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The purpose of the study is to evaluate the safety, tolerability, pharmacokinetics and efficacy of APG-5918 in Healthy Subjects or Anemic Patients.
The trial is composed of ttwo 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 volunteers and to explore whether MTDS will be achieved within the range of projected therapeutic doses for anemia.
Part B is an open-label,, multi-dose escalation trial in up to 6 cohorts to evaluate the safety, tolerability, PK and preliminary efficacy of APG-5918 in patients with anemia.
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| Label | Type | Description | Intervention Names |
|---|---|---|---|
| Single Ascending Dose (SAD) cohorts in Healthy Subjects (Part A) | Experimental | Subjects will be randomized to receive a single dose of APG-5918 or placebo. |
|
| Multiple Ascending Dose (MAD) cohorts in Anemic Patients (Part B) | Experimental | Subjects will receive once daily APG-5918 for 84 days or till EOT. |
|
| Name | Type | Description | Arm Group Labels | Other Names |
|---|---|---|---|---|
| APG-5918 | Drug | oral tablets 10mg, 50mg, 200mg. |
|
| Measure | Description | Time Frame |
|---|---|---|
| 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. | up to 7 days in Part A and 84 days or till EOT in Part B |
| Measure | Description | Time Frame |
|---|---|---|
| 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. | Days 1, 2 and 3 in Part A; Days 1, 15 and 28 in Part B |
| Measurement of Hemoglobin |
| Measure | Description | Time Frame |
|---|---|---|
| Expression levels of H3K27me3 | Expression levels of H3K27me3 in circulating monocytes will be evaluated by fluorescence-activated cell sorting (FACS). | 84 days or till EOT in Part B |
Inclusion Criteria:
1. Age: 18 to 55 years. 2. Body Mass Index (BMI): 18-28 kg/m² (inclusive). 3. Hemoglobin value: 120 g/L-160 g/L (inclusive). 4. Normal body iron stores. 2. Anemic Subjects:
3. For female subjects of childbearing potential, a negative blood or urine pregnancy test within 7 days prior to the first dose.
4. Subjects and their partners must voluntarily agree to use effective contraceptive measures as required by the protocol during the treatment period and for at least 3 months after the last dose of study drug.
5. Ability to understand and voluntarily sign a written informed consent form, which must be signed before any trial-specific procedures are performed.
Exclusion Criteria -
1. Healthy Subjects:
2. Anemic Subjects:
3. Positive results for hepatitis B surface antigen (HBsAg), hepatitis C virus (HCV) antibody, human immunodeficiency virus (HIV) antibody, or Treponema pallidum antibody at screening.
4. A history of regular alcohol consumption within 6 months prior to screening, defined as an average daily intake of ≥30 grams (for males) or ≥20 grams (for females) of ethanol.
5. Standard 12-lead ECG with QTcB > 450 ms for males or QTcB > 470 ms for females.
6. Female subjects who are pregnant, planning to become pregnant, or breastfeeding; or male subjects whose partners are planning to become pregnant.
7. Any subject deemed unsuitable for participation in this study based on the investigator's judgment.
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| Name | Role | Phone | Extension | |
|---|---|---|---|---|
| Yifan Zhai, Ph.D. | Contact | +86-20-28069260 | yzhai@ascentage.com | |
| Zhongyuan Xu | Contact | 020-62787926 | nfyygcp@126.com |
| Name | Affiliation | Role |
|---|---|---|
| Zhongyuan Xu, M.D.,Ph.D. | Nanfang Hospital, Southern Medical University | Principal Investigator |
| Yang Liang, M.D.,Ph.D. | Sun Yat-Sen University Cancer Center | Principal Investigator |
| Facility | Status | City | State | ZIP | Country | Contacts |
|---|---|---|---|---|---|---|
| Sun Yat-sen University Cancer Center | Recruiting | Guangzhou | Guangdong | 510000 | China |
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| ID | Term |
|---|---|
| D000740 | Anemia |
| ID | Term |
|---|---|
| D006402 | Hematologic Diseases |
| D006425 | Hemic and Lymphatic Diseases |
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| Placebo | Drug | Matching placebo |
|
Change from baseline in hemoglobin will be measured in peripheral whole blood by flow cytometry. |
| 84 days or till EOT in Part B |
| Nanfang Hospital of Southern Medical University | Recruiting | Guangzhou | Guangdong | 510515 | China |
|