A Single Arm, Open Label, Long Term Efficacy and Safety Study of Subcutaneous (SC) Romiplostim in Children with Immune Thrombocytopenia (ITP)

The TPO receptor agonist romiplostim is approved for use in adults with chronic ITP. The use of romiplostim in children with ITP has been evaluated in phase 1/2 and 3 studies. In this study, children with ITP will receive open label SC romiplostim for up to 3 years (y) Methods: Eligible children, recruited in 16 countries worldwide, had ITP for =6 months, =1 prior ITP therapy, and platelet (plt) count =30x109/L. Weekly SC dosing started at 1 mg/kg and was titrated in 1 mg/kg increments up to 10 mg/kg to target plt counts of 50 200x109/L. In patients in Europe, bone marrow aspirates and biopsies were obtained at baseline and after 1 or 2 y of exposure. The 1o endpoint was the of time in the first 6 months with a plt response, with response defined as a plt count =50x109/L without rescue medication use in the past 4 weeks (wk)  As of 15 Mar 2016, 147 patients enrolled; 145 received =1 romiplostim dose. At baseline, median (min max) age was 10 (2 17) y; 51% were female; 4% had prior splenectomy. Median (min max) ITP duration was 1.9 (0.5 12.3) y and plt count was 13 (2 168)x109/L. The median (Q1, Q3) of time with a plt response in the first 6 months patients were on study was 50% (0% 83.3% that of months 7 12 was 92% (33% 100% Over the course of the study, 80% (114/143) of patients had a plt response. The median (Q1, Q3) of time with an increase in plt counts =20x109/L above baseline was 60% (25% 84% The median dose increased to 10 mg/kg by wk 32 (Figure) Median (min max) treatment duration as of data cutoff was 25 (1 67) wk for a total exposure to date of 79 patient years; 67 (46% patients (or caregivers) self administered romiplostim. Median (min max) average weekly romiplostim dose was 6.1 (0.4 9.0) ug/kg. Thirty two patients (22% discontinued treatment for lack of efficacy (n 17) required other therapy (n 5) patient request (n 4) noncompliance (n 2) adverse event (AE) (n 2) (interstitial lung disease unrelated to treatment in a 15 y old boy and abdominal pain, vomiting, and headache related to treatment per investigator in a 9 y old girl) administrative decision (n 1) and investigator decision (n 1) After wk 12, median plt counts remained =50x109/L (Figure) Thirty four (23% patients received rescue medications. The most frequently reported AEs were headache (27.6% epistaxis (22.8% and nasopharyngitis (23% 15 (10.3% patients had serious AEs (SAEs) including epistaxis (n 4) petechiae (n 2) decreased plt count (n 2) and thrombocytopenia (n 2) A case of abdominal pain was the only SAE deemed treatment related by the investigator. Bleeding over the course of the study was seen in 52% of patients. CTCAE grade 3 bleeding was seen in 8 patients (6% and included epistaxis (n 5) ecchymosis (n 2) petechiae (n 2) and 1 case each of hematemesis, hematoma, SC hemorrhage, injection site hemorrhage, and mouth hemorrhage. No grade 4 or 5 bleeding was observed. One event of grade 2 phlebitis/thrombophlebitis in deep veins in the left arm lasting 14 days was reported in a 13 y old girl; plt counts were 40 70x109/L and the dose was 7 8 ug/kg during this time. Per investigator, this event was not serious or related to romiplostim. She was treated with antibiotics (oral amoxicillin/clavulanic acid and transdermal muciprocin) and continued romiplostim treatment as before. No neutralizing antibodies against romiplostim or TPO were identified. Of 30 patients with baseline bone marrow biopsies [50% female, median (min max) age 10.5 (6 12) y, ITP duration 3.1 (0.6 11) y] all had modified Bauermeister scores of grade 0 (no reticulin) or 1 (fine fibers) and bone marrow typical for ITP. Of these 30 patients, 21 had evaluable on study biopsies, with no increases in 2 or more grades, findings of collagen, or bone marrow abnormalities.  In this year 1 datacut of an ongoing open label study of romiplostim in children with ITP, the of time in the first 6 months with a platelet response was 50% with 80% of children having a platelet response at some point on study. The median romiplostim dose reached 10 mg/kg and there were no new safety signals. No effects of romiplostim were observed in the subset of patients with bone marrow biopsies. Future datacuts for year 2 and 3 in this study, the largest of romiplostim in children with ITP with 79 patient years of exposure to date, will provide more information on platelet response, dose requirements, and safety. Disclosures Grainger:Baxter: Honoraria, Research Funding; Amgen Inc. Honoraria; Novartis: Honoraria; GlaxoSmithKline: Honoraria.  Membership on an entity9s Board of Directors or advisory committees; Symphogen: Membership on an entity9s Board of Directors or advisory committees; Ligand: Membership on an entity9s Board of Directors or advisory committees, Research Funding; GSK: Consultancy, Honoraria, Membership on an entity9s Board of Directors or advisory committees, Research Funding;  Research Funding Membership on an entity9s Board of Directors or advisory committees, Research Funding; Prophylix Pharma: Membership on an entity9s Board of Directors or advisory committees, Research Funding; Novartis: Consultancy, Honoraria, Membership on an entity9s Board of Directors or advisory committees, Research Funding; Rigel Pharmaceuticals: Membership on an entity9s Board of Directors or advisory committees, Research Funding; Protalex: Membership on an entity9s Board of Directors or advisory committees, Research Funding; Physicians Education Resource: Speakers Bureau;  Membership on an entity9s Board of Directors or advisory committees;  Research  Research Funding; Sysmex: Research Funding; Amgen: Consultancy, Honoraria, Membership on an entity9s Board of Directors or advisory committees, UK ITP support association: Research Funding; National Organization for Rare Disorders: Research Funding; Imperial College BRC: Research  Received honoraria for speaking at educational meetings; GlaxoSmithKline: Consultancy, Honoraria, Other: Received honoraria for speaking at educational meetings Amgen Inc. Consultancy, Honoraria, Other: Received honoraria for speaking at educational meetings Tarantino: Research Funding; Novo Nordisk: Membership on an entity9s Board of Directors or advisory committees, Research Funding; Grifols: Membership on an entity9s Board of Directors or advisory committees, Research Funding, Speakers Bureau; Biogen: Membership on an entity9s Board of Directors or advisory committees, Speakers Bureau; Baxalta: Membership on an entity9s Board of Directors or advisory committees.  Honoraria, Membership on an entity9s Board of Directors or advisory committees, Other: Data safety monitoring boards Research Funding; Bayer Healthcare: Honoraria, Membership on an entity9s Board of Directors or advisory committees, Research Funding; Novo Nordisk: Honoraria, Membership on an entity9s Board of Directors or advisory committees; Pfizer: Honoraria, Membership on an entity9s Board of Directors or advisory committees;  Data safety monitoring boards Carpenter:Amgen Inc. Employment, Equity Ownership. Amgen Inc. Employment, Equity Ownership. Amgen Inc. Employment, Equity Ownership.