AMG 531 Treatment of Thrombocytopenic Subjects With Immune (Idiopathic) Thrombocytopenic Purpura (ITP) Refractory to Splenectomy

Inclusion criteria

• Diagnosis of ITP according to American Society of Hematology (ASH) guidelines (Appendix F)
• Have had a splenectomy for the treatment of ITP greater than or equal to 24 weeks prior to study entry
• Subjects greater than 60 years of age must have a documented history of chronic ITP with a bone marrow report to confirm the diagnosis
• The platelet count (calculated from the mean of the 2 counts taken during the screening and pre-treatment periods) must be:
• * less than 30 x 10^9/L for those subjects not receiving any ITP therapy, with no count greater than 35 x 10^9/L,
• * less than 50 x 10^9/L for those subjects receiving a constant dose schedule of corticosteroids, azathioprine or danazol with no count greater than 55 x 10^9/L
• A serum creatinine concentration less than or equal to 2 mg/dl(less than or equal to 176.8 µmol/L)
• Adequate liver function, as evidenced by a serum bilirubin less than or equal to 1.5 times the laboratory normal range
• Hemoglobin greater than 11.0 g/dL
• Written informed consent (see Section 12.1)

Exclusion criteria

• Any known history of bone marrow stem cell disorder (Any abnormal bone marrow findings other than those typical of ITP must be approved by Amgen before a subject may be enrolled in the study)
• Any active malignancy. If prior history of cancer other than basal cell carcinoma or cervical carcinoma in situ, no treatment or active disease within 5 years before randomization
• Documented diagnosis of arterial thrombosis (i.e., stroke, transient ischemic attack or myocardial infarction) in the past year
• History of venous thrombosis (i.e., deep vein thrombosis, pulmonary embolism) including those subjects who are on ant-coagulation therapy
• Unstable or uncontrolled disease or condition related to or impacting cardiac function (e.g., unstable angina, congestive heart failure [NYHA greater than class II], uncontrolled hypertension [diastolic greater than 100 mmHg] or cardiac arrhythmia)
• Have 3 or more of the following predisposing factors for thromboembolic events: diabetes; smoker; using oral contraceptives; on estrogen therapy; known positive for anti-phospholipid antibodies; hypertriglyceridemia; hypercholesteremia (greater than 240 mg/dL); treatment for hypertension
• Known positive test for human immunodeficiency virus (HIV) infection or hepatitis C virus
• Currently receiving any treatment for ITP except corticosteroids, azathioprine or danazol administered at a constant dose and schedule
• IV Ig or anti-D Ig within 2 weeks before the screening visit
• Rituximab (for any indication) within 14 weeks before the screening visit or anticipated use during the time of the proposed study
• Received hematopoietic growth factors, including IL-11 (oprelvekin) within 4 weeks before the screening visit
• Past or present participation in any study evaluating PEG-rHuMGDF, recombinant human thrombopoietin (rHuTPO), AMG 531 or related platelet product
• Received any aklylating agents within 8 weeks before the screening visit or anticipated use during the time of the proposed study
• Less than 4 weeks since receipt of any therapeutic drug or device that is not FDA approved for any indication before the screening period
• Less than 8 weeks since major surgery
• Pregnant or breast feeding
• Subjects of reproductive potential who are not using adequate contraceptive precautions, in the judgment of the investigator
• Known hypersensitivity to any recombinant E coli-derived product
• Concerns for subject's compliance with the protocol