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

Primary Myelofibrosis Clinical Trial

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)

Clinical Trial Details — Status: Recruiting

Administrative data

• NCT number: NCT04854096
• Other study ID #: NS-018-201
• Status: Recruiting
• Phase: Phase 2
• Start date: January 31, 2023
• Est. completion date: May 24, 2024

Study information

• Verified date: April 2024
• Source: NS Pharma, Inc.
• Contact: NS Pharma, Inc.
• Email: trialinfo[@]nspharma.com
• Is FDA regulated: No
• Study type: Interventional

Clinical Trial 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).

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.

Recruitment information / eligibility

• Status: Recruiting
• Enrollment: 120
• Est. completion date: May 24, 2024
• Est. primary completion date: May 24, 2024
• Accepts healthy volunteers: No
• Gender: All
• Age group: 18 Years and older

Eligibility

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.

Related Conditions & MeSH terms

• Polycythemia
• Polycythemia Vera
• Post-essential Thrombocythemia Myelofibrosis
• Post-polycythemia Vera Myelofibrosis
• Primary Myelofibrosis
• Thrombocythemia, Essential
• Thrombocytosis

Intervention

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

Locations

Country	Name	City	State
Germany	Hamatologisch-onkologische Praxis Heinric/Bangerter Ausgsburg GbR	Augsburg
Germany	Universitaetsklinikum Halle (Saale)	Halle
Germany	Universitaetsklinikum Jena	Jena
Germany	Universitätsmedizin Rostock	Rostock
Italy	AO SS Antonio	Alessandria
Italy	Azienda Ospedaliera SS. Antonio	Alessandria
Italy	ASST Spedali Civili di Brescia	Brescia
Italy	Azienda Socio Sanitaria Territoriale degli Spedali Civili di Brescia	Brescia
Italy	AOU "Policlinico - San Marco"	Catania
Italy	ASST Fatebenefratelli Sacco	Milano
Italy	Fondazione IRCCS CA' Granda Ospedale Maggiore Policlinico	Milano
Italy	AO di Rilievo Ntl A Cardarelli	Naples
Italy	Azienda Ospedaliera di Rilievo Nazionale	Naples
Italy	AO di Rilievo Nazionale	Napoli
Italy	Azienda Ospedaliera di Padova	Padova
Italy	Azienda Ospedaliero Universitaria Policlinico Paolo Giaccone	Palermo
Italy	Azienda Ospedaliera Universitaria Policlinico Umberto I	Roma
Italy	Istituto Nazionale Tumori Regina Elena IRCCS	Roma
Italy	AO Uni Policlinico Umberto I	Rome
Korea, Republic of	The Catholic University of Korea, Seoul St. Mary's Hospital	Banpo-dong
Korea, Republic of	Gachon University Gil Medical Center	Incheon
Korea, Republic of	Gyeongsang National University Hospital	Jinju-si
Korea, Republic of	CHA Bundang Medical Center, CHA University	Seongnam
Korea, Republic of	Soon Chun Hyang Central Medical Center	Seoul
Malaysia	Hospital Ampang	Ampang
Malaysia	Hospital Raja Permaisuri Bainun	Ipoh	Perak
Malaysia	Hospital Sultanah Aminah	Johor Bahru
Malaysia	Hospital Raja Perempuan Zainab II	Kota Bahru
Malaysia	Hospital Queen Elizabeth	Kota Kinabalu
Malaysia	University Malaya Medical Centre	Kuala Lumpur
Malaysia	Sunway Medical Centre	Petaling Jaya
Malaysia	Hospital Pulau Pinang	Pulau Pinang
Poland	Szpital Uniwersytecki nr 2 im. dr J. Biziela	Bydgoszcz
Poland	Pratia Onkologia Katowice	Katowice
Poland	Dolnoslaskie Centrum Onkologii we Wroclawiu, Oddzial Hematologiczny	Wroclaw
Thailand	Srinagarind Hospital	Khon Kaen
Thailand	Songklanagarind Hospital	Songkla
Turkey	Istanbul Medipol University	Bagcilar	Istanbul
Turkey	Ege Universitesi Tip Fak,	Izmir
Turkey	Namik Kemal University Medicine School	Tekirdag
Turkey	Karadeniz Teknik Universitesi Tip Fak,	Trabzon
United Kingdom	Royal United Hospitals - Bath	Bath	England
United Kingdom	Western General Hospital	Edinburgh	Scotland
United Kingdom	Western General Hospital	Edinburgh	Scotland
United Kingdom	Guys Hospital	London	England
United Kingdom	University College London Hospitals	London	England
United Kingdom	The Christie NHS Foundation Trust	Manchester	England
United Kingdom	Derriford Hospital	Plymouth	England
United Kingdom	Sandwell & West Birmingham Hospital	West Bromwich	England
United States	Houston Methodist Hospital	Houston	Texas
United States	MD Anderson Cancer Center	Houston	Texas
United States	University of Massachusetts Chan Medical School	Worcester	Massachusetts

Sponsors (2)

Lead Sponsor	Collaborator
NS Pharma, Inc.	Nippon Shinyaku Co., Ltd.

Countries where clinical trial is conducted

United States,  Germany,  Italy,  Korea, Republic of,  Malaysia,  Poland,  Thailand,  Turkey,  United Kingdom, 

Outcome

Type	Measure	Description	Time frame	Safety issue
Primary	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
Primary	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	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
Secondary	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