A Phase 3, Randomized, Double-Blind, Placebo-Controlled Study to Determine the Safety and Efficacy of Romiplostim in Children with Immune Thrombocytopenia (ITP)

Abstract

Introduction: Approximately 20% of children diagnosed with ITP have chronic thrombocytopenia, some requiring immunosuppressive treatments. The TPO receptor agonist romiplostim could be a treatment option for symptomatic children with ITP. Methods: In this phase 3, double-blind study, children with ITP for ≥6 months were randomized to weekly romiplostim or placebo (2:1) for 24 weeks, with the dose adjusted weekly from 1-10 μg/kg to target platelet counts of 50-200×109/L. Platelet response was defined as platelet counts ≥50×109/L any week of weeks 2-25 (excluding 4 weeks after rescue medication use). The 1° endpoint, durable platelet response, was defined as ≥6 weekly platelet responses during the final 8 weeks, weeks 18-25. Overall platelet response was defined as ≥4 weekly platelet responses during weeks 2-25. Antibodies to romiplostim or TPO were assayed at baseline and weeks 12 and 25. The Kid9s ITP Tool (KIT), in which higher scores reflect improved quality of life, was administered to children and their parents. Results: Patients (n = 62) had median (range) age 9.5 (3-17) years, ITP duration 2.1 (0.5-10.7) years, and baseline platelet counts 18 (1-94) × 109/L; 44% were male. Sixty-six percent of patients were Caucasian, 13% African American, 8% Asian, and 15% other. For the 1° endpoint, measured in the final 8 weeks after 16 weeks of dose titration, rates of durable platelet response were romiplostim: 52% and placebo: 10% (p Conclusions: In children with symptomatic ITP of ≥6 months duration, romiplostim was effective in inducing high rates of durable and overall platelet responses. There were no new safety signals. By the final 8 weeks of the study, noncutaneous bleeding was decreased with romiplostim. Romiplostim may be a viable treatment option for children with symptomatic chronic ITP. Disclosures Tarantino:Grifols: Honoraria, Membership on an entity9s Board of Directors or advisory committees, Research Funding, Speakers Bureau; BPL: Membership on an entity9s Board of Directors or advisory committees; Baxter: Membership on an entity9s Board of Directors or advisory committees, Research Funding; Novo Nordisk: Membership on an entity9s Board of Directors or advisory committees, Research Funding, Speakers Bureau; Octapharma: Membership on an entity9s Board of Directors or advisory committees; Pfizer: Membership on an entity9s Board of Directors or advisory committees; Cangene: Research Funding; UptoDate, Inc.: Patents & Royalties: royalties; Amgen, Inc: Membership on an entity9s Board of Directors or advisory committees. Off Label Use: Romiplostim is indicated for use in adults with chronic immune thrombocytopenia who have had an insufficient response to corticosteroids, immunoglobulins, or splenectomy. The use of romiplostim in children with ITP is investigational.. Bussel:Amgen, Cangene, GlaxoSmithKline (GSK), Genzyme, IgG of America, Immunomedics, Ligand, Eisai, Shionogi and Sysmex: Research Funding; Portola: Consultancy; Amgen, GSK, Ligand, Shionogi, and Eisai: Other: Advisory board. Blanchette:Baxter Corporation, Bayer Healthcare, Novo Nordisk, Pfizer: Honoraria; Baxter Corporation, Bayer Healthcare: Research Funding; Baxter Corporation, Bayer Healthcare, Novo Nordisk, Pfizer; Data Safety Monitoring Board Baxter Corporation, Octapharma: Other: Advisory board; Baxter Corporation, Octapharma: Other: Data Safety Monitoring Board. Morales:CSL Behring: Membership on an entity9s Board of Directors or advisory committees; Baxter: Membership on an entity9s Board of Directors or advisory committees. Carpenter:Amgen Inc.: Employment, Other: Stockholder. Nie:Amgen Inc.: Employment, Other: Stockholder. Eisen:Amgen Inc.: Employment, Other: Stockholder.