PK/Efficacy Bridging Study of ASTX727 in Chinese Subjects With Myelodysplastic Syndromes

An Open-label, Crossover, Pharmacokinetic and Efficacy Bridging Study of Oral ASTX727 Versus IV Decitabine in Chinese Subjects With Myelodysplastic Syndromes

This is an Open-Label, Crossover, Pharmacokinetic and Efficacy Bridging Study of Oral ASTX727 versus IV Decitabine in Chinese Subjects with Myelodysplastic Syndromes

Study Overview

• Status: Active, not recruiting
• Conditions: Myelodysplastic Syndromes
• Intervention / Treatment: Drug: IV Decitabine; Drug: Decitabine and cedazuridine; Drug: only Decitabine and cedazuridine

• Study Type: Interventional
• Enrollment (Estimated): 72
• Phase: Phase 2; Phase 1

Contacts and Locations

Study Locations

• China
  • Zhejiang
    • Hangzhou, Zhejiang, China, 310003
      • The First Affiliated Hospital，Zhejiang University School of Medicine

Participation Criteria

Eligibility Criteria

• Ages Eligible for Study: Adult; Older Adult
• Accepts Healthy Volunteers: No

Description

Inclusion Criteria:

1. Agree to participate in this trial and voluntarily sign the informed consent form.
2. Men or women ≥ 18 years at the time of signing the informed consent form.
3. Subjects with MDS previously treated or untreated with de novo or secondary MDS.
4. Eastern Cooperative Oncology Group (ECOG) performance status of 0 to 1 at screening.

Exclusion Criteria:

1. Prior treatment with more than 1 cycle of azacitidine or decitabine.
2. Cytotoxic chemotherapy or prior azacitidine or decitabine within 4 weeks of first dose of study treatment.
3. Conditions as judged by the investigator to be inappropriate for participation in the clinical trial.
4. Previous diagnosis of malignant tumor.
5. History of immune deficiency.
6. Acute myeloid leukemia (AML) with bone marrow or peripheral blast count ≥ 20% or other malignant hematological diseases.

Study Plan

How is the study designed?

Design Details

• Primary Purpose: Treatment
• Allocation: Randomized
• Interventional Model: Crossover Assignment
• Masking: None (Open Label)

Number of Arms

3

Arms and Interventions

Participant Group / Arm	Intervention / Treatment
Experimental: ASTX727 and IV Decitabine; Cycle1：ASTX727 tablets, oral, 1 tablet/day for 5 days；Cycle2：IV Decitabine, 20 mg/m^2, is administered for 1 hour at a time for 5 days；≥ Cycle 3：ASTX727 tablets, oral, 1 tablet/day for 5 days	Drug: IV Decitabine; The subjects will receive decitabine 20 mg/m^2 IV daily × 5 days in 28-day cycles.; Drug: Decitabine and cedazuridine; subjects will receive treatment with ASTX727, 1 tablet/day for 5 consecutive days, in 28-day cycles.; Drug: only Decitabine and cedazuridine; subjects will receive treatment with ASTX727, 1 tablet/day for 5 consecutive days, in 28-day cycles, until disease progression, unacceptable toxicity, or the subject/investigator decides that the subject should discontinue treatment or withdraw from the trial.
Active Comparator: IV Decitabine and ASTX727; Cycle1：IV Decitabine, 20 mg/m^2, is administered for 1 hour at a time for 5 days； Cycle2：ASTX727 tablets, oral, 1 tablet/day for 5 days；≥ Cycle 3：ASTX727 tablets, oral, 1 tablet/day for 5 days	Drug: IV Decitabine; The subjects will receive decitabine 20 mg/m^2 IV daily × 5 days in 28-day cycles.; Drug: Decitabine and cedazuridine; subjects will receive treatment with ASTX727, 1 tablet/day for 5 consecutive days, in 28-day cycles.; Drug: only Decitabine and cedazuridine; subjects will receive treatment with ASTX727, 1 tablet/day for 5 consecutive days, in 28-day cycles, until disease progression, unacceptable toxicity, or the subject/investigator decides that the subject should discontinue treatment or withdraw from the trial.
Experimental: ASTX727; ASTX727 tablets, oral, 1 tablet/day for 5 days；	Drug: only Decitabine and cedazuridine; subjects will receive treatment with ASTX727, 1 tablet/day for 5 consecutive days, in 28-day cycles, until disease progression, unacceptable toxicity, or the subject/investigator decides that the subject should discontinue treatment or withdraw from the trial.

What is the study measuring?

Primary Outcome Measures

Outcome Measure	Measure Description	Time Frame
Complete Response Rate	Assess efficacy [Complete Response Rate (CR)] of treatment with ASTX727 in Chinese subjects with myelodysplastic syndromes (MDS);	An analysis is planned when the last enrolled patient have completed Follow-up 12 months.
5day_AUC0-τ	Assess pharmacokinetic (PK) parameters (Total 5-day AUC exposures of decitabine) after treatment with ASTX727 (oral) versus decitabine for IV infusion for 5 days;	An analysis is planned when the last enrolled patient have completed the treatment with ASTX727 (oral) versus decitabine for IV infusion for 5 day.

Secondary Outcome Measures

Outcome Measure	Measure Description	Time Frame
Objective Response Rate	Objective Response Rate (ORR): The proportion of subjects who achieve CR and partial response (PR) based on IWG 2006 criteria;	through study completion, an average of 1 year.
Clinical Response Rate	Clinical Response Rate: The proportion of subjects who achieve CR, PR, marrow complete response (mCR), and hematologic improvement (HI) based on IWG 2006 criteria.	through study completion, an average of 1 year.
Rate of transfusion independence	Rate of transfusion independence: The proportion of subjects who had no blood transfusion of 2 or more units of PRBCs for 56 days or more after treatment;	through study completion, an average of 1 year.
disease progression	Time to progression to acute myeloid leukemia (AML);	through study completion, an average of 1 year.
Overall survival	Overall survival (OS).	through study completion, an average of 1 year.
Safety assessment	Safety as assessed by adverse events (AEs), concomitant medications, physical examination, clinical laboratory tests (hematology , serum chemistry and urinalysis), vital signs, Eastern Cooperative Oncology Group (ECOG) performance status, and electrocardiogram (ECG).	through study completion, an average of 1 year.
peak concentration (Cmax)	Decitabine PK parameters: peak concentration (Cmax).	through study completion, an average of 1 year.
time to peak concentration (Tmax)	Decitabine PK parameters: time to peak concentration (Tmax).	through study completion, an average of 1 year.
area under the plasma concentration-time curve over a dosing interval (AUC0-τ).	Decitabine PK parameters: area under the plasma concentration-time curve over a dosing interval (AUC0-τ).	through study completion, an average of 1 year.
accumulation ratio based on AUC0-τ (Rac_AUC0-τ).	Decitabine PK parameters: accumulation ratio based on AUC0-τ (Rac_AUC0-τ).	through study completion, an average of 1 year.
accumulation ratio based on Cmax (Rac_Cmax).	Decitabine PK parameters: accumulation ratio based on Cmax (Rac_Cmax).	through study completion, an average of 1 year.
Cmax	PK parameters of E7727 and E7727-epimer: Cmax.	through study completion, an average of 1 year.
Tmax	PK parameters of E7727 and E7727-epimer: Tmax.	through study completion, an average of 1 year.
AUC0-τ	PK parameters of E7727 and E7727-epimer: area under the plasma concentration-time curve over a dosing interval .	through study completion, an average of 1 year.
Rac_AUC0-τ	PK parameters of E7727 and E7727-epimer: accumulation ratio based on AUC0-τ.	through study completion, an average of 1 year.
Rac_Cmax	PK parameters of E7727 and E7727-epimer: accumulation ratio based on Cmax.	through study completion, an average of 1 year.

Collaborators and Investigators

• Sponsor: Otsuka Beijing Research Institute

Study record dates

Study Major Dates

• Study Start (Actual): October 16, 2023
• Primary Completion (Estimated): May 31, 2026
• Study Completion (Estimated): June 30, 2027

Study Registration Dates

• First Submitted: September 22, 2023
• First Submitted That Met QC Criteria: October 12, 2023
• First Posted (Actual): October 19, 2023

Study Record Updates

• Last Update Posted (Actual): January 30, 2026
• Last Update Submitted That Met QC Criteria: January 29, 2026
• Last Verified: January 1, 2026

More Information

Terms related to this study

• Additional Relevant MeSH Terms: Hematologic Diseases; Bone Marrow Diseases; Hemic and Lymphatic Diseases; Myelodysplastic Syndromes; Organic Chemicals; Heterocyclic Compounds, 1-Ring; Heterocyclic Compounds; Nucleic Acids, Nucleotides, and Nucleosides; Cytidine; Pyrimidine Nucleosides; Pyrimidines; Aza Compounds; Nucleosides; Ribonucleosides; Azacitidine; Decitabine; decitabine and cedazuridine drug combination; cedazuridine
• Other Study ID Numbers: 393-403-00072

Drug and device information, study documents

• Studies a U.S. FDA-regulated drug product: No
• Studies a U.S. FDA-regulated device product: No
• product manufactured in and exported from the U.S.: No