Efficacy and Safety of Eculizumab for Treatment of Antibody-mediated Rejection Following Renal Transplantation

Study Overview
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Brief Summary
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This is an open-label analysis that will compare eculizumab versus Plasmapheresis (PP) and Immunoglobulin (IVIg) for the treatment of antibody-mediated rejection (AMR) in renal transplant recipients. All patients will be evaluated from the time of AMR diagnosis for 12 months.

Official Title
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Efficacy and Safety of Eculizumab for Treatment of Antibody-mediated Rejection Following Renal Transplantation.

Conditions
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Antibody-mediated Rejection, Humoral Rejection

Intervention / Treatment
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* Drug: Eculizumab
* Biological: Immunoglobulin
* Procedure: Plasmapheresis


Participation Criteria
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Eligibility Criteria
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Inclusion Criteria: Adult renal transplant recipients, men and women between 18 and 75 years of age. Any patient with acute graft dysfunction (elevation of creatinine above post transplant nadir) AND, two out of three, of the following Inclusion Criteria: Presence of circulating anti human leukocyte antigen (HLA) antibody (DSA donor specific antibody). Histological findings compatible with Banff Class II or III AMR on transplant biopsy. Peritubular capillary c4d positivity on transplant biopsy. Exclusion Criteria: Patients that have received eculizumab prior to enrolling in the study. Patients with ongoing non-acute antibody mediated rejection. Patients with predominantly chronic antibody mediated rejection or interstitial fibrosis/tubular atrophy. History of severe cardiac disease (e.g., New York Heart Association [NYHA] Functional Class III or IV, myocardial infarction ≤ 6 months of randomization, ventricular tachyarrhythmias requiring ongoing treatment, unstable angina or other significant cardiovascular diseases) Prior splenectomy Has a known bleeding disorder Has any active bacterial or other infection which is clinically significant in the opinion of the Investigator and is a contraindication to transplantation Has participated in any other investigational drug study or was exposed to an investigational drug or device within 30 days of screening Has received rituximab (Rituxan®) ≤ 3 months prior to screening Has received bortezomib (Velcade®) ≤ 3 months prior to screening Has received alemtuzumab (Campath®) ≤ 6 months prior to screening Need for concurrent treatment with anti thymocyte globulin (Thymoglobulin®) Hypersensitivity to murine proteins or to one of the product excipients History of illicit drug use or alcohol abuse within the previous year Unresolved meningococcal disease Pregnancy or lactation Current cancer or a history of cancer within the 5 years prior to screening with the exception of patients who have successfully treated non-metastatic basal or squamous cell carcinoma of the skin; carcinoma in situ of the cervix; or breast carcinoma in situ Any medical condition that, in the opinion of the Investigator, might interfere with the patient's participation in the study, poses an added risk for the patient, or confounds the assessment of the patient Active infection with Hepatitis B (HBV), Hepatitis C (HCV) or human immunodeficiency virus (HIV)

Ages Eligible for Study
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Minimum Age: 18 Years
Maximum Age: 75 Years

Sexes Eligible for Study
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All

Accepts Healthy Volunteers
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No

Study Plan
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How is the study designed?
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Design Details

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


Arms and Interventions

| Participant Group/Arm | Intervention/Treatment |
| --- | --- |
| Active Comparator: Standard of Care<br>Plasmapheresis (PP) x 3, at 40-60 cc/kg. Immunoglobulin (IVIg), to be administered after each PP | Biological: Immunoglobulin<br> <br> * Other names: IVIg;Procedure: Plasmapheresis<br> <br> |
| Experimental: Soliris (eculizumab)<br>1200 mg first dose (Time: Screening/Week 0, after Biopsy Proven AMR) 900 mg weekly for 4 doses (Weeks 1, 2, 3, 4) 1200 mg week 5 Week 6: If donor specific antibody < 50% of baseline DSA then no further treatment, otherwise 1200 mg weeks 7, 9 | Drug: Eculizumab<br> <br> * Other names: Soliris;|

What is the study measuring?
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Primary Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| Percent Change in Estimated Glomerular Filtration (eGFR) Rate | Percent change in eGFR rate at 3 months post-treatment using the modified Chronic Kidney Disease Epidemiology Collaboration (CKD-EPI) equation. | Month 3 | 

 Terms related to the study
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Keywords Provided by Centre Hospitalier Valida
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Humoral, Kidney Transplant, Renal Transplant, Rejection, Antibody mediated, Eculizumab