Romiplostim Treatment of Thrombocytopenia in Subjects With Low or Intermediate-1 Risk Myelodysplastic Syndrome (MDS)

A Randomized, Double Blind, Placebo Controlled Study Evaluating the Efficacy and Safety of Romiplostim Treatment of Thrombocytopenia in Subjects With Low or Intermediate-1 Risk Myelodysplastic Syndrome (MDS)

The Data Monitoring Committee (DMC) for study 20060198 recommended that all subjects discontinue treatment of study drug and continue to be followed for long term follow-up. Amgen adopted the DMC recommendation.

This is a Phase 2, multicenter, randomized, double blind, placebo controlled study designed to assess the efficacy and safety of romiplostim (formerly, AMG 531) treatment in thrombocytopenic MDS patients. The study is composed of a 26-week placebo controlled test treatment period (romiplostim versus Placebo), a 4 week interim wash-out period, a 24-week placebo controlled extended treatment period, and a 4-week follow-up period followed by an End of Study (EOS) visit. During the interim wash-out period, a bone marrow biopsy will be performed in the absence of growth factor to assess changes in the marrow. In the extended treatment period, safety assessments will continue and participants will be allowed to receive any standard of care treatments for MDS. Patients will be followed for survival for an additional 60 months following the End of Study (EOS) visit.

Inclusion Criteria: • Diagnosis of MDS using the World Health Organization (WHO) classification for myeloid neoplasms as assessed during the screening period. • Per MDS International Prognostic Scoring System (IPSS), low or intermediate-1 risk MDS as assessed during the screening period. • Mean of the 2 platelet counts taken within 4 weeks prior to randomization must be: - ≤ 20 x 10^9/L, (with no individual count >30 x 10^9/L during the screening period), with or without history of bleeding associated with diagnosis of MDS, OR - ≤ 50 x 10^9/L, (with no individual count >60 x 10^9/L during the screening period) with a history of bleeding associated with the diagnosis of MDS. • Patients must be ≥18 and ≤ 90 years of age at time of informed consent. Patients between 85 and 90 years of age must have been diagnosed with MDS ≤ 5 years from study start. • Eastern Cooperative Oncology Group (ECOG) performance status of 0-2. • Adequate liver function, as evidenced by alanine aminotransferase (ALT) ≤ 3 times laboratory normal range, aspartate aminotransferase (AST) ≤ 3 times laboratory normal range and total bilirubin ≤ 2.0 times laboratory normal range. (Adequate liver function for patients with confirmed diagnosis of Gilbert's Disease evidenced by ALT ≤ 3 times laboratory normal range, and AST ≤ 3 times laboratory normal range.) • Serum creatinine concentration ≤ 2 mg/dl (≤176.8 μmol/L). • Bone marrow biopsy and aspirate with cytogenetics within 3 months of starting first dose of investigational product. • Written Informed Consent. Exclusion Criteria: • Have ever received any disease-modifying treatment for MDS. • Previously diagnosed with intermediate-2 or high risk MDS using the IPSS. • Prior history of leukemia, aplastic anemia, or other non-MDS related bone marrow stem cell disorder. • Prior history of hematopoietic stem cell transplantation. • Persistent peripheral blood monocytosis (≥ 3 months with an absolute monocyte count >1,000/μL) or known diagnosis of Chronic Myelomonocytic Leukemia per French-American-British Classification System for MDS (FAB) criteria. • Prior malignancy (other than in situ cervical cancer, non-melanoma skin cancer, or in situ carcinoma) unless treated with curative intent and without evidence of disease for ≥ 3 years before randomization. • Active or uncontrolled infections. • Unstable angina, congestive heart failure (New York Heart Association [NYHA] > class II), uncontrolled hypertension (diastolic >100 mmHg), uncontrolled cardiac arrhythmia, or recent (within 1 year) myocardial infarction. • History of arterial thrombosis (eg, stroke or transient ischemic attack) within the past year. • History of venous thrombosis that currently requires anti-coagulation therapy. • Received Interleukin (IL)-11 within 4 weeks of first dose of investigational product. • Have previously received any thrombopoietic growth factor. • Receipt of granulocyte-colony stimulating factor, (G-CSF), pegylated-G-CSF, or granulocyte macrophage-colony stimulating factor (GM-CSF) within 4 weeks of first dose of investigational product. • Planned receipt of peg-G-CSF or GM-CSF after first dose of investigational product. • Pregnant or breast feeding. • Patients of reproductive potential who are not using adequate contraceptive precautions, in the judgment of the investigator. Amgen recommends double barrier contraception is used for all applicable patients enrolled on this study. A double barrier method is defined as two methods of contraception, for example 2 actual barrier methods, or one actual barrier method and one hormonal method. • Patient has known sensitivity to any recombinant E coli-derived product (eg, Infergen®, Neupogen®, Somatropin, and Actimmune). • Previously enrolled into the 20060198 study or another romiplostim study. • Inability to comply with study procedures. • Patient currently is enrolled in or has not yet completed at least 30 days since ending other investigational device or drug study.