who may qualify
- Ages
- 18 to 65 years
- Sex
- All
- Healthy volunteers
- Not accepted
- Age groups
- Adult, Older adult
Key inclusion criteria (7 listed)
- 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
Key exclusion criteria (13 listed)
- 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
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 |
|---|---|---|
| efalizumabAlso: Raptiva is the brand name FDA approved for the treatment of psoriasis.Administration of a test dose of efalizumab 0.7mg/kg will be administered at enrollment. Weekly subcutaneous injections of efalizumab 1mg/kg will begin with study visit 2 and continue for 1 year for this pilot study. | Drug | 1 |
Primary outcome
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.
Time frame: 6 months from conversion
1 secondary outcome
Safety, Including Incidence of Post- Transplant Infections, Malignancies, Morbidities, Hypertension, Glucose Intolerance, Serum Cholesterol and Triglycerides Profile Over Time, Development of New Anti-donor Antibodies.
Time frame: 1 year
Results and safety
Loading the posted results from ClinicalTrials.gov…
Research links
- Official record on ClinicalTrials.govLast updated by the sponsor 27 Jan 2014.
- Posted resultsParticipant flow, baseline, all outcome measures and adverse events.
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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.
Kenneth A Newell, MD, PhD principal investigator
Emory University
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 Kidney Transplantation and Chronic Kidney Failure, run by Emory University 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 7 inclusion and 13 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: stopped early, as of the sponsor's last update on 27 Jan 2014. 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?
Yes. Results are posted in the registry (first posted 6 Dec 2012). A summary is in the For doctors view, and the full results are on ClinicalTrials.gov.
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?
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. (time frame: 6 months from conversion). It is what the study was designed to measure, not a finding.
Where can I read the original study information?
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 27 Jan 2014.