Jaktinib Hydrochloride Tablets in Intermediate-risk and High-risk Myelofibrosis.

• Status: Recruiting
• Trial end date: 2021-08-01
• Target enrollment: 0
• Participant gender: All

Summary

This was an open-label, multi-center, randomized phase 2 study. This is a two-stage design.In the first stage, two dose groups were set up, the 100 mg bid dose group and the 200 mg qd dose group, which were randomized at 1:1, with 50 subjects in each group, and a total of 100 cases in the two groups. In the second stage, approximately 36 subjects were added to the randomized group.

• Phase: Phase 2
• Accepts Healthy Volunteers?: No

Details

• Lead Sponsor: Suzhou Zelgen Biopharmaceuticals Co.,Ltd

Criteria

Inclusion criteria:

1、18 years age or older ,male or female;

2、Patients diagnosed with Primary Myelofibrosis according to WHO standard (2016 version), or patients diagnosed with Post-Polycythemia Vera Myelofibrosis or Post-Essential Thrombocythemia Myelofibrosis according to International Working Group Myeloproliferative Neoplasms Research and Treatment(IWG-MRT) standard. Both Janus Kinase 2(JAK2)mutation and JAK2 wild can be enrolled；

3、According to Dynamic International Prognostic Scoring System plus(DIPSS-plus) risk grouping criteria, patients with medium-risk-2 or high-risk myelofibrosis were assessed,Patients with grade 1 medium-risk myelofibrosis with hepatosplenomegaly and no response to existing treatment and requiring treatment can also be enrolled;

4、Subjects did not have a recent stem cell transplant program;

5、a life expectancy > 24 weeks;

6、Eastern Cooperative Oncology Group (ECOG) performance status of 0 to 2；

7、Splenomegaly: palpation of the splenic margin to or above the subcostal at least 5 cm；

8、Peripheral blood protocells ≤10%；

9、Patients who have not previously been treated with JAK inhibitors；

10、Absolute neutrophil count（ANC） ≥1000/uL, platelet count ≥75 × 109/L without growth factor, platelet production factor or platelet infusion.Subjects did not receive growth factor infusion within 2 weeks before randomization;

11、Seven days before randomization, the main organs were functioning normally, which met the following criteria： alanine transaminase（ALT）and aspartate aminotransferase（AST）≤2.5×upper limit of normal (ULN)； direct bilirubin（DBIL）and total bilirubin (TBIL)≤1.5×upper limit of normal (ULN）；serum creatinine ≤2.5×upper limit of normal (ULN)，calculated creatinine clearance（CrCl）≥50mL/min；

12、 Voluntarily sign informed consent in accordance with the requirements of the ethics committee;

13、Ability to follow study and follow-up procedures；

Exclusion Criteria:

1. Any significant clinical or laboratory abnormalities that the investigator considers to affect safety assessment, such as: a. uncontrolled diabetes (> 250 mg/dL, or 13.9 mmol > / L), b. had high blood pressure and antihypertensive drug treatment under two or unable to descend to the ranges (systolic blood pressure < 160 mmHg, diastolic pressure < 100 mmHg), c. peripheral neuropathy (NCI - CTC AE v4.03 standard grade 2 or above), d. thyroid dysfunction (> NCI - CTC AE v4.03 standard grade 2 or above);

2. The patients had a history of congestive heart failure, uncontrollable or unstable angina or myocardial infarction, cerebrovascular accident or pulmonary embolism in the first 6 months;

3. Screening of patients who have not fully recovered from surgery within the first 4 weeks;

4. Screening for patients with arrhythmia requiring treatment or QTc interval (QTcB) >480ms;

5. Screening for bacterial, viral, parasitic or fungal infections with any clinical symptoms that require treatment;

6. Patients with a history of congenital or acquired hemorrhagic diseases;

7. Patients who had previously undergone splenectomy or who had received radiotherapy of the splenic region within the first 12 months of screening;

8. Screening for HIV positive, active hepatitis b virus positive (HBsAg positive, hbv- dna positive or greater than 1000 copies /ml), anti-hcv antibody or hcv-rna positive;

9. Patients suffering from epilepsy or using psychotropic or sedative drugs at the time of screening;

10. Women who are planning to become pregnant or who are pregnant or breast- feeding, as well as those who were unable to use effective contraceptives throughout the trial;Male patients who do not use condoms during the administration and within 2 days (approximately 5 half-lives) after the last administration;

11. Patients who have suffered from malignant tumors (except cured basal cell carcinoma of the skin and carcinoma in situ of the cervix) in the past 5 years;

12. Combined with other serious diseases, the researchers believe that patients' safety or compliance may be affected;

13. Suspected allergic to Jakatinib hydrochloride or similar drugs;

14. Patients who have participated in the clinical trials of other new drugs or medical devices within the first 3 months;

15. Patients who were treated with any MF drug (e.g., hydroxyl urea), any immunomulator (e.g., thalidomide), any immunosuppressant, prednisone at or above 10mg/ day or equivalent bioactive level of glucocorticoid, growth factor (e.g.,erythropoietin ), or who were within 6 half-lives of the drug within 2 weeks prior to randomization;