Primary MyelofibrosisPhase 1/2NCT01423851

Safety and Tolerability Study of Oral NS-018 in Patients With Primary Myelofibrosis (MF), Post-polycythemia Vera MF or Post-essential Thrombocythemia MF

A Phase 1/2 study testing NS-018 in people with Primary Myelofibrosis and Post-Polycythemia Vera Myelofibrosis, run by NS Pharma, Inc. at 9 sites in United States.

Completed

Finished. The study has ended and is not enrolling. Results may be posted on the official record.

Official record

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Trial summary

The purpose of this study is to determine the safety and tolerability of orally administered NS-018 in patients with Primary Myelofibrosis (PMF), Post-polycythemia Vera Myelofibrosis (post-PV MF), or Post-essential Thrombocythemia Myelofibrosis (post-ET MF) Read more about this study

Who is it for?: Ages 18 years and older
Conditions the study is for: Primary Myelofibrosis, Post-Polycythemia Vera Myelofibrosis, Post-Essential Thrombocythemia Myelofibrosis
What is being tested?: NS-018
Type of treatment: Pill or oral medicine
Could I receive a placebo?: No, everyone receives an active treatment
How many people: 77 participants
Where: 9 sitesUnited States
Study dates: Jun 2011to 22 Apr 2020
Phase: Phase 1/2
Are there results?: Yes, posted in the registrySummary in the doctors' view

Key requirements

Who can take part, as listed by the sponsor. Only the study team can confirm whether you are eligible, so take this list to your doctor.

Ages 18 years and older
All sexes
No healthy volunteers
Adult, Older adult

Who may be able to join

Primary myelofibrosis, post-PV MF, or post-ET MF that requires therapy
MF patients must have received prior JAK2 inhibitor therapy, and been found to be intolerant, or refractory/relapsed from prior JAK2 inhibitor therapy, based on investigator assessment
≥18 years old
ECOG Performance Status of ≤ 3
Estimated life expectancy of ≥12 weeks
Male or non-pregnant, non-lactating female patients

Show all 11Show fewer

Serum creatinine of ≤1.5 × the upper limit of normal (ULN)OR estimated creatinine clearance (CrCl) ≥ 40 ml/min/1.73 m2
Aspartate aminotransferase (AST) and alanine aminotransferase (ALT) ≤3 × the upper limit of normal (ULN) and total bilirubin ≤1.5 × ULN. If the total bilirubin is elevated between 1.5 x and 3 x ULN, patients with a direct bilirubin ≤ 1.5 X ULN are eligible during the Phase II portion.
Absolute neutrophil count (ANC) >1000/μL and Platelet count > 25,000/μL
QTcB ≤ 480 msec
No MF-directed treatment for at least 2 weeks prior to initiation of NS-018, including any use of corticosteroids for Myelofibrosis symptom or blood count management. Low dose corticosteroids ≤ 10 mg/day prednisone or equivalent is allowed for non-myelofibrosis purposes.

Who cannot join

Active, uncontrolled systemic infection
Patients with any unresolved toxicity greater than Grade 1 from previous anticancer therapy
Potentially curative therapy is available
Currently taking medication that is substantially metabolized by cytochrome P450 (CYP) 1A2 or CYP3A4 or taking medication known to be strong inhibitors or inducers of CYP3A4
Patients with a serious cardiac condition within the past 6 months
Pregnant or lactating

Show all 10Show fewer

Radiation therapy for splenomegaly within 6 months prior to study entry
Splenectomy (Phase 2 portion of the study only)
Known HIV positive status
Known active hepatitis, a history of viral hepatitis B or hepatitis C

Trial locations and contacts

9 sites in 1 country.

City, postcode or hospital

9 sites in 1 country

United States9 sites

University of Michigan
Ann Arbor, Michigan, 48109
Dana Farber Cancer Institute
Boston, Massachusetts, 02115
Northwestern University
Chicago, Illinois, 60611
University of Chicago
Chicago, Illinois, 60637
MD Anderson Cancer Center, Department of Leukemia
Houston, Texas, 77030
Mayo Clinic, Jacksonville
Jacksonville, Florida, 32224
Weill Cornell Medical College
New York, New York, 10021
UC San Diego Moores Cancer Center
San Diego, California, 92093-0698
Mayo Clinic Scottsdale Recruiting
Scottsdale, Arizona, 85259-5499

Other trials in United States

About this study

Official title: A Phase 1/2, Open-label, Dose-Escalation Multi-center Study to Assess the Safety, Tolerability, PK and PD of Orally Administered NS-018 in Patients With Primary Myelofibrosis (MF), Post-polycythemia Vera MF, or Post-essential Thrombocythemia MF

Read the detailed description

This is a Phase 1/2 study that is currently enrolling Janus kinase 2 (JAK2) failures into the Phase 2 portion of the study.

Conditions: Primary Myelofibrosis, Post-Polycythemia Vera Myelofibrosis, Post-Essential Thrombocythemia Myelofibrosis
Being tested: NS-018
Keywords: Keywords provided by NS Pharma, Inc.:, JAK2 kinase inhibitor, NS-018, Myeloproliferative Neoplasms, Primary Myelofibrosis, post-Polycythemia Vera Myelofibrosis, post-Essential Thrombocythemia Myelofibrosis, Additional relevant MeSH terms:, Bone Marrow Diseases, Hematologic Diseases, Polycythemia Vera, Thrombocythemia, Essential, PMF, post-PV MF, post-ET MF
Medical subject headings: Primary Myelofibrosis, Myeloproliferative Disorders, Bone Marrow Diseases, Hematologic Diseases, Polycythemia Vera, Thrombocythemia, Essential

What participants receive

What participants receive. In a randomised study each person is assigned to one group by chance.

NS-018Drug
Treatment will be administered continuously as oral daily therapy in cycles of 4 weeks in duration (28 day treatment cycles).

Study groups in NCT01423851
Study group	Role	What they receive
Intervention: Drug: NS-018	Experimental	In Phase 1 part, subjects were treated with oral NS-018 at a dose of 75 - 400 mg once daily or 100 - 400 mg twice daily. In Phase 2 part, subjects were treated with oral NS-018 at a dose of 300 mg once daily. Receives: Drug: NS-018

What is being measured

The primary outcome is the main question the study is designed to answer.

Part 1 and Part 2: Number of Subjects With Adverse Events and Serious Adverse Event
AEs (non-serious, serious) as variables of safety and tolerability of NS-018 were assesed. The number of patients were presented as Overall summary of AEs including treatment-emergent AEs (TEAEs); Treatment-emergent SAEs; Drug-related TEAEs; Treatment-emergent AEs leading to permanent discontinuation of study drug; Hospitalization or prolongation of existing hospitalization; Death.
Measured: From screening to until study discontinuation (approximate 8 years 10 months)
Part 2: Number of Patient With Objective Response Using International Working Group-Myeloproliferative Neoplasms Research and Treatment (IWG-MRT) and European Leukemia Net (ELN)
Six response categories are listed: complete remission (CR) and partial remission signify treatment effects that are consistent with disease modification, whereas drug-induced improvements in MF-symptomatic burden were annotated as clinical improvement, anemia response, spleen response, orsymptoms response. Additional criteria are provided for progressive disease, stable disease, and relapse. The objective response was defined as the number of patients with confirmed complete remission (CR) + partial response (PR) + clinical improvement (CI) during the treatment period.
Measured: Cycle 7 Day 1 (duration of cycle was 4 weeks)
Part 2: Change From Baseline in Spleen Size
Change from baseline in spleen size was assessed by magnetic resonance imaging (MRI) (computed tomography [CT] scan for patients not able to tolerate MRI).
Measured: From Baseline to Cycle 7 Day 1 (duration of cycle was 4 weeks)
Part 2: Change From Baseline in Bone Marrow Assessment
Bone marrow was assessed by aspiration and biopsy for grade changes in osteomyelofibrosis. Fibrosis was graded according to European Consensus Myelofibrosis Grading Criteria, ranging from grade 0, which corresponds to normal bone marrow, to grade 3, in which coarse bundles of collagen fibrosis are identifiable with significant osteosclerosis.
Measured: From baseline to Cycle 7 Day 1 (duration of cycle was 4 weeks)

Secondary outcomes (12)

Part 1: Number of Patients With Objective Response Using International Working Group-Myeloproliferative Neoplasms Research and Treatment (IWG-MRT)
Six response categories are listed: complete remission (CR) and partial remission signify treatment effects that are consistent with disease modification, whereas drug-induced improvements in MF-symptomatic burden were annotated as clinical improvement, anemia response, spleen response, orsymptoms response. Additional criteria are provided for progressive disease, stable disease, and relapse. The objective response was defined as the number of patients with confirmed "complete remission (CR) + partial response (PR) + clinical improvement (CI)" during the treatment period.
Measured: Cycle 7 Day 1 (duration of cycle was 4 weeks)
Part 1: Change From Baseline in Spleen Size
Change from baseline in spleen size was assessed by palpation.
Measured: From Baseline to Cycle 7 Day 1 (duration of cycle was 4 weeks)
Part 1: Change From Baseline in Bone Marrow Assessment
Bone marrow was assessed by aspiration and biopsy for grade changes in osteomyelofibrosis. Fibrosis was graded according to European Consensus Myelofibrosis Grading Criteria, ranging from grade 0, which corresponds to normal bone marrow, to grade 3, in which coarse bundles of collagen fibrosis are identifiable with significant osteosclerosis.
Measured: From baseline to Cycle 7 Day 1 (duration of cycle was 4 weeks)
Part 1: Change From Baseline in Quality of Life Assessments Using Myelofibrosis Symptom Assessment Form (MF-SAF)
MF SAF is a 20-item instrument comprised of 4 subscales: 1) the Brief Fatigue Inventory [= average of 9 fatigue scores], 2) Splenomegaly associated symptoms [= average of 4 splenomegaly and associated scores], 3) Catabolic/proliferative Symptoms [= average of 3 catabolic/proliferative associated scores] and 4) Overall Quality of Life. The items were on a scale from 1 to 10 where 1= most favorable, and 10= least favorable.
Measured: From baseline to Cycle 7 Day 1 (duration of cycle was 4 weeks)
Part 2: Change From Baseline in Quality of Life Assessments Using Myeloproliferative Neoplasm Symptom Assessment Form (MPN SAF (MPN 10)
Symptoms are evaluated by the MPN-SAF Total Symptom Score (TSS). The MPN-SAF TSS is assessed by the patients themselves and this includes fatigue, concentration, early satiety, inactivity, night sweats, itching, bone pain, abdominal discomfort, weight loss, and fevers. Scoring is from 0 (absent/as good as it can be) to 10 (worst imaginable/as bad as it can be) for each item. The MPN-SAF TSS is the summation of all the individual scores (0-100 scale). Symptoms response requires >50% reduction in the MPN-SAF TSS.
Measured: From baseline to Cycle 7 Day 1 (duration of cycle was 4 weeks)
Part 1 and Part 2: Change in Baseline in Janus Kinase 2 (JAK2) V617F Allele Burden Levels
The JAK2 V617F allele burden mean changes from baseline (%) are presented as pharmacodynamics parameters.
Measured: Part 1 and Part 2: From baseline to Cycle 7 Day 1 (duration of cycle was 4 weeks)
Part 2: Change From Baseline in Phosphorylated Signal Transducer and Activator of Transcription 3 (Phospho-STAT3)
The Phospho-STAT3 mean changes from baseline (%) are presented as pharmacodynamics parameters.
For phospho-STAT3 values (Phase 2 only), study samples were incubated (± IL-6) and labeled with CD markers. Surface markers included CD3+ (CD4+ [helper T cells] and CD8+ [cytotoxic T cells]) and CD14+ (monocytes) to which intracellular phospho STAT3 was targeted. The levels of phospho-STAT3 in CD14+, CD3+CD4+ and CD3+CD8+ cell subtypes were quantified. Phosphorylated-STAT3 levels were evaluated in the cell types before and after IL-6 incubation (stimulation) and reported both as mean fluorescence intensity (MFI) and the percentage of positive cells. For each sample time point, the MFI was normalized to a fold change.
The fold change was calculated by MFI after IL-6 treatment/MFI before IL-6 treatment. The percent positive cells were normalized by subtracting the percent positive cells before IL-6 treatment from the percent positive cells after IL-6 treatment.
Measured: From Baseline to Pre-dose at Cycle 1 Day 1, Cycle 1 Day 15, Cycle 2 Day 1 (duration of cycle was 4 weeks)
Part1 and Part 2: Observed Maximum Concentration (Cmax)
To determine the Cmax as pharmacokinetic parameters of NS-018.
Measured: Pre-dose, 0.5 to 24 hours post-dose for Part 1: Cycle 1 Day 1, Cycle 1 Day 8, Cycle 2 Day 1 and for Part 2: Cycle 1 Day 1, Cycle 1 Day 15, Cycle 2 Day 1 (duration of cycle was 4 weeks)
Part 1 and Part 2: Time to Maximum Plasma Concentration (Tmax)
To determine the Tmax as pharmacokinetic parameters of NS-018.
Measured: Pre-dose, 0.5 to 24 hours post-dose for Part 1: Cycle 1 Day 1, Cycle 1 Day 8, Cycle 2 Day 1 and for Part 2: Cycle 1 Day 1, Cycle 2 Day 1 (duration of cycle was 4 weeks)
Part1 and Part 2: Area Under the Plasma Concentration-time Curve (AUC0-24)
To determine the AUC0-24 as pharmacokinetic parameters of NS-018.
Measured: Pre-dose, 0.5 to 24 hours post-dose for Part 1: Cycle 1 Day 1, Cycle 2 Day 1 and for Part 2: Cycle 1 Day 1 (duration of cycle was 4 weeks)
Part 1 and Part 2: Terminal Elimination Half-life (t½)
To determine the t½ as pharmacokinetic parameters of NS-018.
Measured: Pre-dose, 0.5 to 24 hours post-dose for Part 1: Cycle 1 Day 1, Cycle 1 Day 8, Cycle 2 Day 1 and for Part 2: Cycle 1 Day 1, Cycle 2 Day 1 (duration of cycle was 4 weeks)
Part1 and Part 2: Accumulation Ratio (AR)
To determine the AR as pharmacokinetic parameters of NS-018. AR was calculated as AR = (AUC0-24) Cycle 2 Day 1/ (AUC0-24) Cycle 1 Day 1.
Measured: Part 1 and Part 2: Cycle 2 Day 1 (duration of cycle was 4 weeks)

Timeline

From the start of the study to its completion; the mark is today. Estimated dates are the sponsor’s plan.

Jun 201122 Apr 2020

First posted26 Aug 2011 (estimated)
Study startJun 2011
Primary completion22 Apr 2020
Study completion22 Apr 2020

Resources

Official record on ClinicalTrials.govThe registry entry this page is built from, with its full change history.
Posted resultsParticipant flow, outcome measures and adverse events reported by the sponsor.
Publications (1)Papers the sponsor has linked to this study.
Other trials for Primary MyelofibrosisStudies of the same condition, open and under way.
What the trial phases meanHow a treatment moves from first tests in people to approval.

More details

For doctors and researchers: how the study is designed, who runs it, and its registry IDs.

Study design

Study type: Interventional
Phase: Phase 1/2
Primary purpose: Treatment
Allocation: Not applicable
Intervention model: Sequential
Model description: Phase 1: 75, 125, 200, 300, 400 mg QD and 100, 200, 250, 300, 400 mg BID Phase 2: 300 mg QD
Masking: None (open label)
Enrolment: 77 participants (actual)

IDs, dates and publications

ClinicalTrials.gov ID: NCT01423851
Sponsor's protocol ID: NS-018-101
Status last verified: Feb 2022
First submitted: 15 Aug 2011
Last updated: 9 Mar 2022
Results posted: Yes, on ClinicalTrials.gov
Data monitoring committee: Yes

Publications

Verstovsek S, Talpaz M, Ritchie E, Wadleigh M, Odenike O, Jamieson C, Stein B, Uno T, Mesa RA. A phase I, open-label, dose-escalation, multicenter study of the JAK2 inhibitor NS-018 in patients with myelofibrosis. Leukemia. 2017 Feb;31(2):393-402. doi: 10.1038/leu.2016.215. Epub 2016 Aug 1.
PubMed 27479177

Want to know more?

The sponsor has not listed a contact. The official record may have more details.

Talk to your doctor first and take this page with you. Only the study team can confirm whether you can join.

Questions to ask the study team

What is the study trying to find out?
What would I need to do, and how often would I visit?
Could I receive a placebo instead of the treatment?
What are the possible risks and benefits for me?
Will it cost me anything? Are travel or time paid for?
Can I keep seeing my own doctor during the study?
What happens when the study ends?

See locations

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Myelofibrosis, Anemia
Active, not recruitingPhase 3
Study of Selinexor in Combination With Ruxolitinib in Myelofibrosis
Myelofibrosis
RecruitingPhase 2
Study of Momelotinib in Combination With Luspatercept in Participants With Transfusion Dependent Myelofibrosis
Primary Myelofibrosis, Myelofibrosis; Primary Myelofibrosis; Post-polycythemia Vera Myelofibrosis; Post-essential Thrombocythemia Myelofibrosis
Not yet recruitingPhase 1
Maintenance Treatment With Imetelstat in Patients With High-Risk Myeloid Neoplasms After Allo-SCT
High-risk Myeloid Malignancy, Allogenic Stem Cell Transplantation

All Primary Myelofibrosis trials

Study at a glance

From the registry record, last updated by the sponsor on 9 Mar 2022. Recruitment status is as the sponsor reported it: confirm with the study team.

Official title: A Phase 1/2, Open-label, Dose-Escalation Multi-center Study to Assess the Safety, Tolerability, PK and PD of Orally Administered NS-018 in Patients With Primary Myelofibrosis (MF), Post-polycythemia Vera MF, or Post-essential Thrombocythemia MF
ClinicalTrials.gov ID: NCT01423851
Acronym / sponsor ID: NS-018-101
Conditions: Primary Myelofibrosis, Post-Polycythemia Vera Myelofibrosis, Post-Essential Thrombocythemia Myelofibrosis
Keywords: Keywords provided by NS Pharma, Inc.:, JAK2 kinase inhibitor, NS-018, Myeloproliferative Neoplasms, Primary Myelofibrosis, post-Polycythemia Vera Myelofibrosis, post-Essential Thrombocythemia Myelofibrosis, Additional relevant MeSH terms:
Phase: Phase 1/2
Study type: Interventional
Recruitment status: Completed
Enrolment: 77 participants (actual)
Lead sponsor: NS Pharma, Inc.Industry (pharma, biotech, devices)
Study start: Jun 2011
Primary completion: 22 Apr 2020 (actual)
Study completion: 22 Apr 2020 (actual)
First posted: 26 Aug 2011 (estimated)
Results: Posted 9 Mar 2022

Clinical summary

The research question as the sponsor registered it. This describes what the study plans to test, not what it found.

Detailed description

This is a Phase 1/2 study that is currently enrolling Janus kinase 2 (JAK2) failures into the Phase 2 portion of the study.

Study design

Primary purpose: Treatment
Allocation: Not applicable
Intervention model: Sequential
Masking: None (open label)
Number of arms: 1
Model description: Phase 1: 75, 125, 200, 300, 400 mg QD and 100, 200, 250, 300, 400 mg BID Phase 2: 300 mg QD

Arm	Type	Receives
Intervention: Drug: NS-018	Experimental	Drug: NS-018In Phase 1 part, subjects were treated with oral NS-018 at a dose of 75 - 400 mg once daily or 100 - 400 mg twice daily. In Phase 2 part, subjects were treated with oral NS-018 at a dose of 300 mg once daily.

Who may qualify

Ages: 18 years and older
Sex: All
Healthy volunteers: Not accepted
Age groups: Adult, Older adult

Key inclusion criteria (11 listed)

Primary myelofibrosis, post-PV MF, or post-ET MF that requires therapy
MF patients must have received prior JAK2 inhibitor therapy, and been found to be intolerant, or refractory/relapsed from prior JAK2 inhibitor therapy, based on investigator assessment
≥18 years old
ECOG Performance Status of ≤ 3
Estimated life expectancy of ≥12 weeks

Key exclusion criteria (10 listed)

Active, uncontrolled systemic infection
Patients with any unresolved toxicity greater than Grade 1 from previous anticancer therapy
Potentially curative therapy is available
Currently taking medication that is substantially metabolized by cytochrome P450 (CYP) 1A2 or CYP3A4 or taking medication known to be strong inhibitors or inducers of CYP3A4
Patients with a serious cardiac condition within the past 6 months

Eligibility is decided by the study team after screening; this overview does not establish that a patient qualifies. Full inclusion and exclusion criteria.

Interventions

Intervention	Type	Arms
NS-018Treatment will be administered continuously as oral daily therapy in cycles of 4 weeks in duration (28 day treatment cycles).	Drug	Intervention: Drug: NS-018

Primary outcome

Part 1 and Part 2: Number of Subjects With Adverse Events and Serious Adverse Event
Time frame: From screening to until study discontinuation (approximate 8 years 10 months)
AEs (non-serious, serious) as variables of safety and tolerability of NS-018 were assesed. The number of patients were presented as Overall summary of AEs including treatment-emergent AEs (TEAEs); Treatment-emergent SAEs; Drug-related TEAEs; Treatment-emergent AEs leading to permanent discontinuation of study drug; Hospitalization or prolongation of existing hospitalization; Death.
Part 2: Number of Patient With Objective Response Using International Working Group-Myeloproliferative Neoplasms Research and Treatment (IWG-MRT) and European Leukemia Net (ELN)
Time frame: Cycle 7 Day 1 (duration of cycle was 4 weeks)
Six response categories are listed: complete remission (CR) and partial remission signify treatment effects that are consistent with disease modification, whereas drug-induced improvements in MF-symptomatic burden were annotated as clinical improvement, anemia response, spleen response, orsymptoms response. Additional criteria are provided for progressive disease, stable disease, and relapse. The objective response was defined as the number of patients with confirmed complete remission (CR) + partial response (PR) + clinical improvement (CI) during the treatment period.
Part 2: Change From Baseline in Spleen Size
Time frame: From Baseline to Cycle 7 Day 1 (duration of cycle was 4 weeks)
Change from baseline in spleen size was assessed by magnetic resonance imaging (MRI) (computed tomography [CT] scan for patients not able to tolerate MRI).
Part 2: Change From Baseline in Bone Marrow Assessment
Time frame: From baseline to Cycle 7 Day 1 (duration of cycle was 4 weeks)
Bone marrow was assessed by aspiration and biopsy for grade changes in osteomyelofibrosis. Fibrosis was graded according to European Consensus Myelofibrosis Grading Criteria, ranging from grade 0, which corresponds to normal bone marrow, to grade 3, in which coarse bundles of collagen fibrosis are identifiable with significant osteosclerosis.

12 secondary outcomes

Part 1: Number of Patients With Objective Response Using International Working Group-Myeloproliferative Neoplasms Research and Treatment (IWG-MRT)
Time frame: Cycle 7 Day 1 (duration of cycle was 4 weeks)
Part 1: Change From Baseline in Spleen Size
Time frame: From Baseline to Cycle 7 Day 1 (duration of cycle was 4 weeks)
Part 1: Change From Baseline in Bone Marrow Assessment
Time frame: From baseline to Cycle 7 Day 1 (duration of cycle was 4 weeks)
Part 1: Change From Baseline in Quality of Life Assessments Using Myelofibrosis Symptom Assessment Form (MF-SAF)
Time frame: From baseline to Cycle 7 Day 1 (duration of cycle was 4 weeks)
Part 2: Change From Baseline in Quality of Life Assessments Using Myeloproliferative Neoplasm Symptom Assessment Form (MPN SAF (MPN 10)
Time frame: From baseline to Cycle 7 Day 1 (duration of cycle was 4 weeks)
Part 1 and Part 2: Change in Baseline in Janus Kinase 2 (JAK2) V617F Allele Burden Levels
Time frame: Part 1 and Part 2: From baseline to Cycle 7 Day 1 (duration of cycle was 4 weeks)
Part 2: Change From Baseline in Phosphorylated Signal Transducer and Activator of Transcription 3 (Phospho-STAT3)
Time frame: From Baseline to Pre-dose at Cycle 1 Day 1, Cycle 1 Day 15, Cycle 2 Day 1 (duration of cycle was 4 weeks)
Part1 and Part 2: Observed Maximum Concentration (Cmax)
Time frame: Pre-dose, 0.5 to 24 hours post-dose for Part 1: Cycle 1 Day 1, Cycle 1 Day 8, Cycle 2 Day 1 and for Part 2: Cycle 1 Day 1, Cycle 1 Day 15, Cycle 2 Day 1 (duration of cycle was 4 weeks)
Part 1 and Part 2: Time to Maximum Plasma Concentration (Tmax)
Time frame: Pre-dose, 0.5 to 24 hours post-dose for Part 1: Cycle 1 Day 1, Cycle 1 Day 8, Cycle 2 Day 1 and for Part 2: Cycle 1 Day 1, Cycle 2 Day 1 (duration of cycle was 4 weeks)
Part1 and Part 2: Area Under the Plasma Concentration-time Curve (AUC0-24)
Time frame: Pre-dose, 0.5 to 24 hours post-dose for Part 1: Cycle 1 Day 1, Cycle 2 Day 1 and for Part 2: Cycle 1 Day 1 (duration of cycle was 4 weeks)
Part 1 and Part 2: Terminal Elimination Half-life (t½)
Time frame: Pre-dose, 0.5 to 24 hours post-dose for Part 1: Cycle 1 Day 1, Cycle 1 Day 8, Cycle 2 Day 1 and for Part 2: Cycle 1 Day 1, Cycle 2 Day 1 (duration of cycle was 4 weeks)
Part1 and Part 2: Accumulation Ratio (AR)
Time frame: Part 1 and Part 2: Cycle 2 Day 1 (duration of cycle was 4 weeks)

Results and safety

Results posted to the registry on 9 Mar 2022, as reported by the sponsor. Figures are copied from the record, not re-analysed. Full results on ClinicalTrials.gov.

Participant flow

Group	Started	Completed
Part 1: 75 mg QD	3	0
Part 1: 125 mg QD	3	0
Part 1: 200 mg QD	3	0
Part 1: 300 mg QD	6	0
Part 1: 400 mg QD	3	0
Part 1: 100 mg BID	3	0
Part 1: 200 mg BID	3	0
Part 1: 250 mg BID	8	0
Part 1: 300 mg BID	8	0
Part 1: 400 mg BID	8	0
Part 2: 300 mg QD	29	0

Primary outcome: Part 1 and Part 2: Number of Subjects With Adverse Events and Serious Adverse Event

Time frame: From screening to until study discontinuation (approximate 8 years 10 months). Count of participants. Unit: Participants

Measure	Part 1: 75 mg QD n = 3	Part 1: 125 mg QD n = 4	Part 1: 200 mg QD n = 10	Part 1: 300 mg QD n = 15	Part 1: 400 mg QD n = 4	Part 1: 100 mg BID n = 5	Part 1: 200 mg BID n = 13	Part 1: 250 mg BID n = 8	Part 1: 300 mg BID n = 12	Part 1: 400 mg BID n = 8	Part 2: 300 mg QD n = 29
Not TEAE	0	0	0	0	1	2	1	3	4	2	6
Any AE	3	4	9	14	4	4	11	8	12	8	29
Any Treatment Emergent AE	3	4	9	14	4	4	11	8	12	8	29
Drug Related TEAE	1	1	8	11	4	2	4	5	10	7	24
Any Serious TEAE	2	2	2	6	1	1	4	3	4	3	13
TEAE Leading to Discontinuation of study drug	1	0	0	4	0	0	0	3	4	2	5
Hospitalization or Prolongation of Existing Hospitalization	1	2	2	6	1	1	3	2	3	1	11
Death	0	0	0	0	0	0	0	0	0	0	1

Population analysed: The safety population included all patients who received at least 1 dose of study drug. NS-018-101 study was dose-finding study, Principal investigator (PI) could increase or decrease dose-level per protocol. Totals are based on number of patients and not on dose-level cohort. Patients can appear in more than one dose-level cohort.

Primary outcome: Part 2: Number of Patient With Objective Response Using International Working Group-Myeloproliferative Neoplasms Research and Treatment (IWG-MRT) and European Leukemia Net (ELN)

Time frame: Cycle 7 Day 1 (duration of cycle was 4 weeks). Count of participants. Unit: Participants

Measure	Part 2: 300 mg QD n = 12
Value	1

Population analysed: The efficacy population included all patients who received at least one dose of study drug and had one baseline and at least one post-baseline efficacy assessment. Here, the overall number of subjects analyzed signifies only the subjects with available data that were analyzed evaluated on that specific cycle day.

Primary outcome: Part 2: Change From Baseline in Spleen Size

Time frame: From Baseline to Cycle 7 Day 1 (duration of cycle was 4 weeks). Mean (Standard Deviation). Unit: cubic millimeter (mm3)

Measure	Part 2: 300 mg QD n = 16
Value	-335918.1 (558459.9)

Primary outcome: Part 2: Change From Baseline in Bone Marrow Assessment

Time frame: From baseline to Cycle 7 Day 1 (duration of cycle was 4 weeks). Count of participants. Unit: Participants

Measure	Part 2: 300 mg QD n = 3
Increased by at least 1 grade level	1
Increased by at least 2 grade level	0
Decreased by at least 1 grade level	2
Decreased by at least 2 grade level	0

12 secondary outcomes are reported in the full results.

Adverse events

Time frame: Part 1 and Part 2: From screening to until study discontinuation (approximate 8 years 10 months). Other adverse events reported at 5% frequency or more

Group	Serious adverse events	Other adverse events	Deaths
Part 1: 75 mg QD	2 of 3 (66.7%)	3 of 3 (100%)	0 of 3
Part 1: 125 mg QD	2 of 4 (50%)	4 of 4 (100%)	0 of 4
Part 1: 200 mg QD	2 of 10 (20%)	9 of 10 (90%)	0 of 10
Part 1: 300 mg QD	6 of 15 (40%)	14 of 15 (93.3%)	0 of 15
Part 1: 400 mg QD	1 of 4 (25%)	4 of 4 (100%)	0 of 4
Part 1: 100 mg BID	1 of 5 (20%)	4 of 5 (80%)	0 of 5
Part 1: 200 mg BID	4 of 13 (30.8%)	11 of 13 (84.6%)	0 of 13
Part 1: 250 mg BID	3 of 8 (37.5%)	8 of 8 (100%)	0 of 8
Part 1: 300 mg BID	4 of 12 (33.3%)	12 of 12 (100%)	0 of 12
Part 1: 400 mg BID	3 of 8 (37.5%)	7 of 8 (87.5%)	0 of 8
Part 2: 300 mg QD	13 of 29 (44.8%)	29 of 29 (100%)	1 of 29

Loading the posted results from ClinicalTrials.gov…

Research links

Official record on ClinicalTrials.govLast updated by the sponsor 9 Mar 2022.
Posted resultsParticipant flow, baseline, all outcome measures and adverse events.
Derived from this study: PubMed 27479177Verstovsek S, Talpaz M, Ritchie E, Wadleigh M, Odenike O, Jamieson C, Stein B, Uno T, Mesa RA. A phase I, open-label, dose-escalation, multicenter study of the JAK2 inhibitor NS-018 in patients with myelofibrosis. Leukemia. 2017 Feb;31(2):393-402. doi: 10.1038/leu.2016.215. Epub 2016 Aug 1.

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Referral and contact

AzTrials does not enrol participants or take referrals. Contact the study team or a site listed below; they decide who can take part. This study is not recruiting at the moment.

Srdan Verstovsek, M.D., Ph.D. principal investigator

MD Anderson Cancer Center, Houston, TX, 77030

9 sites in 1 country: see every site and its status.

Questions about this trial

What is this clinical trial studying?

A Phase 1/2 study testing NS-018 in people with Primary Myelofibrosis and Post-Polycythemia Vera Myelofibrosis, run by NS Pharma, Inc. at 9 sites in United States.

The full registered description is in the About this study section and the official record.

Who may be eligible to take part?

The sponsor lists 11 inclusion and 10 exclusion criteria. Eligibility is decided by the study team after screening, so read the full criteria and contact a listed site.

Is this clinical trial currently recruiting?

The record says: finished, as of the sponsor's last update on 9 Mar 2022. Status can change between updates, so confirm with the study contact before making plans.

Where is the study taking place?

The record lists 9 sites in United States. Whether a site is taking part right now should be confirmed with that site. See every site.

What are the possible benefits and risks?

They depend on the study and the treatment, and no study can promise a benefit. The study team explains the known risks during informed consent, before anyone joins; the record itself does not list them.

What does this combined phase mean?

Phase 1 studies test a treatment in a small group of people for the first time or in a new way, mainly to check safety and find the right dose.

Phase 2 studies give the treatment to a larger group to see whether it has the intended effect and to keep checking safety.

Not every study follows the same path, and some studies (observational studies, device studies) have no phase.

Are results available for this study?

Yes. Results are posted in the registry (first posted 9 Mar 2022). A summary is in the For doctors view, and the full results are on ClinicalTrials.gov.

How can a doctor refer a patient or contact the research team?

The record lists no contact. The official record names the sponsor, who can be asked directly. AzTrials does not enrol participants or take referrals.

What does the primary outcome measure?

Part 1 and Part 2: Number of Subjects With Adverse Events and Serious Adverse Event (time frame: From screening to until study discontinuation (approximate 8 years 10 months)). The study lists 4 primary outcomes in all. It is what the study was designed to measure, not a finding.

Where can I read the original study information?

On the ClinicalTrials.gov record for NCT01423851, which also lists 1 linked publication.

Does a listing mean the treatment is approved or proven to work?

No. A listing means the study is registered. It does not show that the treatment is safe, works, or is approved by a regulator.

How often is this information updated?

AzTrials copies changed records from ClinicalTrials.gov every night and reloads the whole registry every week. The sponsor last updated this record on 9 Mar 2022.