APG-1387 Study of Safety, Tolerability ,PK/PD in Patients With Chronic Hepatitis B

NCT03585322 | Completed Phase 1

• 1 other identifier: APG-1387-CN-HBV-001
• Study Type: interventional
• Target: 49
• Locations: 1 country
• Sites: 2

Brief Summary

This study is a Multiple Ascending Dose study to Explore the Tolerability, Safety and Pharmacokinetics/Pharmacodynamics of APG-1387 in Chronic Hepatitis B Patients.

Conditions

Chronic Hepatitis B

Outcome Measures

Primary Outcomes (1)

• Maximum Tolerated Dose (MTD)

  Patients with APG-1387 treatment related adverse events (AE), serious adverse events (SAE) will be assessed according NCI CTCAE Version 4.0.3

  28 days

Secondary Outcomes (8)

• Pharmacokinetic evaluation

  28 days

• Pharmacokinetic evaluation

  28 days

• Change in serum HBV DNA from baseline at Day 1, Day 8, Day15, Day 22, Day28，Day56，Day84 and Day 112.

  Day 1, Day 8, Day15, Day 22, Day28，Day56，Day84，and Day 112

• Change in serum HBsAg from baseline at Day 1, Day 8, Day15, Day 22, Day28，Day56，Day84 and Day 112.

  Day 1, Day 8, Day15, Day 22, Day28，Day56，Day84，and Day 112

• Change in serum HBeAg from baseline at Day 1, Day 8, Day15, Day 22, Day28，Day56，Day84 and Day 112.

  Day 1, Day 8, Day15, Day 22, Day28，Day56，Day84，and Day 112

Study Arms (1)

APG-1387 for Injection

EXPERIMENTAL

APG-1387 will be explored sequentially using a escalation scheme at the dose escalation phase.

Drug: APG-1387 for Injection

Interventions

APG-1387 for Injection DRUG

Multiple dose cohorts, 30 minute IV infusion, once weekly for 4 weeks .

APG-1387 for Injection

Eligibility Criteria

• Age: 18 Years - 65 Years
• Sex: all
• Healthy Volunteers: No
• Age Groups: Adult (18-64), Older Adult (65+)

You may qualify if:

• Age ≥18 and ≤ 65 years old.
• Confirmed diagnosis of chronic hepatitis B, HBsAg positive≥6 months.
• HBV DNA≥2×103 IU/mL for HBeAg negative patients, HBV DNA≥1×104IU/mL for HBeAg positive patients in screening phase.
• ALT≥ ULN and \<10 ×ULN in screening phase (exclude non-HBV related ALT elevation such as drug or alcohol et al).
• BMI 18\~26.
• Patients should not use antivirus treatment such as NAs and IFN within 6 months before screening.
• Adequate hematologic function.
• QTc interval ≤ 450 ms in males, and ≤ 470 ms in females.
• Adequate renal and liver function.
• Negative serum pregnancy test (for women of childbearing potential) documented within the 24-hour prior to the first dose of investigational product. Willing to use contraception by a method that is deemed effective by the investigator by Subject and their partners throughout the treatment period and for at least three months following the last dose of study drug.
• Ability to understand and willing to sign a written informed consent form, the consent form must be signed by the patient prior to any study-specific procedures.

You may not qualify if:

• Clinical confirmed HCC or suspected HCC or AFP\>50μg/L.
• A history of decompensated liver function (such as Child-Pugh B or C or history of ascites, digestive tract bleeding, hepatic encephalopathy or spontaneous bacterial peritonitis et al.).
• Advanced fibrosis/cirrhosis, defined as a fiber screening scan≥12.4kPa during screening phase or liver biopsy at any time found Metavir score F3, F4 fibrosis.
• Patients with other liver diseases except hepatitis B, including chronic alcoholic hepatitis, drug-induced liver injury, autoimmune liver disease, hereditary liver disease and other causes of active hepatitis.
• Patients with malignant tumours (excluding basal cell and in situ cervical cancer that have been cured without recurrence) or lymphatic proliferative diseases.
• Have a clear history of neurological or psychiatric disorders, such as epilepsy, dementia, poor compliance.
• Chronic kidney disease, renal insufficiency.
• Poor control of other important primary diseases of the viscera, such as clear history of nervous system, cardiovascular system, urinary system, digestive system, respiratory system, Metabolism and skeletal muscle system (such as poor control diabetes, hypertension and etc.), which the investigator considers not suitable for the study.
• Females who are pregnant or nursing.
• History of alcoholism (average daily ethanol intake of 30 grams (male) or ≥ 20 grams (female) for 1 years), drug abuse history or drug abuse screening results positive.
• Severe infection, trauma or a major surgical operation within 4 weeks prior to screening.
• Use of immunomodulators (eg, corticosteroids) or biologics (eg, monoclonal antibody, IFN) within 3 months prior to screening, or will use immunomodulators (eg, corticosteroids) or biologics (eg, monoclonal antibody, IFN) during the study.
• Treatment with an investigational agent or device within three months prior to screening.
• Anti-HDV total antibody/IgM antibody positive, HCV antibody positive and HCV-RNA positive, anti-HIV antibody positive, or treponema pallidum antibody positive.
• Known or suspected Wilson's Disease, or other disease that may affect copper accumulates or regulates.

Sponsors & Collaborators

• Ascentage Pharma Group Inc.: lead
• HealthQuest Pharma Inc.: collaborator

Study Sites (2)

Nanfang Hospital of Southern Medical University

Guangzhou, Guangdong, 510515, China

Location

Guangzhou Eighth People's Hospital

Guangzhou, Guangdong, China

Location

MeSH Terms

Conditions

Hepatitis B, Chronic

Interventions

APG-1387; Injections

Condition Hierarchy (Ancestors)

Hepatitis B; Blood-Borne Infections; Communicable Diseases; Infections; Hepadnaviridae Infections; DNA Virus Infections; Virus Diseases; Hepatitis, Viral, Human; Hepatitis, Chronic; Hepatitis; Liver Diseases; Digestive System Diseases; Chronic Disease; Disease Attributes; Pathologic Processes; Pathological Conditions, Signs and Symptoms

Intervention Hierarchy (Ancestors)

Drug Administration Routes; Drug Therapy; Therapeutics

Study Officials

• Yifan Zhai, M.D., Ph.D.

  Ascentage Pharma Group Inc.

  STUDY DIRECTOR

Study Design

• Study Type: interventional
• Phase: phase 1
• Allocation: NA
• Masking: NONE
• Purpose: TREATMENT
• Intervention Model: SINGLE GROUP
• Sponsor Type: INDUSTRY
• Responsible Party: SPONSOR

Model Details: dose escalation study

Study Record Dates

• First Submitted: June 26, 2018
• First Posted: July 13, 2018
• Study Start: July 4, 2018
• Primary Completion: October 15, 2021
• Study Completion: October 15, 2021
• Last Updated: November 8, 2021

Record last verified: 2021-11

Data Sharing

• IPD Sharing: Will not share

Locations

CN (2)