Aplastic Anemia
Conditions
Sponsors
Kyowa Kirin Co., Ltd.
Eligibility
Sex/Gender
All
Inclusion criteria
Inclusion criteria: 1) Diagnosis of AA confirmed by peripheral blood and bone-marrow examinations, etc. 2) Refractory to at least one course of immunosuppressive therapy including horse or rabbit anti-human thymocyte immunoglobulin (ATG); or ineligible for ATG treatment and refractory to cyclosporin (CyA) 3) Thrombocytopenia defined as a PLT of == 20 years of age at the time of obtaining informed consent 7) Patients who have provided written informed consent of their free will to participate in this study
Exclusion criteria
Exclusion criteria: 1) Concurrent active infection not adequately responding to appropriate therapy 2) Bone marrow reticulin grade of >= 2 based on the grading scale for reticulin indicated in Bone Marrow Pathology (2nd edition) 3) Proportion of blasts in bone marrow > 2% 4) Previous or concurrent active malignancies, other than localized tumors diagnosed more than one year previously and treated surgically with curative intent (basal cell carcinoma; or surgically resected in situ carcinoma of the cervix with an apparent success of >= 12 months prior to enrollment; as well as other cancers which have not been treated and remained disease-free for at least 5 years before enrollment are eligible) 5) Clinically significant cardiac disease (class III or IV of the New York Heart Association classification; unstable angina pectoris; myocardial infarction within 6 months before enrollment; cardiac disease accompanied by angioplasty or stenting within 6 months before enrollment; or clinically significant cardiac arrhythmias) or uncontrollable hypertension 6) Arterial or venous thrombosis within one year before enrollment 7) Positive for anti-human immunodeficiency virus antibodies, hepatitis B surface antigen, or hepatitis C virus-RNA at screening 8) Thrombocytopenia due to any other cause (e.g., MDS, idiopathic thrombocytopenic purpura, or liver cirrhosis) 9) Patients with AML or chronic myelomonocytic leukemia 10) Concurrent occurrence of hemolytic predominant paroxysmal nocturnal hemoglobinuria Hemolytic predominant is defined as lactate dehydrogenase > 1.5 times the upper limit of the laboratory normal range. 11) Uncontrolled diabetes mellitus 12) Receiving other investigational products within 16 weeks before AMG531 treatment initiation 13) Receiving any agent to treat AA, including the following agents before AMG531 treatment initiation; - ATG treatment within 6 months before AMG531 treatment initiation - CyA or anabolic steroid treatment within 6 weeks before AMG531 treatment initiation: However, the patients who are treated with a CyA or anabolic steroid for at least 6 months before AMG531 treatment initiation may be enrolled if their blood cell count are stable at screening, and their dosage and administration will be kept for 6 weeks before AMG531 treatment initiation and during AMG531 dosing period. 14) A history of polyethylene glycol-conjugated recombinant human megakaryocyte growth and development factor, recombinant human TPO, AMG531, or other TPO-receptor agonists 15) Having a plan to undergo hematopoietic stem cell transplantation within 1 year 16) Having hypersensitivity to any recombinant protein E. coli derivative protein 17) Lactating or pregnant women or women of child-bearing potential who have no intention of using oral contraceptives or birth control 18) Having abnormalities by the cytogenetic test in bone marrow cells 19) Patients who are considered to be ineligible for the study by the investigator or subinvestigator for reasons other than above
Design outcomes
Primary
| Measure | Time frame |
|---|---|
| efficacy Proportion of subjects achieving a hematological response (any of the platelet response, erythroid response, and neutrophil response) at Week 27 | — |
Secondary
| Measure | Time frame |
|---|---|
| efficacy Proportion of subjects with a hematological response at the end-of-treatment-period examination (Week 53) Time from the first AMG531 administration to hematological response In subjects receiving platelet transfusion as a pretreatment within 8 weeks prior to the first AMG531 administration; proportion of subjects with transfusion independence or decreased platelet transfusion requirement Proportion of subjects achieving platelet response, erythroid response, or neutrophil response at each of Week 27 and end-of-treatment-period examination (Week 53) | — |
Countries
Asia except Japan, Japan
Outcome results
None listed