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

• ClinicalTrials.gov Identifier: NCT04854096
• Recruitment Status: Recruiting
• First Posted: April 22, 2021
• Last Update Posted: May 16, 2024
• Sponsor: NS Pharma, Inc.
• Collaborator: Nippon Shinyaku Co., Ltd.
• Information provided by (Responsible Party): NS Pharma, Inc.

Tracking Information

• First Submitted Date: April 9, 2021
• First Posted Date: April 22, 2021
• Last Update Posted Date: May 16, 2024
• Actual Study Start Date: January 31, 2023
• Estimated Primary Completion Date: May 24, 2024 (Final data collection date for primary outcome measure)

Current Primary Outcome Measures (submitted: November 5, 2021)

• Change in spleen volume [ Time Frame: from baseline to week 24 ]
  Proportion of subjects who achieve ≥35% change in spleen volume from baseline to Week 24 as measured by MRI (or by CT for applicable subjects)
• Change in Total Symptom Score (TSS) [ Time Frame: from baseline to week 24 ]
  Proportion of subjects who achieve ≥50% change in total symptom score from baseline to Week 24 as measured by the MFSAF v4.0

Original Primary Outcome Measures (submitted: April 20, 2021)

Change in spleen volume [ Time Frame: from baseline to week 24 ]

Proportion of subjects who achieve ≥35% change in spleen volume from baseline to Week 24 as measured by MRI (or by CT for applicable subjects)

Current Secondary Outcome Measures (submitted: November 5, 2021)

• Change in spleen volume [ Time Frame: from baseline at anytime up to week 24 ]
  Proportion of subjects in NS-018 vs BAT arm who achieve ≥35% change 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 [ Time Frame: from baseline to week 24 ]
  Laboratory events graded by the NCI CTCAE v5.0 will be assessed in both arms, NS-018 vs BAT.

Original Secondary Outcome Measures (submitted: April 20, 2021)

• Change in Total Symptom Score (TSS) [ Time Frame: from baseline to week 24 ]
  Proportion of subjects who achieve ≥50% change in total symptom score from baseline to Week 24 as measured by the MFSAF v4.0
• Change in spleen volume [ Time Frame: from baseline at anytime up to week 24 ]
  Proportion of subjects who achieve ≥35% change 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 [ Time Frame: from baseline to week 24 ]
  Laboratory events graded by the NCI CTCAE v5.0 will be assessed in both arms, NS-018 vs BAT.

• Current Other Pre-specified Outcome Measures: Not Provided
• Original Other Pre-specified Outcome Measures: Not Provided

Descriptive Information

• Brief Title: Study to Assess Efficacy and Safety of NS-018 Compared to BAT in Patients With Myelofibrosis
• Official Title: A Phase 2b, Open-label, Multicenter, Randomized, Controlled, 2-Arm Study to Assess the Efficacy and Safety of Orally Administered NS-018 Versus Best Available Therapy in Subjects With Primary Myelofibrosis, Post Polycythemia Vera Myelofibrosis, or Post-Essential Thrombocythemia Myelofibrosis With Severe Thrombocytopenia (Platelet Count <50,000/μL)
• 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 Type: Interventional
• Study Phase: Phase 2
• Study Design: Allocation: Randomized; Intervention Model: Parallel Assignment; Masking: Single (Outcomes Assessor); Primary Purpose: Treatment

Condition

• Primary Myelofibrosis
• Post-essential Thrombocythemia Myelofibrosis
• Post-polycythemia Vera Myelofibrosis

Intervention

• Drug: NS-018
  Experimental
• Drug: Best Available Therapy
  Active Comparator

Study Arms

• Experimental: 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
  Intervention: Drug: NS-018
• Active Comparator: Best Available Therapy (BAT)
  Single agent per Investigator discretion or no therapy
  Intervention: Drug: Best Available Therapy

• Publications *: Not Provided

Recruitment Information

• Recruitment Status: Recruiting
• Estimated Enrollment (submitted: November 5, 2021): 120
• Original Estimated Enrollment (submitted: April 20, 2021): 100
• Estimated Study Completion Date: May 24, 2024
• Estimated Primary Completion Date: May 24, 2024 (Final data collection date for primary outcome measure)

Eligibility Criteria

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.

Sex/Gender

• Sexes Eligible for Study: All

• Ages: 18 Years and older (Adult, Older Adult)
• Accepts Healthy Volunteers: No

Contacts

Contact: NS Pharma, Inc.; trialinfo@nspharma.com

• Listed Location Countries: Germany, Italy, Korea, Republic of, Malaysia, Poland, Thailand, Turkey, United Kingdom, United States

Administrative Information

• NCT Number: NCT04854096
• Other Study ID Numbers: NS-018-201
• Has Data Monitoring Committee: Yes

U.S. FDA-regulated Product

• Studies a U.S. FDA-regulated Drug Product: Yes
• Studies a U.S. FDA-regulated Device Product: No

IPD Sharing Statement

• Plan to Share IPD: No
• Plan Description: Submission to the FDA

• Current Responsible Party: NS Pharma, Inc.
• Original Responsible Party: Same as current
• Current Study Sponsor: NS Pharma, Inc.
• Original Study Sponsor: Same as current
• Collaborators: Nippon Shinyaku Co., Ltd.
• Investigators: Not Provided
• PRS Account: NS Pharma, Inc.
• Verification Date: April 2024