Ropeginterferon Alfa-2b (P1101) vs. Anagrelide in Essential Thrombocythemia Patients With Hydroxyurea Resistance or Intolerance

This is a Phase 3 open-label, multicenter, randomized, active-controlled study designed to compare the efficacy and safety and tolerability of P1101 compared with ANA after 12 months of treatment as second-line therapy for subjects with ET who have had a suboptimal or failed response to HU.

Inclusion Criteria: 1. Male or female subjects ≥18 years old 2. Subjects diagnosed with high-risk ET (either older than 60 years and JAK2V617-positive at screening, or having disease-related thrombosis or hemorrhage in the past), diagnosed according to the World Health Organization (WHO) 2016 criteria 3. Subjects have received prior HU for ET, while the washout between the last dose of HU and randomization should not be shorter than 7 days 4. Interferon treatment-naïve, or anti-P1101 binding antibody negative at screening and the washout between last dose of interferon and randomization should not be shorter than 14 days. 5. Documented resistance/intolerance to prior HU for ET, referencing modified ELN criteria (Barosi, et al, 2007), whereby at least one of the following criteria is met: Platelet count \>600 x 10\^9/L at ≥2 g/day (or ≥2.5 g/day if subject body weight \>80 kg) or maximally tolerated dose if \400 x 10\^9/L and WBC count \400 x 10\^9/L and hemoglobin (HGB) \450 x 10\^9/L at any dose and any duration of HU. The actual dose and duration of HU must be recorded on the eCRF. Moreover, if patient received one dose of HU, the reason why subject was judged to be HU resistance/intolerance must be recorded on the eCRF. 6. Platelets \>450 x 10\^9/L at screening 7. WBC \>10 x 10\^9/L at screening 8. HGB ≥11 g/dL at screening for males and 10 g/dL at screening for females 9. Neutrophil count ≥1.0 x 10\^9/L at screening 10. Adequate hepatic function defined as bilirubin ≤1.5 x upper limit normal (ULN), prothrombin time (PT) (international normalized ratio, INR) ≤1.5 x ULN, albumin \>3.5 g/dL, alanine aminotransferase ≤2.0 x ULN, aspartate aminotransferase ≤2.0 x ULN at screening 11. Creatinine clearance ≥40 mL/min (by Cockcroft-Gault equation) 12. Males and females of childbearing potential, as well as all women \