Evaluation of Romiplostim In a Randomized Placebo-Controlled Phase 3 Study of a Japanese Population with Chronic Immune Thrombocytopenia (ITP).

Abstract Abstract 3704 Introduction: Chronic immune thrombocytopenia (ITP) is an autoimmune disorder characterized by both increased platelet destruction and decreased platelet production. Romiplostim increases platelet counts by binding and activating the thrombopoietin receptor. Romiplostim has been approved for the treatment of adult ITP in the United States, Europe, Canada, and Australia. This study evaluated dosing, efficacy, and safety in a Japanese population of adults with ITP. Methods: This phase 3 study was placebo-controlled, double-blind, and randomized 2:1 (romiplostim:placebo). Patients were eligible for the study if they were Japanese patients with ITP diagnosed at least 6 months before the initial screening, were aged ≥ 20 years, and were H pylori negative or had received at least 1 treatment for H pylori eradication. Patients were stratified by splenectomy status (yes or no). After a 3-week evaluation period, patients were treated for 12 weeks with a weekly subcutaneous injection of either romiplostim or placebo. The starting dose was 3 mcg/kg with dose adjustments to a maximum of 10 mcg/kg to achieve a platelet count within the target range of ≥ 50 to ≤ 200 × 109/L. Patients were monitored posttreatment until their platelet count dropped to ≤ 50 × 109/L or for a maximum of 12 weeks. The primary endpoint was number of weeks with platelet response (platelet count ≥ 50 × 109/L). Results: Thirty-four patients enrolled (22 romiplostim, 12 placebo), 24 (71%) were female, the median (range) age was 55 (44 - 64) years, and the median (range) baseline platelet count was 19 (3 – 32) × 109/L. Patients had received a median of 4 (1 – 19) prior ITP therapies, and 15 (44%) had previously undergone a splenectomy; 23 (68%) patients were receiving concurrent ITP therapy at baseline. All patients completed the study. Romiplostim demonstrated superiority to placebo on weekly platelet response, incidence of increase in platelet count ≥ 20 × 109/L from baseline, change from baseline in mean of last 4 platelet counts during week 2 to week 13, and number of weeks with platelet counts within the target range (Table 1), and 16 (73%) romiplostim patients had platelet counts ≥ 200 × 109/L. Twenty-one (95%) patients in the romiplostim group had a platelet response with a median time of 1 week until first response. Results for weekly platelet response were comparable irrespective of splenectomy status and baseline concurrent ITP therapy. Two (17%) patients in the placebo group achieved a platelet response. In romiplostim-treated patients, posttreatment platelet counts remained > 50 × 109/L for 8 weeks in one and for 12 weeks in another. The mean weekly dose of romiplostim for the study was 2.6 mcg/kg compared with the dose range of 3–4 mcg/kg in prior phase 3 studies (Kuter et al. Lancet. 2008;371:395–403). There was a low incidence of rescue medication use in the study (Table 1). The adverse events profile was comparable to that seen in non-Japanese studies. Patients in both treatment groups experienced similar proportions of adverse events (91% romiplostim, 92% placebo). Adverse events with > 10% higher frequency in the romiplostim group than placebo group) were (romiplostim, placebo) nasopharyngitis (41%, 17%), headache (32%, 17%), peripheral edema (18%, 0%), back pain (14%, 0%), and pain in extremity (14%, 0%). Significant (≥ grade 3) bleeding events occurred in 1 patient in the romiplostim group (subarachnoid hemorrhage) and 1 patient in the placebo group (subarachnoid hemorrhage, cerebral hemorrhage, and gastrointestinal hemorrhage). There were no adverse events of bone marrow reticulin, thrombosis, or detection of neutralizing antibodies. Conclusion: Romiplostim significantly increased and maintained platelet counts and was well-tolerated in a Japanese ITP population. Disclosures: Tomiyama: Kyowa Hakko Kirin Co.: Speakers Bureau; GlaxoSmithKline: Speakers Bureau. Kurokawa:Novartis: Consultancy; Shionogi & Co., Ltd.: Consultancy. Wei:Amgen Inc.: Employment, Equity Ownership. Lizambri:Amgen Inc.: Employment, Equity Ownership.