Primary Myelofibrosis, Post-essential Thrombocythemia Myelofibrosis, Post-polycythemia Vera Myelofibrosis
Conditions
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.
Interventions
DRUGNS-018
Experimental
Active Comparator
Sponsors
Nippon Shinyaku Co., Ltd.
NS Pharma, Inc.
Study design
Allocation
RANDOMIZED
Intervention model
PARALLEL
Primary purpose
TREATMENT
Masking
SINGLE (Outcomes Assessor)
Eligibility
Sex/Gender
ALL
Age
18 Years to No maximum
Healthy volunteers
No
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.
Design outcomes
Primary
| Measure | Time frame | Description |
|---|---|---|
| Change in Spleen Volume | baseline and week 24 | Proportion of subjects who achieve ≥35% reduction in spleen volume from baseline compared to Week 24 as measured by MRI (or by CT for applicable subjects) |
| Change in Total Symptom Score (TSS) | baseline and week 24 | Proportion of subjects who achieve ≥50% reduction in total symptom score from baseline compared to Week 24 as measured by the MF-SAF v4.0 |
Secondary
| Measure | Time frame | Description |
|---|---|---|
| Change in Spleen Volume | from baseline to anytime before or at week 24 | Proportion of subjects in NS-018 vs BAT arm who achieve ≥35% reduction 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 Between NS-018 and BAT | from baseline to week 24 | Laboratory events graded by the NCI CTCAE v5.0 will be assessed in both arms, to compare the safety profile of NS-018 versus BAT. |
Countries
Germany, Italy, Malaysia, Poland, South Korea, Thailand, Turkey (Türkiye), United Kingdom, United States
Participant flow
Participants by arm
| Arm | Count |
|---|---|
| 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
NS-018: Experimental | 5 |
| Best Available Therapy (BAT) Single agent per Investigator discretion or no therapy
Best Available Therapy: Active Comparator | 2 |
| Total | 7 |
Withdrawals & dropouts
| Period | Reason | FG000 | FG001 |
|---|---|---|---|
| Overall Study | Adverse Event | 1 | 0 |
| Overall Study | Other reasons | 1 | 0 |
| Overall Study | Study terminated by Sponsor due to business reasons. | 2 | 2 |
| Overall Study | Withdrawal by Subject | 1 | 0 |
Baseline characteristics
| Characteristic | NS-018 | Best Available Therapy (BAT) | Total |
|---|---|---|---|
| Age, Categorical <=18 years | 0 Participants | 0 Participants | 0 Participants |
| Age, Categorical >=65 years | 3 Participants | 2 Participants | 5 Participants |
| Age, Categorical Between 18 and 65 years | 2 Participants | 0 Participants | 2 Participants |
| Age, Continuous | 65.0 Years STANDARD_DEVIATION 16.48 | 70.5 Years STANDARD_DEVIATION 0.71 | 66.6 Years STANDARD_DEVIATION 13.72 |
| Ethnicity (NIH/OMB) Hispanic or Latino | 0 Participants | 0 Participants | 0 Participants |
| Ethnicity (NIH/OMB) Not Hispanic or Latino | 5 Participants | 2 Participants | 7 Participants |
| Ethnicity (NIH/OMB) Unknown or Not Reported | 0 Participants | 0 Participants | 0 Participants |
| Race (NIH/OMB) American Indian or Alaska Native | 0 Participants | 0 Participants | 0 Participants |
| Race (NIH/OMB) Asian | 3 Participants | 0 Participants | 3 Participants |
| Race (NIH/OMB) Black or African American | 0 Participants | 0 Participants | 0 Participants |
| Race (NIH/OMB) More than one race | 0 Participants | 0 Participants | 0 Participants |
| Race (NIH/OMB) Native Hawaiian or Other Pacific Islander | 0 Participants | 0 Participants | 0 Participants |
| Race (NIH/OMB) Unknown or Not Reported | 0 Participants | 0 Participants | 0 Participants |
| Race (NIH/OMB) White | 2 Participants | 2 Participants | 4 Participants |
| Sex: Female, Male Female | 3 Participants | 1 Participants | 4 Participants |
| Sex: Female, Male Male | 2 Participants | 1 Participants | 3 Participants |
Adverse events
| Event type | EG000 affected / at risk | EG001 affected / at risk |
|---|---|---|
| deaths Total, all-cause mortality | 0 / 5 | 0 / 2 |
| other Total, other adverse events | 5 / 5 | 2 / 2 |
| serious Total, serious adverse events | 1 / 5 | 0 / 2 |
Outcome results
Primary
Change in Spleen Volume
Proportion of subjects who achieve ≥35% reduction in spleen volume from baseline compared to Week 24 as measured by MRI (or by CT for applicable subjects)
Time frame: baseline and week 24
Population: The primary outcome measure for an efficacy endpoint to compare the efficacy of NS-018 to the Best Available Therapy (BAT) was analyzed among the limited participants enrolled before the study was terminated early for business reasons.
| Arm | Measure | Value (COUNT_OF_PARTICIPANTS) |
|---|---|---|
| NS-018 | Change in Spleen Volume | 0 Participants |
| Best Available Therapy (BAT) | Change in Spleen Volume | 0 Participants |
Primary
Change in Total Symptom Score (TSS)
Proportion of subjects who achieve ≥50% reduction in total symptom score from baseline compared to Week 24 as measured by the MF-SAF v4.0
Time frame: baseline and week 24
Population: This co-primary outcome measure for an efficacy endpoint to compare NS-018 to the Best Available Therapy (BAT) was analyzed among the limited participants enrolled before the study was terminated early for business reasons. .
| Arm | Measure | Value (COUNT_OF_PARTICIPANTS) |
|---|---|---|
| NS-018 | Change in Total Symptom Score (TSS) | 0 Participants |
| Best Available Therapy (BAT) | Change in Total Symptom Score (TSS) | 1 Participants |
Secondary
Change in Spleen Volume
Proportion of subjects in NS-018 vs BAT arm who achieve ≥35% reduction in spleen volume from baseline at any time up to Week 24 as measured by MRI (or by CT for applicable subjects)
Time frame: from baseline to anytime before or at week 24
Population: This secondary outcome measure for an efficacy endpoint to compare the efficacy of NS-018 to the Best Available Therapy (BAT) was analyzed among the limited participants enrolled before the study was terminated early for business reasons.
| Arm | Measure | Value (COUNT_OF_PARTICIPANTS) |
|---|---|---|
| NS-018 | Change in Spleen Volume | 1 Participants |
| Best Available Therapy (BAT) | Change in Spleen Volume | 0 Participants |
Secondary
Comparison of Treatment-emergent AEs Between NS-018 and BAT
Laboratory events graded by the NCI CTCAE v5.0 will be assessed in both arms, to compare the safety profile of NS-018 versus BAT.
Time frame: from baseline to week 24
Population: TEAE's were evaluated in the participants who received NS-018 or BAT.
| Arm | Measure | Value (COUNT_OF_PARTICIPANTS) |
|---|---|---|
| NS-018 | Comparison of Treatment-emergent AEs Between NS-018 and BAT | 5 Participants |
| Best Available Therapy (BAT) | Comparison of Treatment-emergent AEs Between NS-018 and BAT | 2 Participants |