Study to Assess Efficacy and Safety of NS-018 Compared to BAT in Patients With Myelofibrosis
- Conditions
- Primary MyelofibrosisPost-polycythemia Vera MyelofibrosisPost-essential Thrombocythemia Myelofibrosis
- Interventions
- Drug: NS-018Drug: 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.
Recruitment & Eligibility
- Status
- TERMINATED
- Sex
- All
- Target Recruitment
- 7
- 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.
- 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 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) 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
- Secondary Outcome Measures
Name Time Method Change in spleen volume 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 from baseline to week 24 Laboratory events graded by the NCI CTCAE v5.0 will be assessed in both arms, NS-018 vs BAT.
Trial Locations
- Locations (51)
University of Massachusetts Chan Medical School
🇺🇸Worcester, Massachusetts, United States
Houston Methodist Hospital
🇺🇸Houston, Texas, United States
Universitaetsklinikum Halle (Saale)
🇩🇪Halle, Germany
Hamatologisch-onkologische Praxis Heinric/Bangerter Ausgsburg GbR
🇩🇪Augsburg, Germany
Universitaetsklinikum Jena
🇩🇪Jena, Germany
Universitätsmedizin Rostock
🇩🇪Rostock, Germany
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
Azienda Ospedaliera di Rilievo Nazionale
🇮🇹Naples, Italy
Fondazione IRCCS CA' Granda Ospedale Maggiore Policlinico
🇮🇹Milano, Italy
Azienda Ospedaliero Universitaria Policlinico Paolo Giaccone
🇮🇹Palermo, Italy
AO di Rilievo Nazionale
🇮🇹Napoli, Italy
AO di Rilievo Ntl A Cardarelli
🇮🇹Naples, Italy
Azienda Ospedaliera di Padova
🇮🇹Padova, Italy
AO Uni Policlinico Umberto I
🇮🇹Rome, Italy
Azienda Ospedaliera Universitaria Policlinico Umberto I
🇮🇹Roma, Italy
Istituto Nazionale Tumori Regina Elena IRCCS
🇮🇹Roma, Italy
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, Korea, Republic of
Hospital Pulau Pinang
🇲🇾Pulau Pinang, Malaysia
Namik Kemal University Medicine School
🇹🇷Tekirdağ, Turkey
Karadeniz Teknik Universitesi Tip Fak,
🇹🇷Trabzon, Turkey
Guys Hospital
🇬🇧London, England, United Kingdom
Derriford Hospital
🇬🇧Plymouth, England, United Kingdom
Hospital Sultanah Aminah
🇲🇾Johor Bahru, Malaysia
Hospital Ampang
🇲🇾Ampang, Malaysia
University Malaya Medical Centre
🇲🇾Kuala Lumpur, Malaysia
Western General Hospital
🇬🇧Edinburgh, Scotland, United Kingdom
Pratia Onkologia Katowice
🇵🇱Katowice, Poland
Royal United Hospitals - Bath
🇬🇧Bath, England, United Kingdom
Sandwell & West Birmingham Hospital
🇬🇧West Bromwich, England, United Kingdom
Sunway Medical Centre
🇲🇾Petaling Jaya, Malaysia
Szpital Uniwersytecki nr 2 im. dr J. Biziela
🇵🇱Bydgoszcz, Poland
Srinagarind Hospital
🇹🇭Khon Kaen, Thailand
Hospital Raja Perempuan Zainab II
🇲🇾Kota Bahru, Malaysia
Songklanagarind Hospital
🇹🇭Songkla, Thailand
Istanbul Medipol University
🇹🇷Bagcilar, Istanbul, Turkey
Hospital Queen Elizabeth
🇲🇾Kota Kinabalu, Malaysia
Dolnośląskie Centrum Onkologii we Wrocławiu, Oddział Hematologiczny
🇵🇱Wrocław, Poland
The Christie NHS Foundation Trust
🇬🇧Manchester, England, United Kingdom
MD Anderson Cancer Center
🇺🇸Houston, Texas, United States
Hospital Raja Permaisuri Bainun
🇲🇾Ipoh, Perak, Malaysia
University College London Hospitals
🇬🇧London, England, United Kingdom
AO SS Antonio
🇮🇹Alessandria, Italy
Ege Universitesi Tip Fak,
🇹🇷İzmir, Turkey
ASST Fatebenefratelli Sacco
🇮🇹Milano, Italy