This trial adopts an open, randomized, parallel controlled, multicenter clinical trial design planning to enroll patients with polycythemia vera who are resistant/intolerant to hydroxyurea or interferon. The study divided into two stages: dose exploration stage: three dose groups are set, with three subjects in each group, totally nine subjects in each group; Dose expansion stage: Based on the safety, efficacy, and pharmacokinetic results of the comprehensive dose exploration stage, 2-3 dose groups are planned to be selected for dose expansion stage.
Age >= 18 years old and gender not limited when signing the informed consent form;
Diagnosed as PV according to WHO standards (2016 edition), and resistant/intolerant to hydroxyurea or interferon treatment (refer to attachments 1 and 2);
When screening, the peripheral blood blasts are 0%;
Individuals with allergies or suspected allergies to the test drug and its excipients;
The toxic reactions of previous anti-cancer treatments have not recovered to grade 1 or below (excluding hair loss, blood routine and blood biochemical indicators refer to inclusion criteria 4 and 5), or have not fully recovered from previous surgeries (having undergone major surgery within 4 weeks);
In addition to PV, any other myeloproliferative neoplasms (MPN), including post polycythemia vera myelofibrosis (PPV-MF), may also be present;
Any active infections that require systemic treatment (oral, intravenous, subcutaneous, intramuscular, etc.) during screening;
Sequential
Flonoltinib 75mg
DrugFlonoltinib Maleate Tablet 75mg, oral administration, once daily, given on an empty stomach for 8 consecutive weeks of treatment.
Flonoltinib 100mg
DrugFlonoltinib Maleate Tablet 100mg, oral administration, once daily, given on an empty stomach for 8 consecutive weeks of treatment.
Flonoltinib 125mg
DrugFlonoltinib Maleate Tablet 125mg, oral administration, once daily, given on an empty stomach for 8 consecutive weeks of treatment.
Extended Phase Dose Group
DrugBased on the safety, efficacy, and pharmacokinetic results of the comprehensive dose exploration stage
The proportion of subjects who achieved HCT control
Achieve HCT\<45% without undergoing Phlebotomy or apheresis treatmen
The proportion of subjects who achieved complete hematological remission
Without undergoing venous bloodletting or apheresis, achieve HCT\<45%, PLT \<= 400×10\^9/L, and WBC\<10×10\^9/L
The duration of HCT control
The duration of HCT control (defined as the time elapsed from the date when HCT control was first recorded from the start of Day 29 treatment to the date when HCT increased to \>= 45%)
Changes in the total symptom score of MPN-SAF TSS scale
The MPN-SAF-TSS is used to assess the symptom burden of patients with myeloproliferative neoplasms. The questionnaire also reflects the quality of life of patients to a certain extent. During the diagnosis and treatment process, the MPN-10 questionnaire includes 10 sub symptoms (fatigue, early satiety, abdominal discomfort, poor activity, lack of concentration, night sweats, skin itching, bone pain, fever, and weight loss). Each item is graded from 0 (none) to 10 (heaviest), with a total score of 0-100 points. The higher the total score, the heavier the symptom burden.
Proportion of subjects who did not experience thrombosis or bleeding events
Proportion of subjects who did not experience thrombosis or bleeding events at the end of treatment in weeks 28 and 52
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