A Study to Evaluate the Safety, Pharmacokinetics and Preliminary Efficacy of APG-5918.

Ascentage Pharma Group

Status and phase: Enrolling; Phase 1

Conditions: Anemia

Treatments: Drug: APG-5918; Drug: Placebo

Study type: Interventional

Funder types: Industry

Identifiers

NCT05773586

APG5918AC101

Details and patient eligibility

About

The purpose of the study is to evaluate the safety, tolerability, pharmacokinetics and efficacy of APG-5918 in Healthy Subjects or Anemic Patients.

Full description

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.

Enrollment: 105 estimated patients

Sex: All

Ages: 18+ years old

Volunteers: Accepts Healthy Volunteers

Inclusion and exclusion criteria

Inclusion Criteria:

1. Healthy Subjects:

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:

1. Age: ≥ 18 years.
2. Including beta-thalassemia and other related anemias, with screening Hb ≤ 100.0 g/L.
3. Body weight ≥ 40 kg.
4. Serum folate and vitamin B12 levels above the lower limit of normal (LLN).
5. ALT, AST ≤ 2×ULN, and direct (unconjugated) total bilirubin (DBIL) ≤ 2×ULN. Higher levels may be accepted after excluding other diseases based on investigator judgment.
6. No active or chronic bleeding.
7. Eastern Cooperative Oncology Group (ECOG) performance status score of 0-1.

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:

1. History of any disease or clinical condition that, in the investigator's opinion, may confound the study results or pose additional risk to the subject with administration of the study drug.
2. ALT or AST > 2×ULN, or TBIL > 1.5×ULN at screening.
3. Undergone surgery (excluding minor cosmetic or dental procedures) within 3 months prior to screening.
4. Blood donation or blood loss exceeding 400 mL within 3 months prior to screening, or planned donation of blood or blood components during the study period.
5. Use of another investigational product within 30 days or 5 half-lives (whichever is longer) prior to dosing, or current participation in a prospective study of an investigational product or medical device.
6. History of substance abuse within 6 months prior to screening.
7. Positive alcohol breath test.

2. Anemic Subjects:

1. Presence of clinically significant or uncontrolled ongoing autoimmune disease.
2. Severe cardiac disease.
3. Severe renal disease, defined as estimated glomerular filtration rate (eGFR) < 30 mL/min/1.73m², or dependence on dialysis.
4. Active malignancy, history of cancer, or presence of a known or suspected familial cancer syndrome in linealrelatives.
5. A history of persistent hemolysis or hemolytic syndrome due to causes other than the study diseases.
6. A history of thrombosis or newly developed thrombus within 4 weeks prior to screening.
7. Receipt of intravenous iron supplementation within 28 days prior to first dosing.
8. Any active infection requiring systemic antibiotic therapy (including oral, intravenous, or intraperitoneal administration) within 14 days prior to first dosing.
9. A history of organ transplantation.
10. Any condition that may affect drug absorption.
11. Participation in another clinical study and still using another investigational products, or without completion of a washout period of at least 5 half-lives within 4 weeks prior to first dosing.
12. Receipt of cytotoxic agents, high-dose systemic corticosteroids, immunosuppressive agents, or anticoagulant therapy such as warfarin within 28 days prior to first dosing.

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.

Trial design

Primary purpose: Treatment

Allocation: Randomized

Interventional model: Parallel Assignment

Masking: Double Blind

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105 participants in 2 patient groups

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

Experimental group

Description:

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

Treatment:

Drug: Placebo

Drug: APG-5918

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

Experimental group

Description:

Subjects will receive once daily APG-5918 for 84 days or till EOT.

Treatment:

Drug: APG-5918