Cold Agglutinin Disease
Conditions
Keywords
cold agglutinin disease, hemolysis, eculizumab, terminal complement inhibition
Brief summary
Evaluation of the efficacy and safety of eculizumab in symptomatic or transfusion-dependent patients with untreated or refractory hemolytic cold agglutinin disease(CAD)
Interventions
DRUGEculizumab
Weekly treatment with eculizumab (600 mg) via IV infusion for 4 doses followed the next week by eculizumab (900 mg) IV infusion and maintenance treatment with Eculizumab (900 mg) via IV infusion every other week for 21 weeks
Sponsors
Alexion Pharmaceuticals, Inc.
University Hospital, Essen
Study design
Allocation
NA
Intervention model
SINGLE_GROUP
Primary purpose
TREATMENT
Masking
NONE
Eligibility
Sex/Gender
ALL
Age
18 Years to No maximum
Healthy volunteers
No
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
Design outcomes
Primary
| Measure | Time frame | Description |
|---|---|---|
| LDH | From baseline to 26 weeks | Primary endpoint for this study is: lactate dehydrogenase (LDH) in U/l change from baseline to 26 weeks |
Secondary
| Measure | Time frame |
|---|---|
| Transfusion avoidance | From baseline to 26 weeks |
| PRBC units transfused | From baseline to 26 weeks |
| Change in hemoglobin levels | From baseline to 26 weeks |
| Haptoglobin | From baseline to 26 weeks |
| Hemopexin | From baseline to 26 weeks |
| Circulatory symptoms | From baseline to 26 weeks |
| Reticulocytes | From baseline to 26 weeks |
| SF-36v2 QLQ | From baseline to 26 weeks |
| FACIT-F SCALE version 4 | From baseline to 26 weeks |
| Six-Minute Walk Test | From baseline to 26 weeks |
| Thrombosis record | From baseline to 26 weeks |
| Free hemoglobin | From baseline to 26 weeks |
Countries
Germany
Outcome results
None listed