Kidney TransplantPhase 1/2NCT01106027
Dosing Regimen of Eculizumab Added to Conventional Treatment in Positive Crossmatch Deceased Donor Kidney Transplant
A Phase 1/2 study testing Eculizumab in people with Kidney Transplant, run by Mayo Clinic at 1 site in United States.
Trial summary
The purpose of this study is to test whether a dosing regimen of eculizumab in addition to standard posttransplant care in positive crossmatch deceased donor kidney transplant recipients will reduce the incidence of acute humoral rejection (AHR). Read more about this study
- Who is it for?
- Ages 18 years and older
- Conditions the study is for
- Kidney Transplant
- What is being tested?
- Eculizumab
- Type of treatment
- Injection or infusion
- Could I receive a placebo?
- No, everyone receives an active treatment
- How many people
- 2 participants
- Where
- 1 siteUnited States
- Study dates
- Mar 2010to 19 Aug 2016
- 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 years and older
- All sexes
- No healthy volunteers
- Adult, Older adult
Who may be able to join
- 18 years of age
- Has end stage renal disease (ESRD) and is to receive a kidney transplant from a deceased donor (DD) to whom he/she has a positive T or B cell crossmatch >200 at the time of transplant and DSA demonstrated by solid phase assays.
- Willing to comply with the protocol
- Females of child-bearing potential must have a negative pregnancy test (serum β-HCG) and sexually active females must agree to use a reliable and medically approved method of contraception
- Willing and able to give written informed consent
- Vaccinated against Neisseria meningitides (quadrivalent vaccine), Pneumococcus and H. influenzae at least two weeks prior to beginning desensitization
Who cannot join
- Unstable cardiovascular condition
- Previous splenectomy
- Active bacterial or other infection which is clinically significant in the opinion of the investigator
- Known or suspected hereditary complement deficiency
- Participation in any other investigational drug study or was exposed to an investigational drug or device within 30 days of randomization
- Pregnant, breast-feeding, or intending to conceive during the course of the study, including a one month follow-up period after drug discontinuation
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- Known hypersensitivity to the treatment drug or any of its excipients
- History of illicit drug use or alcohol abuse within the previous year
- History of meningococcal disease
- Medical condition that, in the opinion of the investigator, might interfere with the patient's participation in the study, pose an added risk for the patient, or confound the assessment of the patient (e.g. severe cardiovascular or pulmonary disease)
Trial locations and contacts
1 site in 1 country.
About this study
Official title: A Single Center, Open-label Study to Determine the Safety and Efficacy of a Dosing Regimen of Eculizumab Added to Conventional Treatment in the Prevention of Acute Humoral Rejection (AHR) in Positive Crossmatch Deceased Donor Kidney Transplantation
The purpose of this study is to test whether a dosing regimen of eculizumab in addition to standard posttransplant care in positive crossmatch deceased donor kidney transplant recipients will reduce the incidence of acute humoral rejection (AHR).
Patients included in this study will be those who have demonstrable anti-human leukocyte antigen (HLA) antibody specific for their deceased donor. It is our hypothesis that blockade of terminal complement activation with eculizumab at the time of transplant in combination with our current protocols will reduce the incidence of AHR in recipients of deceased donor kidney transplants who have anti-donor HLA antibody
Read the detailed description
A strongly positive crossmatch has long been considered an absolute contraindication to kidney transplantation and most patients with anti-HLA antibody never were able to receive a kidney transplant. Over the past decade, significant progress has been made in overcoming early antibody-mediated renal allograft injury. Despite our best efforts, transplantation in these patients is still complicated by a high rate of acute humoral rejection.
While we have successfully transplanted more than 250 patients with DSA using living donors, applying these protocols to recipients of deceased donors has been problematic. This primarily is due to the fact that in contrast to living donation, the timing of a deceased donor kidney transplant cannot be planned. This leads to inadequate time to perform the multiple pretransplant plasmapheresis treatments needed to achieve a safe level of DSA at transplant. Thus, there is a major unmet need to develop therapy that will allow for the successful transplantation of deceased donor kidneys in recipients who have DSA.
- At the time of deceased donor kidney transplantation, patients will undergo one plasmapheresis prior to surgery.
- Patients will be given 1200 mg of eculizumab intravenously over 30 minutes, 1 hour prior to surgery.
- Patients will be given 900 mg of eculizumab on Day 1 post-transplant.
- Patients will then be given 900 mg of eculizumab weekly through 4 weeks post-transplant
- At week 4, patients will be assessed for DSA. Patients with total DSA normalized values <5000 will stop eculizumab treatment. Patients with total DSA normalized values >5000 will continue eculizumab treatment every 14 days from week 5 through week 9. The dose will be increased to 1200 mg and dosing will now be every 2 weeks instead of weekly. Similar "discontinuation assessments" will be performed at week 9, 26, 39 and 52.
- Conditions
- Kidney Transplant
- Being tested
- Eculizumab
What participants receive
What participants receive. In a randomised study each person is assigned to one group by chance.
EculizumabDrug
Also called Soliris
Eculizumab 900 mg and 1200 mg, administered intravenously (IV)
| Study group | Role | What they receive |
|---|---|---|
| Eculizumab | Experimental | Patients will be given 1200 mg of eculizumab intravenously over 30 minutes, 1 hour prior to surgery. Patients will be given 900 mg of eculizumab on Day 1 post-transplant. Patients will then be given 900 mg of eculizumab weekly through 4 weeks post-transplant.
At week 4, patients will be assessed for donor specific anti-donor human leukocyte antigen (HLA) antibody (DSA). Patients with total DSA normalized values <5000 will stop eculizumab treatment. Patients with total DSA normalized values >5000 will continue eculizumab treatment every 14 days from week 5 through week 9. The dose will be increased to 1200 mg and dosing will now be every 2 weeks instead of weekly. Receives: Drug: Eculizumab |
What is being measured
The primary outcome is the main question the study is designed to answer.
Number of Subjects With Acute Humoral Rejection (AHR) up to One Year Post Transplant.
Diagnosis of AHR will be based histological findings using Banff '05 criteria.
Measured: 1 year posttransplant
Timeline
From the start of the study to its completion; the mark is today. Estimated dates are the sponsor’s plan.
- First posted19 Apr 2010 (estimated)
- Study startMar 2010
- Primary completion19 Aug 2016
- Study completion19 Aug 2016
Why it stopped: Difficulty enrolling; competing industry-funded multi-center clinical trial
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 TransplantStudies of the same condition, open and under way.
- More trials run by Mayo ClinicThe 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
- Prevention
- Allocation
- Not applicable
- Intervention model
- Single group
- Masking
- None (open label)
- Enrolment
- 2 participants (actual)
Sponsor and investigators
- Lead sponsor
- Mayo Clinic
- Sponsor type
- University, hospital or other
- Collaborators
- Alexion Pharmaceuticals, Inc.
- Responsible party
- Principal investigator, Mark Stegall, Mayo Clinic
- Investigators
- Mark Stegall, MD, Principal investigator, Mayo Clinic
IDs, dates and publications
- ClinicalTrials.gov ID
- NCT01106027
- Sponsor's protocol ID
- 09-005627DD
- Status last verified
- Jan 2018
- First submitted
- 29 Mar 2010
- Last updated
- 31 Jan 2018
- Results posted
- Yes, on ClinicalTrials.gov
- Data monitoring committee
- No
- FDA-regulated drug
- Yes
- FDA-regulated device
- No
Study at a glance
From the registry record, last updated by the sponsor on 31 Jan 2018. Recruitment status is as the sponsor reported it: confirm with the study team.
- Official title
- A Single Center, Open-label Study to Determine the Safety and Efficacy of a Dosing Regimen of Eculizumab Added to Conventional Treatment in the Prevention of Acute Humoral Rejection (AHR) in Positive Crossmatch Deceased Donor Kidney Transplantation
- ClinicalTrials.gov ID
- NCT01106027
- Acronym / sponsor ID
- 09-005627DD
- Conditions
- Kidney Transplant
- Phase
- Phase 1/2
- Study type
- Interventional
- Recruitment status
- TerminatedReason stopped: Difficulty enrolling; competing industry-funded multi-center clinical trial
- Enrolment
- 2 participants (actual)
- Lead sponsor
- Mayo ClinicUniversity, hospital or other
- Collaborators
- Alexion Pharmaceuticals, Inc.
- Study start
- Mar 2010 (actual)
- Primary completion
- 19 Aug 2016 (actual)
- Study completion
- 19 Aug 2016 (actual)
- First posted
- 19 Apr 2010 (estimated)
- Results
- Posted 14 Nov 2017
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 study is to test whether a dosing regimen of eculizumab in addition to standard posttransplant care in positive crossmatch deceased donor kidney transplant recipients will reduce the incidence of acute humoral rejection (AHR).
Patients included in this study will be those who have demonstrable anti-human leukocyte antigen (HLA) antibody specific for their deceased donor. It is our hypothesis that blockade of terminal complement activation with eculizumab at the time of transplant in combination with our current protocols will reduce the incidence of AHR in recipients of deceased donor kidney transplants who have anti-donor HLA antibody
Detailed description
A strongly positive crossmatch has long been considered an absolute contraindication to kidney transplantation and most patients with anti-HLA antibody never were able to receive a kidney transplant. Over the past decade, significant progress has been made in overcoming early antibody-mediated renal allograft injury. Despite our best efforts, transplantation in these patients is still complicated by a high rate of acute humoral rejection.
While we have successfully transplanted more than 250 patients with DSA using living donors, applying these protocols to recipients of deceased donors has been problematic. This primarily is due to the fact that in contrast to living donation, the timing of a deceased donor kidney transplant cannot be planned. This leads to inadequate time to perform the multiple pretransplant plasmapheresis treatments needed to achieve a safe level of DSA at transplant. Thus, there is a major unmet need to develop therapy that will allow for the successful transplantation of deceased donor kidneys in recipients who have DSA.
- At the time of deceased donor kidney transplantation, patients will undergo one plasmapheresis prior to surgery.
- Patients will be given 1200 mg of eculizumab intravenously over 30 minutes, 1 hour prior to surgery.
- Patients will be given 900 mg of eculizumab on Day 1 post-transplant.
- Patients will then be given 900 mg of eculizumab weekly through 4 weeks post-transplant
- At week 4, patients will be assessed for DSA. Patients with total DSA normalized values <5000 will stop eculizumab treatment. Patients with total DSA normalized values >5000 will continue eculizumab treatment every 14 days from week 5 through week 9. The dose will be increased to 1200 mg and dosing will now be every 2 weeks instead of weekly. Similar "discontinuation assessments" will be performed at week 9, 26, 39 and 52.
Study design
- Primary purpose
- Prevention
- Allocation
- Not applicable
- Intervention model
- Single group
- Masking
- None (open label)
- Number of arms
- 1
| Arm | Type | Receives |
|---|---|---|
| Eculizumab | Experimental | Drug: EculizumabPatients will be given 1200 mg of eculizumab intravenously over 30 minutes, 1 hour prior to surgery. Patients will be given 900 mg of eculizumab on Day 1 post-transplant. Patients will then be given 900 mg of eculizumab weekly through 4 weeks post-transplant. At week 4, patients will be assessed for donor specific anti-donor human leukocyte antigen (HLA) antibody (DSA). Patients with total DSA normalized values <5000 will stop eculizumab treatment. Patients with total DSA normalized values >5000 will continue eculizumab treatment every 14 days from week 5 through week 9. The dose will be increased to 1200 mg and dosing will now be every 2 weeks instead of weekly. |
Who may qualify
- Ages
- 18 years and older
- Sex
- All
- Healthy volunteers
- Not accepted
- Age groups
- Adult, Older adult
Key inclusion criteria (6 listed)
- 18 years of age
- Has end stage renal disease (ESRD) and is to receive a kidney transplant from a deceased donor (DD) to whom he/she has a positive T or B cell crossmatch >200 at the time of transplant and DSA demonstrated by solid phase assays.
- Willing to comply with the protocol
- Females of child-bearing potential must have a negative pregnancy test (serum β-HCG) and sexually active females must agree to use a reliable and medically approved method of contraception
- Willing and able to give written informed consent
Key exclusion criteria (10 listed)
- Unstable cardiovascular condition
- Previous splenectomy
- Active bacterial or other infection which is clinically significant in the opinion of the investigator
- Known or suspected hereditary complement deficiency
- Participation in any other investigational drug study or was exposed to an investigational drug or device within 30 days of randomization
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: SolirisEculizumab 900 mg and 1200 mg, administered intravenously (IV) | Drug | Eculizumab |
Primary outcome
Number of Subjects With Acute Humoral Rejection (AHR) up to One Year Post Transplant.
Time frame: 1 year posttransplant
Diagnosis of AHR will be based histological findings using Banff '05 criteria.
Results and safety
Loading the posted results from ClinicalTrials.gov…
Research links
- Official record on ClinicalTrials.govLast updated by the sponsor 31 Jan 2018.
- 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.
Mark Stegall, MD principal investigator
Mayo Clinic
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 Eculizumab in people with Kidney Transplant, run by Mayo Clinic 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 10 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 31 Jan 2018. 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 14 Nov 2017). 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?
Number of Subjects With Acute Humoral Rejection (AHR) up to One Year Post Transplant. (time frame: 1 year posttransplant). 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 31 Jan 2018.