Eculizumab Therapy for Chronic Complement-Mediated Injury in Kidney Transplantation

July 2, 2019 updated by: Sanjay Kulkarni

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.

Study Overview

Status

Completed

Conditions

Intervention / Treatment

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 Type

Interventional

Enrollment (Actual)

16

Phase

  • Phase 1

Contacts and Locations

This section provides the contact details for those conducting the study, and information on where this study is being conducted.

Study Locations

  • United States
    • Connecticut
      • New Haven, Connecticut, United States, 06520
        • Yale University

Participation Criteria

Researchers look for people who fit a certain description, called eligibility criteria. Some examples of these criteria are a person's general health condition or prior treatments.

Eligibility Criteria

Ages Eligible for Study

18 years to 65 years (Adult, Older Adult)

Accepts Healthy Volunteers

No

Genders Eligible for Study

All

Description

Inclusion Criteria:

  • 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)

Exclusion Criteria:

  • 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
  • History of poor vascular access
  • Refusal to use double barrier contraception during study participation
  • Patients actively enrolled in other clinical trials

Study Plan

This section provides details of the study plan, including how the study is designed and what the study is measuring.

How is the study designed?

Design Details

  • Primary Purpose: Treatment
  • Allocation: Randomized
  • Interventional Model: Parallel Assignment
  • Masking: None (Open Label)

Arms and Interventions

Participant Group / Arm
Intervention / Treatment
Experimental: Eculizumab

eculizumab will be given in addition to standard immunosuppression regimen (oral tacrolimus or equivalent, MMF [mycophenolate mofetil

], prednisone)
Drug: eculizumab
  • 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
Other Names:
  • Soliris
  • h5G1.1-mAb
No Intervention: no additional therapy
patients in this arm will receive standard immunosuppression regimen (oral tacrolimus or equivalent, MMF, prednisone only, no additional therapy

What is the study measuring?

Primary Outcome Measures

Outcome Measure
Measure Description
Time Frame
Baseline eGFR (Estimated Glomerular Filtration Rate)
Time Frame: Baseline
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.
Months 2,3,4,5,6
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".
6 months

Collaborators and Investigators

This is where you will find people and organizations involved with this study.

Sponsor

Sanjay Kulkarni

Collaborators

Alexion Pharmaceuticals

Investigators

  • Principal Investigator: Sanjay Kulkarni, MD, Yale University

Publications and helpful links

The person responsible for entering information about the study voluntarily provides these publications. These may be about anything related to the study.

General Publications

Study record dates

These dates track the progress of study record and summary results submissions to ClinicalTrials.gov. Study records and reported results are reviewed by the National Library of Medicine (NLM) to make sure they meet specific quality control standards before being posted on the public website.

Study Major Dates

Study Start

March 1, 2011

Primary Completion (Actual)

February 1, 2015

Study Completion (Actual)

February 1, 2015

Study Registration Dates

First Submitted

March 30, 2011

First Submitted That Met QC Criteria

March 31, 2011

First Posted (Estimate)

April 1, 2011

Study Record Updates

Last Update Posted (Actual)

August 12, 2019

Last Update Submitted That Met QC Criteria

July 2, 2019

Last Verified

July 1, 2019

More Information

Terms related to this study

Keywords

Additional Relevant MeSH Terms

Other Study ID Numbers

  • 100700716

This information was retrieved directly from the website clinicaltrials.gov without any changes. If you have any requests to change, remove or update your study details, please contact register@clinicaltrials.gov. As soon as a change is implemented on clinicaltrials.gov, this will be updated automatically on our website as well.

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