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

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

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.

Study Overview

• Status: Terminated
• Conditions: Antibody-mediated Rejection; Humoral Rejection
• Intervention / Treatment: Biological: Immunoglobulin; Procedure: Plasmapheresis; Drug: Eculizumab

• Study Type: Interventional
• Enrollment (Actual): 11
• Phase: Phase 2

Contacts and Locations

Study Locations

• United States
  • California
    • San Francisco, California, United States, 94122
      • UCSF Medical Center
  • Massachusetts
    • Boston, Massachusetts, United States, 02115
      • Brigham and Women's Hospital
  • Michigan
    • Ann Arbor, Michigan, United States, 48109
      • University of Michigan Medical Center

Participation Criteria

Eligibility Criteria

• Ages Eligible for Study: 18 years to 75 years (Adult, Older Adult)
• Accepts Healthy Volunteers: No
• Genders Eligible for Study: All

Description

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)

Study Plan

How is the study designed?

Design Details

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

Number of Arms

2

Arms and Interventions

Participant Group / Arm	Intervention / Treatment
Active Comparator: Standard of Care; Plasmapheresis (PP) x 3, at 40-60 cc/kg.; Immunoglobulin (IVIg), to be administered after each PP	Biological: Immunoglobulin; Other Names: IVIg; Procedure: Plasmapheresis
Experimental: Soliris (eculizumab); 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; Other Names: Soliris

What is the study measuring?

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

Collaborators and Investigators

• Sponsor: Brigham and Women's Hospital
• Collaborators: Alexion Pharmaceuticals
• Investigators: Principal Investigator: Anil K Chandraker, MD, Brigham and Women's Hospital

Study record dates

Study Major Dates

• Study Start: November 1, 2013
• Primary Completion (Actual): April 1, 2016
• Study Completion (Actual): April 1, 2016

Study Registration Dates

• First Submitted: June 28, 2013
• First Submitted That Met QC Criteria: July 5, 2013
• First Posted (Estimate): July 10, 2013

Study Record Updates

• Last Update Posted (Actual): September 21, 2017
• Last Update Submitted That Met QC Criteria: August 24, 2017
• Last Verified: August 1, 2017

More Information

Terms related to this study

• Keywords: Rejection; Kidney Transplant; Eculizumab; Renal Transplant; Antibody mediated; Humoral
• Additional Relevant MeSH Terms: Physiological Effects of Drugs; Immunosuppressive Agents; Immunologic Factors; Complement Inactivating Agents; Antibodies; Immunoglobulins; Immunoglobulins, Intravenous; Eculizumab
• Other Study ID Numbers: 2013P001292