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

NCT04617028 | Completed Phase 3

• 1 other identifier: ZGJAK016
• Study Type: interventional
• Target: 105
• Locations: 1 country
• Sites: 1

Brief Summary

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

Conditions

Myelofibrosis

Outcome Measures

Primary Outcomes (1)

• 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 Outcomes (1)

• 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

Study Arms (2)

Jaktinib

EXPERIMENTAL

Participants will receive Jaktinib plus placebo to match Hydroxycarbamide.

Drug: Jaktinib; Drug: Placebo to match Hydroxycarbamide

Hydroxycarbamide

ACTIVE COMPARATOR

Participants will receive Hydroxycarbamide plus placebo to match Jaktinib.

Drug: Hydroxycarbamide Tablets; Drug: Placebo to match Jaktinib

Interventions

Jaktinib DRUG

Jaktinib Hydrochloride Tablets administered orally twice daily

Jaktinib

Placebo to match Hydroxycarbamide DRUG

Placebo to match Hydroxycarbamide Tablets administered orally twice daily

Jaktinib

Hydroxycarbamide Tablets DRUG

Hydroxycarbamide Tablets administered orally twice daily

Hydroxycarbamide

Placebo to match Jaktinib DRUG

Placebo to match Jaktinib Tablets administered orally twice daily

Hydroxycarbamide

Eligibility Criteria

• Age: 18 Years - 75 Years
• Sex: all
• Healthy Volunteers: No
• Age Groups: Adult (18-64), Older Adult (65+)

You may qualify if:

• 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.

You may not qualify if:

• 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.

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

Related Publications (1)

• Zhang Y, Zhou H, Suo S, Zhuang J, Yang L, He A, Liu Q, Du X, Gao S, Li Y, Li Y, Chen Y, Wu W, Zhu H, He G, Hong M, Jiang Q, Jiang Z, Jing H, Wang J, Xu N, Yue L, Zheng C, Zhou Z, Jin C, Li X, Liu L, Xu Y, Wu D, Zhang F, Zhang J, Wu L, Yin H, Lv B, Xiao Z, Jin J. Evaluation of gecacitinib vs hydroxyurea in patients with intermediate-2 or high-risk myelofibrosis: final analysis results from a randomized phase 3 study. Blood Cancer J. 2024 Dec 18;14(1):216. doi: 10.1038/s41408-024-01202-8.

  PMID: 39695117 DERIVED

MeSH Terms

Conditions

Primary Myelofibrosis

Interventions

Hydroxyurea

Condition Hierarchy (Ancestors)

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

Intervention Hierarchy (Ancestors)

Urea; Amides; Organic Chemicals

Study Officials

• Jie Jin, PhD

  The First Affiliated Hospital of Medical School of Zhejiang University

  PRINCIPAL INVESTIGATOR

Study Design

• Study Type: interventional
• Phase: phase 3
• Allocation: RANDOMIZED
• Masking: DOUBLE
• Who Masked: PARTICIPANT, INVESTIGATOR
• Purpose: TREATMENT
• Intervention Model: PARALLEL
• Sponsor Type: INDUSTRY
• Responsible Party: SPONSOR

Study Record Dates

• First Submitted: October 26, 2020
• First Posted: November 5, 2020
• Study Start: February 5, 2021
• Primary Completion: October 18, 2023
• Study Completion: October 18, 2023
• Last Updated: November 13, 2023

Record last verified: 2023-11

Data Sharing

• IPD Sharing: Will not share

Locations

CN (1)