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

NCT03886415 | Completed Phase 2

• 1 other identifier: ZGJAK002
• Study Type: interventional
• Target: 118
• Locations: 1 country
• Sites: 1

Brief 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.

Conditions

Myelofibrosis

Outcome Measures

Primary Outcomes (1)

• effective rate

  The proportion of all subjects whose spleen volume decreased by 35% or more at 24 weeks

  24 weeks

Secondary Outcomes (7)

• Overall response rate （CR+PR）

  24 weeks

• The spleen response

  24 weeks

• Anemia response

  24 weeks

• MF related symptom response rate

  24 weeks

• Progression-free survival (PFS)

  24 weeks

Study Arms (2)

Jaktinib hydrochloride tablets 1

EXPERIMENTAL

This is the dose group was given once a day. Jaktinib hydrochloride tablets 1 200mg qd dose group

Drug: Jaktinib hydrochloride tablets

Jaktinib hydrochloride tablets 2

EXPERIMENTAL

This is the dose group was given twice a day. Jaktinib hydrochloride tablets 2 100mg bid dose group

Drug: Jaktinib hydrochloride tablets

Interventions

Jaktinib hydrochloride tablets DRUG

Jaktinib hydrochloride tablets 100mg bid dose group and Jaktinib hydrochloride tablets 200mg qd dose group

Jaktinib hydrochloride tablets 1; Jaktinib hydrochloride tablets 2

Eligibility Criteria

• Age: 18 Years+
• Sex: all
• Healthy Volunteers: No
• Age Groups: Adult (18-64), Older Adult (65+)

You may qualify if:

• 、18 years age or older ,male or female;
• 、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；
• 、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;
• 、Subjects did not have a recent stem cell transplant program;
• 、a life expectancy \> 24 weeks;
• 、Eastern Cooperative Oncology Group (ECOG) performance status of 0 to 2；
• 、Splenomegaly: palpation of the splenic margin to or above the subcostal at least 5 cm；
• 、Peripheral blood protocells ≤10%；
• 、Patients who have not previously been treated with JAK inhibitors；
• 、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;
• 、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；
• 、 Voluntarily sign informed consent in accordance with the requirements of the ethics committee;
• 、Ability to follow study and follow-up procedures；

You may not qualify if:

• 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);
• 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;
• Screening of patients who have not fully recovered from surgery within the first 4 weeks;
• Screening for patients with arrhythmia requiring treatment or QTc interval (QTcB) \>480ms;
• Screening for bacterial, viral, parasitic or fungal infections with any clinical symptoms that require treatment;
• Patients with a history of congenital or acquired hemorrhagic diseases;
• Patients who had previously undergone splenectomy or who had received radiotherapy of the splenic region within the first 12 months of screening;
• 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;
• Patients suffering from epilepsy or using psychotropic or sedative drugs at the time of screening;
• 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;
• 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;
• Combined with other serious diseases, the researchers believe that patients' safety or compliance may be affected;
• Suspected allergic to Jakatinib hydrochloride or similar drugs;
• Patients who have participated in the clinical trials of other new drugs or medical devices within the first 3 months;
• 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;

Sponsors & Collaborators

• Suzhou Zelgen Biopharmaceuticals Co.,Ltd: lead

Study Sites (1)

The First Affiliated Hospital of Medical School of Zhejiang University

Hangzhou, Zhejiang, 310003, China

Location

MeSH Terms

Conditions

Primary Myelofibrosis

Condition Hierarchy (Ancestors)

Myeloproliferative Disorders; Bone Marrow Diseases; Hematologic Diseases; Hemic and Lymphatic Diseases

Study Officials

• Jie Jin, MD

  The First Affiliated Hospital of Medical School of Zhejiang University

  STUDY CHAIR

Study Design

• Study Type: interventional
• Phase: phase 2
• Allocation: RANDOMIZED
• Masking: NONE
• Purpose: TREATMENT
• Intervention Model: PARALLEL
• Sponsor Type: INDUSTRY
• Responsible Party: SPONSOR

Study Record Dates

• First Submitted: March 20, 2019
• First Posted: March 22, 2019
• Study Start: January 8, 2019
• Primary Completion: February 2, 2021
• Study Completion: February 2, 2021
• Last Updated: November 29, 2022

Record last verified: 2022-11

Data Sharing

• IPD Sharing: Will not share

Locations

CN (1)