A Clinical Trial of Flonoltinib Maleate for Intermediate or High-Risk Myelofibrosis

Chengdu Zenitar Biomedical Technology

Status and phase: Begins enrollment in 1 month; Phase 3

Conditions: MF

Treatments: Drug: Flonoltinib 75mg; Drug: Ruxolitinib Phosphate

Study type: Interventional

Funder types: Industry

Identifiers

NCT07317700

FMF-03

Details and patient eligibility

About

This trial adopts a multicenter, open label, positive drug parallel controlled clinical trial design, with a planned enrollment of approximately 105 participants in the MF trial. Successful trial participants were selected and assigned to either the experimental group or the control group in a 2:1 stratified manner, with the stratification factor being the Dynamic International Prognostic Scoring System (DIPSS) prognostic grading criteria. Continuously take the test drug/control drug until it meets the withdrawal criteria.

Enrollment: 105 estimated patients

Sex: All

Ages: 18 to 80 years old

Volunteers: No Healthy Volunteers

Inclusion criteria

1. Age range of 18-80 years old (including threshold), gender not limited;
2. Patients diagnosed with primary myelofibrosis (PMF) according to WHO criteria (2016 edition) or patients diagnosed with post polycythemia vera myelofibrosis (PPV-MF) or post thrombocytopenia myelofibrosis (PET-MF) according to IWG-MRT criteria;
3. Expected survival period greater than 24 weeks;
4. ECOG score 0-2 points;
5. Splenomegaly: Palpation of the splenic margin reaching or exceeding 5cm below the rib (distance from the intersection of the left clavicle midline and left rib margin to the farthest point of the spleen); Or due to physical reasons (such as obesity), it may not be palpable, but MRI/CT spleen evaluation during screening confirms a volume of >= 450 cm^3;
6. Within 7 days prior to randomization, the main organ functions were generally normal, meeting the following criteria: ALT and AST <= 2.5 × ULN; TBIL<=2.0×ULN； Serum creatinine <=1.5 × ULN or serum creatinine clearance rate (Ccr)>50 mL/min; INR, PT, and APTT <= 1.5 × ULN;
7. Can understand and voluntarily sign an informed consent form.

Exclusion criteria

1. The toxic reactions of previous anti-cancer treatments have not recovered to grade 1 or below (excluding hair loss), or have not fully recovered from previous surgeries;
2. Allergy to experimental drugs and their excipients;
3. For any significant clinical and laboratory abnormalities, the researchers believe that they affect the safety evaluators, such as: a. uncontrollable diabetes - fasting blood glucose>250 mg/dL (13.9 mmol/L), b. hypertension and cannot be reduced to the following range after treatment with two or more antihypertensive drugs (systolic blood pressure<160 mmHg, diastolic blood pressure<100 mmHg), c. peripheral neuropathy;
4. Patients with a history of congestive heart failure (NYHA grade III or above), unstable angina or myocardial infarction, cerebrovascular accidents or thromboembolism within the first 6 months of screening;
5. Individuals with impaired cardiac function (those with ejection fraction<45% detected by echocardiography, congenital ventricular arrhythmia, QTcF>450 ms on electrocardiogram (males), QTcF>470 ms on electrocardiogram (females), or those with arrhythmia requiring treatment at the time of screening);
6. Patients with congenital or acquired bleeding disorders or unstable thrombotic diseases requiring anticoagulant therapy;
7. Any active infection requiring systemic treatment (oral, intravenous, subcutaneous, intramuscular, etc.) within the first 14 days of randomization;
8. Active infection of hepatitis B virus (HBV) or hepatitis C virus (HCV), except for the following patients: a) HBV infection: patients who are positive for hepatitis B surface antigen (HBsAg) or hepatitis B core antibody (HBcAb) and undergo peripheral blood HBV-DNA testing, with the lower limit of HBV-DNA detection value (i.e. the upper limit of normal value in the laboratory of each research center) can be enrolled; If the baseline HBsAg is positive, continuous antiviral treatment is required after enrollment, and HBV-DNA testing should be conducted every 12 weeks and at EOT visits; b) Patients who are positive for HCV serology but negative for HCV-RNA can be included in the study;
9. Patients who are positive for human immunodeficiency virus antibodies (HIV Ab) or anti Treponema pallidum antibodies (TP Ab) (Treponema pallidum antibodies positive);
10. Patients with epilepsy or those taking psychotropic or sedative drugs during screening;
11. Pregnant or lactating female patients, female/male patients with fertility who refuse to use contraceptive measures during the trial period and within 6 months after the trial ends;
12. Patients who have suffered from other malignant tumors within the past 5 years before the first administration (excluding cured carcinoma in situ and basal cell carcinoma of the skin);
13. Patients with combined swallowing difficulties;
14. Patients who participated in clinical trials of other new drugs or medical devices within the first month of randomization and took the study drug or used the study device;
15. Researchers believe that there are other factors that are not suitable for participating in the experiment.

Trial design

Primary purpose: Treatment

Allocation: Randomized

Interventional model: Parallel Assignment

Masking: None (Open label)

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105 participants in 2 patient groups

Experimental group

Experimental group

Description:

Flonoltinib Maleate Tablets 75mg, taken orally, qd， Administer on an empty stomach

Treatment:

Drug: Flonoltinib 75mg

control group

Active Comparator group

Description:

he dosage of Ruxolitinib Phosphate Tablets should be administered orally according to the instructions, bid， Administer on an empty stomach

Treatment:

Drug: Ruxolitinib Phosphate