This is a multicenter, randomized, open-label Phase 2 clinical study. It is aimed to enroll 27 essential thrombocytopenia (ET) patients who are resistant to or intolerant of hydroxyurea(HU). Eligible patients will be randomized to receive either Peginterferon α-2b 135 mcg or Peginterferon α-2b 180 mcg at a ratio of 1:2, and all subjects will go through a target treatment period (Weeks 1 ~ Week 48), an extension treatment period (Weeks 49 ~ Week 96) and a follow-up period (Weeks 97 ~ Week 100). Pharmacokinetics, safety, efficacy will be evaluated.

Inclusion Criteria:

• Male or female subjects, aged greater or equal to 18 years old at screening;

• Subjects diagnosed as high-risk ET according to the World Health Organization (WHO) 2016 criteria：1) who is older than 60 years and JAK2V617F positive at screening, 2) or who previously suffered from disease-related thrombosis or hemorrhage;

• Subjects who have previously received HU for ET, and the time interval between the last HU dose and the first dose of the study drug should not be less than 7 days;

• Interferon treatment-naïve, and for those who have previously received interferon the the time interval between the last dose of interferon and randomization should not be less than 1 month;

• Patients with confirmed hydroxyurea resistance or intolerant, as at least one of the following criteria is met:

  1. Platelet count remain greater than 600×10^9 /L after at least 3 months of HU treatment at a dose ≥2g/d (dose ≥2.5 g/d if subject weight > 80 kg);
  2. Platelet count greater than 400*10^9/L while white blood cell (WBC) count lower than 2.5*10^9/L, or platelet count greater than 400*10^9 /L while hemoglobin lower than 100 g/L at any dose of HU;
  3. Presence of HU-related toxicities at any dose of HU: e.g. ulcers in legs, or any unacceptable skin mucosal manifestations or fever;

• Platelet counts > 450*10^9/L at screening;

• Neutrophil count ≥1.0*10^9/L at screening;

• Haemoglobin ≥11 g/dL at screening for males and 10 g/dL for females at screening;

• There is no serious function damage in liver and kidney: total bilirubin ≤1.5 upper limit of normal (ULN), alanine aminotransferase≤2.0 ULN, aspartate aminotransferase≤2.0 ULN, prothrombin time is prolonged by less than 4 seconds, Creatinine clearance ≥50 mL/min (according to Cockcroft-Gault formula) at screening;

• Both male and female subjects must agree take an appropriate contraceptive method, including:

  1. Male subjects: must agree to use reliable contraception from inform consent until 6 months following the last dose of the study drug.
  2. Female subjects: Must meet at least one of the following conditions:

  i) Women without childbearing potential; ii) Women of childbearing potential: no pregnant or breastfeed, negative in blood pregnancy test within 4 days prior to the first dosing, and must agree to use reliable contraception from inform consent until 6 months following the last dose of the study drug;

• Subjects understand the objective, characteristic, method and possible adverse reactions of the study, voluntarily participate in this study, and sign informed consent.

Exclusion Criteria:

• History of any other myeloproliferative tumors, or evidence of the presence of any other myeloproliferative tumors;
• Contraindications or hypersensitivities to interferons of any of its excipients;
• Severe medical conditions or serious comorbidities that the investigators determined could jeopardize the safety or protocol adherence, e.g. New York Heart Association [NYHA] Class III-IV, congestive heart failure, symptomatic arrhythmias，pulmonary hypertension;
• History of major organ transplantation;
• Documented autoimmune disease or history of autoimmune disease at screening, e.g. medication un-controlled thyroid dysfunction, autoimmune hepatitis, idiopathic thrombocytopenic purpura, scleroderma, psoriasis, or any autoimmune arthritis;
• Clinically significant pulmonary infiltration, infectious pneumonia, and non-infectious pneumonia at screening that, in the investigator's opinion, would jeopardize the safety of the subject or their compliance with the protocol;
• Infection with systemic clinical manifestations at screening, e.g., bacteria, fungi, human immunodeficiency virus, excluding hepatitis B and/or C;
• Evidence of severe retinopathy, e.g., cytomegalovirus retinitis, symptomatic macular degeneration, or clinically significant eye disease, e.g. due to diabetes mellitus or hypertension;
• Diagnosed clinically significant depression or a history of depression and, in the investigator's opinion, previous suicide attempts or at any risk of suicide at screening;
• Diagnosed clinically significant neurological disease or a history of clinically significant neurological disease, except for a history of stable cerebral thrombosis or cerebral hemorrhage;
• History of any malignancy within 5 years (except stage 0 chronic lymphocytic leukemia, basal cell carcinoma, squamous cell carcinoma, and superficial melanoma);
• A history of alcohol or drug abuse within 1 year;
• Have used any investigational drug within 4 weeks prior to first dose of investigational drug, or not recovered from the effects of prior investigational drug administration;
• Other situations that, in the investigator's opinion, not appropriate for inclusion.