Clinical trial NCT03906695: 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
Study type: INTERVENTIONAL
Overall status: ACTIVE_NOT_RECRUITING
Phase: PHASE1
Conditions: Lower-risk Myelodysplastic
Lead sponsor: Otsuka Pharmaceutical Co., Ltd.
Sponsor class: INDUSTRY
First posted: 2019-04-08
Enrollment: 30
Sex: ALL
Minimum age (years): 20
Standard ages: ADULT
OLDER_ADULT
Accepts healthy volunteers: no
Allocation: NON_RANDOMIZED
Intervention model: PARALLEL
Primary purpose: TREATMENT

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


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

Primary outcomes:
measure: Dose Limiting Toxicity
timeFrame: 28days
Secondary outcomes:
measure: Area under the curve (AUC)
timeFrame: Pre-dose, 15 min, 30 min, 60 min, 90 min, 2 h, 3 h, 4 h, 6 h, 8 h, 24 h after dosing
measure: Maximum plasma concentration (Cmax)
timeFrame: Pre-dose, 15 min, 30 min, 60 min, 90 min, 2 h, 3 h, 4 h, 6 h, 8 h, 24 h after dosing
Other outcomes:
Locations:
city: Tokyo
country: Japan
facility: NTT Medical Center Tokyo
Study officials:
affiliation: Otsuka Pharmaceutical Co., Ltd.
name: Nobuhito Sanada
role: STUDY_DIRECTOR
References: