AzTrials
AzTrials

Kidney TransplantPhase 1/2NCT00670774

Dosing Regimen of Eculizumab Added to Conventional Treatment in Positive Cross Match Living Donor Kidney Transplant

A Phase 1/2 study testing Eculizumab in people with Kidney Transplant, run by Mark Stegall at 1 site in United States.

Completed

Finished. The study has ended and is not enrolling. Results may be posted on the official record.

Official record
Search all trials

Trial summary

A strongly positive crossmatch has long been considered an absolute contraindication to kidney transplantation and most patients with anti-human leukocyte antigen (HLA) antibody never were able to receive a kidney transplant. 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
31 participants
Where
1 siteUnited States
Study dates
Mar 2008to Aug 2017
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 living donor (LD) to whom he/she has either:
  • A positive crossmatch requiring pretransplant desensitization (defined as a positive T-cell FCXM of greater than or equal to 300 but less than 450 prior to desensitization, or as a positive B-cell FCXM of > 300 but < 450 prior to desensitization with demonstrable Class II donor specific alloantibody (DSA) on solid-phase assays). Subsequent to desensitization, patient must have, at the time of transplant, a T-cell and B-cell FCXM less than 300; or
  • A positive crossmatch not requiring desensitization (defined as FCXM between 200 and 299)
  • 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 or 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 the two month follow-up period after drug discontinuation
Show all 11Show fewer
  • 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)
  • Previously been enrolled in this trial.

Trial locations and contacts

1 site in 1 country.

United States1 site

  • Mayo Clinic

    Rochester, Minnesota, 55905

Other trials in United States

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 Antibody-mediated Rejection (AMR) in Positive Crossmatch Living Donor Kidney Transplantation

A strongly positive crossmatch has long been considered an absolute contraindication to kidney transplantation and most patients with anti-human leukocyte antigen (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. Our group has performed more than 200 such transplants providing the possibility of transplant to previously untransplantable patients. Despite our best efforts, transplantation in these patients is still complicated by a high rate of acute humoral rejection (AHR).

Patients included in this study will be those who have demonstrable anti-HLA antibody specific for their living donor. It is our hypothesis that blockade of terminal complement activation at the time of transplant in combination with our current protocols will reduce the incidence of AHR in patients with anti-donor HLA antibody.

Read the detailed description

The eculizumab dosing regimen was modified from that used in the treatment of paroxysmal nocturnal hemoglobinuria and consisted of 1200 mg immediately prior to transplantation, 600 mg on postoperative day 1, and 600 mg weekly thereafter for 4 weeks. At week 4, assessment of DSA levels was performed. Eculizumab was discontinued in patients whose DSA had significantly decreased (B flow crossmatch channel shift<200). In patients with persistently high DSA and thus believed to have continued high risk for AMR, eculizumab treatment continued (1200 mg week 5, and then every 2 weeks). Another DSA assessment was performed at week 9 and eculizumab was discontinued if the B flow crossmatch channel shift was <200.

The eculizumab group were compared to a historical control group consisting of consecutive transplants between 1/1/2005 and 1/10/2017 who met the inclusion criteria. The historical control group had been treated with a similar plasma exchange based protocol without eculizumab.

Being tested
Eculizumab
Keywords
Kidney, Transplant, donor

What participants receive

What participants receive. In a randomised study each person is assigned to one group by chance.

  • EculizumabDrug

    Also called Soliris

    • 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 B cell flow cytometry cross match (FCXM). Patients with B cell FCXM less than 200 will stop eculizumab treatment. Patients with B cell FCXM greater than or equal to 200 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.
    • In addition, eculizumab 600 mg will be administered immediately after each plasmapheresis (PP) and immediately after any fresh frozen plasma (FFP) that is given post-transplant during the treatment period
Study groups in NCT00670774
Study groupRoleWhat they receive
EculizumabExperimentalPatients received eculizumab intravenously according to details provided in the intervention description.
Receives: Drug: Eculizumab

What is being measured

The primary outcome is the main question the study is designed to answer.

  1. Number of Subjects With Antibody-Mediated Rejection (AMR) in the First 3 Months After Living Donor Kidney Transplantation

    AMR can cause acute graft loss or shorten allograft survival. Renal allograft biopsies were obtained percutaneously using ultrasound guidance processed for light microscopy and immunofluorescence for peritubular capillary staining for C4d. All biopsies were reviewed by a pathologist in a blinded fashion. AMR was diagnosed using standard Banff criteria in combination with graft dysfunction (increase in serum creatinine >/=0.3 mg/dL over nadir.)

    Measured: up to 3 months

Secondary outcomes (7)

  1. Number of Patients Developing High DSA Levels at Less Than or Equal to 3 Months

    High DSA levels were defined as B flow cross match channel shift >350 at any time point in the first 3 months.

    Measured: 3 months

  2. Number of Patients Requiring Splenectomy

    A splenectomy is a surgical operation involving removal of the spleen. Splenectomy was performed for severe AMR in the setting of a rising serum creatinine (usually >2.0) and a rising serum DSA level despite daily plasma exchange treatments.

    Measured: 1 year

  3. Graft Dysfunction in First Month Post Transplant

    (Maximum serum creatinine-nadir serum creatinine)

    Measured: 1 month

  4. Length of Follow-up

    Following the completion of dosing, subjects were to return for follow-up visits at 3 and 6 months post transplant to obtain biopsies and collect follow-up data. Subjects who continued the drug for 12 months were to receive their final assessment at 15 months.

    Measured: up to 15 months

  5. Number of Subjects With Graft Survival at One Year

    Graft survival means the kidney has not been rejected by the body.

    Measured: 1 year

  6. Number of Subjects Receiving Posttransplant Plasma Exchange (PE)

    Plasma exchange is needed when there is poor kidney functioning, and donor specific alloantibody (DSA) is high

    Measured: up to one year

  7. Transplant Glomerulopathy Incidence at One Year

    Transplant glomerulopathy is a morphologic lesion of renal allografts that is characterized histologically by duplication and/or multilayering of the glomerular basement membrane. It is widely accepted as a manifestation of chronic antibody-mediated rejection (AMR). This is determined by histology.

    Measured: 1 year

Timeline

From the start of the study to its completion; the mark is today. Estimated dates are the sponsor’s plan.

  1. First posted2 May 2008 (estimated)
  2. Study startMar 2008
  3. Primary completionMay 2017
  4. Study completionAug 2017

Resources

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
31 participants (actual)
IDs, dates and publications
ClinicalTrials.gov ID
NCT00670774
Sponsor's protocol ID
07-007208
Status last verified
May 2018
First submitted
28 Apr 2008
Last updated
26 Jun 2018
Data monitoring committee
Yes
FDA-regulated drug
Yes
FDA-regulated device
No

Publications

  • Stegall MD, Diwan T, Raghavaiah S, Cornell LD, Burns J, Dean PG, Cosio FG, Gandhi MJ, Kremers W, Gloor JM. Terminal complement inhibition decreases antibody-mediated rejection in sensitized renal transplant recipients. Am J Transplant. 2011 Nov;11(11):2405-13. doi: 10.1111/j.1600-6143.2011.03757.x. Epub 2011 Sep 22.

    PubMed 21942930

  • Bentall A, Tyan DB, Sequeira F, Everly MJ, Gandhi MJ, Cornell LD, Li H, Henderson NA, Raghavaiah S, Winters JL, Dean PG, Stegall MD. Antibody-mediated rejection despite inhibition of terminal complement. Transpl Int. 2014 Dec;27(12):1235-43. doi: 10.1111/tri.12396. Epub 2014 Aug 20.

    PubMed 24990476

Questions about this trial

What is this clinical trial studying?

A Phase 1/2 study testing Eculizumab in people with Kidney Transplant, run by Mark Stegall 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 8 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: finished, as of the sponsor's last update on 26 Jun 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 26 Jun 2018). 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 Antibody-Mediated Rejection (AMR) in the First 3 Months After Living Donor Kidney Transplantation (time frame: up to 3 months). 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 NCT00670774, which also lists 2 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 26 Jun 2018.

AzTrials uses cookies for analytics and advertising. You can accept or reject them; the site works either way. Privacy Policy.

Free account

Log in to keep searching

You’ve used your 3 free searches. AzTrials is free: log in or create a free account to keep searching clinical trials and save the ones you want to follow.

Create a free accountLog in