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

NCT03906695 | Active Not Recruiting Phase 1

• 2 other identifiers: 393-102-00002JapicCTI-194654
• Study Type: interventional
• Target: 30
• Locations: 1 country
• Sites: 1

Brief Summary

To investigate the tolerability and safety of ASTX727 in Japanese subjects with lower-risk MDS.

Conditions

Lower-risk Myelodysplastic

Outcome Measures

Primary Outcomes (1)

• Dose Limiting Toxicity

  28days

Secondary Outcomes (2)

• Area under the curve (AUC)

  Pre-dose, 15 min, 30 min, 60 min, 90 min, 2 h, 3 h, 4 h, 6 h, 8 h, 24 h after dosing

• Maximum plasma concentration (Cmax)

  Pre-dose, 15 min, 30 min, 60 min, 90 min, 2 h, 3 h, 4 h, 6 h, 8 h, 24 h after dosing

Study Arms (5)

10-Day Schedule

EXPERIMENTAL

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

5-Day Schedule A

EXPERIMENTAL

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

Drug: ASTX727

5-Day Schedule B

EXPERIMENTAL

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

Drug: ASTX727

5-Day Schedule C

EXPERIMENTAL

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

Drug: ASTX727

7-Day Schedule

EXPERIMENTAL

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

Drug: ASTX727

Interventions

ASTX727 DRUG

oral decitabine 5mg + cedazuridine

10-Day Schedule

Eligibility Criteria

• Age: 20 Years+
• Sex: all
• Healthy Volunteers: No
• Age Groups: Adult (18-64), Older Adult (65+)

You may qualify if:

• Subjects with a definitive diagnosis of MDS and classified as low or Intermediate-1 risk by the International Prognostic Scoring System (IPSS) risk category
• 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
• Subjects with Eastern Cooperative Oncology Group Performance Status (ECOG PS) of 0 or 1
• Adequate hepatic and renal function
• 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.
• Subjects who have provided written informed consent using the form approved by the institutional review board

You may not qualify if:

• Subjects who have received cytokine therapy, immunosuppressant therapy, or chemotherapy within 4 weeks prior to initial investigational medicinal product (IMP) administration
• Subjects who have received any other IMP or privately-imported medicine within 2 weeks prior to initial IMP administration
• Subjects with deletion 5q who are to be treated with lenalidomide
• Subjects with current or previous bone marrow blast percentage of \>10%
• Subjects with a diagnosis of chronic myelomonocytic leukemia
• Subjects with heart disease of New York Heart Association (NYHA) Functional Class 3 or 4
• Subjects with an uncontrolled systemic disease or active uncontrolled infection
• Subjects with diabetes mellitus requiring medical treatment
• 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
• Subjects with prior malignancy
• Subjects who test positive for human immunodeficiency virus antibody, hepatitis B virus DNA, or hepatitis C virus antibody
• Subjects with a history of surgical gastrectomy
• Subjects with previous organ transplantation
• Subjects with a ≥Grade 2 AE attributable to treatment of underlying disease, excluding the AEs
• Subjects who have undergone an invasive and extensive operation within 2 weeks prior to initial IMP administration

Sponsors & Collaborators

• Otsuka Pharmaceutical Co., Ltd.: lead

Study Sites (1)

NTT Medical Center Tokyo

Tokyo, Japan

Location

MeSH Terms

Interventions

decitabine and cedazuridine drug combination

Study Officials

• Nobuhito Sanada

  Otsuka Pharmaceutical Co., Ltd.

  STUDY DIRECTOR

Study Design

• Study Type: interventional
• Phase: phase 1
• Allocation: NON RANDOMIZED
• Masking: NONE
• Purpose: TREATMENT
• Intervention Model: PARALLEL
• Sponsor Type: INDUSTRY
• Responsible Party: SPONSOR

Study Record Dates

• First Submitted: April 5, 2019
• First Posted: April 8, 2019
• Study Start: March 15, 2019
• Primary Completion: January 31, 2026
• Study Completion: January 31, 2026
• Last Updated: March 20, 2025

Record last verified: 2025-03

Data Sharing

• IPD Sharing: Will not share

Locations

JP (1)