NCT05773586RecruitingPhase 1
A Phase 1, Ascending Dose Study to Evaluate Safety and Tolerability, Pharmacokinetics and Preliminary Efficacy of APG-5918 in Healthy Volunteers and Patients With Anemia.
Ascentage Pharma Group Inc.2 sites in 1 country105 target enrollmentStarted: March 13, 2023Last updated:
Conditions
Interventions
Drugs
Trial Snapshot
- Phase
- Phase 1
- Status
- Recruiting
- Sponsor
- Ascentage Pharma Group Inc.
- Enrollment
- 105
- Locations
- 2
- Primary Endpoint
- Treatment-Emergent Adverse Events (TEAEs)
Study Overview
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 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.
Study Design
- Study Type
- Interventional
- Allocation
- Randomized
- Intervention Model
- Parallel
- Primary Purpose
- Treatment
- Masking
- Double (Participant, Investigator)
Eligibility Criteria
- Ages
- 18 Years to — (Adult, Older Adult)
- Sex
- All
- Accepts Healthy Volunteers
- Yes
Inclusion Criteria
- •Healthy Subjects:
- •1. Age: 18 to 55 years.
- •Body Mass Index (BMI): 18-28 kg/m² (inclusive).
- •Hemoglobin value: 120 g/L-160 g/L (inclusive).
- •Normal body iron stores.
- •Anemic Subjects:
- •Age: ≥ 18 years.
- •Including beta-thalassemia and other related anemias, with screening Hb ≤ 100.0 g/L.
- •Body weight ≥ 40 kg.
- •Serum folate and vitamin B12 levels above the lower limit of normal (LLN).
- •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.
- •No active or chronic bleeding.
- •Eastern Cooperative Oncology Group (ECOG) performance status score of 0-
- •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:
- •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.
- •ALT or AST > 2×ULN, or TBIL > 1.5×ULN at screening.
- •Undergone surgery (excluding minor cosmetic or dental procedures) within 3 months prior to screening.
- •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.
- •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.
- •History of substance abuse within 6 months prior to screening.
- •Positive alcohol breath test.
- •2. Anemic Subjects:
- •Presence of clinically significant or uncontrolled ongoing autoimmune disease.
- •Severe cardiac disease.
- •Severe renal disease, defined as estimated glomerular filtration rate (eGFR) < 30 mL/min/1.73m², or dependence on dialysis.
- •Active malignancy, history of cancer, or presence of a known or suspected familial cancer syndrome in linealrelatives.
- •A history of persistent hemolysis or hemolytic syndrome due to causes other than the study diseases.
- •A history of thrombosis or newly developed thrombus within 4 weeks prior to screening.
- •Receipt of intravenous iron supplementation within 28 days prior to first dosing.
- •Any active infection requiring systemic antibiotic therapy (including oral, intravenous, or intraperitoneal administration) within 14 days prior to first dosing.
- •A history of organ transplantation.
- •Any condition that may affect drug absorption.
- •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.
- •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.
Arms & Interventions
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.
Intervention: APG-5918 (Drug)
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.
Intervention: Placebo (Drug)
Multiple Ascending Dose (MAD) cohorts in Anemic Patients (Part B)
Experimental
Subjects will receive once daily APG-5918 for 84 days or till EOT.
Intervention: APG-5918 (Drug)
Outcomes
Primary Outcomes
Treatment-Emergent Adverse Events (TEAEs)
Time Frame: up to 7 days in Part A and 84 days or till EOT in Part B
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 Outcomes
- Plasma Concentrations of APG-5918(Days 1, 2 and 3 in Part A; Days 1, 15 and 28 in Part B)
- Plasma Concentrations of APG-5918(Days 1, 2 and 3 in Part A; Days 1, 15 and 28 in Part B)
- Measurement of Hemoglobin(84 days or till EOT in Part B)
Investigators
Study Sites (2)
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