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

NCT ID: NCT01895127

Last Updated: 2017-09-21

Study Results

Results available

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Basic Information

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Recruitment Status

TERMINATED

Clinical Phase

PHASE2

Total Enrollment

11 participants

Study Classification

INTERVENTIONAL

Study Start Date

2013-11-30

Study Completion Date

2016-04-30

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.

Detailed Description

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Conditions

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Antibody-mediated Rejection Humoral Rejection

Study Design

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Allocation Method

RANDOMIZED

Intervention Model

PARALLEL

Primary Study Purpose

TREATMENT

Blinding Strategy

NONE

Study Groups

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Standard of Care

* Plasmapheresis (PP) x 3, at 40-60 cc/kg.
* Immunoglobulin (IVIg), to be administered after each PP

Group Type ACTIVE_COMPARATOR

Immunoglobulin

Intervention Type BIOLOGICAL

Plasmapheresis

Intervention Type PROCEDURE

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

Group Type EXPERIMENTAL

Eculizumab

Intervention Type DRUG

Interventions

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Eculizumab

Intervention Type DRUG

Immunoglobulin

Intervention Type BIOLOGICAL

Plasmapheresis

Intervention Type PROCEDURE

Other Intervention Names

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Soliris IVIg

Eligibility Criteria

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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)

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)
Minimum Eligible Age

18 Years

Maximum Eligible Age

75 Years

Eligible Sex

ALL

Accepts Healthy Volunteers

No

Sponsors

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Alexion Pharmaceuticals, Inc.

INDUSTRY

Sponsor Role collaborator

Brigham and Women's Hospital

OTHER

Sponsor Role lead

Responsible Party

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Anil K. Chandraker, MD

Medical Director of Kidney and Pancreas Transplantation

Responsibility Role PRINCIPAL_INVESTIGATOR

Principal Investigators

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Anil K Chandraker, MD

Role: PRINCIPAL_INVESTIGATOR

Brigham and Women's Hospital

Locations

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UCSF Medical Center

San Francisco, California, United States

Site Status

Brigham and Women's Hospital

Boston, Massachusetts, United States

Site Status

University of Michigan Medical Center

Ann Arbor, Michigan, United States

Site Status

Countries

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United States

Other Identifiers

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2013P001292

Identifier Type: -

Identifier Source: org_study_id