Eculizumab to Enable Renal Transplantation in Patients With History of Catastrophic Antiphospholipid Antibody Syndrome

This study is currently recruiting participants. (see Contacts and Locations)
Verified August 2011 by Johns Hopkins University
Sponsor:
Information provided by:
Johns Hopkins University
ClinicalTrials.gov Identifier:
NCT01029587
First received: December 9, 2009
Last updated: August 16, 2011
Last verified: August 2011
  Purpose

Catastrophic Antiphospholipid Antibody Syndrome (CAPS) is a rare condition in which life-threatening blood clots form in multiple organs simultaneously and can lead to multi-organ system failure and death. The causes of CAPS are not entirely understood, but CAPS episodes are often triggered by stressful events such as infections, surgery, or trauma. For patients who survive an episode of CAPS, permanent kidney failure is not uncommon because the kidneys are the organ system most frequently affected in CAPS. Kidney transplantation is the treatment of choice for end-stage kidney disease, but patients with a history of CAPS are exceptionally high-risk kidney transplant recipients because the chance that surgery itself could trigger a life-threatening or transplant-threatening episode of CAPS is significant. As a result, patients with CAPS are not generally considered candidates for transplantation. Despite this, these patients have a severely decreased life-expectancy on dialysis and their long-term survival and quality of life would be greatly increased by a successful kidney transplant. In this trial, a drug called eculizumab will be tested for its ability to prevent CAPS after kidney transplantation in patients with a prior history of CAPS. Eculizumab is an inhibitor of the complement system, which is believed to be important in generating the inflammatory environment that leads to diffuse clotting of blood vessels in CAPS. The investigators hypothesize that by blocking the complement cascade using eculizumab, in conjunction with blocking the coagulation system, that kidney transplantation can be safely and successfully performed in patients with a history of CAPS.


Condition Intervention Phase
Antiphospholipid Antibody Syndrome
End Stage Renal Disease
Drug: Eculizumab
Phase 2

Study Type: Interventional
Study Design: Endpoint Classification: Efficacy Study
Intervention Model: Single Group Assignment
Masking: Open Label
Primary Purpose: Prevention
Official Title: Phase 2 Study of the Use of Eculizumab to Prevent Thrombosis After Renal Transplantation in Patients With a History of Catastrophic Antiphospholipid Antibody Syndrome (CAPS)

Resource links provided by NLM:


Further study details as provided by Johns Hopkins University:

Primary Outcome Measures:
  • Prevention of CAPS after kidney transplant [ Time Frame: 1 year ] [ Designated as safety issue: No ]

Secondary Outcome Measures:
  • Kidney transplant graft survival [ Time Frame: 1 year, 5 years ] [ Designated as safety issue: No ]
  • Patient survival [ Time Frame: 1 year, 5 years ] [ Designated as safety issue: No ]

Estimated Enrollment: 10
Study Start Date: November 2009
Estimated Study Completion Date: August 2015
Estimated Primary Completion Date: August 2015 (Final data collection date for primary outcome measure)
Arms Assigned Interventions
Experimental: Eculizumab
Patients will receive eculizumab in conjunction with systemic anticoagulation before and after kidney transplant operation
Drug: Eculizumab
Eculizumab will be administered by intravenous infusion. Eculizumab will be administered at a dose of 1200mg by intravenous (IV) infusion on the day of or on the day prior to kidney transplantation, and at a dose of 900mg IV on post-operative day 1. Subsequently, the post-operative dosing regimen would be comprised of an induction phase of weekly doses of 900mg IV per dose followed by a maintenance phase of every other week dosing of 1200mg IV per dose. The weekly induction dosing regimen would begin on postoperative day 8, and would continue for three doses (specifically, doses of 900mg IV would be given on postoperative days 8, 15, and 22). The maintenance phase of dosing would begin with a dose of 1200mg on postoperative day 29, and would continue for a total of 5 doses (specifically, doses of 1200mg IV would be given on postoperative days 29, 43, 47, 72, and 85). In most cases, eculizumab would be discontinued after the 5th maintenance dose.
Other Name: Soliris

  Eligibility

Ages Eligible for Study:   18 Years to 70 Years
Genders Eligible for Study:   Both
Accepts Healthy Volunteers:   No
Criteria

Inclusion Criteria:

  • Age 18 years or older
  • History of Catastrophic Antiphospholipid Antibody Syndrome (CAPS)
  • End-stage renal disease

Exclusion Criteria:

  • Any contraindications to transplantation other than CAPS
  • Pregnant women
  • Women who intend to become pregnant over the study period
  • Ongoing or untreated meningococcal infections
  • History of serious adverse reaction to eculizumanb
  Contacts and Locations
Choosing to participate in a study is an important personal decision. Talk with your doctor and family members or friends about deciding to join a study. To learn more about this study, you or your doctor may contact the study research staff using the Contacts provided below. For general information, see Learn About Clinical Studies.

Please refer to this study by its ClinicalTrials.gov identifier: NCT01029587

Contacts
Contact: Bonnie E Lonze, MD, PhD 410-955-7120 bel@jhmi.edu
Contact: Cinda Grisbach 410-614-8297 cgrisba1@jhmi.edu

Locations
United States, Maryland
Johns Hopkins Medical Institutions Recruiting
Baltimore, Maryland, United States, 21205
Principal Investigator: Robert A Montgomery, MD, DPhil         
Sponsors and Collaborators
Johns Hopkins University
  More Information

No publications provided

Responsible Party: Robert A. Montgomery MD DPhil, Director, Comprehensive Transplant Center, Johns Hopkins Hospital, The Johns Hopkins University School of Medicine, Dept of Surgery, Division of Transplantation
ClinicalTrials.gov Identifier: NCT01029587     History of Changes
Other Study ID Numbers: NA_00032637
Study First Received: December 9, 2009
Last Updated: August 16, 2011
Health Authority: United States: Food and Drug Administration

Keywords provided by Johns Hopkins University:
CAPS
Kidney transplant
Renal transplant
Catastrophic Antiphospholipid Antibody Syndrome

Additional relevant MeSH terms:
Antiphospholipid Syndrome
Antibodies, Antiphospholipid
Kidney Diseases
Kidney Failure, Chronic
Urologic Diseases
Renal Insufficiency, Chronic
Renal Insufficiency
Autoimmune Diseases
Immune System Diseases
Antibodies
Immunologic Factors
Physiological Effects of Drugs
Pharmacologic Actions

ClinicalTrials.gov processed this record on August 18, 2014