Study to Assess Efficacy and Safety of NS-018 Compared to BAT in Patients With Myelofibrosis

Phase 2

Terminated

• Conditions: Primary Myelofibrosis; Post-polycythemia Vera Myelofibrosis; Post-essential Thrombocythemia Myelofibrosis
• Interventions: Drug: NS-018; Drug: Best Available Therapy

• Registration Number: NCT04854096
• Lead Sponsor: NS Pharma, Inc.

Brief Summary

This study will enroll male and female subjects who are 18 years of age or older with Primary Myelofibrosis, post-polycythemia Vera Myelofibrosis, or post-essential Thrombocythemia Myelofibrosis with severe thrombocytopenia (platelet count \<50,000/µL) including subjects with intermediate-2 or high-risk MF according to the Dynamic International Prognostic Scoring System (DIPSS).

Detailed Description

NS-018 will be self-administered orally at a dose of 300 mg BID. The BAT will be administered according to manufacturer's instructions and Investigator discretion. Subjects will complete study visits at Screening, Day 1 and Day 15 of Cycle 1, 2, 3, 4, 5, 6 and Day 1 of every cycle thereafter. At these visits, blood/urine sampling, spleen measurements, bone marrow assessments, patient-reported outcome (PRO) assessments, and safety assessments may be performed.

Study Timeline

• Study First Submitted: 2021-04-09
• Study First Submitted QC: 2021-04-20
• Study First Posted: 2021-04-22
• Study Start: 2023-01-31
• Primary Completion: 2024-05-16
• Study Completion: 2024-05-16
• Results First Submitted: 2024-12-10
• Status Verified: 2025-05
• Results First Submitted QC: 2025-05-22
• Last Update Submitted: 2025-05-22
• Results First Posted: 2025-05-23
• Last Update Posted: 2025-05-23

Recruitment & Eligibility

• Status: TERMINATED
• Sex: All
• Target Recruitment: 7

Inclusion Criteria

• Primary MF, post-PVMF or post-ETMF according to the DIPSS risk categories of intermediate-2 or high-risk MF
• Average platelet count of <50,000/µL at Screening based on 2 measurements taken on different days; both measurements must be <50,000/µL.
• ECOG performance status ≤2.
• Life expectancy >6 months.
• Spleen volume of at least 450 cm3 measured by MRI (or by CT for applicable subjects).
• Total Symptom Score (TSS) ≥10 on the Myelofibrosis Symptom Assessment Form (MFSAF) version 4.0.
• Peripheral blast count <10%.
• No MF-directed treatment for at least 2 weeks prior to initiation of NS-018, including JAK inhibitor, erythropoietic, thrombopoietic agent, or any use of corticosteroids for MF symptom or blood count management. Low dose corticosteroids <10 mg/day prednisone or equivalent is allowed for non-MF purposes.

Exclusion Criteria

• Active, uncontrolled systemic infection.
• Any prior treatment with more than two JAK inhibitors.
• Previous treatment with NS-018.
• Subjects actively receiving a concurrent investigational agent.
• Subjects with any unresolved AE greater than Grade 1 other than hematological AEs from previous anticancer therapy.
• Currently taking medication that is substantially metabolized by cytochrome P450 (CYP) 1A2 or CYP3A4 (see Appendix 5) or taking medication known to be strong inhibitors or inducers of CYP3A4 (see Appendix 5).
• Radiation therapy for splenomegaly within 6 months prior to study entry (screening).
• History of splenectomy or planning to undergo splenectomy.
• Subjects with a serious cardiac condition within the past 6 months such as uncontrolled arrhythmias, myocardial infarction, angina or heart disease
• Subjects diagnosed with another malignancy within 2 years prior to an enrollment.
• Subjects who have had surgery (other than placement of vascular access and bone marrow biopsy) within 4 weeks of study entry (screening), or subjects with incomplete recovery from any prior surgical procedures.

Study & Design

• Study Type: INTERVENTIONAL
• Study Design: PARALLEL

Arm && Interventions

Group	Intervention	Description
NS-018	NS-018	Self-administered NS-018 300 mg orally, twice daily, preferably at the same time each day in consecutive 4-week (28-day) cycles
Best Available Therapy (BAT)	Best Available Therapy	Single agent per Investigator discretion or no therapy

Primary Outcome Measures

Name	Time	Method
Change in Spleen Volume	baseline and week 24	Proportion of subjects who achieve ≥35% reduction in spleen volume from baseline compared to Week 24 as measured by MRI (or by CT for applicable subjects)
Change in Total Symptom Score (TSS)	baseline and week 24	Proportion of subjects who achieve ≥50% reduction in total symptom score from baseline compared to Week 24 as measured by the MF-SAF v4.0

Secondary Outcome Measures

Name	Time	Method
Change in Spleen Volume	from baseline to anytime before or at week 24	Proportion of subjects in NS-018 vs BAT arm who achieve ≥35% reduction in spleen volume from baseline at any time up to Week 24 as measured by MRI (or by CT for applicable subjects)
Comparison of Treatment-emergent AEs Between NS-018 and BAT	from baseline to week 24	Laboratory events graded by the NCI CTCAE v5.0 will be assessed in both arms, to compare the safety profile of NS-018 versus BAT.

Trial Locations

Locations (51)

University of Massachusetts Chan Medical School; 🇺🇸 Worcester, Massachusetts, United States

Houston Methodist Hospital; 🇺🇸 Houston, Texas, United States

MD Anderson Cancer Center; 🇺🇸 Houston, Texas, United States

Hamatologisch-onkologische Praxis Heinric/Bangerter Ausgsburg GbR; 🇩🇪 Augsburg, Germany

Universitaetsklinikum Halle (Saale); 🇩🇪 Halle, Germany

Universitaetsklinikum Jena; 🇩🇪 Jena, Germany

Universitätsmedizin Rostock; 🇩🇪 Rostock, Germany

AO SS Antonio; 🇮🇹 Alessandria, Italy

Azienda Ospedaliera SS. Antonio; 🇮🇹 Alessandria, Italy

ASST Spedali Civili di Brescia; 🇮🇹 Brescia, Italy

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