Phase 2/3 Study of Romiplostim(AMG531) in Subjects With Aplastic Anemia Refractory to or Ineligible for Immunosuppressive Therapy
Phase 2/3 Study of Romiplostim(AMG531) in Subjects With Aplastic Anemia Refractory to or Ineligible for Immunosuppressive Therapy
The objective of this study is to evaluate the efficacy of romiplostim administered once weekly to Aplastic Anemia (AA) patients with thrombocytopenia refractory to or ineligible for immunosuppressive therapy in Japan and Korea.
Safety and pharmacokinetics of romiplostim after repeated administration will also be assessed.
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;
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;
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.