Clinical trial NCT04617028: Jaktinib Versus Hydroxycarbamide in Subjects With Intermediate-2 or High-risk Myelofibrosis
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
Study type: INTERVENTIONAL
Overall status: COMPLETED
Phase: PHASE3
Conditions: Myelofibrosis
Lead sponsor: Suzhou Zelgen Biopharmaceuticals Co.,Ltd
Sponsor class: INDUSTRY
First posted: 2020-11-05
Enrollment: 105
Sex: ALL
Minimum age (years): 18
Maximum age (years): 75
Standard ages: ADULT
OLDER_ADULT
Accepts healthy volunteers: no
Allocation: RANDOMIZED
Intervention model: PARALLEL
Primary purpose: TREATMENT

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


Eligibility criteria: 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.

Primary outcomes:
measure: Splenic response rate at Week 24
timeFrame: Week 24
Secondary outcomes:
measure: Proportion of transfusion dependent patients converted to non-transfusion dependent patients at baseline
timeFrame: From start of drug administration up to 7 days after last dose of study treatment
Other outcomes:
Locations:
city: Hangzhou
country: China
facility: The First Affiliated Hospital of Medical School of Zhejiang University
state: Zhejiang
Study officials:
affiliation: The First Affiliated Hospital of Medical School of Zhejiang University
name: Jie Jin, PhD
role: PRINCIPAL_INVESTIGATOR
References: