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.
Overview
- Phase
- Phase 1
- Intervention
- APG-5918
- Conditions
- Anemia
- Sponsor
- Ascentage Pharma Group Inc.
- Enrollment
- 105
- Locations
- 4
- Primary Endpoint
- Treatment-Emergent Adverse Events (TEAEs)
- Status
- Recruiting
- Last Updated
- 17 days ago
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.
Investigators
Eligibility Criteria
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).
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.
Arms & Interventions
Single Ascending Dose (SAD) cohorts in Healthy Subjects (Part A)
Subjects will be randomized to receive a single dose of APG-5918 or placebo.
Intervention: APG-5918
Single Ascending Dose (SAD) cohorts in Healthy Subjects (Part A)
Subjects will be randomized to receive a single dose of APG-5918 or placebo.
Intervention: Placebo
Multiple Ascending Dose (MAD) cohorts in Anemic Patients (Part B)
Subjects will receive once daily APG-5918 for 84 days or till EOT.
Intervention: APG-5918
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)