Clinical trial NCT00122330: Study Using Eculizumab in Transfusion Dependent Paroxysmal Nocturnal Hemoglobinuria (PNH) Patients
Official title: Randomized, Double-Blind, and Placebo-Controlled Study Using Eculizumab in Transfusion Dependent PNH Patients
Study type: INTERVENTIONAL
Overall status: COMPLETED
Phase: PHASE3
Conditions: Hemoglobinuria, Paroxysmal
Lead sponsor: Alexion Pharmaceuticals, Inc.
Sponsor class: INDUSTRY
First posted: 2005-07-22
Enrollment: 75
Sex: ALL
Minimum age (years): 18
Standard ages: ADULT
OLDER_ADULT
Accepts healthy volunteers: no
Allocation: RANDOMIZED
Intervention model: PARALLEL
Primary purpose: ECT

Brief summary: The primary objective is to evaluate the safety and efficacy of eculizumab in transfusion dependent patients with hemolytic PNH.


Eligibility criteria: Inclusion Criteria:

* Must have required at least 4 transfusions in the past 12 months
* PNH type III red blood cell (RBC) clone by flow cytometry of \>10%
* Lactate dehydrogenase (LDH) level \> 1.5 x upper limit of normal
* Platelet count \> 100,000/mm3
* Patient taking erythropoietin must be on a stable dose for at least 26 weeks
* Patient taking immunosuppressants must be on a stable dose for at least 26 weeks
* Patient taking corticosteroids must be on a stable dose for at least 4 weeks
* Patient taking coumadin must be at a stable INR for at least 4 weeks
* Patient taking iron supplements or folic acid must be on a stable dose for 4 weeks
* Willing and able to give written informed consent
* Must avoid conception

Exclusion Criteria:

* Mean hemoglobin level prior to transfusion over the previous 12 months is \>10.5 gm/dl
* Absolute neutrophil count \<500/ul
* Active bacterial infection
* Hereditary complement deficiency
* Participation in any other investigational drug trial or exposure to other investigational agent, device, or procedures within 30 days
* Pregnant, breast-feeding, or intending to conceive
* History of meningococcal disease
* History of bone marrow transplantation

Primary outcomes:
Secondary outcomes:
Other outcomes:
Locations:
city: Duarte
country: United States
facility: City of Hope National Medical Center, Div. of Hematology & Bone Marrow Transplant
state: California
city: Los Angeles
country: United States
facility: University of California at Los Angeles
state: California
city: San Diego
country: United States
facility: Scripps Cancer Center
state: California
city: Stanford
country: United States
facility: Stanford University Medical Center, Division of Hematology
state: California
city: Hartford
country: United States
facility: Hartford Hospital, Cancer Clinical Research Office
state: Connecticut
city: Weston
country: United States
facility: Cleveland Clinic, Dept. of Clinical Research
state: Florida
city: Indianapolis
country: United States
facility: Indiana University Cancer Pavilion, Div. of Hematology-Oncology, Hematological Malignancy Program/Immunology
state: Indiana
city: Baltimore
country: United States
facility: Johns Hopkins University Medical Center
state: Maryland
city: Bethesda
country: United States
facility: National Heart, Blood, and Lung Institute, National Institutes of Health
state: Maryland
city: Boston
country: United States
facility: Massachusetts General Hospital
state: Massachusetts
city: St. Louis
country: United States
facility: Washington University School of Medicine, Dept. of Internal Medicine/Division of Hematology
state: Missouri
city: New York
country: United States
facility: NYU Clinical Cancer Center
state: New York
city: New York
country: United States
facility: Memorial Sloan Kettering Cancer Center
state: New York
city: Durham
country: United States
facility: Duke University Health System, Division of Cell Therapy, Heme Malignancies Program
state: North Carolina
city: Cleveland
country: United States
facility: Cleveland Clinic Foundation
state: Ohio
city: Philadelphia
country: United States
facility: Presbyterian Medical Center, PENN Comprehensive Hemophilia & Thrombosis Program
state: Pennsylvania
city: Woolloongabba
country: Australia
facility: Princess Alexandra Hospital, Oncology Haematology Radiation Department
state: Queensland
city: Woodville South
country: Australia
facility: Queen Elizabeth Hospital, Dept. of Haematology
state: South Australia
city: Parkville
country: Australia
facility: Royal Melbourne Hospital, Dept. of Clinical Haematology & Medical Oncology
state: Victoria
city: Perth
country: Australia
facility: The Royal Perth Hosptial, Department of Haematology/Level 2
state: Western Australia
city: Brussels
country: Belgium
facility: Ucl St. Luc, Hematology Department
city: Edmonton
country: Canada
facility: University of Alberta, Cross Cancer Institute
state: Alberta
city: Cedex
country: France
facility: Hospital De L'Hotel Dieu, Hematologie et Oncologie Medicale
state: Paris
city: Cedex
country: France
facility: Hopital Saint-Louis, Centre G. Hayem-Secteur Bleu Porte 7, Laboratoire De Pathologie/Greffe de Moelle
state: Paris
city: Essen
country: Germany
facility: Universitatsklinikum Essen, Zentrum fur Innere Medizin
city: Greifswald
country: Germany
facility: Universitatsklinik Greifswald, Innere Medizin C - Hamato-Onkologie
city: Hannover
country: Germany
facility: Medizinische Hochschule Hannover, Abt. Hamatologie/Onkologie, Zentrum fur Innere Medizin
city: Homburg/Saar
country: Germany
facility: Saarland University Medical School, Internal Medicine 1
city: Ulm
country: Germany
facility: Institut fur Klinische Transfusionmedizin und Immungenetik, Abtlg. Transfusionsmedizin des Universitatskinikums Ulm
city: Dublin
country: Ireland
facility: St. James Hospital, Haematology Department
city: Firenze
country: Italy
facility: Azienda Ospedaliera Universitaria Careggi, Dipartimento di area critica medico-chirurgica
city: Genova
country: Italy
facility: Ospedale San Martino, Dept. of Hematology
city: Milano
country: Italy
facility: Ospedale Maggiore di Milano, Divisione di Ematologia
city: Napoli
country: Italy
facility: Universitar degli Studi di Napoli, Divisione di Ematologia, Azienda Universitar Policlinico
city: Vicenza
country: Italy
facility: Ospedale San Bortolo, Divisione di Ematologia
city: Nijmegen
country: Netherlands
facility: UMC St. Radboud, Dept. of Hematology
state: GA
city: Lund
country: Sweden
facility: Lund University Hospital, Department of Internal Medicine, Section of Hematology
city: Umea
country: Sweden
facility: Umea University Hospital, Dept. of Internal Medicine 3, Section for Hematology
city: Basel
country: Switzerland
facility: Universitatsklinik Basel, Division of Hematology
state: CH
city: Truro
country: United Kingdom
facility: Royal Cornwall Hospital, Haematology Dept.
state: Cornwall
city: Belfast
country: United Kingdom
facility: Belfast City Hospital, Dept. of Haematology C Floor
city: Leeds
country: United Kingdom
facility: Leeds General Infirmary, D Floor Brotherton Wing
city: London
country: United Kingdom
facility: St. George's Hospital, Department of Haematology
Study officials:
References:
citation: Hillmen P, Young NS, Schubert J, Brodsky RA, Socie G, Muus P, Roth A, Szer J, Elebute MO, Nakamura R, Browne P, Risitano AM, Hill A, Schrezenmeier H, Fu CL, Maciejewski J, Rollins SA, Mojcik CF, Rother RP, Luzzatto L. The complement inhibitor eculizumab in paroxysmal nocturnal hemoglobinuria. N Engl J Med. 2006 Sep 21;355(12):1233-43. doi: 10.1056/NEJMoa061648.
citation: Hill A, Rother RP, Wang X, Morris SM Jr, Quinn-Senger K, Kelly R, Richards SJ, Bessler M, Bell L, Hillmen P, Gladwin MT. Effect of eculizumab on haemolysis-associated nitric oxide depletion, dyspnoea, and measures of pulmonary hypertension in patients with paroxysmal nocturnal haemoglobinuria. Br J Haematol. 2010 May;149(3):414-25. doi: 10.1111/j.1365-2141.2010.08096.x. Epub 2010 Mar 8.