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

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)

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).

Study Overview

• Status: Recruiting
• Conditions: Primary Myelofibrosis; Post-polycythemia Vera Myelofibrosis; Post-essential Thrombocythemia Myelofibrosis
• Intervention / Treatment: Drug: NS-018; Drug: Best Available Therapy

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
• Enrollment (Estimated): 120
• Phase: Phase 2

Contacts and Locations

• Study Contact: Name: NS Pharma, Inc.; Email: trialinfo@nspharma.com

Study Locations

• Germany
  • Augsburg, Germany, 86150
    • Withdrawn
    • Hamatologisch-onkologische Praxis Heinric/Bangerter Ausgsburg GbR
  • Halle, Germany, 6120
    • Recruiting
    • Universitaetsklinikum Halle (Saale)
  • Jena, Germany, 07747
    • Recruiting
    • Universitaetsklinikum Jena
  • Rostock, Germany, 18057
    • Recruiting
    • Universitatsmedizin Rostock
• Italy
  • Alessandria, Italy, 15121
    • Not yet recruiting
    • Azienda Ospedaliera SS. Antonio
  • Alessandria, Italy, 15121
    • Not yet recruiting
    • AO SS Antonio
  • Brescia, Italy, 25123
    • Recruiting
    • Azienda Socio Sanitaria Territoriale degli Spedali Civili di Brescia
  • Brescia, Italy, 25123
    • Recruiting
    • ASST Spedali Civili di Brescia
  • Catania, Italy, 95123
    • Not yet recruiting
    • AOU "Policlinico - San Marco"
  • Milano, Italy, 20122
    • Not yet recruiting
    • Fondazione IRCCS Ca' Granda Ospedale Maggiore Policlinico
  • Milano, Italy, 20121
    • Not yet recruiting
    • ASST Fatebenefratelli Sacco
  • Naples, Italy, 80131
    • Not yet recruiting
    • AO di Rilievo Ntl A Cardarelli
  • Naples, Italy, 80131
    • Withdrawn
    • Azienda Ospedaliera di Rilievo Nazionale
  • Napoli, Italy, 80131
    • Recruiting
    • AO di Rilievo Nazionale
  • Padova, Italy, 35128
    • Not yet recruiting
    • Azienda Ospedaliera di Padova
  • Palermo, Italy, 90127
    • Not yet recruiting
    • Azienda Ospedaliero Universitaria Policlinico Paolo Giaccone
  • Roma, Italy, 00144
    • Not yet recruiting
    • Istituto Nazionale Tumori Regina Elena Irccs
  • Roma, Italy, 00161
    • Not yet recruiting
    • Azienda Ospedaliera Universitaria Policlinico Umberto I
  • Rome, Italy, 00161
    • Recruiting
    • AO Uni Policlinico Umberto I
• Korea, Republic of
  • Banpo-dong, Korea, Republic of, 164 KR
    • Recruiting
    • The Catholic University of Korea, Seoul St. Mary's Hospital
  • Incheon, Korea, Republic of, 21565
    • Recruiting
    • Gachon University Gil Medical Center
  • Jinju-si, Korea, Republic of, 52727
    • Recruiting
    • Gyeongsang National University Hospital
  • Seongnam, Korea, Republic of, 164 KR
    • Withdrawn
    • CHA Bundang Medical Center, CHA University
  • Seoul, Korea, Republic of, 4401
    • Recruiting
    • Soon Chun Hyang Central Medical Center
• Malaysia
  • Ampang, Malaysia, 68000
    • Recruiting
    • Hospital Ampang
  • Johor Bahru, Malaysia, 80100
    • Recruiting
    • Hospital Sultanah Aminah
  • Kota Bahru, Malaysia, 15586
    • Recruiting
    • Hospital Raja Perempuan Zainab Ii
  • Kota Kinabalu, Malaysia, 88586
    • Recruiting
    • Hospital Queen Elizabeth
  • Kuala Lumpur, Malaysia, 59100
    • Recruiting
    • University Malaya Medical Centre
  • Petaling Jaya, Malaysia
    • Recruiting
    • Sunway Medical Centre
  • Pulau Pinang, Malaysia, 10990
    • Recruiting
    • Hospital Pulau Pinang
  • Perak
    • Ipoh, Perak, Malaysia, 30450
      • Withdrawn
      • Hospital Raja Permaisuri Bainun
• Poland
  • Bydgoszcz, Poland, 85-168
    • Not yet recruiting
    • Szpital Uniwersytecki nr 2 im. dr J. Biziela
  • Katowice, Poland, 40-519
    • Recruiting
    • Pratia Onkologia Katowice
  • Wrocław, Poland, 53-413 ,
    • Not yet recruiting
    • Dolnośląskie Centrum Onkologii we Wrocławiu, Oddział Hematologiczny
• Thailand
  • Khon Kaen, Thailand, 40002
    • Withdrawn
    • Srinagarind Hospital
  • Songkla, Thailand, 90110
    • Withdrawn
    • Songklanagarind Hospital
• Turkey
  • Tekirdağ, Turkey, 59100
    • Not yet recruiting
    • Namik Kemal University Medicine School
  • Trabzon, Turkey, 61100
    • Not yet recruiting
    • Karadeniz Teknik Universitesi Tip Fak,
  • İzmir, Turkey
    • Not yet recruiting
    • Ege Universitesi Tip Fak,
  • Istanbul
    • Bagcilar, Istanbul, Turkey, 34200
      • Not yet recruiting
      • Istanbul Medipol University
• United Kingdom
  • England
    • Bath, England, United Kingdom, BA1 3NG
      • Recruiting
      • Royal United Hospitals - Bath
    • London, England, United Kingdom, SE1 9RT
      • Not yet recruiting
      • Guys Hospital
    • London, England, United Kingdom, WC1E 6HX
      • Not yet recruiting
      • University College London Hospitals
    • Manchester, England, United Kingdom, M20 4BX
      • Recruiting
      • The Christie NHS Foundation Trust
    • Plymouth, England, United Kingdom, PL6 8DH
      • Recruiting
      • Derriford Hospital
    • West Bromwich, England, United Kingdom, B71 4HJ
      • Recruiting
      • Sandwell & West Birmingham Hospital
  • Scotland
    • Edinburgh, Scotland, United Kingdom, EH4 2XU
      • Not yet recruiting
      • Western General Hospital
    • Edinburgh, Scotland, United Kingdom, EH2XU 4
      • Not yet recruiting
      • Western General Hospital
• United States
  • Massachusetts
    • Worcester, Massachusetts, United States, 01655
      • Recruiting
      • University of Massachusetts Chan Medical School
  • Texas
    • Houston, Texas, United States, 77030
      • Recruiting
      • MD Anderson Cancer Center
    • Houston, Texas, United States, 77002
      • Recruiting
      • Houston Methodist Hospital

Participation Criteria

Eligibility Criteria

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

Description

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 Plan

How is the study designed?

Design Details

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

Number of Arms

2

Arms and Interventions

Participant Group / Arm	Intervention / Treatment
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	Drug: NS-018; Experimental
Active Comparator: Best Available Therapy (BAT); Single agent per Investigator discretion or no therapy	Drug: Best Available Therapy; Active Comparator

What is the study measuring?

Primary Outcome Measures

Outcome Measure	Measure Description	Time Frame
Change in spleen volume	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)	from baseline to week 24
Change in Total Symptom Score (TSS)	Proportion of subjects who achieve ≥50% change in total symptom score from baseline to Week 24 as measured by the MFSAF v4.0	from baseline to week 24

Secondary Outcome Measures

Outcome Measure	Measure Description	Time Frame
Change in spleen volume	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)	from baseline at anytime up to week 24
Comparison of treatment-emergent AEs	Laboratory events graded by the NCI CTCAE v5.0 will be assessed in both arms, NS-018 vs BAT.	from baseline to week 24

Collaborators and Investigators

• Sponsor: NS Pharma, Inc.
• Collaborators: Nippon Shinyaku Co., Ltd.

Study record dates

Study Major Dates

• Study Start (Actual): January 31, 2023
• Primary Completion (Estimated): May 24, 2024
• Study Completion (Estimated): May 24, 2024

Study Registration Dates

• First Submitted: April 9, 2021
• First Submitted That Met QC Criteria: April 20, 2021
• First Posted (Actual): April 22, 2021

Study Record Updates

• Last Update Posted (Actual): April 18, 2024
• Last Update Submitted That Met QC Criteria: April 16, 2024
• Last Verified: April 1, 2024

More Information

Terms related to this study

• Additional Relevant MeSH Terms: Neoplasms; Neoplasms by Site; Bone Marrow Diseases; Hematologic Diseases; Hemorrhagic Disorders; Myeloproliferative Disorders; Blood Coagulation Disorders; Blood Platelet Disorders; Bone Marrow Neoplasms; Hematologic Neoplasms; Primary Myelofibrosis; Thrombocytosis; Thrombocythemia, Essential; Polycythemia Vera; Polycythemia
• Other Study ID Numbers: NS-018-201

Plan for Individual participant data (IPD)

• Plan to Share Individual Participant Data (IPD)?: NO
• IPD Plan Description: Submission to the FDA

Drug and device information, study documents

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