A Clinical Study of APG-1387 in Combination With Entecavir in Patients With Chronic Hepatitis B

NCT04568265 | Unknown Phase 2 FDA Drug

• 1 other identifier: APG1387BC201
• Study Type: interventional
• Target: 122
• Locations: 1 country
• Sites: 4

Brief Summary

This study is a multicenter, open-label, phase II clinical study in subjects with chronic hepatitis B (CHB), to characterize the safety, tolerability, pharmacokinetic profile and preliminary anti-hepatitis B virus (HBV) efficacy of APG-1387 in combination with entecavir, and to determine the optimal dose of APG-1387 in combination with entecavir.

Conditions

Hepatitis B; Chronic Hep B; HBV

Keywords

HBeAg-positive; HBeAg-negative

Outcome Measures

Primary Outcomes (2)

• Dose-limiting toxicity (DLT) rate at each dose level

  DLT will be assessed within the first 28-day cycle of study treatment via NCI CTCAE version 5.0

  28 days

• Decline in Hepatitis B surface Antigen (HBsAg)

  The difference in HBsAg decline between APG-1387 combined with entecavir arms and entecavir monotherapy arm

  12 weeks

Study Arms (4)

APG-1387 12 mg combined with entecavir 0.5 mg

EXPERIMENTAL

Drug: APG-1387; Drug: Entecavir 0.5 mg

APG-1387 20 mg combined with entecavir 0.5 mg

EXPERIMENTAL

Drug: APG-1387; Drug: Entecavir 0.5 mg

APG-1387 30 mg combined with entecavir 0.5 mg

EXPERIMENTAL

Drug: APG-1387; Drug: Entecavir 0.5 mg

entecavir 0.5 mg

EXPERIMENTAL

Drug: Entecavir 0.5 mg

Interventions

APG-1387 DRUG

Weekly intravenous infusion for 30 minutes

APG-1387 12 mg combined with entecavir 0.5 mg; APG-1387 20 mg combined with entecavir 0.5 mg; APG-1387 30 mg combined with entecavir 0.5 mg

Entecavir 0.5 mg DRUG

Taken daily by mouth

Also known as: Baraclude

APG-1387 12 mg combined with entecavir 0.5 mg; APG-1387 20 mg combined with entecavir 0.5 mg; APG-1387 30 mg combined with entecavir 0.5 mg; entecavir 0.5 mg

Eligibility Criteria

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

You may qualify if:

• Body mass index (BMI) within the range of 18 - 27.9
• Documented chronic HBV infection (e.g., HBsAg positive for at least 6 months).
• HBeAg-positive or HBeAg-negative
• Treatment-naïve and treatment-experienced subjects are required to:
• Treatment-naïve subjects:
• No antiviral therapies including nucleos(t)ide analogues or immunomodulators such as interferon within 180 days prior to screening
• HBV DNA ≥ 2x10˄3 IU/mL for HBeAg negative subjects and ≥ 2x10˄4 IU/mL for HBeAg positive subjects (PCR)
• Alanine transaminase (ALT) ≥ upper limit of normal (ULN) and \< 10 × ULN (and excluding ALT elevation caused by non-HBV reasons such as drug or alcohol consumption)
• Treatment-experienced subjects:
• Using entecavir \> 180 days prior to screening, and should continue the treatment regimen until enrolled into the study
• HBV DNA less than the lower limit of quantification (LLOQ) or \< 20 IU/mL (PCR)
• ALT \< 1.5 × ULN
• Adequate hematological function:
• White blood cell count (WBC) ≥ 3.5 × 10˄9/L
• Hemoglobin ≥ 120 g/L for males and ≥ 110 g/L for females

You may not qualify if:

• Co-infection with HIV, hepatitis C virus (HCV), or hepatitis delta virus (HDV); or other active and severe infections
• Syphilis with positive antibody for treponema pallidum
• Subjects with liver disease other than hepatitis B, including but not limited to chronic alcoholic hepatitis, drug-induced liver injury, autoimmune liver disease, hereditary liver disease (such as Wilson's disease), and active hepatitis due to other causes
• History or manifestation of hepatic decompensation (e.g., Child-Pugh Class B or C, or history of ascites, gastrointestinal bleeding, hepatic encephalopathy, or spontaneous bacterial peritonitis)
• Progressive fibrosis/cirrhosis, defined by liver fibrosis scan ≥ 12 kilopascal (kPa) at screening, or cirrhosis diagnosed by imaging examinations, or Metavir score F3, F4 fibrosis on liver biopsy at any time
• Clinically diagnosed hepatocellular carcinoma, or diagnosis of hepatocellular carcinoma cannot be excluded, or serum alpha-fetoprotein greater than 50 μg/L
• History of malignancy (except cured and no evidence of recurrence of basal cell carcinoma of the skin or situ cervical cancer) or lymphoproliferative disease
• History of neurological or mental disorders, such as epilepsy, dementia, and poor compliance
• Uncontrolled primary diseases of other important organs, such as clear medical history of nervous system, cardiovascular system, urinary system (including chronic or intermittent urinary system diseases), digestive system, respiratory system, endocrine/metabolic and musculoskeletal system, such as poorly controlled diabetes, hypertension, etc., making the investigator consider the subject unsuitable
• QTcB \[QTcB = QT/(RR\^ 0.5); RR is the normalized heart rate value, obtained by dividing 60 by heart rate in seconds; other parameters in milliseconds\] \> 450 milliseconds for men and \> 470 milliseconds for women; any clinically important abnormality in the rhythm, conduction, or morphology of the resting electrocardiogram (ECG) (e.g., complete left bundle branch block, third degree heart block, second degree heart block); congenital long QT syndrome or family history of long QT syndrome
• History of alcoholism (mean daily intake of ethanol ≥ 30 g (male) or ≥ 20 g (female) within 1 year), and drug abuse
• Subjects planning to become pregnant within 1 year, who are pregnant or breastfeeding
• Received or may receive continuous treatment with immunomodulators (e.g., steroids) or biological agents (e.g., monoclonal antibodies, interferons) within 3 months before screening
• Participated in clinical trials within 3 months before screening
• Trauma or major surgical operation within 4 weeks before screening

Sponsors & Collaborators

• Ascentage Pharma Group Inc.: lead

Study Sites (4)

Guangzhou Eighth People's Hospital

Guangzhou, Guangdong, China

RECRUITING

Nanfang Hospital of Southern Medical University

Guangzhou, Guangdong, China

RECRUITING

Huashan Hospital affiliated to Fudan University

Shanghai, Shanghai Municipality, China

NOT YET RECRUITING

West China Hospital, Sichuan University

Chengdu, Sichuan, China

NOT YET RECRUITING

MeSH Terms

Conditions

Hepatitis B; Hepatitis B, Chronic

Interventions

APG-1387; entecavir

Condition Hierarchy (Ancestors)

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

Study Officials

• Yifan Zhai, MD, PhD

  Ascentage Pharma Group Inc.

  STUDY CHAIR

Study Design

• Study Type: interventional
• Phase: phase 2
• Allocation: RANDOMIZED
• Masking: NONE
• Purpose: TREATMENT
• Intervention Model: PARALLEL
• Sponsor Type: INDUSTRY
• Responsible Party: SPONSOR

Study Record Dates

• First Submitted: September 24, 2020
• First Posted: September 29, 2020
• Study Start: June 3, 2020
• Primary Completion: October 31, 2022
• Study Completion: October 31, 2025
• Last Updated: August 26, 2021

Record last verified: 2021-08

Data Sharing

• IPD Sharing: Will not share

Locations

CN (4)