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

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

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

Study Overview

• Status: Completed
• Conditions: Myelofibrosis
• Intervention / Treatment: Drug: Jaktinib; Drug: Placebo to match Hydroxycarbamide; Drug: Hydroxycarbamide Tablets; Drug: Placebo to match Jaktinib

• Study Type: Interventional
• Enrollment (Actual): 105
• Phase: Phase 3

Contacts and Locations

• Study Contact: Name: Jie Jin, PhD; Phone Number: +86-0571-87236896; Email: jiej0503@163.com

Study Locations

• China
  • Zhejiang
    • Hangzhou, Zhejiang, China, 310003
      • The First Affiliated Hospital of Medical School of Zhejiang University

Participation Criteria

Eligibility Criteria

• Ages Eligible for Study: 18 years to 75 years (Adult, Older Adult)
• Accepts Healthy Volunteers: No

Description

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.

Study Plan

How is the study designed?

Design Details

• Primary Purpose: Treatment
• Allocation: Randomized
• Interventional Model: Parallel Assignment
• Masking: Double

Number of Arms

2

Arms and Interventions

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

What is the study measuring?

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	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

Collaborators and Investigators

• Sponsor: Suzhou Zelgen Biopharmaceuticals Co.,Ltd
• Investigators: Principal Investigator: Jie Jin, PhD, The First Affiliated Hospital of Medical School of Zhejiang University

Study record dates

Study Major Dates

• Study Start (Actual): February 5, 2021
• Primary Completion (Actual): October 18, 2023
• Study Completion (Actual): October 18, 2023

Study Registration Dates

• First Submitted: October 26, 2020
• First Submitted That Met QC Criteria: October 30, 2020
• First Posted (Actual): November 5, 2020

Study Record Updates

• Last Update Posted (Actual): November 13, 2023
• Last Update Submitted That Met QC Criteria: November 9, 2023
• Last Verified: November 1, 2023

More Information

Terms related to this study

• Additional Relevant MeSH Terms: Bone Marrow Diseases; Hematologic Diseases; Myeloproliferative Disorders; Primary Myelofibrosis; Molecular Mechanisms of Pharmacological Action; Nucleic Acid Synthesis Inhibitors; Enzyme Inhibitors; Antineoplastic Agents; Antisickling Agents; Hydroxyurea
• Other Study ID Numbers: ZGJAK016

Plan for Individual participant data (IPD)

• Plan to Share Individual Participant Data (IPD)?: NO

Drug and device information, study documents

• Studies a U.S. FDA-regulated drug product: No
• Studies a U.S. FDA-regulated device product: No