Evaluation of the efficacy and safety of eculizumab in symptomatic or transfusion-dependent patients with untreated or refractory hemolytic cold agglutinin disease(CAD)

Inclusion Criteria:

• Individuals at least 18 years of age
• Diagnosis of CAD defined by the combination of chronic hemolysis, cold agglutinin titer (IgM or IgA) >64 at 4°C, positive direct antiglobulin test (DAT) when performed with polyspecific antiserum, negative (or only weakly positive) anti-IgG, and strongly positive with anti-C3d
• LDH level > 2 x upper limit of normal (ULN)
• Clinical symptoms requiring treatment, such as anemia, anemia-related symptoms or hemolysis-related symptoms
• Sufficient supplementation of iron, folic acid and vitamin B12 prior to treatment phase
• Patient must be willing and able to give written informed consent;
• Patients must be vaccinated against N. meningitidis at least 14 days prior treatment
• Patient must avoid conception during the trial using a method that is most appropriate for their physical state and culture

Exclusion Criteria:

• Active aggressive lymphoma requiring therapy or an active non-lymphatic malignant disease other than basal cell carcinoma or CIS of the cervix
• Liver disease with elevated LDH
• Absolute neutrophil count < 500/µL
• Presence or suspicion of active bacterial or viral infection, in the opinion of the Investigator, at treatment start or severe recurrent bacterial infections
• Participation in any other investigational drug trial or exposure to other investigational agent, device, or procedure within 30 days prior to screening period
• Pregnant, breast-feeding, or intending to conceive during the course of the study, including the Post-treatment Phase
• History of bone marrow/stem cell transplantation
• Inability to cooperate or any condition that, in the opinion of the investigator, could increase the patient's risk by participating in the study or confound the outcome of the study
• Hypersensitivity to eculizumab, to murine proteins or to one of the excipients