A Phase 1 Trial of ASTX030 in Patients With Myelodysplastic Syndrome

A Phase 1, Multi-center, Open-label, Uncontrolled, Dose-escalation Study to Evaluate the Pharmacokinetics of ASTX030 in Patients With Myelodysplastic Syndrome (MDS)

The purpose of this study is to identify the doses of the oral azacitidine formulations and cedazuridine (CED) tablets which achieve a total AUC for AZA comparable to that for AZA injection at 75 mg/m2

Study Overview

• Status: Recruiting
• Conditions: Myelodysplastic Syndrome (MDS)
• Intervention / Treatment: Drug: ASTX030

• Study Type: Interventional
• Enrollment (Estimated): 40
• Phase: Phase 1

Contacts and Locations

• Study Contact: Name: Drug Information Center; Phone Number: +81-3-6361-7314

Study Locations

• Japan
  • Yamagata, Japan
    • Recruiting
    • Yamagata University Hospital

Participation Criteria

Eligibility Criteria

• Ages Eligible for Study: 20 years and older (Adult, Older Adult)
• Accepts Healthy Volunteers: No

Description

Inclusion Criteria:

• Patients aged 20 years or older
• Patients with a diagnosis of MDS (refractory anemia [RA], refractory anemia with ringed sideroblasts [RARS], refractory anemia with excess blasts [RAEB], refractory anemia with excess blasts in transformation [RAEB-T], or chronic myelomonocytic leukemia [CMML]) according to the French-American-British (FAB) classification Low-risk patients who fall under the risk category of low or intermediate-1 (Int-1) based on the International Prognostic Scoring System (IPSS) can be enrolled only if they are unlikely to respond to any other treatment or if they are currently being treated with azacytidine (AZA) injection
• Patients with an ECOG PS score of 0 or 1 or with an ECOG PS score of 2 due to primary disease-associated conditions

• Patients with adequate organ function as indicated below

  1. Hepatic function: All of the following criteria must be satisfied.

     • Total bilirubin ≤ 2.0 × upper limit of normal (ULN)
     • Aspartate aminotransferase (AST) ≤ 2.5 × ULN
     • Alanine aminotransferase (ALT) ≤ 2.5 × ULN

  2. Renal function: Either of the following criteria must be satisfied.

     • Serum creatinine ≤ 1.5 × ULN
     • Creatinine clearance or glomerular filtration rate ≥ 50 mL/min
  3. Respiratory function: percutaneous arterial oxygen saturation (SpO2) ≥ 90%
• Patients who are expected to survive for at least 3 months
• Patients who give written consent to participate in the trial using the informed consent form approved by the institutional review board

Exclusion Criteria:

• Patients who are unlikely to respond to AZA
• Patients who have received chemotherapy, hormone therapy, antibody therapy, radiotherapy, or other exploratory anti-cancer treatments for the primary disease within 3 weeks prior to the first administration of the investigational medicinal product (IMP)
• Patients who have used any other IMP or any privately imported medicine within 4 weeks prior to the first administration of IMP
• Patients with heart disease of Class 3 or 4 according to the New York Heart Association classification
• Patients with uncontrolled systemic disease or active infection
• Patients with uncontrolled gastric or duodenal ulcer
• Patients with prior or current interstitial lung disease
• Patients with a history of surgical gastrectomy
• Patients with life-threatening conditions/symptoms, multiple organ failure, or other factors (including laboratory abnormalities) that, in the opinion of the investigator, are likely to affect their safety or the absorption and metabolism of AZA and cedazuridine (CED), or influence the trial evaluation
• Patients with other malignancies (except appropriately treated basal cell carcinoma, squamous cell carcinoma, or cervical carcinoma in situ; prostate or breast cancer stabilized by endocrine therapies; and malignancies that have not relapsed for at least 1 year since the last successful treatment)
• Patients who are positive for HIV antibody, HBV-DNA, or HCV antibody
• Patients with any ≥ Grade 2 AE (except alopecia) associated with prior treatment of the primary disease. However, the parameters defined in inclusion criterion above are excluded.
• Patients who have undergone a highly invasive and extensive surgical procedure within 4 weeks prior to the first administration of IMP
• Patients who previously underwent or plan on undergoing hematopoietic stem cell transplantation
• Patients with a history of hypersensitivity to the active ingredient or any excipient of IMP
• Patients who are, in the opinion of the investigator, at high risk for being unable to comply with the trial protocol because of mental disorders or other medical conditions (alcohol/substance abuse or addiction)
• Pregnant or nursing female patients, or female patients with a positive pregnancy test at screening. Nursing patients cannot participate in the trial even if they discontinue breastfeeding. Female patients must undergo a pregnancy test to confirm that they are not pregnant at screening. However, a pregnancy test is not necessary for female patients without childbearing potential (ie, patients with a history of bilateral oophorectomy or hysterectomy or who have been postmenopausal for at least 12 months except for cases where menopause could be due to the effect of antineoplastic treatment).
• Sexually active males (except those with a history of bilateral orchiectomy) or females of childbearing potential who do not agree to practice 2 different methods of birth control or remain abstinent during the trial and for 3 months (males) and 6 months (females) after the last dose of IMP. If birth control is employed, 2 of the following precautions must be used: vasectomy, tubal ligation, intrauterine device, oral contraceptive, and condom (all methods approved or certified in Japan)
• Patients who, in the opinion of the investigator, are otherwise ineligible to participate in the trial

Study Plan

How is the study designed?

Design Details

• Primary Purpose: Treatment
• Allocation: Non-Randomized
• Interventional Model: Single Group Assignment
• Masking: None (Open Label)

Number of Arms

1

Arms and Interventions

Participant Group / Arm	Intervention / Treatment
Experimental: Azacitidine + Cedazuridine; Drug: Azacitidine Tablets or capsules for oral administration and powder for reconstitution to aqueous suspension for subcutaneous administration Drug: Cedazuridine Tablets for oral administration	Drug: ASTX030; In Cycle 1 (28 days per cycle), single dose oral azacitidine formulations will be administered on day -3, followed by subcutaneous (SC) azacitidine on day 1, oral azacitidine formulations and cedazuridine tablets on day 2-7; in Cycle 2 and onward, oral azacitidine formulations and cedazuridine tablets will be administered on day 1-7

What is the study measuring?

Primary Outcome Measures

Outcome Measure	Time Frame
• AUC ratio of AZA after administration of oral azacitidine formultions in combination with CED tablets compared with subcutaneous (SC) administration of AZA injection	Up to 1 month

Collaborators and Investigators

• Sponsor: Otsuka Pharmaceutical Co., Ltd.
• Investigators: Study Director: Nobuhito Sanada, Mr, Otsuka Pharmaceutical Co., Ltd.

Study record dates

Study Major Dates

• Study Start (Actual): October 30, 2020
• Primary Completion (Estimated): November 1, 2024
• Study Completion (Estimated): December 1, 2024

Study Registration Dates

• First Submitted: October 23, 2020
• First Submitted That Met QC Criteria: October 23, 2020
• First Posted (Actual): October 29, 2020

Study Record Updates

• Last Update Posted (Actual): July 25, 2023
• Last Update Submitted That Met QC Criteria: July 23, 2023
• Last Verified: July 1, 2023

More Information

Terms related to this study

• Additional Relevant MeSH Terms: Pathologic Processes; Neoplasms; Disease; Bone Marrow Diseases; Hematologic Diseases; Precancerous Conditions; Syndrome; Myelodysplastic Syndromes; Preleukemia
• Other Study ID Numbers: 418-102-00001

Plan for Individual participant data (IPD)

• Plan to Share Individual Participant Data (IPD)?: YES
• IPD Plan Description: Anonymized Individual participant data (IPD) that underlie the results of this study will be shared with researchers to achieve aims pre-specified in a methodologically sound research proposal.
• IPD Sharing Time Frame: Data will be available after marketing approval in global markets, or beginning 1-3 years following article Publication. There is no end date to the availability of the data.
• IPD Sharing Access Criteria: Otsuka will share data on an Otsuka-owned remotely accessible data sharing platform with Python and R analytical software. Research requests should be directed to clinicaltransparency@Otsuka-us.com.
• IPD Sharing Supporting Information Type: STUDY_PROTOCOL; SAP

Drug and device information, study documents

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