Eculizumab to Enable Renal Transplantation in Patients With History of Catastrophic Antiphospholipid Antibody Syndrome
Condition: Antiphospholipid Antibody Syndrome; End Stage Renal Disease
MeSH terms: Kidney Failure, Chronic; Antiphospholipid Syndrome; Syndrome
Intervention: Eculizumab
Intervention description: 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.
Intervention MeSH terms: Eculizumab
Phase: Phase 2
Study type: Interventional
Primary purpose: Prevention
Intervention model: Single Group Assignment
Masking: None (Open Label)
Enrollment: 1.0
Sex: All
Minimum age: 18 Years
Maximum age: 70 Years
Healthy volunteers: No
Keywords: CAPS; Kidney transplant; Renal transplant; Catastrophic Antiphospholipid Antibody Syndrome

Summary:

      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.
    

Eligibility 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 eculizumab