Home
Search
Study Topics
Glossary
|
|
|
|
|
Sponsors and Collaborators: |
National Heart, Lung, and Blood Institute (NHLBI) Alexion Pharmaceuticals |
---|---|
Information provided by: | National Institutes of Health Clinical Center (CC) |
ClinicalTrials.gov Identifier: | NCT00133120 |
This study will evaluate the safety and effectiveness of the experimental drug eculizumab for long-term treatment of paroxysmal nocturnal hemoglobinuria (PNH). PNH can cause premature destruction of red blood cells, resulting in anemia that requires blood transfusions. Patients may be at high risk of life-threatening blood clots in their veins. Some patients can develop bone marrow failure or aplastic anemia. Other symptoms include urine discoloration, stomach pain, difficulty in swallowing, tiredness, and poor quality of life. Men may have problems getting or maintaining an erection.
Eculizumab is a monoclonal antibody that may improve the survival of red blood cells in patients with PNH.
Patients with PNH who have fully completed the SHEPHERD study or have completed the TRIUMPH study through at least visit 18 may be eligible for this study.
Participants from the SHEPHERD study will receive infusions of 900 mg of eculizumab through a needle in a vein every other week for about 53 doses.
Participants who received placebo in the TRIUMPH study will receive 600 mg of eculizumab once a week for four doses, followed by 900 mg of drug a week later for one dose, and then 900 mg of drug every other week for another 50 doses. Patients who received eculizumab in the TRIUMPH study will receive 900 mg eculizumab every other week at visits 1 and 3 and placebo every other week at visits 2 and 4, followed by 900 mg of drug every other week for about 53 doses. Visits are scheduled every week for the first five visits and then every other week until the end of the study.
At every treatment visit, each patient updates health status, transfusion record and medication use, reviews their laboratory results from the preceding visit, and receives an infusion of eculizumab. At selected visits, they have a full physical examination, complete a questionnaire about how the illness affects their everyday life, provide blood and urine samples, and undergo an electrocardiogram. Blood is collected more often if clinically indicated.
All patients receive a prescription for an antibiotic with instructions on signs and symptoms of Neisseria meningitides infection. N. meningitides is a common bacterium that can cause symptoms, possibly including life-threatening meningitis, in susceptible people, including people who take eculizumab.
Participants are re-vaccinated against this bacterium when more than 2.5 to 3 years have passed since their previous inoculation.
Participants who leave the study early are followed for an additional 16 weeks with six visits to update their health status, transfusion record, and medication use, have their temperature, heart rate, and blood pressure measured, and provide a blood sample.
Condition | Intervention | Phase |
---|---|---|
Paroxysmal Hemoglobinuria, Nocturnal |
Drug: Eculizumab |
Phase III |
Study Type: | Interventional |
Study Design: | Treatment, Randomized, Open Label, Uncontrolled, Single Group Assignment, Safety/Efficacy Study |
Official Title: | A Phase III, Open-Label, Extension Study of Eculizumab in Patients With Transfusion Dependent, Hemolytic Paroxysmal Nocturnal Hemoglobinuria (PNH) Who Have Participated in the TRIUMPH (C04-001), SHEPHERD (E05-001) or X03-001 Studies |
Estimated Enrollment: | 18 |
Study Start Date: | August 2005 |
Estimated Study Completion Date: | December 2007 |
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 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 (h5G1.1-mAb) is a humanized monoclonal antibody that like CD59 inhibits terminal complement.
This study is an open label, multi-center study of eculizumab, administered intravenously for 104 weeks to approximately 170 PNH patients (11-13 at the NIH) who have participated on the TRIUMPH (randomized trial) or SHEPHERD (open label trial). This study is designed to evaluate the long term safety of eculizumab inpatients with transfusion dependent paroxysmal nocturnal hemoglobinuria (PNH).
Ages Eligible for Study: | 18 Years and older |
Genders Eligible for Study: | Both |
Accepts Healthy Volunteers: | No |
Each patient must meet the following criteria to be enrolled in this study:
EXCLUSION CRITERIA:
Any patient meeting any of the following criteria will be excluded from the study:
Study ID Numbers: | 050226, 05-H-0226 |
Study First Received: | August 20, 2005 |
Last Updated: | December 11, 2007 |
ClinicalTrials.gov Identifier: | NCT00133120 History of Changes |
Health Authority: | United States: Federal Government |
h5g.1 Paroxysmal Nocturnal Hemoglobinuria |
Urination Disorders Hematologic Diseases Myelodysplastic Syndromes Anemia Marchiafava-Micheli Disease Anemia, Hemolytic Hemoglobinuria |
Signs and Symptoms Proteinuria Preleukemia Paroxysmal Nocturnal Hemoglobinuria Urologic Diseases Hemoglobinuria, Paroxysmal Bone Marrow Diseases |
Signs and Symptoms Urological Manifestations Hemoglobinuria Proteinuria Urologic Diseases Hematologic Diseases |
Urination Disorders Myelodysplastic Syndromes Anemia Hemoglobinuria, Paroxysmal Anemia, Hemolytic Bone Marrow Diseases |