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

A Multicenter, Open-label, Dose-escalation, Phase 1 Trial to Investigate the Tolerability and Safety of ASTX727 in Subjects With Lower-risk Myelodysplastic Syndromes

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

Study Overview

• Status: Active, not recruiting
• Conditions: Lower-risk Myelodysplastic
• Intervention / Treatment: Drug: ASTX727; Drug: ASTX727; Drug: ASTX727

• Study Type: Interventional
• Enrollment (Anticipated): 30
• Phase: Phase 1

Contacts and Locations

Study Locations

• Japan
  • Tokyo, Japan
    • NTT Medical Center Tokyo

Participation Criteria

Eligibility Criteria

• Ages Eligible for Study: 20 years and older (ADULT, OLDER_ADULT)
• Accepts Healthy Volunteers: No
• Genders Eligible for Study: All

Description

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

Study Plan

How is the study designed?

Design Details

• Primary Purpose: TREATMENT
• Allocation: NON_RANDOMIZED
• Interventional Model: PARALLEL
• Masking: NONE

Number of Arms

5

Arms and Interventions

Participant Group / 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; Drug: ASTX727; oral decitabine 10mg + cedazuridine; Drug: ASTX727; oral decitabine 20mg + 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; Drug: ASTX727; oral decitabine 10mg + cedazuridine; Drug: ASTX727; oral decitabine 20mg + 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 5mg + cedazuridine; Drug: ASTX727; oral decitabine 10mg + cedazuridine; Drug: ASTX727; oral decitabine 20mg + 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 5mg + cedazuridine; Drug: ASTX727; oral decitabine 10mg + cedazuridine; 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 5mg + cedazuridine; Drug: ASTX727; oral decitabine 10mg + cedazuridine; Drug: ASTX727; oral decitabine 20mg + cedazuridine

What is the study measuring?

Primary Outcome Measures

Outcome Measure	Time Frame
Dose Limiting Toxicity	28days

Secondary Outcome Measures

Outcome Measure	Measure Description	Time Frame
Area under the curve (AUC)	pharmacokinetics parameter	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)	pharmacokinetics parameter	Pre-dose, 15 min, 30 min, 60 min, 90 min, 2 h, 3 h, 4 h, 6 h, 8 h, 24 h after dosing

Collaborators and Investigators

• Sponsor: Otsuka Pharmaceutical Co., Ltd.

Study record dates

Study Major Dates

• Study Start (ACTUAL): March 15, 2019
• Primary Completion (ANTICIPATED): December 31, 2023
• Study Completion (ANTICIPATED): December 31, 2023

Study Registration Dates

• First Submitted: April 5, 2019
• First Submitted That Met QC Criteria: April 5, 2019
• First Posted (ACTUAL): April 8, 2019

Study Record Updates

• Last Update Posted (ACTUAL): February 13, 2023
• Last Update Submitted That Met QC Criteria: February 9, 2023
• Last Verified: February 1, 2023

More Information

Terms related to this study

• Additional Relevant MeSH Terms: Neoplasms; Bone Marrow Diseases; Hematologic Diseases; Precancerous Conditions; Myelodysplastic Syndromes; Preleukemia
• Other Study ID Numbers: 393-102-00002; JapicCTI-194654 (OTHER: Japic)

Plan for Individual participant data (IPD)

• Plan to Share Individual Participant Data (IPD)?: NO
• IPD Plan Description: The focus of this study is a rare disease.

Drug and device information, study documents

• Studies a U.S. FDA-regulated drug product: No
• Studies a U.S. FDA-regulated device product: No