A Clinical Study of Gecacitinib Combined With Pegylated Interferon in Patients With PV

Inclusion criteria

• Aged ≥18 years
• Diagnosis of polycythemia vera (PV) according to the 2022 International Consensus Classification (ICC) criteria;
• Presence of at least one of the following disease manifestations, defined as:

a. Peripheral hematological abnormality: HCT ≥45% and/or PLT >400×10⁹/L and/or WBC ≥10×10⁹/L in the absence of phlebotomy; b. Presence of weight loss >10% over the past 6 months, night sweats, pruritus, or unexplained fever (>37.5°C); c. Progressive splenomegaly (previous splenomegaly with an increase >5 cm from baseline or newly developed splenomegaly); d. History of prior thrombotic or hemorrhagic events;

• No current plan for stem cell transplantation;
• Life expectancy >24 weeks;
• ECOG performance status 0-2;
• Able to swallow tablets;
• Patients without prior pegylated interferon or JAK inhibitor treatment; patients previously treated with hydroxyurea or therapeutic phlebotomy are eligible; patients who discontinued interferon for ≥6 months due to causes other than resistance or intolerance can be enrolled；
• No receipt of growth factors, colony-stimulating factors, thrombopoietin, or platelet transfusion within 2 weeks prior to screening, with platelet count ≥100×10⁹/L and ANC ≥1.5×10⁹/L;
• Adequate major organ function, defined asALT and AST ≤2.5 × ULN;DBIL and TBIL ≤2.0 × ULN;Serum creatinine ≤1.5 × ULN;
• Peripheral blood blasts 0%;
• Voluntary signed informed consent in accordance with ethics committee requirements;
• Able to comply with study and follow-up procedures.

Exclusion criteria

• Any significant clinical or laboratory abnormality considered by the investigator to affect safety assessment, such as:a. Uncontrolled diabetes (>250 mg/dL or >13.9 mmol/L);b. Hypertension that cannot be reduced to the following range despite combination antihypertensive therapy (systolic blood pressure <160 mmHg, diastolic blood pressure <100 mmHg);c. Peripheral neuropathy (Grade ≥2 according to NCI-CTCAE V5.0).
• History of congestive heart failure (Grade ≥3 according to NCI-CTCAE V5.0), uncontrolled or unstable angina pectoris or myocardial infarction, cerebrovascular accident, or pulmonary embolism within 24 weeks prior to screening.
• Patients who have undergone major surgery within 4 weeks prior to screening and have not fully recovered.
• Patients who have received PEG-IFN-α-2a or have a history of ³²P therapy within 5 weeks prior to screening.
• Patients diagnosed with primary immunodeficiency syndrome (e.g., X-linked agammaglobulinemia and common variable immunodeficiency).
• Patients with arrhythmic disorders requiring treatment at screening (except digoxin).
• Patients with any clinically symptomatic bacterial, viral, parasitic, or fungal infection requiring treatment at screening.
• Patients with active pulmonary infection indicated by chest CT examination at screening.
• Patients previously diagnosed with active tuberculosis infection, or subjects judged as suspected active tuberculosis infection by investigator at screening.
• Patients who have undergone splenectomy or have received splenic radiation therapy within 48 weeks prior to screening.
• Patients who are HIV positive, have active hepatitis B virus infection (HBsAg positive and HBV-DNA positive or above the normal reference range), or are anti-HCV antibody positive with HCV-RNA positive at screening.
• Patients with epilepsy or those using psychiatric or sedative medications at screening (except for Estazolam tablets).
• Female patients who are planning to become pregnant, are pregnant, or are breastfeeding, and patients who are unable to use effective contraception throughout the study period; male patients who do not use condoms during the administration period and for 2 days (approximately 5 half-lives) after the last dose.
• Patients with a history of malignancy within the past 5 years (except for cured basal cell carcinoma of the skin or carcinoma in situ of the cervix).
• Presence of other severe diseases that, in the investigator's opinion, may affect patient safety or compliance.
• Patients with suspected allergy to Gecacitinib Hydrochloride, interferon, or similar drugs.
• Patients with active alcohol or drug addiction that would interfere with their ability to comply with study requirements.
• Patients who have participated in another investigational new drug or medical device study and have received study drug or used study device within 12 weeks prior to screening.
• Patients who have used any immunomodulators, any immunosuppressants, ≥10 mg/day prednisone or equivalent corticosteroids, or are within 6 half-lives of such medications within 2 weeks prior to enrollment, whichever is longer.