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出境医 / 临床实验 / Phase 1 Trial of ASTX727 in Subjects With Lower-risk Myelodysplastic Syndromes

Phase 1 Trial of ASTX727 in Subjects With Lower-risk Myelodysplastic Syndromes

Study Description
Brief Summary:
To investigate the tolerability and safety of ASTX727 in Japanese subjects with lower-risk MDS.

Condition or disease Intervention/treatment Phase
Lower-risk Myelodysplastic Drug: ASTX727 Phase 1

Study Design
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Study Type : Interventional  (Clinical Trial)
Estimated Enrollment : 30 participants
Allocation: Non-Randomized
Intervention Model: Parallel Assignment
Masking: None (Open Label)
Primary Purpose: Treatment
Official Title: A Multicenter, Open-label, Dose-escalation, Phase 1 Trial to Investigate the Tolerability and Safety of ASTX727 in Subjects With Lower-risk Myelodysplastic Syndromes
Actual Study Start Date : March 15, 2019
Estimated Primary Completion Date : December 2021
Estimated Study Completion Date : December 2021
Arms and Interventions
Arm Intervention/treatment
Experimental: 10-Day Schedule

10-Day Schedule

Investigational Medicinal Products (IMP) will be administered for 10 days in total per 4 weeks, i.e. a 28-day cycle.

 Drug: ASTX727
oral decitabine 5mg + cedazuridine
Experimental: 5-Day Schedule A

5-Day Schedule A

IMP will be administered for 5 days in total per 4 weeks, i.e. a 28-day cycle.

 Drug: ASTX727
oral decitabine 5mg + cedazuridine
Experimental: 5-Day Schedule B

5-Day Schedule B

IMP will be administered for 5 days in total per 4 weeks, i.e. a 28-day cycle.

 Drug: ASTX727
oral decitabine 10mg + cedazuridine
Experimental: 5-Day Schedule C

5-Day Schedule C

IMP will be administered for 5 days in total per 4 weeks, i.e. a 28-day cycle.

 Drug: ASTX727
oral decitabine 20mg + cedazuridine
Experimental: 7-Day Schedule

7-Day Schedule

IMP will be administered for 7 days in total per 4 weeks, i.e. a 28-day cycle.

 Drug: ASTX727
oral decitabine 10mg + cedazuridine
Outcome Measures
Primary Outcome Measures :
  1. Dose Limiting Toxicity [ Time Frame: 28days ]

Secondary Outcome Measures :
  1. Area under the curve (AUC) [ Time Frame: Pre-dose, 15 min, 30 min, 60 min, 90 min, 2 h, 3 h, 4 h, 6 h, 8 h, 24 h after dosing ]
    pharmacokinetics parameter

  2. Maximum plasma concentration (Cmax) [ Time Frame: Pre-dose, 15 min, 30 min, 60 min, 90 min, 2 h, 3 h, 4 h, 6 h, 8 h, 24 h after dosing ]
    pharmacokinetics parameter


Eligibility Criteria
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Ages Eligible for Study:   20 Years and older   (Adult, Older Adult)
Sexes Eligible for Study:   All
Accepts Healthy Volunteers:   No
Criteria

Key Inclusion Criteria:

  1. Subjects with a definitive diagnosis of MDS and classified as low or Intermediate-1 risk by the International Prognostic Scoring System (IPSS) risk category
  2. Subjects meeting at least one of the disease-related criteria for Red blood cell (RBC) transfusion, hemoglobin (Hb) ,Absolute neutrophil count,Platelet count within 8 weeks prior to initial administration of IMP
  3. Subjects with Eastern Cooperative Oncology Group Performance Status (ECOG PS) of 0 or 1
  4. Adequate hepatic and renal function
  5. Sexually active men with reproductive capacity (except those who have undergone bilateral orchidectomy) must agree to use 2 effective contraceptive measures or remain abstinent during the trial and for 3 months after final administration of IMP. Sexually active women of child-bearing potential must agree to use 2 effective contraceptive measures or remain abstinent during the trial and for 6 months after final administration of IMP.
  6. Subjects who have provided written informed consent using the form approved by the institutional review board

Key Exclusion Criteria:

  1. Subjects who have received cytokine therapy, immunosuppressant therapy, or chemotherapy within 4 weeks prior to initial investigational medicinal product (IMP) administration
  2. Subjects who have received any other IMP or privately-imported medicine within 2 weeks prior to initial IMP administration
  3. Subjects with deletion 5q who are to be treated with lenalidomide
  4. Subjects with current or previous bone marrow blast percentage of >10%
  5. Subjects with a diagnosis of chronic myelomonocytic leukemia
  6. Subjects with heart disease of New York Heart Association (NYHA) Functional Class 3 or 4
  7. Subjects with an uncontrolled systemic disease or active uncontrolled infection
  8. Subjects with diabetes mellitus requiring medical treatment
  9. Subjects with a life-threatening illness, medical condition or multiple organ dysfunction, or other reason, including laboratory abnormalities, which in the investigator's or subinvestigator's opinion could compromise the subject's safety, interfere with the absorption or metabolism of IMP, or compromise the integrity of the trial outcome
  10. Subjects with prior malignancy
  11. Subjects who test positive for human immunodeficiency virus antibody, hepatitis B virus DNA, or hepatitis C virus antibody
  12. Subjects with a history of surgical gastrectomy
  13. Subjects with previous organ transplantation
  14. Subjects with a ≥Grade 2 AE attributable to treatment of underlying disease, excluding the AEs
  15. Subjects who have undergone an invasive and extensive operation within 2 weeks prior to initial IMP administration
  16. Subjects with hypersensitivity to the IMPs or their excipients
  17. Subjects with known significant mental illness or other condition, such as active alcohol or other substance abuse or addiction, that in the opinion of the investigator or subinvestigator predisposes the subject to high risk of noncompliance with the protocol
  18. Female subjects who are pregnant, breast-feeding, or who test positive for pregnancy at screening
Contacts and Locations

Contacts
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Contact: Drug Information Center +81-3-6361-7314

Locations
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Japan
NTT Medical Center Tokyo Recruiting
Tokyo, Japan
Sponsors and Collaborators
Otsuka Pharmaceutical Co., Ltd.
Investigators
Layout table for investigator information
Study Director: Osamu Sato Otsuka Pharmaceutical Co., Ltd.
Tracking Information
First Submitted Date  ICMJE April 5, 2019
First Posted Date  ICMJE April 8, 2019
Last Update Posted Date December 11, 2020
Actual Study Start Date  ICMJE March 15, 2019
Estimated Primary Completion Date December 2021   (Final data collection date for primary outcome measure)
Current Primary Outcome Measures  ICMJE
 (submitted: April 5, 2019) 		Dose Limiting Toxicity [ Time Frame: 28days ]
Original Primary Outcome Measures  ICMJE Same as current
Change History
Current Secondary Outcome Measures  ICMJE
 (submitted: April 5, 2019)
  • Area under the curve (AUC) [ Time Frame: Pre-dose, 15 min, 30 min, 60 min, 90 min, 2 h, 3 h, 4 h, 6 h, 8 h, 24 h after dosing ]
    pharmacokinetics parameter
  • Maximum plasma concentration (Cmax) [ Time Frame: Pre-dose, 15 min, 30 min, 60 min, 90 min, 2 h, 3 h, 4 h, 6 h, 8 h, 24 h after dosing ]
    pharmacokinetics parameter
Original Secondary Outcome Measures  ICMJE Same as current
Current Other Pre-specified Outcome Measures Not Provided
Original Other Pre-specified Outcome Measures Not Provided
 
Descriptive Information
Brief Title  ICMJE Phase 1 Trial of ASTX727 in Subjects With Lower-risk Myelodysplastic Syndromes
Official Title  ICMJE A Multicenter, Open-label, Dose-escalation, Phase 1 Trial to Investigate the Tolerability and Safety of ASTX727 in Subjects With Lower-risk Myelodysplastic Syndromes
Brief Summary To investigate the tolerability and safety of ASTX727 in Japanese subjects with lower-risk MDS.
Detailed Description Not Provided
Study Type  ICMJE Interventional
Study Phase  ICMJE Phase 1
Study Design  ICMJE Allocation: Non-Randomized
Intervention Model: Parallel Assignment
Masking: None (Open Label)
Primary Purpose: Treatment
Condition  ICMJE Lower-risk Myelodysplastic
Intervention  ICMJE
  • Drug: ASTX727
    oral decitabine 5mg + cedazuridine
  • Drug: ASTX727
    oral decitabine 10mg + cedazuridine
  • Drug: ASTX727
    oral decitabine 20mg + cedazuridine
Study Arms  ICMJE
  • Experimental: 10-Day Schedule

    10-Day Schedule

    Investigational Medicinal Products (IMP) will be administered for 10 days in total per 4 weeks, i.e. a 28-day cycle.

    Intervention: Drug: ASTX727
  • Experimental: 5-Day Schedule A

    5-Day Schedule A

    IMP will be administered for 5 days in total per 4 weeks, i.e. a 28-day cycle.

    Intervention: Drug: ASTX727
  • Experimental: 5-Day Schedule B

    5-Day Schedule B

    IMP will be administered for 5 days in total per 4 weeks, i.e. a 28-day cycle.

    Intervention: Drug: ASTX727
  • Experimental: 5-Day Schedule C

    5-Day Schedule C

    IMP will be administered for 5 days in total per 4 weeks, i.e. a 28-day cycle.

    Intervention: Drug: ASTX727
  • Experimental: 7-Day Schedule

    7-Day Schedule

    IMP will be administered for 7 days in total per 4 weeks, i.e. a 28-day cycle.

    Intervention: Drug: ASTX727
Publications * Not Provided

*   Includes publications given by the data provider as well as publications identified by ClinicalTrials.gov Identifier (NCT Number) in Medline.
 
Recruitment Information
Recruitment Status  ICMJE Recruiting
Estimated Enrollment  ICMJE
 (submitted: April 5, 2019) 		30
Original Estimated Enrollment  ICMJE Same as current
Estimated Study Completion Date  ICMJE December 2021
Estimated Primary Completion Date December 2021   (Final data collection date for primary outcome measure)
Eligibility Criteria  ICMJE

Key Inclusion Criteria:

  1. Subjects with a definitive diagnosis of MDS and classified as low or Intermediate-1 risk by the International Prognostic Scoring System (IPSS) risk category
  2. Subjects meeting at least one of the disease-related criteria for Red blood cell (RBC) transfusion, hemoglobin (Hb) ,Absolute neutrophil count,Platelet count within 8 weeks prior to initial administration of IMP
  3. Subjects with Eastern Cooperative Oncology Group Performance Status (ECOG PS) of 0 or 1
  4. Adequate hepatic and renal function
  5. Sexually active men with reproductive capacity (except those who have undergone bilateral orchidectomy) must agree to use 2 effective contraceptive measures or remain abstinent during the trial and for 3 months after final administration of IMP. Sexually active women of child-bearing potential must agree to use 2 effective contraceptive measures or remain abstinent during the trial and for 6 months after final administration of IMP.
  6. Subjects who have provided written informed consent using the form approved by the institutional review board

Key Exclusion Criteria:

  1. Subjects who have received cytokine therapy, immunosuppressant therapy, or chemotherapy within 4 weeks prior to initial investigational medicinal product (IMP) administration
  2. Subjects who have received any other IMP or privately-imported medicine within 2 weeks prior to initial IMP administration
  3. Subjects with deletion 5q who are to be treated with lenalidomide
  4. Subjects with current or previous bone marrow blast percentage of >10%
  5. Subjects with a diagnosis of chronic myelomonocytic leukemia
  6. Subjects with heart disease of New York Heart Association (NYHA) Functional Class 3 or 4
  7. Subjects with an uncontrolled systemic disease or active uncontrolled infection
  8. Subjects with diabetes mellitus requiring medical treatment
  9. Subjects with a life-threatening illness, medical condition or multiple organ dysfunction, or other reason, including laboratory abnormalities, which in the investigator's or subinvestigator's opinion could compromise the subject's safety, interfere with the absorption or metabolism of IMP, or compromise the integrity of the trial outcome
  10. Subjects with prior malignancy
  11. Subjects who test positive for human immunodeficiency virus antibody, hepatitis B virus DNA, or hepatitis C virus antibody
  12. Subjects with a history of surgical gastrectomy
  13. Subjects with previous organ transplantation
  14. Subjects with a ≥Grade 2 AE attributable to treatment of underlying disease, excluding the AEs
  15. Subjects who have undergone an invasive and extensive operation within 2 weeks prior to initial IMP administration
  16. Subjects with hypersensitivity to the IMPs or their excipients
  17. Subjects with known significant mental illness or other condition, such as active alcohol or other substance abuse or addiction, that in the opinion of the investigator or subinvestigator predisposes the subject to high risk of noncompliance with the protocol
  18. Female subjects who are pregnant, breast-feeding, or who test positive for pregnancy at screening
Sex/Gender  ICMJE
Sexes Eligible for Study: All
Ages  ICMJE 20 Years and older   (Adult, Older Adult)
Accepts Healthy Volunteers  ICMJE No
Contacts  ICMJE
Contact: Drug Information Center +81-3-6361-7314
Listed Location Countries  ICMJE Japan
Removed Location Countries  
 
Administrative Information
NCT Number  ICMJE NCT03906695
Other Study ID Numbers  ICMJE 393-102-00002
Has Data Monitoring Committee No
U.S. FDA-regulated Product
Studies a U.S. FDA-regulated Drug Product: No
Studies a U.S. FDA-regulated Device Product: No
IPD Sharing Statement  ICMJE
Plan to Share IPD: No
Responsible Party Otsuka Pharmaceutical Co., Ltd.
Study Sponsor  ICMJE Otsuka Pharmaceutical Co., Ltd.
Collaborators  ICMJE Not Provided
Investigators  ICMJE
Study Director: Osamu Sato Otsuka Pharmaceutical Co., Ltd.
PRS Account Otsuka Pharmaceutical Co., Ltd.
Verification Date December 2020

ICMJE     Data element required by the International Committee of Medical Journal Editors and the World Health Organization ICTRP

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