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

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

Official Title
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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

Conditions
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Myelofibrosis

Intervention / Treatment
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* Drug: Jaktinib
* Drug: Placebo to match Hydroxycarbamide
* Drug: Hydroxycarbamide Tablets
* Drug: Placebo to match Jaktinib


Participation Criteria
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Eligibility Criteria
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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;γ-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.

Ages Eligible for Study
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Minimum Age: 18 Years
Maximum Age: 75 Years

Sexes Eligible for Study
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All

Accepts Healthy Volunteers
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No

Study Plan
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How is the study designed?
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Design Details

Primary Purpose: Treatment
Allocation: Randomized
Intervention Model: Parallel Assignment
Masking: Double


Arms and Interventions

| Participant Group/Arm | Intervention/Treatment |
| --- | --- |
| Experimental: Jaktinib<br>Participants will receive Jaktinib plus placebo to match Hydroxycarbamide. | Drug: Jaktinib<br>* Jaktinib Hydrochloride Tablets administered orally twice daily<br>Drug: Placebo to match Hydroxycarbamide<br>* Placebo to match Hydroxycarbamide Tablets administered orally twice daily<br>|
| Active Comparator: Hydroxycarbamide<br>Participants will receive Hydroxycarbamide plus placebo to match Jaktinib. | Drug: Hydroxycarbamide Tablets<br>* Hydroxycarbamide Tablets administered orally twice daily<br>Drug: Placebo to match Jaktinib<br>* Placebo to match Jaktinib Tablets administered orally twice daily<br>|

What is the study measuring?
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Primary Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| 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 Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| 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 |