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

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

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.

Study Overview

• Status: Completed
• Conditions: End Stage Renal Disease; Antiphospholipid Antibody Syndrome
• Intervention / Treatment: Drug: Eculizumab

• Study Type: Interventional
• Enrollment (Actual): 1
• Phase: Phase 2

Contacts and Locations

Study Locations

• United States
  • Maryland
    • Baltimore, Maryland, United States, 21205
      • Johns Hopkins University School of Medicine

Participation Criteria

Eligibility Criteria

• Ages Eligible for Study: 18 years to 70 years (Adult, Older Adult)
• Accepts Healthy Volunteers: No
• Genders Eligible for Study: All

Description

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 eculizumab

Study Plan

How is the study designed?

Design Details

• Primary Purpose: Prevention
• Allocation: N/A
• Interventional Model: Single Group Assignment
• Masking: None (Open Label)

Number of Arms

1

Arms and Interventions

Participant Group / Arm

Intervention / Treatment

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 Names: Soliris

What is the study measuring?

Primary Outcome Measures

Outcome Measure	Time Frame
Number of Patients With Prevention of Catastrophic Antiphospholipid Antibody Syndrome (CAPS) After Kidney Transplant	6 months

Secondary Outcome Measures

Outcome Measure	Time Frame
Number of Patients With Kidney Transplant Graft Survival	6 months
Number of Patients Who Survive	6 months

Collaborators and Investigators

• Sponsor: Johns Hopkins University
• Investigators: Principal Investigator: Benjamin Philosophe, MD, PHD, Johns Hopkins University

Study record dates

Study Major Dates

• Study Start (Actual): November 1, 2009
• Primary Completion (Actual): May 6, 2010
• Study Completion (Actual): May 6, 2010

Study Registration Dates

• First Submitted: December 9, 2009
• First Submitted That Met QC Criteria: December 9, 2009
• First Posted (Estimate): December 10, 2009

Study Record Updates

• Last Update Posted (Actual): October 26, 2020
• Last Update Submitted That Met QC Criteria: October 1, 2020
• Last Verified: October 1, 2020

More Information

Terms related to this study

• Keywords: Kidney transplant; CAPS; Renal transplant; Catastrophic Antiphospholipid Antibody Syndrome
• Additional Relevant MeSH Terms: Pathologic Processes; Immune System Diseases; Autoimmune Diseases; Kidney Diseases; Urologic Diseases; Disease; Renal Insufficiency; Renal Insufficiency, Chronic; Syndrome; Kidney Failure, Chronic; Antiphospholipid Syndrome; Physiological Effects of Drugs; Immunosuppressive Agents; Immunologic Factors; Complement Inactivating Agents; Eculizumab
• Other Study ID Numbers: NA_00029904