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

Launched by ASCENTAGE PHARMA GROUP INC. · Sep 24, 2020

Keywords

ClinConnect Summary

This clinical trial is studying a new treatment called APG-1387 when combined with an existing medication, entecavir, for people with chronic hepatitis B (CHB). The main goals are to understand how safe this combination is, how well it works against the hepatitis B virus, and to find the best dose for patients. The trial is currently looking for participants, including both men and women aged between 18 and 74, who have been diagnosed with chronic hepatitis B for at least six months. Eligible participants should not have taken certain antiviral medications recently and must meet specific health criteria, such as having a healthy body weight and normal liver function.

If you decide to join this trial, you'll receive the study medications and will be monitored closely by doctors throughout the process. This includes regular check-ups and tests to ensure your safety and to see how well the treatment is working. It's important to know that participants must be willing to use effective birth control during the study and for some time after to prevent pregnancy. Overall, this trial could be a valuable opportunity for those looking for new treatment options for chronic hepatitis B.

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Eligibility criteria

• 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