Efficacy and Safety of Eculizumab for Treatment of Antibody-mediated Rejection Following Renal Transplantation
Condition: Antibody-mediated Rejection; Humoral Rejection
Intervention: Eculizumab; Immunoglobulin; Plasmapheresis
Intervention MeSH terms: Immunoglobulins; Immunoglobulins, Intravenous; Antibodies; Eculizumab
Phase: Phase 2
Study type: Interventional
Primary purpose: Treatment
Allocation: Randomized
Intervention model: Parallel Assignment
Masking: None (Open Label)
Enrollment: 11.0
Sex: All
Minimum age: 18 Years
Maximum age: 75 Years
Healthy volunteers: No
Keywords: Kidney Transplant; Renal Transplant; Rejection; Antibody mediated; Humoral; Eculizumab

Summary:

      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.
    

Eligibility criteria:

        Inclusion Criteria:

          1. Adult renal transplant recipients, men and women between 18 and 75 years of age.

          2. Any patient with acute graft dysfunction (elevation of creatinine above post
             transplant nadir)

             AND, two out of three, of the following Inclusion Criteria:

          3. Presence of circulating anti human leukocyte antigen (HLA) antibody (DSA "donor
             specific antibody").

          4. Histological findings compatible with Banff Class II or III AMR on transplant biopsy.

          5. Peritubular capillary c4d positivity on transplant biopsy.

        Exclusion Criteria:

          1. Patients that have received eculizumab prior to enrolling in the study.

          2. Patients with ongoing non-acute antibody mediated rejection.

          3. Patients with predominantly chronic antibody mediated rejection or interstitial
             fibrosis/tubular atrophy.

          4. 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)

          5. Prior splenectomy

          6. Has a known bleeding disorder

          7. Has any active bacterial or other infection which is clinically significant in the
             opinion of the Investigator and is a contraindication to transplantation

          8. Has participated in any other investigational drug study or was exposed to an
             investigational drug or device within 30 days of screening

          9. Has received rituximab (Rituxan®) ≤ 3 months prior to screening

         10. Has received bortezomib (Velcade®) ≤ 3 months prior to screening

         11. Has received alemtuzumab (Campath®) ≤ 6 months prior to screening

         12. Need for concurrent treatment with anti thymocyte globulin (Thymoglobulin®)

         13. Hypersensitivity to murine proteins or to one of the product excipients

         14. History of illicit drug use or alcohol abuse within the previous year

         15. Unresolved meningococcal disease

         16. Pregnancy or lactation

         17. 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

         18. 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)