Clinical trial NCT01303952: Therapy of Chronic Cold Agglutinin Disease With Eculizumab
Official title: Therapy for Chronic Cold Agglutinin Disease: A Prospective, Non-Randomized Multi-Center Study Demonstrating the Efficacy of Terminal Complement Inhibition in Patients With Cold Agglutinin Disease Using Eculizumab
Study type: INTERVENTIONAL
Overall status: COMPLETED
Phase: PHASE2
Conditions: Cold Agglutinin Disease
Keywords: cold agglutinin disease
hemolysis
eculizumab
terminal complement inhibition
Lead sponsor: University Hospital, Essen
Sponsor class: OTHER
Collaborators: name: Alexion Pharmaceuticals, Inc.
First posted: 2011-02-25
Enrollment: 13
Sex: ALL
Minimum age (years): 18
Standard ages: ADULT
OLDER_ADULT
Accepts healthy volunteers: no
Allocation: NA
Intervention model: SINGLE_GROUP
Primary purpose: TREATMENT

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)


Eligibility criteria: 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

Primary outcomes:
measure: LDH
timeFrame: From baseline to 26 weeks
Secondary outcomes:
measure: Transfusion avoidance
timeFrame: From baseline to 26 weeks
measure: PRBC units transfused
timeFrame: From baseline to 26 weeks
measure: Change in hemoglobin levels
timeFrame: From baseline to 26 weeks
measure: Haptoglobin
timeFrame: From baseline to 26 weeks
measure: Hemopexin
timeFrame: From baseline to 26 weeks
measure: Free hemoglobin
timeFrame: From baseline to 26 weeks
measure: Reticulocytes
timeFrame: From baseline to 26 weeks
measure: SF-36v2 QLQ
timeFrame: From baseline to 26 weeks
measure: FACIT-F SCALE version 4
timeFrame: From baseline to 26 weeks
measure: Six-Minute Walk Test
timeFrame: From baseline to 26 weeks
measure: Circulatory symptoms
timeFrame: From baseline to 26 weeks
measure: Thrombosis record
timeFrame: From baseline to 26 weeks
Other outcomes:
Locations:
city: Essen
country: Germany
facility: Department of Hematology, University Hospital Essen
Study officials:
affiliation: Department of Hematology, University Hospital Essen
name: Alexander Roeth, MD
role: PRINCIPAL_INVESTIGATOR
References:
citation: Roth A, Huttmann A, Rother RP, Duhrsen U, Philipp T. Long-term efficacy of the complement inhibitor eculizumab in cold agglutinin disease. Blood. 2009 Apr 16;113(16):3885-6. doi: 10.1182/blood-2009-01-196329. No abstract available.
citation: Roth A, Duhrsen U. Cold agglutinin disease. Eur J Haematol. 2010 Jan 1;84(1):91. doi: 10.1111/j.1600-0609.2009.01320.x. Epub 2009 Jul 14. No abstract available.
citation: Roth A, Bommer M, Huttmann A, Herich-Terhurne D, Kuklik N, Rekowski J, Lenz V, Schrezenmeier H, Duhrsen U. Eculizumab in cold agglutinin disease (DECADE): an open-label, prospective, bicentric, nonrandomized phase 2 trial. Blood Adv. 2018 Oct 9;2(19):2543-2549. doi: 10.1182/bloodadvances.2018024190.