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A Study to Investigate the Safety, Pharmacokinetics and Efficacy of APG-5918 in Healthy Subjects or Anemic Patients

Primary Purpose

Anemia

Status
Recruiting
Phase
Phase 1
Locations
China
Study Type
Interventional
Intervention
APG-5918
Placebo
APG-5918
Placebo
Sponsored by
Ascentage Pharma Group Inc.
About
Eligibility
Locations
Arms
Outcomes
Full info

About this trial

This is an interventional treatment trial for Anemia focused on measuring APG-5918, Anemia

Eligibility Criteria

18 Years - undefined (Adult, Older Adult)All SexesAccepts Healthy Volunteers

Inclusion Criteria: - 1.Inclusion criteria for healthy subjects Age ≥ 18 years and ≤ 55 years. Body mass index (BMI) 18~28kg/m² (inclusive). Hb: 120 g/L~160 g/L (inclusive). Normal iron stores (normal serum iron and serum ferritin). 2.Inclusion criteria for anemic subjects Age ≥ 18 years. Chronic patients with anemia, including but not limited to β-thalassemia, with Hb ≤ 100 g/L at screening. BMI: 16~32 kg/m2 (inclusive). Serum folate and vitamin B12 levels above lower limit of normal (LLN). Ferritin ≥ 40 ng/mL without small cells or hypochromic RBCs. Serum transferrin saturation (TSAT) is 20% to 50%. ALT, AST ≤ 2 × ULN, or total bilirubin (TBIL) ≤ 1.5 × ULN. No active or chronic bleeding. ECOG performance status score of 0 to 1. 3. Female subjects of childbearing potential who have a negative serum pregnancy test within 7 days prior to the first dose. 4. Subjects and their partners volunteer to use protocol-specified effective contraception during treatment and for at least 3 months after the last dose of study drug (see Section 8.7 for details). 5. Ability to understand and willingness to sign a written informed consent form (the consent form must be signed by the subject prior to any study-specific procedures). Exclusion criteria 1.Exclusion criteria for healthy subjects History of any disease or clinical condition that, in the opinion of the investigator, could confound the results of the study or pose an additional risk to the subject by administering study drug. Including but not limited to history or presence of cardiac, endocrine, hematologic, hepatic, gastrointestinal, immunologic, metabolic, urologic, pulmonary, neurologic, dermatologic, psychiatric, renal, and/or other diseases. Alanine aminotransferase (ALT) or aspartate aminotransferase (AST) > 2 × upper limit of normal (ULN), or total bilirubin (TBIL) > 1.5 × ULN at screening. Surgery (except minor cosmetic surgery or minor dental surgery) within 3 months prior to screening. Blood donation or blood loss of more than 400 ml within 3 months before screening or plans to donate blood or blood components during the study. Use of another investigational product within 30 days or 5 half-lives, whichever is longer, or currently participating in a prospective study of an investigational product or medical device. History of addictive substance abuse. History of regular alcohol consumption within 6 months before screening, daily average intake of ethanol ≥ 30 grams (male) or ≥ 20 grams (female). Alcohol breath test fails. Female subjects who are pregnant, planning to become pregnant, or breastfeeding, or male subjects whose partners intend to become pregnant. 2.Exclusion criteria for anemic subjects Clinically significant or uncontrolled persistent autoimmune diseases (e.g., rheumatoid arthritis, Crohn's disease, celiac disease, etc.). Uncontrolled hypertension (diastolic blood pressure > 110 mmHg or systolic blood pressure > 170 mmHg at screening) or diabetes as judged by the investigator. New York Heart Association Class II to IV congestive heart failure, or recent myocardial infarction or acute coronary syndrome. History of diagnosis of persistent hemolysis or hemolytic syndrome. History of thrombosis or new blood clots within 4 weeks prior to screening. Received red blood cell or whole blood transfusion within 12 weeks before screening. Intravenous iron within 60 days prior to screening. Previous history of organ transplantation. Patients who participated in other clinical studies within 4 weeks and were still taking other study drugs or had not exceeded 5 half-lives. 3.Positive screening results for hepatitis B virus surface antigen (HBsAg), hepatitis C virus (HCV) antibody, human immunodeficiency virus antibody (HIV Ab), or treponema pallidum antibody at screening. 4.Standard 12-lead ECG QTcB > 450 ms in men and > 470 ms in women. 5. Female subjects who are pregnant, planning to become pregnant, or breastfeeding, or male subjects whose partners intend to become pregnant. 6. Any subject who is not suitable for participating in this study as judged by the investigator.

Sites / Locations

  • Nanfang Hospital of Southern Medical UniversityRecruiting

Arms of the Study

Arm 1

Arm 2

Arm Type

Experimental

Experimental

Arm Label

Single Ascending Dose (SAD) cohorts in Healthy Subjects (Part A)

Multiple Ascending Dose (MAD) cohorts in Anemic Patients (Part B)

Arm Description

Subjects will be randomized to receive a single dose of APG-5918 or placebo.

Subjects will be randomized to receive once daily APG-5918 or placebo for 28 days.

Outcomes

Primary Outcome Measures

Treatment-Emergent Adverse Events (TEAEs)
TEAEs will be assessed via CTCAE version 5.0 based on the frequency of adverse events/serious adverse events (AEs/SAEs), clinically significant laboratory test results, 12-lead ECGs, and vital signs.

Secondary Outcome Measures

Plasma Concentrations of APG-5918
Blood samples will be collected to measure the plasma concentration of APG-5918 by a validated liquid chromatography with tandem mass spectrometry (LC-MS/MS) method.
Measurement of Hemoglobin
Change from baseline in hemoglobin will be measured in peripheral whole blood by flow cytometry.

Full Information

First Posted
February 22, 2023
Last Updated
March 23, 2023
Sponsor
Ascentage Pharma Group Inc.
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1. Study Identification

Unique Protocol Identification Number
NCT05773586
Brief Title
A Study to Investigate the Safety, Pharmacokinetics and Efficacy of APG-5918 in Healthy Subjects or Anemic Patients
Official Title
A Phase 1 Randomized, Double-Blinded, Placebo-Controlled, Dose-Escalating Study to Evaluate Safety and Tolerability, Pharmacokinetics and Efficacy of APG-5918 in Healthy Subjects or Anemic Patients
Study Type
Interventional

2. Study Status

Record Verification Date
March 2023
Overall Recruitment Status
Recruiting
Study Start Date
March 15, 2023 (Actual)
Primary Completion Date
August 31, 2025 (Anticipated)
Study Completion Date
March 15, 2026 (Anticipated)

3. Sponsor/Collaborators

Responsible Party, by Official Title
Sponsor
Name of the Sponsor
Ascentage Pharma Group Inc.

4. Oversight

Studies a U.S. FDA-regulated Drug Product
No
Studies a U.S. FDA-regulated Device Product
No

5. Study Description

Brief Summary
The purpose of the study is to evaluate the safety, tolerability, pharmacokinetics and efficacy of APG-5918 in Healthy Subjects or Anemic Patients.
Detailed Description
The trial has two parts. Part A is a randomized, double-blind, placebo- controlled, single-dose escalation study in up to 7 cohorts to evaluate the safety, tolerability, and PK characteristics of APG-5918 in healthy subjects and to explore whether MTDS will be achieved within the range of projected therapeutic doses for anemia. Part B is a randomized, double-blind, placebo-controlled, multi-dose escalation trial in up to 7 cohorts to evaluate the safety, tolerability, PK and preliminary efficacy of APG-5918 in anemic subjects.

6. Conditions and Keywords

Primary Disease or Condition Being Studied in the Trial, or the Focus of the Study
Anemia
Keywords
APG-5918, Anemia

7. Study Design

Primary Purpose
Treatment
Study Phase
Phase 1
Interventional Study Model
Parallel Assignment
Masking
ParticipantInvestigator
Allocation
Randomized
Enrollment
115 (Anticipated)

8. Arms, Groups, and Interventions

Arm Title
Single Ascending Dose (SAD) cohorts in Healthy Subjects (Part A)
Arm Type
Experimental
Arm Description
Subjects will be randomized to receive a single dose of APG-5918 or placebo.
Arm Title
Multiple Ascending Dose (MAD) cohorts in Anemic Patients (Part B)
Arm Type
Experimental
Arm Description
Subjects will be randomized to receive once daily APG-5918 or placebo for 28 days.
Intervention Type
Drug
Intervention Name(s)
APG-5918
Intervention Description
oral tablets 10mg, 50mg.
Intervention Type
Drug
Intervention Name(s)
Placebo
Intervention Description
Matching placebo
Intervention Type
Drug
Intervention Name(s)
APG-5918
Intervention Description
oral tablets 10mg, 50mg.
Intervention Type
Drug
Intervention Name(s)
Placebo
Intervention Description
Matching placebo
Primary Outcome Measure Information:
Title
Treatment-Emergent Adverse Events (TEAEs)
Description
TEAEs will be assessed via CTCAE version 5.0 based on the frequency of adverse events/serious adverse events (AEs/SAEs), clinically significant laboratory test results, 12-lead ECGs, and vital signs.
Time Frame
up to 7 days in Part A and 42 days in Part B
Secondary Outcome Measure Information:
Title
Plasma Concentrations of APG-5918
Description
Blood samples will be collected to measure the plasma concentration of APG-5918 by a validated liquid chromatography with tandem mass spectrometry (LC-MS/MS) method.
Time Frame
Days 1, 2 and 3 in Part A; Days 1, 8, 15, 22 and 28 in Part B
Title
Measurement of Hemoglobin
Description
Change from baseline in hemoglobin will be measured in peripheral whole blood by flow cytometry.
Time Frame
up to 28 days in Part B
Other Pre-specified Outcome Measures:
Title
Expression levels of H3K27me3
Description
Expression levels of H3K27me3 in circulating monocytes will be evaluated by fluorescence-activated cell sorting (FACS).
Time Frame
up to 28 days in Part B

10. Eligibility

Sex
All
Minimum Age & Unit of Time
18 Years
Accepts Healthy Volunteers
Accepts Healthy Volunteers
Eligibility Criteria
Inclusion Criteria: - 1.Inclusion criteria for healthy subjects Age ≥ 18 years and ≤ 55 years. Body mass index (BMI) 18~28kg/m² (inclusive). Hb: 120 g/L~160 g/L (inclusive). Normal iron stores (normal serum iron and serum ferritin). 2.Inclusion criteria for anemic subjects Age ≥ 18 years. Chronic patients with anemia, including but not limited to β-thalassemia, with Hb ≤ 100 g/L at screening. BMI: 16~32 kg/m2 (inclusive). Serum folate and vitamin B12 levels above lower limit of normal (LLN). Ferritin ≥ 40 ng/mL without small cells or hypochromic RBCs. Serum transferrin saturation (TSAT) is 20% to 50%. ALT, AST ≤ 2 × ULN, or total bilirubin (TBIL) ≤ 1.5 × ULN. No active or chronic bleeding. ECOG performance status score of 0 to 1. 3. Female subjects of childbearing potential who have a negative serum pregnancy test within 7 days prior to the first dose. 4. Subjects and their partners volunteer to use protocol-specified effective contraception during treatment and for at least 3 months after the last dose of study drug (see Section 8.7 for details). 5. Ability to understand and willingness to sign a written informed consent form (the consent form must be signed by the subject prior to any study-specific procedures). Exclusion criteria 1.Exclusion criteria for healthy subjects History of any disease or clinical condition that, in the opinion of the investigator, could confound the results of the study or pose an additional risk to the subject by administering study drug. Including but not limited to history or presence of cardiac, endocrine, hematologic, hepatic, gastrointestinal, immunologic, metabolic, urologic, pulmonary, neurologic, dermatologic, psychiatric, renal, and/or other diseases. Alanine aminotransferase (ALT) or aspartate aminotransferase (AST) > 2 × upper limit of normal (ULN), or total bilirubin (TBIL) > 1.5 × ULN at screening. Surgery (except minor cosmetic surgery or minor dental surgery) within 3 months prior to screening. Blood donation or blood loss of more than 400 ml within 3 months before screening or plans to donate blood or blood components during the study. Use of another investigational product within 30 days or 5 half-lives, whichever is longer, or currently participating in a prospective study of an investigational product or medical device. History of addictive substance abuse. History of regular alcohol consumption within 6 months before screening, daily average intake of ethanol ≥ 30 grams (male) or ≥ 20 grams (female). Alcohol breath test fails. Female subjects who are pregnant, planning to become pregnant, or breastfeeding, or male subjects whose partners intend to become pregnant. 2.Exclusion criteria for anemic subjects Clinically significant or uncontrolled persistent autoimmune diseases (e.g., rheumatoid arthritis, Crohn's disease, celiac disease, etc.). Uncontrolled hypertension (diastolic blood pressure > 110 mmHg or systolic blood pressure > 170 mmHg at screening) or diabetes as judged by the investigator. New York Heart Association Class II to IV congestive heart failure, or recent myocardial infarction or acute coronary syndrome. History of diagnosis of persistent hemolysis or hemolytic syndrome. History of thrombosis or new blood clots within 4 weeks prior to screening. Received red blood cell or whole blood transfusion within 12 weeks before screening. Intravenous iron within 60 days prior to screening. Previous history of organ transplantation. Patients who participated in other clinical studies within 4 weeks and were still taking other study drugs or had not exceeded 5 half-lives. 3.Positive screening results for hepatitis B virus surface antigen (HBsAg), hepatitis C virus (HCV) antibody, human immunodeficiency virus antibody (HIV Ab), or treponema pallidum antibody at screening. 4.Standard 12-lead ECG QTcB > 450 ms in men and > 470 ms in women. 5. Female subjects who are pregnant, planning to become pregnant, or breastfeeding, or male subjects whose partners intend to become pregnant. 6. Any subject who is not suitable for participating in this study as judged by the investigator.
Central Contact Person:
First Name & Middle Initial & Last Name or Official Title & Degree
Yifan Zhai, Ph.D.
Phone
+86-20-28069260
Email
yzhai@ascentage.com
First Name & Middle Initial & Last Name or Official Title & Degree
Zhongyuan Xu
Phone
020-62787926
Email
nfyygcp@126.com
Overall Study Officials:
First Name & Middle Initial & Last Name & Degree
Zhongyuan Xu
Organizational Affiliation
Nanfang Hospital, Southern Medical University
Official's Role
Principal Investigator
Facility Information:
Facility Name
Nanfang Hospital of Southern Medical University
City
Guangzhou
State/Province
Guangdong
ZIP/Postal Code
510515
Country
China
Individual Site Status
Recruiting
Facility Contact:
First Name & Middle Initial & Last Name & Degree
Zhongyuan Xu, Ph.D.
Phone
020-62787926

12. IPD Sharing Statement

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A Study to Investigate the Safety, Pharmacokinetics and Efficacy of APG-5918 in Healthy Subjects or Anemic Patients

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