Safety and Efficacy Study of Romiplostim to Treat ITP in Pediatric Subjects

• incidence of overall platelet response defined as subjects who achieve a platelet count ≥ 50 x 10^9/L at a minimum of 4 times during weeks 2 to 25 of the treatment period [ Time Frame: 24 weeks ] [ Designated as safety issue: No ]
• number of weekly platelet counts ≥ 50 x 10^9/L during weeks 2 to 25 of the treatment period [ Time Frame: 24 weeks ] [ Designated as safety issue: No ]
• incidence of rescue ITP medications used [ Time Frame: 25 weeks ] [ Designated as safety issue: No ]
• number of composite bleeding episodes defined as clinically significant bleeding events or the use of a rescue medication to prevent a clinically significant bleeding event during weeks 2 to 25 of the treatment period [ Time Frame: 24 weeks ] [ Designated as safety issue: Yes ]
• incidence of adverse events, including thromboembolic events and hematologic malignancies, clinically significant changes in laboratory values and the incidence of antibody formation [ Time Frame: 25 weeks ] [ Designated as safety issue: Yes ]

The purpose of this study is to evaluate the efficacy of romiplostim in the treatment of thrombocytopenia in pediatric subjects with Immune Thrombocytopenia Purpura (ITP) as measured by durable platelet response.

• Idiopathic Thrombocytopenic Purpura
• Thrombocytopenia
• Thrombocytopenia in Pediatric Subjects With Immune (Idiopathic) Thrombocytopenic Purpura (ITP)
• Thrombocytopenia in Subjects With Immune (Idiopathic) Thrombocytopenic Purpura (ITP)
• Thrombocytopenic Purpura

• Drug: romiplostim
  The starting dose of romiplostim is 1 µg/kg administered weekly by subcutaneous injection. Subjects will return to the clinic weekly to provide platelet counts and undergo dose titrations under the supervision of the treating physician. Weekly dose increases will continue in increments of 1 µg/kg up to a maximum dose of 10 µg/kg in an attempt to reach a target platelet count of ≥ 50 x 10^9/L. Dose adjustment will be allowed during the treatment period to maintain a platelet count between ≥ 50 x 10^9/L and ≤ 200 x 10^9/L.
• Drug: Placebo
  The starting dose is 1 µg/kg administered weekly by subcutaneous injection. Subjects will return to the clinic weekly to provide platelet counts and undergo dose titrations under the supervision of the treating physician. Weekly dose increases will continue in increments of 1 µg/kg up to a maximum dose of 10 µg/kg in an attempt to reach a target platelet count of ≥ 50 x 10^9/L. Dose adjustment will be allowed during the treatment period to maintain a platelet count between ≥ 50 x 10^9/L and ≤ 200 x 10^9/L.

• Experimental: 40 thrombocytopenic (as defined per protocol) subjects
  Intervention: Drug: romiplostim
• Placebo Comparator: 20 thrombocytopenic (as defined per protocol) subjects
  Intervention: Drug: Placebo

Inclusion Criteria:

• Diagnosis of primary ITP according to the ASH Guidelines at least 6 months prior to screening, regardless of splenectomy status
• Subject must be refractory to a prior ITP therapy, having relapsed after at least 1 prior ITP therapy, or ineligible for other ITP therapies; prior therapy includes first-line therapies
• Age ≥ 1 year and < 18 years at the time of providing informed consent
• The mean of 2 platelet counts taken during the screening period must be ≤ 30 x 10^9/L with neither count > 35 x 10^9/L
• A serum creatinine concentration ≤ 1.5 times the laboratory normal range (for each age category) during the screening period
• Adequate liver function; serum bilirubin ≤ 1.5 times the laboratory normal range during the screening period;AST and ALT ≤ 3.0 times the laboratory normal range during the screening period
• Hemoglobin > 10.0 g/dL during the screening period
• Subject and/or subject's legally acceptable representative has provided informed consent prior to any study-specific procedure; subject has provided assent, where required

Exclusion Criteria:

• Known history of a 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
• Known active or prior malignancy except adequately treated basal cell carcinoma
• Known history of congenital thrombocytopenia
• Known history of hepatitis B, hepatitis C, or HIV
• Known history of H. pylori by urea breath test or stool antigen test within 6 months of enrollment or successfully treated with no evidence of infection
• Known history of systemic lupus erythematosus, evans syndrome, or autoimmune neutropenia
• Known history of antiphospholipid antibody syndrome or positive for lupus anticoagulant
• Known history of disseminated intravascular coagulation, hemolytic uremic syndrome, or thrombotic thrombocytopenic purpura
• Previous history of venous thromboembolism or thrombotic events
• Previous use of romiplostim, PEG-rHuMGDF, Eltrombopag, rHuTPO or any platelet producing agent
• Rituximab (for any indication) or 6-MP within 14 weeks before the screening visit, or anticipated use during the time of the proposed study
• Splenectomy within 4 weeks of the screening visit
• All hematopoietic growth factors including IL-11 (oprelvekin) within 4 weeks before the screening visit
• Alkylating agents within 8 weeks before the screening visit or anticipated use during the time of the proposed study
• Vaccinations known to decrease platelet counts within 8 weeks before the screening visit
• Known hypersensitivity to any recombinant E coli-derived product (eg, Infergen, Neupogen, Somatropin, and Actimmune)
• Other criteria may apply