ECULIZUMAB IN PATIENTS WITH TRANSFUSION DEPENDANT, HEMOLYTIC PNH

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This subproject is one of many research subprojects utilizing the resources provided by a Center grant funded by NIH/NCRR. The subproject and investigator (PI) may have received primary funding from another NIH source, and thus could be represented in other CRISP entries. The institution listed is for the Center, which is not necessarily the institution for the investigator. Hypothesis: The long-term safety of Eculizumab, a humanized monoclonal antibody that specifically binds the terminal complement protein C5, will be evaluated in patients with transfusion-dependent hemolytic paroxysmal nocturnal hemoglobinuria (PNH). This is an open-label study of patients who have completed the TRIUMPH (GCRC Protocol #853), SHEPHERD (GCRC Protocol #899) or X03-001 trials. Goals: PNH is an acquired clonal disorder of the hematopoietic stem cell, characterized by intravascular hemolysis, hemoglobinuria, anemia, and thrombosis (1). It is a rare condition with an incidence of 2 to 6 per million and a prevalence between 10,000 and 30,000 in the United States. The estimated survival of PNH patients after diagnosis is 50% at 10 years and 28% at 25 years, with a majority of the deaths resulting from thrombosis or bone marrow hypoplasia. Experimental Design: This is an open-label study of approximately 2 years (104 weeks). Patients who have completed the SHEPHERD or X03-001 trials will directly enter the open-label phase of this extension. To preserve the blinded nature of the TRIUMPH study, patients who have completed the TRIUMPH study will undergo a blind induction period prior to entering the open-label phase of this trial. Open-Label Treatment Phase: Patients will receive 900 mg eculizumab via IV infusion every 2 weeks.