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

Antibody-mediated Rejection Clinical Trial

Official title:

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

Clinical Trial Details — Status: Terminated

Administrative data

• NCT number: NCT01895127
• Other study ID #: 2013P001292
• Status: Terminated
• Phase: Phase 2
• First received: June 28, 2013
• Last updated: August 24, 2017
• Start date: November 2013
• Est. completion date: April 2016

Study information

• Verified date: August 2017
• Source: Brigham and Women's Hospital
• Contact: n/a
• Is FDA regulated: No
• Study type: Interventional

Clinical Trial 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.

Recruitment information / eligibility

• Status: Terminated
• Enrollment: 11
• Est. completion date: April 2016
• Est. primary completion date: April 2016
• Accepts healthy volunteers: No
• Gender: All
• Age group: 18 Years to 75 Years

Eligibility

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)

Related Conditions & MeSH terms

• Antibody-mediated Rejection
• Humoral Rejection

Intervention

Drug:
• Eculizumab

Biological:
• Immunoglobulin

Procedure:
• Plasmapheresis

Locations

Country	Name	City	State
United States	University of Michigan Medical Center	Ann Arbor	Michigan
United States	Brigham and Women's Hospital	Boston	Massachusetts
United States	UCSF Medical Center	San Francisco	California

Sponsors (2)

Lead Sponsor	Collaborator
Brigham and Women's Hospital	Alexion Pharmaceuticals

Country where clinical trial is conducted

United States, 

Outcome

Type	Measure	Description	Time frame	Safety issue
Primary	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