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

NCT ID: NCT03585322

Last Updated: 2021-11-08

Study Results

Results pending

The study team has not published outcome measurements, participant flow, or safety data for this trial yet. Check back later for updates.

Basic Information

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Recruitment Status

COMPLETED

Clinical Phase

PHASE1

Total Enrollment

49 participants

Study Classification

INTERVENTIONAL

Study Start Date

2018-07-04

Study Completion Date

2021-10-15

Brief Summary

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

Detailed Description

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APG-1387 is a potent, bivalent small-molecule IAP antagonist. This study is multi-center, single-agent, open-label, Phase I dose-escalation study of APG-1387.

This study has a 4-dose-schedule which is escalated one by one after confirming safety in the previous lower dose schedule. A total of 60 subjects with Chronic Hepatitis B will be participated in the study. APG-1387 will be administrated via intravenous infusion, once a week for consecutive 4 weeks as one cycle.The start dose is 7mg. 3 patients' cohorts will be evaluated, the dose of APG-1387 will be increased in subsequent cohorts, to 12mg, 20 mg, 30 mg, 45 mg accordingly. 3 patients in 7mg,12mg cohorts and 6 patients in 20mg, 30mg and 45mg cohorts will be recruited. If there is any one of the following event is observed within 28 days of the first dose of APG-1387, the recruitment will be hold and a discussion on MTD dose level will happened.1 ≥1/2 patients experience ≥Grade 2 toxicities\[CTCAE 4.0.3\] related or possibly related with APG-1387 and with clinical manifestation. 2 ≥1/3 patients experience ≥Grade 3 toxicities\[CTCAE 4.0.3\] related or possibly related with APG-1387.3 any SAE related or possibly related with APG-1387. Expansion study will be designed to explore primary efficacy and safety after the dose escalation study. The expansion number and dosage will be decided according to the results of each cohort.(no more than 36 patients).

Conditions

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Chronic Hepatitis B

Study Design

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Allocation Method

NA

Intervention Model

SINGLE_GROUP

dose escalation study
Primary Study Purpose

TREATMENT

Blinding Strategy

NONE

Study Groups

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APG-1387 for Injection

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

Group Type EXPERIMENTAL

APG-1387 for Injection

Intervention Type DRUG

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

Interventions

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APG-1387 for Injection

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

Intervention Type DRUG

Eligibility Criteria

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Inclusion Criteria

1. Age ≥18 and ≤ 65 years old.
2. Confirmed diagnosis of chronic hepatitis B, HBsAg positive≥6 months.
3. HBV DNA≥2×103 IU/mL for HBeAg negative patients, HBV DNA≥1×104IU/mL for HBeAg positive patients in screening phase.
4. ALT≥ ULN and \<10 ×ULN in screening phase (exclude non-HBV related ALT elevation such as drug or alcohol et al).
5. BMI 18\~26.
6. Patients should not use antivirus treatment such as NAs and IFN within 6 months before screening.
7. Adequate hematologic function.
8. QTc interval ≤ 450 ms in males, and ≤ 470 ms in females.
9. Adequate renal and liver function.
10. 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.
11. 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.

Exclusion Criteria

1. Clinical confirmed HCC or suspected HCC or AFP\>50μg/L.
2. 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.).
3. 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.
4. 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.
5. Patients with malignant tumours (excluding basal cell and in situ cervical cancer that have been cured without recurrence) or lymphatic proliferative diseases.
6. Have a clear history of neurological or psychiatric disorders, such as epilepsy, dementia, poor compliance.
7. Chronic kidney disease, renal insufficiency.
8. 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.
9. Females who are pregnant or nursing.
10. 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.
11. Severe infection, trauma or a major surgical operation within 4 weeks prior to screening.
12. 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.
13. Treatment with an investigational agent or device within three months prior to screening.
14. Anti-HDV total antibody/IgM antibody positive, HCV antibody positive and HCV-RNA positive, anti-HIV antibody positive, or treponema pallidum antibody positive.
15. Known or suspected Wilson's Disease, or other disease that may affect copper accumulates or regulates.
16. Prior treatment with IAP inhibitors.
17. Any other condition or circumstance of that would, in the opinion of the investigator, make the patient unsuitable for participation in the study.
Minimum Eligible Age

18 Years

Maximum Eligible Age

65 Years

Eligible Sex

ALL

Accepts Healthy Volunteers

No

Sponsors

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HealthQuest Pharma Inc.

INDUSTRY

Sponsor Role collaborator

Ascentage Pharma Group Inc.

INDUSTRY

Sponsor Role lead

Responsible Party

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Responsibility Role SPONSOR

Principal Investigators

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Yifan Zhai, M.D., Ph.D.

Role: STUDY_DIRECTOR

Ascentage Pharma Group Inc.

Locations

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Nanfang Hospital of Southern Medical University

Guangzhou, Guangdong, China

Site Status

Guangzhou Eighth People's Hospital

Guangzhou, Guangdong, China

Site Status

Countries

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China

Other Identifiers

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APG-1387-CN-HBV-001

Identifier Type: -

Identifier Source: org_study_id