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

NCT01895127 | Terminated Phase 2 Results DMC

• 1 other identifier: 2013P001292
• Study Type: interventional
• Target: 11
• Locations: 1 country
• Sites: 3

Brief 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.

Conditions

Antibody-mediated Rejection; Humoral Rejection

Keywords

Kidney Transplant; Renal Transplant; Rejection; Antibody mediated; Humoral; Eculizumab

Outcome Measures

Primary Outcomes (1)

• 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

Study Arms (2)

Standard of Care

ACTIVE COMPARATOR

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

Biological: Immunoglobulin; Procedure: Plasmapheresis

Soliris (eculizumab)

EXPERIMENTAL

* 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

Interventions

Eculizumab DRUG

Also known as: Soliris

Soliris (eculizumab)

Immunoglobulin BIOLOGICAL

Also known as: IVIg

Standard of Care

Plasmapheresis PROCEDURE

Standard of Care

Eligibility Criteria

• Age: 18 Years - 75 Years
• Sex: all
• Healthy Volunteers: No
• Age Groups: Adult (18-64), Older Adult (65+)

You may qualify if:

• 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)
• 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.

You may not qualify if:

• 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

Sponsors & Collaborators

• Brigham and Women's Hospital: lead
• Alexion Pharmaceuticals, Inc.: collaborator

Study Sites (3)

UCSF Medical Center

San Francisco, California, 94122, United States

Location

Brigham and Women's Hospital

Boston, Massachusetts, 02115, United States

Location

University of Michigan Medical Center

Ann Arbor, Michigan, 48109, United States

Location

MeSH Terms

Conditions

Rejection, Psychology

Interventions

eculizumab; Immunoglobulins; Immunoglobulins, Intravenous; Plasmapheresis

Condition Hierarchy (Ancestors)

Social Behavior; Behavior

Intervention Hierarchy (Ancestors)

Immunoproteins; Blood Proteins; Proteins; Amino Acids, Peptides, and Proteins; Serum Globulins; Globulins; Immunoglobulin G; Immunoglobulin Isotypes; Antibodies; Blood Component Removal; Therapeutics; Sorption Detoxification; Extracorporeal Circulation; Surgical Procedures, Operative

Results Point of Contact

• Title: Anil Chandraker
• Organization: Brigham and Women's Hospital

achandraker@bwh.harvard.edu

617-732-7412

Study Officials

• Anil K Chandraker, MD

  Brigham and Women's Hospital

  PRINCIPAL INVESTIGATOR

Publication Agreements

• PI is Sponsor Employee: No
• Restrictive Agreement: No

Study Design

• Study Type: interventional
• Phase: phase 2
• Allocation: RANDOMIZED
• Masking: NONE
• Purpose: TREATMENT
• Intervention Model: PARALLEL
• Sponsor Type: OTHER
• Responsible Party: PRINCIPAL INVESTIGATOR
• PI Title: Medical Director of Kidney and Pancreas Transplantation

Study Record Dates

• First Submitted: June 28, 2013
• First Posted: July 10, 2013
• Study Start: November 1, 2013
• Primary Completion: April 1, 2016
• Study Completion: April 1, 2016
• Last Updated: September 21, 2017
• Results First Posted: September 21, 2017

Record last verified: 2017-08

Locations

US (3)