The De-novo Use of Eculizumab in Presensitized Patients Receiving Cardiac Transplantation
Condition: Antibody-mediated Rejection; Hyperacute Rejection of Cardiac Transplant; Left Ventricular Dysfunction; Cardiac Allograft Vasculopathy; Heart Graft Dysfunction
MeSH terms: Ventricular Dysfunction; Ventricular Dysfunction, Left
Intervention: Eculizumab
Intervention description: At the time of transplantation, 1200mg of Eculizumab will be administered via a 35 minute IV infusion, followed by thymoglobulin 1.5 mg/kg intravenous piggyback (IVPB). The administration of thymoglobulin will be repeated (if blood counts permit) for a total of five doses.
On Day 1 post-transplant, 900 mg of Eculizumab will be given via an IV infusion.
On Day 5 post-transplant, intravenous immunoglobulin (IVIG) 1 gram/kg will be administered daily for two consecutive days.
On post-transplant days 7, 14, and 21 (+/- 2 days) 900mg of Eculizumab will be given via an IV infusion at each scheduled visit.
On post-transplant days 28, 42, and 56 (+/- 2 days) 1200 mg of Eculizumab will be given via an IV infusion at each scheduled visit.
Intervention MeSH terms: Eculizumab
Phase: Phase 3
Study type: Interventional
Primary purpose: Treatment
Intervention model: Single Group Assignment
Masking: None (Open Label)
Enrollment: 36.0
Sex: All
Minimum age: 18 Years
Maximum age: 75 Years
Healthy volunteers: No
Keywords: cardiac transplantation; immunosuppression; acute cellular rejection; antibody mediated rejection; sensitization; antibody production in cardiac patients; panel reactive antibodies; desensitization strategies in heart transplant patients; complement activation; complement c3d and c4d deposition; terminal complement inhibition; complement C5 binding; Eculizumab; monoclonal antibody; donor specific antibodies

Summary:

      All individuals who receive a heart transplant are at risk for developing antibody-mediated
      rejection (AMR). An antibody is a protein produced by the body's immune system when it
      detects a foreign substance, called an antigen. The mechanism of an antibody is to attack an
      antigen. In antibody mediated rejection, antibodies will attack the transplanted heart,
      causing injury to the heart. The purpose of this investigation is to determine if a study
      drug, called eculizumab (Soliris), is safe to use in heart transplant recipients, and
      determine if it reduces risk of antibody-mediated rejection.
    

Eligibility criteria:

        Inclusion Criteria:

          -  Patient is ≥ 18 years of age.

          -  Patient has a panel reactive antibody (PRA) ≥ 70% at any time prior to screening.

          -  Patient is considered compliant and intends to be available for a minimum follow-up
             study period of 1 year.

          -  Patient must be vaccinated against Neisseria meningitides at least 2 weeks prior to
             receiving treatment therapy or receive appropriate antibiotic prophylaxis for the
             duration of eculizumab treatment if timely vaccination could not be achieved prior to
             transplantation.

          -  Voluntary written informed consent must be obtained before performance of any
             study-related procedure not considered routine medical care, with the understanding
             that consent may be withdrawn by the subject at any time without prejudice to future
             medical care.

          -  Female subject is either post-menopausal or surgically sterilized or willing to use
             two acceptable methods of birth control (i.e., a hormonal contraceptive, intra-uterine
             device, diaphragm with spermicide, condom with spermicide, or abstinence) for the
             duration of the study and for up to 2 months after the last dose of study medication.

        Exclusion Criteria:

          -  Donor or recipient age is < 18 years or > 75 years.

          -  Cold ischemia time is > 6 hours.

          -  Current clinical, radiographic, or laboratory evidence of active or latent
             tuberculosis (TB), as determined by local standard of care.

          -  History of active TB within the last 2 years, even if treated.

          -  History of active TB greater than 2 years ago, unless there is documentation of
             adequate treatment according to locally accepted clinical practice.

        (Note: Patients at risk of TB reactivation preclude administration of conventional
        immunosuppression, as determined by the study investigator and based upon appropriate
        evaluation).

          -  Receipt of desensitization treatment with rituximab less than 2 weeks prior to therapy
             and cluster of differentiation antigen 20 (CD20) count >2%.

          -  Receipt of a live vaccine within 4 weeks prior to study entry.

          -  Patients with current or recent severe systemic infections within the 2 weeks prior to
             transplantation.

          -  Prior history of splenectomy.