Description:
To investigate the tolerability and safety of ASTX727 in Japanese subjects with lower-risk
MDS.
Title
- Brief Title: Phase 1 Trial of ASTX727 in Subjects With Lower-risk Myelodysplastic Syndromes
- 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
Clinical Trial IDs
- ORG STUDY ID:
393-102-00002
- NCT ID:
NCT03906695
Conditions
- Lower-risk Myelodysplastic
Interventions
| Drug | Synonyms | Arms |
|---|
| ASTX727 | | 10-Day Schedule |
| ASTX727 | | 5-Day Schedule A |
| ASTX727 | | 5-Day Schedule B |
| ASTX727 | | 5-Day Schedule C |
| ASTX727 | | 7-Day Schedule |
Purpose
To investigate the tolerability and safety of ASTX727 in Japanese subjects with lower-risk
MDS.
Trial Arms
| Name | Type | Description | Interventions |
|---|
| 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. | |
| 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. | |
| 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. | |
| 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. | |
| 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. | |
Eligibility 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
| Maximum Eligible Age: | N/A |
| Minimum Eligible Age: | 20 Years |
| Eligible Gender: | All |
| Healthy Volunteers: | No |
Primary Outcome Measures
| Measure: | Dose Limiting Toxicity |
| Time Frame: | 28days |
| Safety Issue: | |
| Description: | |
Secondary Outcome Measures
| Measure: | 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 |
| Safety Issue: | |
| Description: | pharmacokinetics parameter |
| Measure: | 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 |
| Safety Issue: | |
| Description: | pharmacokinetics parameter |
Details
| Phase: | Phase 1 |
| Primary Purpose: | Interventional |
| Overall Status: | Recruiting |
| Lead Sponsor: | Otsuka Pharmaceutical Co., Ltd. |
Last Updated
December 11, 2020
