Kidney; Complications, AllograftPhase 1NCT01327573
Eculizumab Therapy for Chronic Complement-Mediated Injury in Kidney Transplantation
A Phase 1 study testing eculizumab in people with Kidney; Complications, Allograft, run by Sanjay Kulkarni at 1 site in United States.
Trial summary
This study is designed to assess the effectiveness of eculizumab in recipients of kidney transplantation with donor-specific antibodies (DSA) and worsening kidney function and to assess if eculizumab improves endothelial cell injury in the kidney. Read more about this study
- Who is it for?
- Ages 18 to 65 years
- Conditions the study is for
- Kidney; Complications, Allograft
- What is being tested?
- eculizumab
- Type of treatment
- Pill or oral medicine, Injection or infusion
- Could I receive a placebo?
- No, everyone receives an active treatment
- How many people
- 16 participants
- Where
- 1 siteUnited States
- Study dates
- Mar 2011to Feb 2015
- Phase
- Phase 1
- 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
- Kidney transplant recipients greater than 6 months from the date of transplant
- Must be on standard immunosuppression: tacrolimus, mycophenolate mofetil, prednisone and have stable tacrolimus trough levels over past 3 months
- Deteriorating renal function, as defined by 20% reduction in GFR (MDRD calculation)
- Presence of DSA, as defined as MFI > 1100
- Renal biopsy demonstrating no diffuse, irreversible end-stage organ injury (i.e. stage IV Fibrosis)
- Renal biopsy demonstrating C4d deposition (stratum 1) or no C4d deposition (stratum 2)
Who cannot join
- History of CMV, BK, HSV or other viral infections
- History of chronic, recurrent bacterial infections
- Evidence of tubulitis on renal biopsy or other morphological features of acute cellular rejection or acute humoral rejection
- Renal biopsy demonstrating diffuse, irreversible end-stage organ injury
- Absolute GFR < 25 (MDRD calculation)
- Inability to provide informed consent
Show all 9Show fewer
- History of poor vascular access
- Refusal to use double barrier contraception during study participation
- Patients actively enrolled in other clinical trials
Trial locations and contacts
1 site in 1 country.
About this study
Official title: Eculizumab Therapy for Chronic Complement-Mediated Injury in Kidney Transplantation: A Randomized, Open-Label, Pilot Intervention Trial
This study is designed to assess the effectiveness of eculizumab in recipients of kidney transplantation with donor-specific antibodies (DSA) and worsening kidney function and to assess if eculizumab improves endothelial cell injury in the kidney.
The investigators hypothesize that complement inhibition with eculizumab will reduce allograft injury, resulting from less complement-mediated injury of endothelial cells and less endothelial cell activation.
Read the detailed description
This study will address the clinical challenge that currently exists in the management of kidney transplant recipients who have developed de novo DSA, have deteriorating graft function, yet have no established treatment alternative.
This is a randomized, open-label, pilot intervention trial. Post transplant patients with deteriorating renal function (defined as 20% reduction in GFR) will be screened for the development of DSA and biopsied for the presence of C4d deposition. All patients with DSA and those meeting inclusion/exclusion criteria will undergo protocol renal biopsy and will be assessed for C4d deposition. Participants will be randomized to treatment with eculizumab plus standard of care (SOC) or SOC only. Randomization will be stratified by C4d status (C4d+/C4d-) with 10 subjects (7 eculizumab, 3 SOC only) in each stratum.
Eculizumab is an antibody that has been developed to inhibit the complement protein C5. Eculizumab will be delivered via IV according to the following schedule:
- Eculizumab Induction 600mg IV every 7 days for 4 doses
- Eculizumab 900mg IV 7 days later
- Eculizumab Maintenance 900mg IV every 14 days for total of 26 weeks
- Conditions
- Kidney; Complications, Allograft
- Being tested
- eculizumab
- Keywords
- chronic kidney allograft injury, complement protein, eculizumab, Kidney transplantation
What participants receive
What participants receive. In a randomised study each person is assigned to one group by chance.
eculizumabDrug
Also called h5G1.1-mAb, Soliris
- Eculizumab Induction 600mg IV every 7 days for 4 doses
- Eculizumab 900mg IV 7 days later
- Eculizumab Maintenance 900mg IV every 14 days for total of 26 weeks
| Study group | Role | What they receive |
|---|---|---|
| Eculizumab | Experimental | eculizumab will be given in addition to standard immunosuppression regimen (oral tacrolimus or equivalent, MMF [mycophenolate mofetil
], prednisone) Receives: Drug: eculizumab |
| no additional therapy | No intervention | patients in this arm will receive standard immunosuppression regimen (oral tacrolimus or equivalent, MMF, prednisone only, no additional therapy |
What is being measured
The primary outcome is the main question the study is designed to answer.
Baseline eGFR (Estimated Glomerular Filtration Rate)
Measured: Baseline
Estimated Glomerular Filtration Rate (eGFR) at Months 2,3,4,5,6
Primary statistical analysis of change from baseline was conducted with mixed effects modeling providing calculated estimates.
Measured: Months 2,3,4,5,6
Group Difference Percentage Change in 6-month Estimated Glomerular Filtration Rate (eGFR)
These data were calculated by mean 6-month eGFR minus baseline mean eGFR divided by baseline eGFR. Presented below are the between groups results. These results were derived from the results in the outcome "Estimated Glomerular Filtration Rate (eGFR) at Months 2,3,4,5,6".
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 posted1 Apr 2011 (estimated)
- Study startMar 2011
- Primary completionFeb 2015
- Study completionFeb 2015
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.
- Publications (5)Papers the sponsor has linked to this study.
- Other trials for Kidney; Complications, AllograftStudies of the same condition, open and under way.
- 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
- Primary purpose
- Treatment
- Allocation
- Randomised
- Intervention model
- Parallel groups
- Masking
- None (open label)
- Enrolment
- 16 participants (actual)
Sponsor and investigators
- Lead sponsor
- Sanjay Kulkarni
- Sponsor type
- University, hospital or other
- Collaborators
- Alexion Pharmaceuticals, Inc.
- Responsible party
- Sponsor-investigator, Sanjay Kulkarni, Yale University
- Investigators
- Sanjay Kulkarni, MD, Principal investigator, Yale University
IDs, dates and publications
- ClinicalTrials.gov ID
- NCT01327573
- Sponsor's protocol ID
- 100700716
- Status last verified
- Jul 2019
- First submitted
- 30 Mar 2011
- Last updated
- 12 Aug 2019
- Results posted
- Yes, on ClinicalTrials.gov
- Data monitoring committee
- No
Publications
Terasaki PI, Ozawa M. Predicting kidney graft failure by HLA antibodies: a prospective trial. Am J Transplant. 2004 Mar;4(3):438-43. doi: 10.1111/j.1600-6143.2004.00360.x.
PubMed 14961999Worthington JE, McEwen A, McWilliam LJ, Picton ML, Martin S. Association between C4d staining in renal transplant biopsies, production of donor-specific HLA antibodies, and graft outcome. Transplantation. 2007 Feb 27;83(4):398-403. doi: 10.1097/01.tp.0000251430.11723.b6.
PubMed 17318071Al-Lamki RS, Bradley JR, Pober JS. Endothelial cells in allograft rejection. Transplantation. 2008 Nov 27;86(10):1340-8. doi: 10.1097/TP.0b013e3181891d8b.
PubMed 19034000Brodsky RA, Young NS, Antonioli E, Risitano AM, Schrezenmeier H, Schubert J, Gaya A, Coyle L, de Castro C, Fu CL, Maciejewski JP, Bessler M, Kroon HA, Rother RP, Hillmen P. Multicenter phase 3 study of the complement inhibitor eculizumab for the treatment of patients with paroxysmal nocturnal hemoglobinuria. Blood. 2008 Feb 15;111(4):1840-7. doi: 10.1182/blood-2007-06-094136. Epub 2007 Nov 30.
PubMed 18055865Davin JC, Gracchi V, Bouts A, Groothoff J, Strain L, Goodship T. Maintenance of kidney function following treatment with eculizumab and discontinuation of plasma exchange after a third kidney transplant for atypical hemolytic uremic syndrome associated with a CFH mutation. Am J Kidney Dis. 2010 Apr;55(4):708-11. doi: 10.1053/j.ajkd.2009.08.011. Epub 2009 Oct 25.
PubMed 19854549
Study at a glance
From the registry record, last updated by the sponsor on 12 Aug 2019. Recruitment status is as the sponsor reported it: confirm with the study team.
- Official title
- Eculizumab Therapy for Chronic Complement-Mediated Injury in Kidney Transplantation: A Randomized, Open-Label, Pilot Intervention Trial
- ClinicalTrials.gov ID
- NCT01327573
- Acronym / sponsor ID
- 100700716
- Conditions
- Kidney; Complications, Allograft
- Keywords
- chronic kidney allograft injury, complement protein, eculizumab, Kidney transplantation
- Phase
- Phase 1
- Study type
- Interventional
- Recruitment status
- Completed
- Enrolment
- 16 participants (actual)
- Lead sponsor
- Sanjay KulkarniUniversity, hospital or other
- Collaborators
- Alexion Pharmaceuticals, Inc.
- Study start
- Mar 2011
- Primary completion
- Feb 2015 (actual)
- Study completion
- Feb 2015 (actual)
- First posted
- 1 Apr 2011 (estimated)
- Results
- Posted 12 Aug 2019
Clinical summary
The research question as the sponsor registered it. This describes what the study plans to test, not what it found.
This study is designed to assess the effectiveness of eculizumab in recipients of kidney transplantation with donor-specific antibodies (DSA) and worsening kidney function and to assess if eculizumab improves endothelial cell injury in the kidney.
The investigators hypothesize that complement inhibition with eculizumab will reduce allograft injury, resulting from less complement-mediated injury of endothelial cells and less endothelial cell activation.
Detailed description
This study will address the clinical challenge that currently exists in the management of kidney transplant recipients who have developed de novo DSA, have deteriorating graft function, yet have no established treatment alternative.
This is a randomized, open-label, pilot intervention trial. Post transplant patients with deteriorating renal function (defined as 20% reduction in GFR) will be screened for the development of DSA and biopsied for the presence of C4d deposition. All patients with DSA and those meeting inclusion/exclusion criteria will undergo protocol renal biopsy and will be assessed for C4d deposition. Participants will be randomized to treatment with eculizumab plus standard of care (SOC) or SOC only. Randomization will be stratified by C4d status (C4d+/C4d-) with 10 subjects (7 eculizumab, 3 SOC only) in each stratum.
Eculizumab is an antibody that has been developed to inhibit the complement protein C5. Eculizumab will be delivered via IV according to the following schedule:
- Eculizumab Induction 600mg IV every 7 days for 4 doses
- Eculizumab 900mg IV 7 days later
- Eculizumab Maintenance 900mg IV every 14 days for total of 26 weeks
Study design
- Primary purpose
- Treatment
- Allocation
- Randomised
- Intervention model
- Parallel groups
- Masking
- None (open label)
- Number of arms
- 2
| Arm | Type | Receives |
|---|---|---|
| Eculizumab | Experimental | Drug: eculizumabeculizumab will be given in addition to standard immunosuppression regimen (oral tacrolimus or equivalent, MMF [mycophenolate mofetil ], prednisone) |
| no additional therapy | No intervention | –patients in this arm will receive standard immunosuppression regimen (oral tacrolimus or equivalent, MMF, prednisone only, no additional therapy |
Who may qualify
- Ages
- 18 to 65 years
- Sex
- All
- Healthy volunteers
- Not accepted
- Age groups
- Adult, Older adult
Key inclusion criteria (6 listed)
- Kidney transplant recipients greater than 6 months from the date of transplant
- Must be on standard immunosuppression: tacrolimus, mycophenolate mofetil, prednisone and have stable tacrolimus trough levels over past 3 months
- Deteriorating renal function, as defined by 20% reduction in GFR (MDRD calculation)
- Presence of DSA, as defined as MFI > 1100
- Renal biopsy demonstrating no diffuse, irreversible end-stage organ injury (i.e. stage IV Fibrosis)
Key exclusion criteria (9 listed)
- History of CMV, BK, HSV or other viral infections
- History of chronic, recurrent bacterial infections
- Evidence of tubulitis on renal biopsy or other morphological features of acute cellular rejection or acute humoral rejection
- Renal biopsy demonstrating diffuse, irreversible end-stage organ injury
- Absolute GFR < 25 (MDRD calculation)
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 |
|---|---|---|
| eculizumabAlso: h5G1.1-mAb, Soliris* Eculizumab Induction 600mg IV every 7 days for 4 doses * Eculizumab 900mg IV 7 days later * Eculizumab Maintenance 900mg IV every 14 days for total of 26 weeks | Drug | Eculizumab |
Primary outcome
Baseline eGFR (Estimated Glomerular Filtration Rate)
Time frame: Baseline
Estimated Glomerular Filtration Rate (eGFR) at Months 2,3,4,5,6
Time frame: Months 2,3,4,5,6
Primary statistical analysis of change from baseline was conducted with mixed effects modeling providing calculated estimates.
Group Difference Percentage Change in 6-month Estimated Glomerular Filtration Rate (eGFR)
Time frame: 6 months
These data were calculated by mean 6-month eGFR minus baseline mean eGFR divided by baseline eGFR. Presented below are the between groups results. These results were derived from the results in the outcome "Estimated Glomerular Filtration Rate (eGFR) at Months 2,3,4,5,6".
Results and safety
Loading the posted results from ClinicalTrials.gov…
Research links
- Official record on ClinicalTrials.govLast updated by the sponsor 12 Aug 2019.
- Posted resultsParticipant flow, baseline, all outcome measures and adverse events.
- Background: PubMed 14961999Terasaki PI, Ozawa M. Predicting kidney graft failure by HLA antibodies: a prospective trial. Am J Transplant. 2004 Mar;4(3):438-43. doi: 10.1111/j.1600-6143.2004.00360.x.
- Background: PubMed 17318071Worthington JE, McEwen A, McWilliam LJ, Picton ML, Martin S. Association between C4d staining in renal transplant biopsies, production of donor-specific HLA antibodies, and graft outcome. Transplantation. 2007 Feb 27;83(4):398-403. doi: 10.1097/01.tp.0000251430.11723.b6.
- Background: PubMed 19034000Al-Lamki RS, Bradley JR, Pober JS. Endothelial cells in allograft rejection. Transplantation. 2008 Nov 27;86(10):1340-8. doi: 10.1097/TP.0b013e3181891d8b.
- Background: PubMed 18055865Brodsky RA, Young NS, Antonioli E, Risitano AM, Schrezenmeier H, Schubert J, Gaya A, Coyle L, de Castro C, Fu CL, Maciejewski JP, Bessler M, Kroon HA, Rother RP, Hillmen P. Multicenter phase 3 study of the complement inhibitor eculizumab for the treatment of patients with paroxysmal nocturnal hemoglobinuria. Blood. 2008 Feb 15;111(4):1840-7. doi: 10.1182/blood-2007-06-094136. Epub 2007 Nov 30.
- Background: PubMed 19854549Davin JC, Gracchi V, Bouts A, Groothoff J, Strain L, Goodship T. Maintenance of kidney function following treatment with eculizumab and discontinuation of plasma exchange after a third kidney transplant for atypical hemolytic uremic syndrome associated with a CFH mutation. Am J Kidney Dis. 2010 Apr;55(4):708-11. doi: 10.1053/j.ajkd.2009.08.011. Epub 2009 Oct 25.
Related trials for Kidney; Complications, Allograft
Active, not recruitingObservational study
Australian Genomics Of Chronic Allograft Dysfunction Study
Kidney Transplant Rejection, Kidney Transplant; Complications
Not yet recruitingPhase 3
Study of Tegoprubart Efficacy and Safety Compared With Tacrolimus in Kidney Transplantation
Kidney Transplant Rejection
Active, not recruitingPhase 1
Renal Allograft Tolerance Through Mixed Chimerism - SMC/MGH
Renal Failure
RecruitingEarly Phase 1
Concomitant Renal and Urinary Bladder Allograft Transplantation
Chronic Kidney Diseases, Bladder Dysfunction
Recruiting
The Impact of Intraoperative Diuretic Use on Delayed Graft Function Following Deceased Donor Renal Transplantation
Delayed Graft Function, Kidney Transplantation
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.
Sanjay Kulkarni, MD principal investigator
Yale 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 study testing eculizumab in people with Kidney; Complications, Allograft, run by Sanjay Kulkarni 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 6 inclusion and 9 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: finished, as of the sponsor's last update on 12 Aug 2019. 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 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.
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 12 Aug 2019). 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?
Baseline eGFR (Estimated Glomerular Filtration Rate) (time frame: Baseline). The study lists 3 primary outcomes in all. 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 NCT01327573, which also lists 5 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 12 Aug 2019.