A Multicenter, Prospective, Observational Study of Jaktinib in Newly Diagnosed Myelofibrosis

Efficacy and Safety of Jaktinib in Newly Diagnosed Myelofibrosis: A Multicenter, Prospective, Real-World Observational Study

This is a multicenter, prospective, observational clinical study designed to evaluate the real-world efficacy and safety of jaktinib in patients with newly diagnosed myelofibrosis (MF). The primary outcome measure is the proportion of patients achieving anemia response at week 24. Secondary outcome measures include MF-related symptom response rate (TSS50) at week 24, spleen volume reduction ≥35% (SVR35) at week 24, progression-free survival (PFS), leukemia-free survival (LFS), overall survival (OS), and safety/tolerability. This study will provide real-world evidence supporting the use of jaktinib as a first-line treatment for newly diagnosed MF patients.

Study Overview

• Status: Not yet recruiting
• Conditions: Myeloproliferative Neoplasms/Myelofibrosis
• Intervention / Treatment: Drug: Jaktinib

Detailed Description

Myelofibrosis (MF) is a BCR::ABL1-negative myeloproliferative neoplasm (MPN) characterized by progressive splenomegaly, debilitating systemic symptoms, abnormal blood cell counts, and a risk of leukemic transformation. Patients often suffer from progressive anemia, thrombocytopenia, and systemic symptoms including fatigue, dyspnea, night sweats, weight loss, fever, and bone pain. Notably, the incidence of anemia at diagnosis in Chinese patients with primary myelofibrosis (PMF) is 67%, significantly higher than that observed in Western counterparts (35%), underscoring a critical unmet need for therapies that address both splenomegaly and anemia in this population.

Mutations in JAK2, CALR, or MPL genes, found in approximately 90% of patients, lead to hyperactivation of the JAK-STAT pathway, which is pivotal in the pathogenesis of MF. Advances in understanding this pathway have led to the development of JAK inhibitors, with ruxolitinib (2011), fedratinib (2019), pacritinib (2022), and momelotinib (2023) approved by the U.S. Food and Drug Administration (FDA) for the treatment of MF symptoms and splenomegaly. In China, ruxolitinib is the first JAK inhibitor approved for the treatment of MF. However, its efficacy in the Chinese population is modest, with a ≥35% spleen volume reduction (SVR35) rate of only 27% at week 24 (A2202 study), compared to 31.7% in Asian patients and 41.9% in Western patients (COMFORT-I). Furthermore, treatment-related anemia and thrombocytopenia frequently necessitate dose reductions or discontinuation, with over 60% of patients requiring dose modification due to adverse events. Hydroxyurea (HU) is commonly used as cytoreductive therapy in China, but its efficacy in treating MF-associated splenomegaly is variable and typically limited to approximately one year; nearly 50% of patients experience worsening anemia or cytopenia with HU therapy.

Jaktinib (also known as gecacitinib) is a novel inhibitor targeting both JAK and ACVR1. By inhibiting JAK1, JAK2, JAK3, and TYK2, it blocks the JAK-STAT signaling pathway, thereby alleviating inflammation and splenomegaly. Through a mechanism shared with momelotinib, jaktinib inhibits ACVR1 activity, which downregulates hepcidin expression, improves iron metabolism imbalance, and increases hemoglobin levels, thereby reducing the occurrence of anemia and transfusion dependency in patients with MF. This dual mechanism makes jaktinib particularly well-suited for MF patients who present with or are at risk of developing anemia. Multiple clinical trials of jaktinib in MF have been conducted in China. The phase II study ZGJAK002 (NCT03886415) enrolled 118 patients with intermediate- or high-risk MF and demonstrated a SVR35 rate of 44.5% at week 24 (54.8% in the 100 mg twice-daily group vs. 31.3% in the 200 mg once-daily group, p = 0.0199), with TSS50 response rates of 69.6% and 57.5%, respectively, and low incidences of grade ≥3 drug-related anemia (24.0%) and thrombocytopenia (12.5%). The phase III study ZGJAK016 (NCT04617028) compared jaktinib with HU in JAK inhibitor-naïve intermediate- to high-risk MF patients. The results demonstrated that jaktinib is superior to HU in reducing spleen size, with favorable safety and tolerability, and may offer potential improvements in patients' quality of life. Furthermore, 2026 guidelines of the Chinese Society of Clinical Oncology (CSCO) have recommended jaktinib as a Category I core agent for patients with intermediate- or high-risk MF, as well as low-risk MF with symptomatic disease, further validating its role in first-line management.

Given this robust clinical evidence, the present multicenter, prospective, real-world observational study aims to evaluate the effectiveness and safety of jaktinib in patients with newly diagnosed MF treated under routine clinical practice. As a non-interventional study, it will not influence treatment decisions but will systematically capture longitudinal data to reflect actual clinical outcomes. The primary endpoint is the proportion of patients achieving anemia response at week 24, defined as an increase in hemoglobin level or a reduction in transfusion requirement according to predefined criteria (e.g., IWG-MRT criteria). Secondary endpoints include MF-related symptom response rate (≥50% reduction in MPN-SAF TSS, TSS50) at week 24, the proportion of patients achieving ≥35% spleen volume reduction (SVR35) at week 24, progression-free survival (PFS), leukemia-free survival (LFS), overall survival (OS), and safety/tolerability assessed by adverse events, serious adverse events, laboratory abnormalities, and treatment discontinuation rates. This study will generate essential real-world evidence on jaktinib in newly diagnosed MF, providing clinicians with data to optimize first-line treatment strategies and improve long-term outcomes in this patient population.

• Study Type: Observational
• Enrollment (Estimated): 80

Contacts and Locations

• Study Contact: Name: Yingxin Sun, Dr; Phone Number: +86-13646249970; Email: syx20194132088@163.com

Study Locations

• China
  • Jiangsu
    • Nantong, Jiangsu, China, 226001
      • Affiliated hospital of Nantong University
      • Contact: Yingxin Sun, Dr; Phone Number: +86-13646249970; Email: syx20194132088@163.com

Participation Criteria

Eligibility Criteria

• Ages Eligible for Study: 18 years and older (Adult, Older Adult)
• Accepts Healthy Volunteers: No
• Genders Eligible for Study: All

• Sampling Method: Non-Probability Sample

Study Population

Myelofibrosis patients receiving jaktinib treatment

Description

Inclusion Criteria:

1. Patients with a confirmed diagnosis of primary myelofibrosis (PMF), post-polycythemia vera myelofibrosis (post-PV MF), or post-essential thrombocythemia myelofibrosis (post-ET MF) according to the 2022 World Health Organization (WHO) and modified International Working Group for Myelofibrosis Research and Treatment criteria
2. Age ≥ 18 years at the time of Jaktinib initiation.
3. Newly diagnosed MF: Patients who have not received prior JAK inhibitor therapy and are initiated on Jaktinib as first-line treatment.
4. Willing and able to comply with the study protocol and scheduled follow-up assessments.
5. Patients who have provided written informed consent for the use of their clinical data in this prospective observational study.

Exclusion Criteria:

1. Prior treatment with any JAK inhibitor (including ruxolitinib, fedratinib, pacritinib, momelotinib, or others).
2. Patients with a history of other hematologic malignancies (e.g., acute leukemia, myelodysplastic syndrome) or active solid tumors within the past 5 years.
3. Patients with severe hepatic or renal dysfunction, defined as Child-Pugh class C liver cirrhosis or estimated glomerular filtration rate (eGFR) < 30 mL/min/1.73 m² at baseline.
4. Patients with active, uncontrolled infections (including HIV, active hepatitis B/C, or tuberculosis) at the time of Jaktinib initiation.
5. Pregnant or lactating women.
6. Patients with clinically significant cardiovascular, pulmonary, or other systemic diseases that, in the investigator's judgment, may interfere with the evaluation of efficacy or safety.
7. Patients who do not provide or have not signed the informed consent form (ICF), or who have explicitly declined participation in this study.

Study Plan

How is the study designed?

Design Details

• Observational Models: COHORT
• Time Perspectives: PROSPECTIVE

What is the study measuring?

Primary Outcome Measures

Outcome Measure	Measure Description	Time Frame
anemia response	Proportion of participants achieving anemia response at week 24	24 weeks

Secondary Outcome Measures

Outcome Measure	Measure Description	Time Frame
TSS50	Proportion of participants with a total symptom score reduction of ≥50% (TSS50) at 24 weeks	24 weeks
SVR35	Proportion of participants with a spleen volume reduction of ≥35% (SVR35) from baseline at week 24	24 weeks
Progression-free survival (PFS)	The time from the first dose to any of the following events: spleen volume increased by ≥25% from the lowest value recorded; death of any cause.	24 months
Leukemia-free survival (LFS)	The time from the first dose to any of the following events: bone marrow smear showed blast cells ≥20%; peripheral blood smear blast cells ≥20% and the absolute blast count ≥1×10E9/L lasts for at least 2 weeks; death of any cause.	24 months
Safety and tolerability	The safety and tolerability were evalu- ated from the first dose of jaktinib to 28 days after the last dose. Adverse events (AEs) were graded according to the Common Toxicity Criteria for Adverse Events (CTCAE) version 5.0.	24 months
Overall survival (OS)	OS was defined as the time from the first dose to death.	24 months

Collaborators and Investigators

• Sponsor: Affiliated Hospital of Nantong University

Study record dates

Study Major Dates

• Study Start (Estimated): November 10, 2026
• Primary Completion (Estimated): December 31, 2027
• Study Completion (Estimated): December 31, 2028

Study Registration Dates

• First Submitted: November 4, 2026
• First Submitted That Met QC Criteria: November 4, 2026
• First Posted (Actual): November 9, 2026

Study Record Updates

• Last Update Posted (Actual): November 9, 2026
• Last Update Submitted That Met QC Criteria: November 4, 2026
• Last Verified: August 1, 2026

More Information

Terms related to this study

• Keywords: efficacy and safety; Myelofibrosis; Therapy; myeloproliferative neoplasms; Jaktinib
• Additional Relevant MeSH Terms: Hematologic Diseases; Bone Marrow Diseases; Hemic and Lymphatic Diseases; Myeloproliferative Disorders; Primary Myelofibrosis
• Other Study ID Numbers: MPN-2026-01

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