The purpose of this study is to evaluate the efficacy of romiplostim in the treatment of thrombocytopenia in pediatric patients with Immune thrombocytopenia purpura (ITP) as measured by durable platelet response.
Abstract Background: Immune thrombocytopenia (ITP) is an autoimmune disorder characterized by low platelet count levels and increased risk of bleeding. Symptomatic ITP in children can have a negative impact on their health-related quality of life (HRQoL) and increase their parents' burden. The effect of romiplostim (a thrombopoietin receptor agonist) on HRQoL and parental burden was evaluated in a phase 3 study of children with ITP. Methods: In a phase 3, randomized, double-blind, placebo-controlled study on efficacy and safety of romiplostim, children (<18 years) with ITP ≥ 6 months were randomized to weekly romiplostim or placebo for 24 weeks. The Kids' ITP Tool (KIT), a psychometrically-valid disease-specific HRQoL instrument (Klaassen Ped Blood Cancer2007), was administered to children and/or their parents at baseline, weeks 8, 16, and 25. All three KIT versions were used: Child self-report (to assess HRQoL of children ≥7 years), Parent/Proxy (to assess HRQoL of children <7 years via parent proxy), and Parent self-report (to assess impact of children's ITP on parental burden, for children of all ages). Each KIT version contains 26 items, summarized in a single score ranging from 0 to 100. Higher Child or Parent/Proxy KIT scores reflect better HRQoL of a child with ITP, and higher Parent KIT scores reflect less parental burden. Among efficacy endpoints of the study, overall platelet response was defined as achieving a weekly platelet response (platelet count ≥ 50 x 109/L) for ≥ 4 weeks during weeks 2 to 25, and durable platelet response was defined as achieving a weekly platelet response for ≥ 6 weeks during weeks 18 through 25. As exploratory endpoints of the study, changes in KIT scores from baseline to each follow-up assessment were estimated separately by treatment group (romiplostim or placebo) and by overall/durable platelet response status (yes/no). A mixed effects repeated measures analysis was conducted to estimate the difference in changes of Child and Parent KIT scores between romiplostim group and placebo group, controlling for baseline score, child's age, child's gender, and child's race (analysis of Parent/Proxy data was not conducted due to small sample size). Results: Sixty-two patients were enrolled and randomized to receive romiplostim (42 patients) and placebo (20 patients). Mean age was 9.6 years (range: 3-17, 16 patients <7 years), 57% were female, and 66% were white. Overall and durable platelet response was achieved by 34 and 24 patients, respectively. In general, changes in KIT scores by treatment group and overall platelet response status showed numerically greater and more often statistically significant improvements from baseline to each assessment for children receiving romiplostim (vs placebo) and for platelet responders (vs non-responders) (see Tables 1 and 2). Results based on durable response status were similar to those based on overall response status (data not shown). In the mixed effects analysis, greater improvement from baseline to week 8/16/25 on Parent KIT score was found in the romiplostim group vs placebo (by approximately 8 points, p-value<0.05); no significant difference was found between groups for Child KIT score. Conclusion: Romiplostim treatment is associated with reduced parental burden (measured by Parent KIT score). In some instances sample sizes were small for other KIT versions; therefore, results should be interpreted with caution. Table 1. Mean Change from Baseline in KIT Scores by Treatment Arm KIT Version Assessment week (sample size for romiplostim, placebo) Romiplostim Mean (95% CI) PlaceboMean (95% CI) Child 8 (n=28,11) 16 (n=27,10) 25 (n=28,11) 9 (4, 15) 11 (5, 16) 14 (7, 20) 9 (1, 18) 8 (-3, 20) 10 (-1, 20) Parent/Proxy 8 (n=8,2) 16 (n=8,3) 25 (n=9,3) -0.9 (-7, 5) -0.4 (-12, 11) 8 (2, 13) -40 (-108, 23) -1 (-86, 84) -10 (-80, 59) Parent 8 (n=40,16) 16 (n=39,17) 25 (n=37,16) 13 (10, 17) 15 (10, 21) 18 (12, 23) 4 (-6, 13) 12 (4, 20) 13 (4, 22) Table 2. Mean Change from Baseline in KIT Scores by Overall Platelet Response KIT Version Assessment week (sample size for responders, non-responders) Responders Mean (95% CI) Non RespondersMean (95% CI) Child 8 (n=23,17) 16 (n=22,16) 25 (n=23,16) 11 (4, 18) 11 (4, 18) 16 (8, 24) 4 (-5, 12) 8 (1, 15) 8 (1, 15) Parent/Proxy 8 (n=7,5) 16 (n=8,5) 25 (n=8,6) 0.9 (-7, 9) 4 (-10, 18) 9 (1, 17) -15 (-44, 13) -4 (-31, 22) -3 (-23, 17) Parent 8 (n=30,26) 16 (n=30,26) 25 (n=29,24) 11 (7, 14) 14 (7, 20) 17 (10, 24) 10 (3, 18) 15 (9, 21) 15 (9, 21) Disclosures Mathias: Amgen: Research Funding. Li:Amgen: Employment, Other: Stock Ownership. Eisen:Amgen Inc: Employment, Other: stock ownership. Carpenter:Amgen: Employment, Other: Stock Ownership. Crosby:Amgen: Research Funding. Blanchette:Bayer Healthcare: Honoraria, Membership on an entity's Board of Directors or advisory committees, Research Funding; Octapharma: Other: Data Safety Monitoring Board; Pfizer: Honoraria, Membership on an entity's Board of Directors or advisory committees; Baxter Corporation: Honoraria, Membership on an entity's Board of Directors or advisory committees, Other: Data Safety Monitoring Board, Research Funding; Novo Nordisk: Honoraria, Membership on an entity's Board of Directors or advisory committees.
<b>BACKGROUND: </b>The thrombopoietin receptor agonist romiplostim could be an effective treatment in symptomatic children with persistent or chronic immune thrombocytopenia. We aimed to assess whether romiplostim is safe and effective in children with immune thrombocytopenia of more than 6 months' duration.<b>METHODS: </b>In this phase 3 double-blind study, eligible participants were children with immune thrombocytopenia aged 1 year to 17 years and mean platelet counts 30 × 10(9)/L or less (mean of two measurements during the screening period) with no single count greater than 35 × 10(9)/L, and were recruited from 27 sites in the USA, Canada, and Australia. Participants were randomly assigned (2:1) through the interactive voice response system to receive weekly romiplostim or placebo for 24 weeks stratified by age (1 year to <6 years, 6 years to <12 years, 12 years to <18 years), adjusting the dose weekly from 1 μg/kg to 10 μg/kg to target platelet counts of 50-200 × 10(9)/L. Patients and investigators were blinded to the treatment assignment. The primary analysis included all randomised patients and the safety analysis included all randomised patients who received at least one dose of investigational product. The primary endpoint, durable platelet response, was defined as achievement of weekly platelet responses (platelet counts ≥50 × 10(9)/L without rescue drug use in the preceding 4 weeks) in 6 or more of the final 8 weeks (weeks 18-25). This study is registered with ClinicalTrials.gov, NCT 01444417.<b>FINDINGS: </b>Between Jan 24, 2012, and Sept 3, 2014, 62 patients were randomly assigned; 42 to romiplostim and 20 to placebo. Durable platelet response was seen in 22 (52%) patients in the romiplostim group and two (10%) in the placebo group (p=0·002, odds ratio 9·1 [95% CI 1·9-43·2]). Durable platelet response rates with romiplostim by age were 38% (3/8) for 1 year to younger than 6 years, 56% (10/18) for 6 years to younger than 12 years, and 56% (9/16) for 12 years to younger than 18 years. One (5%) of 19 patients in the placebo group had serious adverse events compared with 10 (24%) of 42 patients in the romiplostim group. Of these serious adverse events, headache and thrombocytosis, in one (2%) of 42 patients in the romiplostim group, were considered treatment related. No patients withdrew due to adverse events.<b>INTERPRETATION: </b>In children with chronic immune thrombocytopenia, romiplostim induced a high rate of platelet response with no new safety signals. Ongoing romiplostim studies will provide further information as to long-term efficacy, safety, and remission in children with immune thrombocytopenia.<b>Funding: </b>Amgen Inc.
<b>BACKGROUND: </b>Chronic immune thrombocytopenia (ITP) in children can negatively impact their health-related quality of life (HRQoL) and impose a burden on their parents. This study sought to examine the effect of romiplostim on HRQoL and parental burden in children with primary ITP.<b>Procedure: </b>This was a phase 3, randomized, double-blind, placebo-controlled study. Children aged <18 years with ITP ≥6 months were randomly assigned to receive romiplostim or placebo for 24 weeks. The Kids' ITP Tool (KIT) was used to measure HRQoL and was administered to patients and/or their parents at baseline and weeks 8, 16, and 25. Mean KIT scores at each assessment and mean changes in KIT scores from baseline were calculated overall by treatment group and platelet response status. Psychometric properties of the KIT were evaluated and the minimally important difference (MID) was estimated for different KIT versions.<b>RESULTS: </b>Sixty-two patients (42 romiplostim and 20 placebo) were enrolled. Changes in KIT scores by treatment group showed numerically greater and more often statistically significant improvements from baseline to each assessment for children receiving romiplostim versus placebo. Mixed-effects analysis demonstrated statistically significantly greater reduction in parental burden from baseline in the romiplostim group versus placebo. Ranges for the MID were estimated as 9-13 points for the Child Self-Report version and 11-13 points for the Parent Impact version.<b>CONCLUSIONS: </b>The treatment with romiplostim may be associated with improved HRQoL in children with primary ITP and reduced burden to their parents.
The purpose of this study is to evaluate the efficacy of romiplostim in the treatment of thrombocytopenia in pediatric patients with Immune thrombocytopenia purpura (ITP) as measured by durable platelet response.
