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    Summary
    EudraCT Number:2021-000369-34
    Sponsor's Protocol Code Number:NS-018-201
    National Competent Authority:Poland - Office for Medicinal Products
    Clinical Trial Type:EEA CTA
    Trial Status:Prematurely Ended
    Date on which this record was first entered in the EudraCT database:2023-02-16
    Trial results
    Index
    A. PROTOCOL INFORMATION
    B. SPONSOR INFORMATION
    C. APPLICANT IDENTIFICATION
    D. IMP IDENTIFICATION
    D.8 INFORMATION ON PLACEBO
    E. GENERAL INFORMATION ON THE TRIAL
    F. POPULATION OF TRIAL SUBJECTS
    G. INVESTIGATOR NETWORKS TO BE INVOLVED IN THE TRIAL
    N. REVIEW BY THE COMPETENT AUTHORITY OR ETHICS COMMITTEE IN THE COUNTRY CONCERNED
    P. END OF TRIAL
    Expand All   Collapse All
    A. Protocol Information
    A.1Member State ConcernedPoland - Office for Medicinal Products
    A.2EudraCT number2021-000369-34
    A.3Full title of the trial
    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)
    A.3.1Title of the trial for lay people, in easily understood, i.e. non-technical, language
    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)
    A.4.1Sponsor's protocol code numberNS-018-201
    A.5.2US NCT (ClinicalTrials.gov registry) numberNCT04854096
    A.7Trial is part of a Paediatric Investigation Plan No
    A.8EMA Decision number of Paediatric Investigation Plan
    B. Sponsor Information
    B.Sponsor: 1
    B.1.1Name of SponsorNS Pharma, Inc.
    B.1.3.4CountryUnited States
    B.3.1 and B.3.2Status of the sponsorCommercial
    B.4 Source(s) of Monetary or Material Support for the clinical trial:
    B.4.1Name of organisation providing supportNS Pharma, Inc.
    B.4.2CountryUnited States
    B.5 Contact point designated by the sponsor for further information on the trial
    B.5.1Name of organisationIQVIA Biotech
    B.5.2Functional name of contact pointEmilie Petitjean
    B.5.3 Address:
    B.5.3.1Street Address17 bis place des Reflets, Tour D2 TSA 64567
    B.5.3.2Town/ cityLA Defense CEDEX
    B.5.3.3Post code92099
    B.5.3.4CountryFrance
    B.5.4Telephone number+33677 97 80 63
    B.5.5Fax number+33174 88 23 71
    B.5.6E-mailEmilie.Petitjean@novellaclinical.com
    D. IMP Identification
    D.IMP: 1
    D.1.2 and D.1.3IMP RoleTest
    D.2 Status of the IMP to be used in the clinical trial
    D.2.1IMP to be used in the trial has a marketing authorisation No
    D.2.5The IMP has been designated in this indication as an orphan drug in the Community No
    D.2.5.1Orphan drug designation number
    D.3 Description of the IMP
    D.3.1Product nameNS-018
    D.3.2Product code NS-018
    D.3.4Pharmaceutical form Tablet
    D.3.4.1Specific paediatric formulation No
    D.3.7Routes of administration for this IMPIntravenous drip use (Noncurrent)
    Oral use
    D.3.8 to D.3.10 IMP Identification Details (Active Substances)
    D.3.8INN - Proposed INNILGINATINIB
    D.3.9.1CAS number 1354799-87-3
    D.3.9.2Current sponsor codeNS-018
    D.3.9.4EV Substance CodeSUB198062
    D.3.10 Strength
    D.3.10.1Concentration unit mg milligram(s)
    D.3.10.2Concentration typeequal
    D.3.10.3Concentration number100
    D.3.11 The IMP contains an:
    D.3.11.1Active substance of chemical origin Yes
    D.3.11.2Active substance of biological/ biotechnological origin (other than Advanced Therapy IMP (ATIMP) No
    The IMP is a:
    D.3.11.3Advanced Therapy IMP (ATIMP) No
    D.3.11.3.1Somatic cell therapy medicinal product No
    D.3.11.3.2Gene therapy medical product No
    D.3.11.3.3Tissue Engineered Product No
    D.3.11.3.4Combination ATIMP (i.e. one involving a medical device) No
    D.3.11.3.5Committee on Advanced therapies (CAT) has issued a classification for this product No
    D.3.11.4Combination product that includes a device, but does not involve an Advanced Therapy No
    D.3.11.5Radiopharmaceutical medicinal product No
    D.3.11.6Immunological medicinal product (such as vaccine, allergen, immune serum) No
    D.3.11.7Plasma derived medicinal product No
    D.3.11.8Extractive medicinal product No
    D.3.11.9Recombinant medicinal product No
    D.3.11.10Medicinal product containing genetically modified organisms No
    D.3.11.11Herbal medicinal product No
    D.3.11.12Homeopathic medicinal product No
    D.3.11.13Another type of medicinal product No
    D.8 Information on Placebo
    E. General Information on the Trial
    E.1 Medical condition or disease under investigation
    E.1.1Medical condition(s) being investigated
    Primary Myelofibrosis, Post-Polycythemia Vera Myelofibrosis, or Post-Essential Thrombocythemia Myelofibrosis with Severe Thrombocytopenia
    E.1.1.1Medical condition in easily understood language
    Myelofibrosis
    E.1.1.2Therapeutic area Diseases [C] - Cancer [C04]
    MedDRA Classification
    E.1.2 Medical condition or disease under investigation
    E.1.2Version 20.0
    E.1.2Level SOC
    E.1.2Classification code 10029104
    E.1.2Term Neoplasms benign, malignant and unspecified (incl cysts and polyps)
    E.1.2System Organ Class 10029104 - Neoplasms benign, malignant and unspecified (incl cysts and polyps)
    E.1.3Condition being studied is a rare disease Yes
    E.2 Objective of the trial
    E.2.1Main objective of the trial
    • To compare the efficacy of the dose of 300 mg BID of NS-018 to the Best Available Therapy (BAT), in subjects with PMF, post-PVMF, or post-ETMF with severe thrombocytopenia
    • To compare the effect on MF-associated symptoms as measured by Myelofibrosis Symptom Assessment Form version 4.0 (MFSAF v4.0) to the BAT
    E.2.2Secondary objectives of the trial
    • To compare the best splenic response of 300 mg BID of NS-018 to the BAT
    • To compare the safety of 300 mg BID of NS-018 to the BAT
    E.2.3Trial contains a sub-study Yes
    E.2.3.1Full title, date and version of each sub-study and their related objectives
    In this study, DNA/RNA testing will be conducted as part of a Genetic Substudy.
    E.3Principal inclusion criteria
    1. Able to provide written informed consent prior to enrollment into the study.
    2. Males and females ≥18 years of age.
    3. Primary MF, post-PVMF or post-ETMF according to the DIPSS risk categories of intermediate-2 or high-risk MF.
    4. Spleen volume of at least 450 cm3 measured by MRI (or by CT for applicable subjects). This baseline scan will be centrally reviewed for spleen volume.
    5. Total symptom score (TSS) ≥10 on MFSAF v4.0. The TSS from the first 7 consecutive days of entry through the screening period will be used for eligibility.
    6. Platelet count < 50,000/µL. Two results taken at least 7 days apart during screening are needed. Each result must be <50,000/µL
    7. No MF-directed treatment (other than ruxolitnib) for at least 2 weeks prior to initiation of NS- 018, including 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. Subjects treated with a ruxolitnib will be required to taper off the ruxolitnib before initiation of NS-018 at Cycle 1 Day 1. The dose of ruxolitnib should be decreased every 7 days by up to 50% until the smallest dose possible has been given for a minimum duration for the total tapering period of 14 days. Ruxolitnib should then be stopped 1 day before starting NS-018. Subjects who are taking 5 mg QD of a ruxolitnib are already on the lowest dose possible; therefore, tapering is not applicable in this case. If recurrence of MF-related symptoms (upon discontinuation of a ruxolitnib therapy) is noted, it is strongly suggested that therapy with a ruxolitnib be restarted. If restart is not possible, then prompt therapy with corticosteroids (eg, prednisone 60 mg QD) is recommended.

    Subjects who are not benefitting from ruxolitinib treatment may be enrolled in the study per the Investigator’s discretion.
    8. ECOG performance status ≤2.
    9. QTcF ≤480 msec.
    10. Peripheral blood blast count <10%.
    11. Estimated creatinine clearance (CrCl) ≥40 mL/min/1.73 m2 calculated using the Cockcroft and Gault equation.
    12. Aspartate aminotransferase (AST) and alanine aminotransferase (ALT) ≤3 × upper limit of normal (ULN) and a direct bilirubin ≤1.5 × ULN.
    13. Absolute neutrophil count >500/μL.
    14. Negative serum pregnancy test within 7 days prior to the first dose of study drug (if subject is a female of childbearing potential).
    15. No treatment with any investigational agent within 28 days or five times the half-life of the drug prior to initiation of NS-018., whichever is longer (not shorter). COVID-19 vaccines that are commercially available or approved by local regulatory authorities and are administered outside of an investigational clinical study are not considered as investigational agents.
    16. Male or non-pregnant, non-lactating female subjects. Male and female subjects who are fertile and their partners must agree to use 2 highly effective methods of contraception from screening through 180 days (for male subjects with partners who are women of childbearing potential [WOCBP], pregnant or breast feeding) and 180 days (for females) following discontinuation of study treatment.

    For Germany and UK Only:
    Male or non-pregnant, non-lactating female subjects. Male and female subjects who are fertile and their partners must agree to use 2 highly effective methods of contraception from screening through 180 days for male subjects with partners who are WOCBP), pregnant or breast feeding) and 180 days for females following discontinuation of study treatment as outlined in Appendix 7.

    Male subjects should not father a child during treatment and for 180 days thereafter.

    Female partners must use highly effective contraceptive methods for 180 days thereafter.

    Additionally, monthly pregnancy tests should be performed for WOCBP. The serum pregnancy test should not be older than 72 hours before taking the first dose.

    17. Life expectancy >6 months.
    E.4Principal exclusion criteria
    1. Active, uncontrolled systemic infection. including active tuberculosis. Inactive (latent) tuberculosis infection testing will be done for UK and South Korea only.
    2. Any prior treatment with more than 2 JAK inhibitors. Subjects with any contraindication to BAT (see the product label) are excluded.
    3. Subjects receiving any clinical benefits from JAK inhibitor per the Investigator's discretion.
    4. Previous treatment with NS-018. Subjects with hypersensitivity to NS-018, any excipient of NS-018 tablets and to any JAK2 inhibitor will be excluded from study participation.
    5. Subjects actively receiving a concurrent investigational agent.
    6. Subjects with any unresolved AE greater than Grade 1 other than hematological AEs from previous anticancer therapy.
    7. Potentially curative therapy is available:
    - Candidates for hematopoietic stem cell transplant in which transplant is an available and viable option and of higher priority than this study are excluded.
    - If the subject has declined hematopoietic stem cell transplant, has no donor for transplant, or in the judgment of the Investigator is not suitable for transplant, the subject may be enrolled.
    8. 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 .
    9. Pregnancy or lactation.
    10. Radiation therapy for splenomegaly within 6 months prior to study entry (Screening).
    11. History of splenectomy or planning to undergo splenectomy.
    12. Known human immunodeficiency virus [HIV] positive status.
    13. Known active hepatitis, or a history of viral hepatitis B or hepatitis C.
    14. Subjects with a serious cardiac condition within the past 6 months such as uncontrolled arrhythmias, myocardial infarction, angina, or heart disease as defined by the New York Heart Association Class III or IV.
    15. Subjects diagnosed with another malignancy within 2 years prior to an enrollment. Subjects with prior malignancies must have completed all treatments with no recurrence within 2 years to an enrollment. Subjects with early stage squamous cell carcinoma of the skin, basal cell carcinoma of the skin, or cervical intraepithelial neoplasia may be eligible for participation at the Investigator’s discretion.
    16. 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.
    17. Other concurrent disease and/or medical condition including cardiac condition, which, in the judgment of the Investigator, would prevent the subject’s participation.
    18. Unwilling or unable to comply with the protocol.
    19. Subjects with suspected (case definition A or B), probable, or confirmed diagnosis of COVID-19 based on the World Health Organization diagnostic criteria (Table 2).
    E.5 End points
    E.5.1Primary end point(s)
    • Proportion of subjects who achieve ≥35% reduction in spleen volume from baseline to Week 24 as measured by MRI (or by CT for applicable subjects)
    • Proportion of subjects who achieve ≥50% reduction in total symptom score from baseline to Week 24 as measured by the MFSAF v4.0
    E.5.1.1Timepoint(s) of evaluation of this end point
    Week 24
    E.5.2Secondary end point(s)
    • Proportion of subjects 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 the safety of NS-018 versus BAT
    E.5.2.1Timepoint(s) of evaluation of this end point
    Week 24
    E.6 and E.7 Scope of the trial
    E.6Scope of the trial
    E.6.1Diagnosis No
    E.6.2Prophylaxis No
    E.6.3Therapy Yes
    E.6.4Safety Yes
    E.6.5Efficacy Yes
    E.6.6Pharmacokinetic Yes
    E.6.7Pharmacodynamic Yes
    E.6.8Bioequivalence No
    E.6.9Dose response No
    E.6.10Pharmacogenetic No
    E.6.11Pharmacogenomic No
    E.6.12Pharmacoeconomic No
    E.6.13Others No
    E.7Trial type and phase
    E.7.1Human pharmacology (Phase I) No
    E.7.1.1First administration to humans No
    E.7.1.2Bioequivalence study No
    E.7.1.3Other No
    E.7.1.3.1Other trial type description
    E.7.2Therapeutic exploratory (Phase II) Yes
    E.7.3Therapeutic confirmatory (Phase III) No
    E.7.4Therapeutic use (Phase IV) No
    E.8 Design of the trial
    E.8.1Controlled Yes
    E.8.1.1Randomised Yes
    E.8.1.2Open Yes
    E.8.1.3Single blind No
    E.8.1.4Double blind No
    E.8.1.5Parallel group No
    E.8.1.6Cross over No
    E.8.1.7Other No
    E.8.2 Comparator of controlled trial
    E.8.2.1Other medicinal product(s) Yes
    E.8.2.2Placebo No
    E.8.2.3Other No
    E.8.2.4Number of treatment arms in the trial2
    E.8.3 The trial involves single site in the Member State concerned No
    E.8.4 The trial involves multiple sites in the Member State concerned Yes
    E.8.4.1Number of sites anticipated in Member State concerned3
    E.8.5The trial involves multiple Member States Yes
    E.8.5.1Number of sites anticipated in the EEA38
    E.8.6 Trial involving sites outside the EEA
    E.8.6.1Trial being conducted both within and outside the EEA Yes
    E.8.6.2Trial being conducted completely outside of the EEA No
    E.8.6.3If E.8.6.1 or E.8.6.2 are Yes, specify the regions in which trial sites are planned
    Argentina
    Malaysia
    Korea, Republic of
    Thailand
    United Kingdom
    United States
    France
    Germany
    Italy
    Poland
    Spain
    Türkiye
    E.8.7Trial has a data monitoring committee Yes
    E.8.8 Definition of the end of the trial and justification where it is not the last visit of the last subject undergoing the trial
    LVLS
    E.8.9 Initial estimate of the duration of the trial
    E.8.9.1In the Member State concerned years3
    E.8.9.1In the Member State concerned months0
    E.8.9.1In the Member State concerned days0
    E.8.9.2In all countries concerned by the trial years3
    E.8.9.2In all countries concerned by the trial months0
    E.8.9.2In all countries concerned by the trial days0
    F. Population of Trial Subjects
    F.1 Age Range
    F.1.1Trial has subjects under 18 No
    F.1.1.1In Utero No
    F.1.1.2Preterm newborn infants (up to gestational age < 37 weeks) No
    F.1.1.3Newborns (0-27 days) No
    F.1.1.4Infants and toddlers (28 days-23 months) No
    F.1.1.5Children (2-11years) No
    F.1.1.6Adolescents (12-17 years) No
    F.1.2Adults (18-64 years) Yes
    F.1.2.1Number of subjects for this age range: 70
    F.1.3Elderly (>=65 years) Yes
    F.1.3.1Number of subjects for this age range: 50
    F.2 Gender
    F.2.1Female Yes
    F.2.2Male Yes
    F.3 Group of trial subjects
    F.3.1Healthy volunteers No
    F.3.2Patients Yes
    F.3.3Specific vulnerable populations Yes
    F.3.3.1Women of childbearing potential not using contraception No
    F.3.3.2Women of child-bearing potential using contraception Yes
    F.3.3.3Pregnant women No
    F.3.3.4Nursing women No
    F.3.3.5Emergency situation No
    F.3.3.6Subjects incapable of giving consent personally No
    F.3.3.7Others No
    F.4 Planned number of subjects to be included
    F.4.1In the member state8
    F.4.2 For a multinational trial
    F.4.2.1In the EEA 55
    F.4.2.2In the whole clinical trial 120
    F.5 Plans for treatment or care after the subject has ended the participation in the trial (if it is different from the expected normal treatment of that condition)
    Based on the benefit-risk profile, if the development of this investigational study treatment has not been discontinued and if not yet commercially available, post-study access may be provided in compliance with local regulations.
    G. Investigator Networks to be involved in the Trial
    N. Review by the Competent Authority or Ethics Committee in the country concerned
    N.Competent Authority Decision Authorised
    N.Date of Competent Authority Decision2023-06-05
    N.Ethics Committee Opinion of the trial applicationFavourable
    N.Ethics Committee Opinion: Reason(s) for unfavourable opinion
    N.Date of Ethics Committee Opinion2023-03-13
    P. End of Trial
    P.End of Trial StatusPrematurely Ended
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