Study of Romiplostim(AMG531) in Subjects With Aplastic Anemia

Inclusion criteria

• Diagnosis of Aplastic Anemia (AA) confirmed by peripheral blood and bone-marrow examinations, etc.
• 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)
• Thrombocytopenia defined as a platelet count of ≤ 30 × 10^9/L
• Preserving main organ function as a result of screening as follows;

• Total bilirubin: < 1.5 times the upper limit of the laboratory normal range
• Alanine aminotransferase: < 3.0 times the upper limit of the laboratory normal range
• Aspartate aminotransferase: < 3.0 times the upper limit of the laboratory normal range
• Creatinine value: ≤ 2.0 mg/dL
• An Eastern Cooperative Oncology Group performance status score of 0 to 2 at screening
• ≥ 20 years of age at the time of obtaining informed consent
• Patients who have provided written informed consent of their free will to participate in this study

Exclusion criteria

• Concurrent active infection not adequately responding to appropriate therapy
• Bone marrow reticulin grade of ≥ 2 based on the grading scale for reticulin indicated in Bone Marrow Pathology (2nd edition)
• Proportion of blasts in bone marrow > 2%
• 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)
• 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
• Arterial or venous thrombosis within one year before enrollment
• Positive for anti-human immunodeficiency virus antibodies, hepatitis B surface antigen, or hepatitis C virus-RNA at screening
• Thrombocytopenia due to any other cause (e.g., myelodysplastic syndrome, idiopathic thrombocytopenic purpura, or liver cirrhosis)
• Patients with acute myeloblastic leukemia or chronic myelomonocytic leukemia
• 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)
• Uncontrolled diabetes mellitus
• Receiving other investigational products within 16 weeks before romiplostim treatment initiation
• Receiving any agent to treat AA, including the following agents before romiplostim treatment initiation;

• ATG treatment within 6 months before romiplostim treatment initiation
• CyA or anabolic steroid treatment within 6 weeks before romiplostim treatment initiation:

However, the patients who are treated with a CyA or anabolic steroid for at least 6 months before romiplostim 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 romiplostim treatment initiation and during romiplostim dosing period.

• A history of polyethylene glycol-conjugated recombinant human megakaryocyte growth and development factor, recombinant human thrombopoietin (TPO), romiplostim, or other TPO-receptor agonists
• Having a plan to undergo hematopoietic stem cell transplantation within 1 year
• Having hypersensitivity to any recombinant protein E. coli derivative protein
• Lactating or pregnant women or women of child-bearing potential who have no intention of using oral contraceptives or birth control
• Having abnormalities by the cytogenetic test in bone marrow cells
• Patients who are considered to be ineligible for the study by the investigator or subinvestigator for reasons other than above