Clinical trial NCT04854096: 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)
Study type: INTERVENTIONAL
Overall status: TERMINATED
Phase: PHASE2
Conditions: Primary Myelofibrosis
Post-essential Thrombocythemia Myelofibrosis
Post-polycythemia Vera Myelofibrosis
Lead sponsor: NS Pharma, Inc.
Sponsor class: INDUSTRY
Collaborators: name: Nippon Shinyaku Co., Ltd.
First posted: 2021-04-22
Enrollment: 7
Sex: ALL
Minimum age (years): 18
Standard ages: ADULT
OLDER_ADULT
Accepts healthy volunteers: no
Allocation: RANDOMIZED
Intervention model: PARALLEL
Primary purpose: TREATMENT

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.

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.

Primary outcomes:
measure: Change in Spleen Volume
timeFrame: baseline and week 24
measure: Change in Total Symptom Score (TSS)
timeFrame: baseline and week 24
Secondary outcomes:
measure: Change in Spleen Volume
timeFrame: from baseline to anytime before or at week 24
measure: Comparison of Treatment-emergent AEs Between NS-018 and BAT
timeFrame: from baseline to week 24
Other outcomes:
Locations:
city: Worcester
country: United States
facility: University of Massachusetts Chan Medical School
state: Massachusetts
city: Houston
country: United States
facility: Houston Methodist Hospital
state: Texas
city: Houston
country: United States
facility: MD Anderson Cancer Center
state: Texas
city: Augsburg
country: Germany
facility: Hamatologisch-onkologische Praxis Heinric/Bangerter Ausgsburg GbR
city: Halle
country: Germany
facility: Universitaetsklinikum Halle (Saale)
city: Jena
country: Germany
facility: Universitaetsklinikum Jena
city: Rostock
country: Germany
facility: Universitätsmedizin Rostock
city: Alessandria
country: Italy
facility: AO SS Antonio
city: Alessandria
country: Italy
facility: Azienda Ospedaliera SS. Antonio
city: Brescia
country: Italy
facility: ASST Spedali Civili di Brescia
city: Brescia
country: Italy
facility: Azienda Socio Sanitaria Territoriale degli Spedali Civili di Brescia
city: Catania
country: Italy
facility: AOU "Policlinico - San Marco"
city: Milano
country: Italy
facility: ASST Fatebenefratelli Sacco
city: Milano
country: Italy
facility: Fondazione IRCCS CA' Granda Ospedale Maggiore Policlinico
city: Naples
country: Italy
facility: AO di Rilievo Ntl A Cardarelli
city: Naples
country: Italy
facility: Azienda Ospedaliera di Rilievo Nazionale
city: Napoli
country: Italy
facility: AO di Rilievo Nazionale
city: Padova
country: Italy
facility: Azienda Ospedaliera di Padova
city: Palermo
country: Italy
facility: Azienda Ospedaliero Universitaria Policlinico Paolo Giaccone
city: Roma
country: Italy
facility: Istituto Nazionale Tumori Regina Elena IRCCS
city: Roma
country: Italy
facility: Azienda Ospedaliera Universitaria Policlinico Umberto I
city: Rome
country: Italy
facility: AO Uni Policlinico Umberto I
city: Banpo-dong
country: Korea, Republic of
facility: The Catholic University of Korea, Seoul St. Mary's Hospital
city: Incheon
country: Korea, Republic of
facility: Gachon University Gil Medical Center
city: Jinju-si
country: Korea, Republic of
facility: Gyeongsang National University Hospital
city: Seongnam
country: Korea, Republic of
facility: CHA Bundang Medical Center, CHA University
city: Seoul
country: Korea, Republic of
facility: Soon Chun Hyang Central Medical Center
city: Ipoh
country: Malaysia
facility: Hospital Raja Permaisuri Bainun
state: Perak
city: Ampang
country: Malaysia
facility: Hospital Ampang
city: Johor Bahru
country: Malaysia
facility: Hospital Sultanah Aminah
city: Kota Bahru
country: Malaysia
facility: Hospital Raja Perempuan Zainab II
city: Kota Kinabalu
country: Malaysia
facility: Hospital Queen Elizabeth
city: Kuala Lumpur
country: Malaysia
facility: University Malaya Medical Centre
city: Petaling Jaya
country: Malaysia
facility: Sunway Medical Centre
city: Pulau Pinang
country: Malaysia
facility: Hospital Pulau Pinang
city: Bydgoszcz
country: Poland
facility: Szpital Uniwersytecki nr 2 im. dr J. Biziela
city: Katowice
country: Poland
facility: Pratia Onkologia Katowice
city: Wrocław
country: Poland
facility: Dolnośląskie Centrum Onkologii we Wrocławiu, Oddział Hematologiczny
city: Khon Kaen
country: Thailand
facility: Srinagarind Hospital
city: Songkla
country: Thailand
facility: Songklanagarind Hospital
city: Bagcilar
country: Turkey
facility: Istanbul Medipol University
state: Istanbul
city: İzmir
country: Turkey
facility: Ege Universitesi Tip Fak,
city: Tekirdağ
country: Turkey
facility: Namik Kemal University Medicine School
city: Trabzon
country: Turkey
facility: Karadeniz Teknik Universitesi Tip Fak,
city: Bath
country: United Kingdom
facility: Royal United Hospitals - Bath
state: England
city: London
country: United Kingdom
facility: Guys Hospital
state: England
city: London
country: United Kingdom
facility: University College London Hospitals
state: England
city: Manchester
country: United Kingdom
facility: The Christie NHS Foundation Trust
state: England
city: Plymouth
country: United Kingdom
facility: Derriford Hospital
state: England
city: West Bromwich
country: United Kingdom
facility: Sandwell & West Birmingham Hospital
state: England
city: Edinburgh
country: United Kingdom
facility: Western General Hospital
state: Scotland
city: Edinburgh
country: United Kingdom
facility: Western General Hospital
state: Scotland
Study officials:
References: