peginterferon α-2b injection for hydroxyurea resistant or intolerant et

Conditions: Essential Thrombocythemia

Summary: 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.


Eligibility criteria:
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.

Keywords: essential thrombocythemia peginterferon α-2b hydroxyurea resistant hydroxyurea intolerant