Therapy of Chronic Cold Agglutinin Disease With Eculizumab

NCT01303952 | Completed Phase 2 DMC

• 2 other identifiers: CAD012009-016966-97
• Study Type: interventional
• Target: 13
• Locations: 1 country
• Sites: 1

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)

Conditions

Cold Agglutinin Disease

Keywords

cold agglutinin disease; hemolysis; eculizumab; terminal complement inhibition

Outcome Measures

Primary Outcomes (1)

• LDH

  Primary endpoint for this study is: lactate dehydrogenase (LDH) in U/l change from baseline to 26 weeks

  From baseline to 26 weeks

Secondary Outcomes (12)

• 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

Study Arms (1)

Eculizumab

EXPERIMENTAL

Drug: Eculizumab

Interventions

Eculizumab DRUG

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

Eculizumab

Eligibility Criteria

• Age: 18 Years+
• Sex: all
• Healthy Volunteers: No
• Age Groups: Adult (18-64), Older Adult (65+)

You may qualify if:

• 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

You may not qualify if:

• 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

Sponsors & Collaborators

• University Hospital, Essen: lead
• Alexion Pharmaceuticals, Inc.: collaborator

Study Sites (1)

Department of Hematology, University Hospital Essen

Essen, 45122, Germany

Location

Related Publications (3)

• 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.

  PMID: 19372265 BACKGROUND

• 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.

  PMID: 19614954 BACKGROUND

• 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.

  PMID: 30291112 DERIVED

MeSH Terms

Conditions

Anemia, Hemolytic, Autoimmune; Hemolysis

Interventions

eculizumab

Condition Hierarchy (Ancestors)

Anemia, Hemolytic; Anemia; Hematologic Diseases; Hemic and Lymphatic Diseases; Autoimmune Diseases; Immune System Diseases; Pathologic Processes; Pathological Conditions, Signs and Symptoms

Study Officials

• Alexander Roeth, MD

  Department of Hematology, University Hospital Essen

  PRINCIPAL INVESTIGATOR

Study Design

• Study Type: interventional
• Phase: phase 2
• Allocation: NA
• Masking: NONE
• Purpose: TREATMENT
• Intervention Model: SINGLE GROUP
• Sponsor Type: OTHER
• Responsible Party: PRINCIPAL INVESTIGATOR
• PI Title: MD

Study Record Dates

• First Submitted: February 24, 2011
• First Posted: February 25, 2011
• Study Start: January 1, 2011
• Primary Completion: September 1, 2014
• Study Completion: June 1, 2015
• Last Updated: July 19, 2017

Record last verified: 2017-07

Locations

DE (1)