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

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Primary Purpose

Status

Recruiting

Phase

Phase 1

Locations

China

Study Type

Interventional

Intervention

IV Decitabine

Decitabine and cedazuridine

only Decitabine and cedazuridine

About this trial

This is an interventional treatment trial for Myelodysplastic Syndromes

Eligibility Criteria

18 Years - undefined (Adult, Older Adult)All SexesDoes not accept healthy volunteers

Inclusion Criteria: Agree to participate in this trial and voluntarily sign the informed consent form. Men or women ≥ 18 years at the time of signing the informed consent form. Subjects with MDS previously treated or untreated with de novo or secondary MDS. Eastern Cooperative Oncology Group (ECOG) performance status of 0 to 1 at screening. Exclusion Criteria: Prior treatment with more than 1 cycle of azacitidine or decitabine. Cytotoxic chemotherapy or prior azacitidine or decitabine within 4 weeks of first dose of study treatment. Conditions as judged by the investigator to be inappropriate for participation in the clinical trial. Previous diagnosis of malignant tumor. History of immune deficiency. Acute myeloid leukemia (AML) with bone marrow or peripheral blast count ≥ 20% or other malignant hematological diseases.

Sites / Locations

The First Affiliated Hospital,Zhejiang University School of MedicineRecruiting

Arms of the Study

Arm 1

Arm 2

Arm 3

Arm Type

Experimental

Active Comparator

Experimental

Arm Label

ASTX727 and IV Decitabine

IV Decitabine and ASTX727

ASTX727

Arm Description

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

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

ASTX727 tablets, oral, 1 tablet/day for 5 days；

Outcomes

Primary Outcome Measures

Complete Response Rate

Assess efficacy [Complete Response Rate (CR)] of treatment with ASTX727 in Chinese subjects with myelodysplastic syndromes (MDS);

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;

Secondary Outcome Measures

Objective Response Rate

Objective Response Rate (ORR): The proportion of subjects who achieve CR and partial response (PR) based on IWG 2006 criteria;

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.

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;

disease progression

Time to progression to acute myeloid leukemia (AML);

Overall survival

Overall survival (OS).

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).

peak concentration (Cmax)

Decitabine PK parameters: peak concentration (Cmax).

time to peak concentration (Tmax)

Decitabine PK parameters: time to peak concentration (Tmax).

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).

accumulation ratio based on AUC0-τ (Rac_AUC0-τ).

Decitabine PK parameters: accumulation ratio based on AUC0-τ (Rac_AUC0-τ).

accumulation ratio based on Cmax (Rac_Cmax).

Decitabine PK parameters: accumulation ratio based on Cmax (Rac_Cmax).

Cmax

PK parameters of E7727 and E7727-epimer: Cmax.

Tmax

PK parameters of E7727 and E7727-epimer: Tmax.

AUC0-τ

PK parameters of E7727 and E7727-epimer: area under the plasma concentration-time curve over a dosing interval .

Rac_AUC0-τ

PK parameters of E7727 and E7727-epimer: accumulation ratio based on AUC0-τ.

Rac_Cmax

PK parameters of E7727 and E7727-epimer: accumulation ratio based on Cmax.

Full Information

NCT ID

NCT06091267

First Posted

September 22, 2023

Last Updated

October 23, 2023

Sponsor

Otsuka Beijing Research Institute

1. Study Identification

Unique Protocol Identification Number

NCT06091267

Brief Title

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

Official Title

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

Study Type

Interventional

2. Study Status

Record Verification Date

October 2023

Overall Recruitment Status

Recruiting

Study Start Date

October 16, 2023 (Actual)

Primary Completion Date

December 30, 2025 (Anticipated)

Study Completion Date

June 30, 2026 (Anticipated)

3. Sponsor/Collaborators

Responsible Party, by Official Title

Sponsor

Name of the Sponsor

Otsuka Beijing Research Institute

4. Oversight

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

5. Study Description

Brief Summary

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

6. Conditions and Keywords

Primary Disease or Condition Being Studied in the Trial, or the Focus of the Study

Myelodysplastic Syndromes

7. Study Design

Primary Purpose

Treatment

Study Phase

Phase 1, Phase 2

Interventional Study Model

Crossover Assignment

Masking

None (Open Label)

Allocation

Randomized

Enrollment

72 (Anticipated)

8. Arms, Groups, and Interventions

Arm Title

ASTX727 and IV Decitabine

Arm Type

Experimental

Arm Description

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

Arm Title

IV Decitabine and ASTX727

Arm Type

Active Comparator

Arm Description

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

Arm Title

ASTX727

Arm Type

Experimental

Arm Description

ASTX727 tablets, oral, 1 tablet/day for 5 days；

Intervention Type

Drug

Intervention Name(s)

IV Decitabine

Intervention Description

The subjects will receive decitabine 20 mg/m^2 IV daily × 5 days in 28-day cycles.

Intervention Type

Drug

Intervention Name(s)

Decitabine and cedazuridine

Intervention Description

subjects will receive treatment with ASTX727, 1 tablet/day for 5 consecutive days, in 28-day cycles.

Intervention Type

Drug

Intervention Name(s)

only Decitabine and cedazuridine

Intervention Description

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.

Primary Outcome Measure Information:

Title

Complete Response Rate

Description

Assess efficacy [Complete Response Rate (CR)] of treatment with ASTX727 in Chinese subjects with myelodysplastic syndromes (MDS);

Time Frame

An analysis is planned when the last enrolled patient have completed Follow-up 12 months.

Title

5day_AUC0-τ

Description

Assess pharmacokinetic (PK) parameters (Total 5-day AUC exposures of decitabine) after treatment with ASTX727 (oral) versus decitabine for IV infusion for 5 days;

Time Frame

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 Measure Information:

Title

Objective Response Rate

Description

Objective Response Rate (ORR): The proportion of subjects who achieve CR and partial response (PR) based on IWG 2006 criteria;

Time Frame