Jaktinib Versus Hydroxycarbamide in Subjects With Intermediate-2 or High-risk Myelofibrosis

Myelofibrosis Clinical Trial

Official title:

A Randomized, Double-blind, Double-simulated, Parallel-controlled, Multicenter Phase III Study Evaluating the Efficacy and Safety of Jaktinib Versus Hydroxycarbamide in Patients With Intermediate-2 or High-risk Myelofibrosis

Clinical Trial Details — Status: Completed

Administrative data

• NCT number: NCT04617028
• Other study ID #: ZGJAK016
• Status: Completed
• Phase: Phase 3
• Start date: February 5, 2021
• Est. completion date: October 18, 2023

Study information

• Verified date: November 2023
• Source: Suzhou Zelgen Biopharmaceuticals Co.,Ltd
• Contact: n/a
• Is FDA regulated: No
• Study type: Interventional

Clinical Trial Summary

This study is to determine the efficacy of Jaktinib versus Hydroxycarbamid in participants with Intermediate-2 or High-risk myelofibrosis

Recruitment information / eligibility

• Status: Completed
• Enrollment: 105
• Est. completion date: October 18, 2023
• Est. primary completion date: October 18, 2023
• Accepts healthy volunteers: No
• Gender: All
• Age group: 18 Years to 75 Years

Eligibility

Inclusion Criteria:

• Age = 18 years old,either male or female;

• Subjects diagnosed with a PMF according to World Health Organiztion criteria (2016 Edition), or patients diagnosed with a Post-PV-MF or Post-EF-MF according to International Working Group for Myeloproliferative Neoplasms Research and Treatment criteria;

• High risk or intermediate-2 risk as defined by the Dynamic International Prognostic Scoring System (DIPSS) for Primary Myelofibrosis;

• Subjects have no plan for stem cell transplantation in the near future;

• Life expectancy of > 24 weeks;

• ECOG performance status of 0-1;

• Palpable splenomegaly at least 5 cm below left costal margin;

• Peripheral blood blast count = 10%;

• Subjects who have not yet received treatment with a JAK inhibitor, or Subjects who have been treated with JAK inhibitors for =10 days;

• Subjects have not received growth factor, thrombopoietin mimetics or platelet transfusion(s) within 2 weeks before the randomization; ANC= 1.0×10^9/L, platelet count = 100×10^9/L within 2 days before the randomization;

• Normal functions in major organs within 7 days before the randomization, fulfilling the following criteria: ALT and AST = 2.5×ULN; DBIL and TBIL = 2.0×ULN; serum creatinine = 1.5×ULN;

• If the subject is receiving any anti-myelofibrosis treatment (except for JAK inhibitors and hydroxyurea) at screening, the dosing regimen must remain unchanged for at least 2 weeks before screening. If the investigator judges that there is no need to continue to use, stop the use of thalidomide, androgens and prednisone> 10 mg during screening. The drugs used to improve anemia should be stopped for at least 6 half-lives or 2 weeks before randomization(whichever is the longer);

• If the subject is receiving Hydroxycarbamide treatment at screening, the drug must be discontinued = 2 weeks before the randomization;

• Meet the requirements of the ethics committee and willing to sign the informed consent form;

• Ability to comply with trial and follow-up procedures.

Exclusion Criteria:

• Subjects with any significant clinical and laboratory abnormalities which may affect the safety evaluation, such as uncontrolled diabetes, uncontrolled hypertension after taking two or more hypotensive drugs, peripheral neuropathy;

• Subjects with congestive heart failure, uncontrolled or unstable angina or myocardial infarction, cerebrovascular accident, or pulmonary embolism within 24 weeks prior to screening;

• Subjects who have not fully recovered from surgical operation within 4 weeks prior to screening;

• Subjects suffering from arrhythmia and requiring treatment at screening;

• Subjects with clinical symptoms of active bacterial, viral, parasitic or fungal infections requiring treatment at screening;

• Chest X-rays suggest an active lung infection at screening;

• Subjects who had active tuberculosis infection within 48 weeks before screening;?-Interferon release test suggests latent tuberculosis infection at screening;

• Subjects who had undergone splenectomy, or received radiotherapy to the spleen within 48 weeks before screening;

• Subjects with known human immunodeficiency virus (HIV), known active infectious Hepatitis B (HepB), and/or known active infectious Hepatitis C (HepC);

• Subjects with epilepsy or patients who have received psychotropic drug or sedatives during screening;

• Female subjects who are pregnant, currently breastfeeding, planning to become pregnant;Subjects who are unable to adopt effective contraceptive methods during the study; Male subjects who did not use condoms during the dosing period and within 2 days after the last dose

• Subjects who had experienced malignant tumors within the past 5 years (except for adequately treated local basal cell carcinoma of the skin and cervical carcinoma in situ that have been cured);

• Subjects who are unsuitable to the trial in combination with other serious diseases, as identified by the investigator;

• Subjects with suspected allergies to Jaktinib or its excipient;

• Subjects who have participated in another clinical trial of a new drug or medical instrument within 12 weeks before screening.

Related Conditions & MeSH terms

• Myelofibrosis
• Primary Myelofibrosis

Intervention

Drug:
• Jaktinib
Jaktinib Hydrochloride Tablets administered orally twice daily
• Placebo to match Hydroxycarbamide
Placebo to match Hydroxycarbamide Tablets administered orally twice daily
• Hydroxycarbamide Tablets
Hydroxycarbamide Tablets administered orally twice daily
• Placebo to match Jaktinib
Placebo to match Jaktinib Tablets administered orally twice daily

Locations

Country	Name	City	State
China	The First Affiliated Hospital of Medical School of Zhejiang University	Hangzhou	Zhejiang

Sponsors (1)

Lead Sponsor	Collaborator
Suzhou Zelgen Biopharmaceuticals Co.,Ltd

Country where clinical trial is conducted

China, 

Outcome

Type	Measure	Description	Time frame	Safety issue
Primary	Splenic response rate at Week 24	Splenic response rate at Week 24 is defined as the proportion of participants achieving a = 35% reduction in spleen volume at Week 24 from baseline as measured by MRI or CT	Week 24
Secondary	Proportion of transfusion dependent patients converted to non-transfusion dependent patients at baseline		From start of drug administration up to 7 days after last dose of study treatment