Context: Low-dose aspirin with hydroxyurea (HU) is first-line therapy in high-risk essential thrombocythemia (ET). However, many patients become HU-intolerant or -resistant. Anagrelide (ANA) and peginterferon alfa-2a are second-line options for high-risk ET patients. Objective: To assess the long-term safety and efficacy of P1101 compared to ANA as a second-line option for ET patients with HU intolerance or resistance Design: Phase 3, open-label, multicenter, randomized, active-controlled study to assess the efficacy, safety, tolerability after 12 months of treatment with a 28-day screening and follow-up, for a total trial duration of 14 months. Study visits are scheduled every 2 weeks. Treatments are assigned in a 1:1 ratio and stratified according to baseline platelet count, TSS, and country. Setting: Results will impact the treatment of patients with high-risk ET. Patients or Other Participants: Subjects diagnosed with high-risk ET (either >60 years and JAK2V617F-positive at screening or having thrombosis or hemorrhage in the past) and according to WHO 2016 criteria, documented resistance/intolerance to HU, and IFN naïve are eligible to participate. Key exclusion criteria include pregnant females, autoimmune disease, and history or presence of clinically significant depression. Interventions: P1101 will be administered subcutaneously every 2 weeks at the starting dose of 250 mcg (Week 0), 350 mcg (Week 2), and target optimal dose of 500 mcg (Week 4) for the remainder of the treatment period. ANA will be dosed according to local country label. All subjects will receive low-dose aspirin unless contraindicated. Main Outcome Measures: The primary endpoint is durable modified European LeukemiaNet composite response at 9 and 12 months from start of dosing. Results: The study involves 58 sites across the world. To date 101 patients have been randomized (45 men and 56 women). The mean and median age at recruitment was 58.9 years (SD: 13.4) and 62 years (range 21 to 80 years). 79 subjects had a TSS <20. Study is overseen by a DSMB and the need to intervene was not identified. Conclusions: Results will provide the first evidence of a second-line ET treatment by comparing P1101 with the only approved treatment option, ANA. This study is sponsored by PharmaEssentia USA.
ASJC Scopus subject areas
- Cancer Research