Eculizumab to Treat Paroxysmal Nocturnal Hemoglobinuria

Hemoglobinuria, Paroxysmal Clinical Trial

Official title: A Hemoglobin Stabilization and Transfusion Reduction Efficacy and Safety Clinical Investigation, Randomized, Multi-Center, Double-Blind, Placebo-Controlled, Using Eculizumab in Paroxysmal Nocturnal Hemoglobinuria Patients

Status Completed

Clinical Trial Summary

This study will examine the safety and effectiveness of the experimental drug eculizumab in treating patients with paroxysmal nocturnal hemoglobinuria (PNH), a rare disorder of red blood cells that leads to premature destruction of the cells and resulting anemia. Patients may be at high risk of blood clots and may develop bone marrow failure or aplastic anemia, with low white blood cell and platelet counts. Eculizumab is a monoclonal antibody that may help improve the survival of red blood cells.

Patients 18 years of age and older with PNH who require blood transfusions for anemia and have received at least four transfusions in the 12 months preceding evaluation for this study may be eligible to enroll. Candidates are screened with a medical history, physical examination, and check of vital signs.

Participants have an electrocardiogram (EKG) and blood and urine tests, and are vaccinated against Neisseria meningitides, a common bacteria that can cause a disabling or fatal type of meningitis. They then enter an observation phase of the study, with monthly visits during which they complete a questionnaire; update their health status, transfusion record, and medication use; have their vital signs checked and PNH symptoms evaluated; have blood and urine tests; and receive a transfusion, if necessary. These visits continue for up to 3 months until patients receive a "qualifying" transfusion; that is, a transfusion given as a consequence of a certain hemoglobin level with symptoms or a different level without symptoms.

Patients are then randomly assigned to receive either eculizumab or a placebo (salt solution with no active ingredient). Both study medications are given intravenously (through a vein) over 30 minutes once a week for five doses and then once every 2 weeks for another 11 doses. At each treatment visit (study weeks 0-24), patients update their health status, transfusion records, and medication use; have their vital signs checked; and provide a blood sample. At various visits, they also complete a questionnaire, provide a urine sample and have an EKG. At the last treatment visit (week 26 or the final visit for patients who end their participation before visit 18) patients have a complete physical examination in addition to the procedures listed above.

Clinical Trial Description

Paroxysmal nocturnal hemoglobinuria (PNH) is an acquired clonal disorder of the hematopoietic stem cell characterized by intravascular hemolysis, hemoglobinuria, anemia, and thrombosis. The clinical features of PNH result from the lack of one or more of the GPI-linked proteins that serve to protect cells from autologous complement mediated attack. Two such proteins, CD55 (decay accelerating factor) and CD59 (reactive lysis inhibitor) have been shown to be absent from PNH erythrocytes and platelets as well as other cell types.

Evidence strongly suggests that lack of the terminal complement inhibitor CD59 is responsible for the sensitivity of PNH erythrocytes and platelets to the effects of autologous complement. Since the pathogenesis of PNH is due to the inability of PNH red cells and platelets to inhibit the activation of terminal complement, it is logical to hypothesize that a terminal complement inhibitor could effectively stop the intravascular hemolysis, obviate or lessen the need for transfusions, and possibly decrease the propensity of life threatening thrombosis. Eculizumab is a humanized monoclonal antibody that like CD59 inhibits terminal complement.

This study is a randomized, double-blind, placebo controlled, multi-center study of eculizumab or placebo administered intravenously to approximately 75 PNH patients. The study is designed to evaluate the safety of eculizumab in transfusion dependent patients with paroxysmal nocturnal hemoglobinuria (PNH) and to determine if the administration of this terminal complement inhibitor could provide a safe and effective substitute for CD59 function. ;

Study Design

Endpoint Classification: Efficacy Study, Primary Purpose: Treatment

Related Conditions & MeSH terms

• Hemoglobinuria
• Hemoglobinuria, Paroxysmal

• NCT number: NCT00098280
• Study type: Interventional
• Source: National Institutes of Health Clinical Center (CC)
• Status: Completed
• Phase: Phase 3
• Start date: December 2004
• Completion date: February 2006