Phase 2
N=77
Safety and Tolerability Study of Oral NS-018 in Patients With Primary Myelofibrosis (MF), Post-polycythemia Vera MF or Post-essential Thrombocythemia MF
Primary Myelofibrosis · Post-Polycythemia Vera Myelofibrosis · Post-Essential Thrombocythemia Myelofibrosis
Bottom Line
View on ClinicalTrials.gov: NCT01423851 ↗Enrolled (actual)
77
Serious AEs
36.9%
Results posted
Mar 2022
Primary outcome: Primary: Part 1 and Part 2: Number of Subjects With Adverse Events and Serious Adverse Event — 0; 0; 0; 0 Participants
Study Design & Population
- Study type
- Interventional
- Phase
- Phase 2
- Interventions
- NS-018 (Drug)
- Age
- Adult, Older Adult · 18+ yrs
- Sex
- All
- Sponsor
- NS Pharma, Inc.
- Primary completion
- Apr 2020
Outcome Measures
| Outcome | Result | p-value |
|---|---|---|
| PRIMARY Part 1 and Part 2: Number of Subjects With Adverse Events and Serious Adverse Event |
0; 0; 0; 0; 1; 2 | — |
| PRIMARY Part 2: Number of Patient With Objective Response Using International Working Group-Myeloproliferative Neoplasms Research and Treatment (IWG-MRT) and European Leukemia Net (ELN) |
1 | — |
| PRIMARY Part 2: Change From Baseline in Spleen Size |
-335918.1 | — |
| PRIMARY Part 2: Change From Baseline in Bone Marrow Assessment |
1; 0; 2; 0 | — |
| SECONDARY Part 1: Number of Patients With Objective Response Using International Working Group-Myeloproliferative Neoplasms Research and Treatment (IWG-MRT) |
0; 0; 0; 2; 0; 0 | — |
| SECONDARY Part 1: Change From Baseline in Spleen Size |
-0.67; -8.25; -3.17; -3.00; -4.33; -7.00 | — |
| SECONDARY Part 1: Change From Baseline in Bone Marrow Assessment |
0; 1; 1; 2; 0; 0 | — |
| SECONDARY Part 1: Change From Baseline in Quality of Life Assessments Using Myelofibrosis Symptom Assessment Form (MF-SAF) |
0.1; -1.3; 0.8; -1.9; 0.4; 0.7 | — |
| SECONDARY Part 2: Change From Baseline in Quality of Life Assessments Using Myeloproliferative Neoplasm Symptom Assessment Form (MPN SAF (MPN 10) |
-0.7 | — |
| SECONDARY Part 1 and Part 2: Change in Baseline in Janus Kinase 2 (JAK2) V617F Allele Burden Levels |
4.360; -0.210; 7.410; -6.720; 8.255; -4.900 | — |
| SECONDARY Part 2: Change From Baseline in Phosphorylated Signal Transducer and Activator of Transcription 3 (Phospho-STAT3) |
-9.406; -2.738; -0.422; -10.614; 6.217; -5.878 | — |
| SECONDARY Part1 and Part 2: Observed Maximum Concentration (Cmax) |
66.5600; 404.5333; 377.8000; 726.0667; 1643.0333; 242.0333 | — |
| SECONDARY Part 1 and Part 2: Time to Maximum Plasma Concentration (Tmax) |
1.00; 1.08; 2.00; 1.04; 1.00; 1.00 | — |
| SECONDARY Part1 and Part 2: Area Under the Plasma Concentration-time Curve (AUC0-24) |
246.3454; 1510.0507; 1326.3929; 2299.2216; 5162.4119; 1022.0977 | — |
| SECONDARY Part 1 and Part 2: Terminal Elimination Half-life (t½) |
2.4878; 5.1659; 3.6685; 4.4899; 6.0302; 9.7153 | — |
| SECONDARY Part1 and Part 2: Accumulation Ratio (AR) |
0.9778; 1.2517; 1.1728; 1.3581; 1.2026; 1.9941 | — |
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)
Eligibility Criteria
Inclusion Criteria
- 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
- 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.
Exclusion Criteria
- 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
- 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
Data sourced from ClinicalTrials.gov (NCT01423851). Outcome figures and adverse-event rates are extracted automatically from the registry's posted results and are provided for clinician reference, not as a substitute for the primary publication.