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

NCT ID: NCT04568265

Last Updated: 2021-08-26

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

RECRUITING

Clinical Phase

PHASE2

Total Enrollment

122 participants

Study Classification

INTERVENTIONAL

Study Start Date

2020-06-03

Study Completion Date

2025-10-31

Brief Summary

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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.

Detailed Description

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The study is divided into two parts:

Part 1 will evaluate the safety, tolerability, and pharmacokinetics of APG-1387 in combination with entecavir, including determination of the maximum tolerated dose (MTD)/ recommended dose in patients with CHB. APG-1387 will be administered once weekly via intravenous infusion for 30 minutes for consecutive 4 weeks. APG-1387 will be escalated at 3 dose cohorts of 12 mg, 20 mg, and 30 mg. Entecavir will be administered orally at 0.5 mg daily for 12 weeks: in combination with APG-1387 for the first 4 weeks, followed by entecavir maintenance monotherapy for additional 8 weeks. The total treatment duration will be 12 weeks.

Part 2 is a randomized, parallel, open-label study to investigate the preliminary anti-HBV efficacy of APG-1387 in combination with entecavir compared with entecavir monotherapy. CHB subjects will be randomly assigned to one of 4 cohorts at 1:1:1:1, including APG-1387 at 3 different doses (12 mg, 20 mg, and 30 mg) in combination with entecavir for 12 weeks, respectively, then continued entecavir monotherapy for additional 12 weeks; and one entecavir monotherapy cohort for 24 weeks. The course of treatment is 24 weeks in all cohorts.

Conditions

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Hepatitis B Chronic Hep B HBV

Study Design

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Allocation Method

RANDOMIZED

Intervention Model

PARALLEL

Primary Study Purpose

TREATMENT

Blinding Strategy

NONE

Study Groups

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APG-1387 12 mg combined with entecavir 0.5 mg

Group Type EXPERIMENTAL

APG-1387

Intervention Type DRUG

Weekly intravenous infusion for 30 minutes

Entecavir 0.5 mg

Intervention Type DRUG

Taken daily by mouth

APG-1387 20 mg combined with entecavir 0.5 mg

Group Type EXPERIMENTAL

APG-1387

Intervention Type DRUG

Weekly intravenous infusion for 30 minutes

Entecavir 0.5 mg

Intervention Type DRUG

Taken daily by mouth

APG-1387 30 mg combined with entecavir 0.5 mg

Group Type EXPERIMENTAL

APG-1387

Intervention Type DRUG

Weekly intravenous infusion for 30 minutes

Entecavir 0.5 mg

Intervention Type DRUG

Taken daily by mouth

entecavir 0.5 mg

Group Type EXPERIMENTAL

Entecavir 0.5 mg

Intervention Type DRUG

Taken daily by mouth

Interventions

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APG-1387

Weekly intravenous infusion for 30 minutes

Intervention Type DRUG

Entecavir 0.5 mg

Taken daily by mouth

Intervention Type DRUG

Other Intervention Names

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Baraclude

Eligibility Criteria

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Inclusion Criteria

* 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:

1. 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)
2. 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
* Platelet count ≥ 100 × 10˄9/L
* Adequate renal and liver function:

* Serum creatinine ≤ 1×ULN
* Serum albumin ≥ 35.0g/L
* Urine protein is negative or 1 + (re-examination is required when 1 + or 24-hour urine protein quantification is added when necessary. If it turns negative or is within the normal range, it can be included)
* Estimated creatinine clearance (CLCr) ≥ 50 mL/min based on serum creatinine measured at the screening assessment and actual body weight (calculated creatinine clearance by the Cockcroft-Gault formula)
* Total bilirubin ≤1.5×ULN
* International normalized ratio (INR) ≤ 1.5×ULN
* Alkaline phosphatase ≤ 2.5×ULN
* Female subjects of childbearing potential should have a negative serum pregnancy test within 7 days prior to the first dose
* Subjects and theirs partners are willing to use effective contraception as defined in the protocol during the treatment and for at least 6 months after the last dose of study drug
* Ability to understand and willingness to sign a written informed consent form (the consent form must be signed by the subject prior to any study-specific procedures)
* Willingness and ability to comply with study procedures and follow-up examination

Exclusion Criteria

* 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
* Previous treatment with inhibitors of apoptosis proteins
* Any subject considered unsuitable for the trial by the investigator
Minimum Eligible Age

18 Years

Eligible Sex

ALL

Accepts Healthy Volunteers

No

Sponsors

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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, MD, PhD

Role: STUDY_CHAIR

Ascentage Pharma Group Inc.

Locations

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Guangzhou Eighth People's Hospital

Guangzhou, Guangdong, China

Site Status RECRUITING

Nanfang Hospital of Southern Medical University

Guangzhou, Guangdong, China

Site Status RECRUITING

Huashan Hospital affiliated to Fudan University

Shanghai, Shanghai Municipality, China

Site Status NOT_YET_RECRUITING

West China Hospital, Sichuan University

Chengdu, Sichuan, China

Site Status NOT_YET_RECRUITING

Countries

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China

Facility Contacts

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Yujuan Guan, Master

Role: primary

+86-020-83710459

Jinlin Hou, Master

Role: primary

+86-020-62787427

Jimin Zhang, Doctor

Role: primary

+86-021-52888262

Enqiang Chen, Doctor

Role: primary

+86-028-8542 3052

Other Identifiers

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APG1387BC201

Identifier Type: -

Identifier Source: org_study_id

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