Chronic Hepatitis B
Conditions
Interventions
Product Name: ABI-H0731
Pharmaceutical Form: Tablet
Pharmaceutical form of the placebo: Tablet
Route of administration of the placebo: Oral use
Trade Name: Entecavir USP
Product Name: Entecavir USP
P
Sponsors
Assembly Biosciences
Eligibility
Sex/Gender
All
Inclusion criteria
Inclusion criteria: - Body mass index (BMI) 18 to 36 kg/m2 and a minimum body weight of 45 kg (inclusive) - Agreement to adhere to Lifestyle Considerations (including abstaining from alcohol abuse [defined as alcohol consumption exceeding 2 standard drinks per day on average (1 standard drink = 10 grams of alcohol)] and the use of illicit substances, herbal or other substances, or unnecessary over-the-counter medications; see Protocol Section 5.4) throughout study duration - In good general health except for chronic HBV infection (defined as HBV infection for at least 6 months documented by at least two repeated HBsAg positivity and/or history of detectable viral load documented at least two times =6 months apart), and serum IgM anti-HBV core-related antibody negative at screening - HBV viral load =2×105 IU/mL - HBeAg-positive at screening - HBsAg >1000 IU/mL at screening - Liver biopsy results of o Metavir F0-F2 (absence of bridging fibrosis or cirrhosis) within 1 year of screening OR o Fasting FibroScan =8 kPa within 3 months of screening (including screening visit) or other Sponsor-approved hepatic imaging study (hepatic magnetic resonance imaging [MRI], or hepatic ultrasound by a ultrasongrapher with expertise in evaluation of liver fibrosis) within 6 months of screening indicating lack of cirrhosis or advanced liver disease (F0-F2 or equivalent). Subjects with an ambiguous non-invasive result, eg, a fasting FibroScan >8 kPa and =10 kPa are excluded unless a biopsy within the 12 months before first visit confirms the absence of bridging fibrosis and cirrhosis. Subjects with a FibroScan >10 kPa are excluded - Have the ability to take oral medication and be willing to adhere to the ABI-H0731-202 regimen in the opinion of the Investigator Are the trial subjects under 18? no Number of subjects for this age range: 0 F.1.2 Adults (18-64 years) yes F.1.2.1 Number of subjects for this age range 24 F.1.3 Elderly (>=65 years) no F.1.3.1 Number of subjects for this age range 0
Exclusion criteria
Exclusion criteria: - Co-infection with human immunodeficiency virus (HIV), hepatitis C virus (HCV), hepatitis E virus (HEV), or hepatitis D virus (HDV) - History or evidence of hepatic decompensation (including gastrointestinal bleeding or esophageal varices) at any time prior to or at time of screening - Subject is febrile (temperature >37.5°C) at screening - Clinically significant cardiac or pulmonary disease, chronic or recurrent renal or urinary tract disease, liver disease other than HBV, endocrine disorder, autoimmune disorder, diabetes mellitus requiring treatment with insulin or hypoglycemic agents, neuromuscular, musculoskeletal, or mucocutaneous conditions requiring frequent treatment, seizure disorders requiring treatment, or other medical conditions requiring frequent medical management or pharmacologic or surgical treatment that in the opinion of the Investigator or the Sponsor makes the subject unsuitable for the study - Any prior treatment with lamivudine or telbivudine, previous treatment with an investigational agent for HBV other than ABI-H0731; or any other SOC treatment for >4 weeks - Participation in another clinical trial of a drug or device whereby the last investigational drug/device administration is within 60 days or five half-lives prior to the first study drug administration, whichever is longer - History of persistent ethanol abuse (alcohol consumption exceeding 2 standard drinks per day on average [1 standard drink = 10 grams of alcohol]) or illicit drug abuse within 3 years before screening - Females who are lactating or pregnant or wish to become pregnant - History of hepatocellular carcinoma (HCC) - A history of malignancy other than HCC unless the subject’s malignancy has been in complete remission off chemotherapy and without additional medical or surgical interventions during the 3 years before screening - Exclusionary laboratory results a. Platelet count 1.2×upper limit of normal (ULN) unless known Gilbert syndrome; subjects with Gilbert syndrome are eligible if direct bilirubin is within normal limits d. Direct bilirubin >1.2×ULN e. ALT >10×ULN at screening f. Serum alpha fetoprotein (AFP) =100 ng/mL. If AFP at screening is >ULN but 1.5×ULN Glomerular filtration rate (GFR) 8% j. Any other laboratory abnormality deemed clinically significant by the Sponsor or the Investigator
Design outcomes
Primary
| Measure | Time frame |
|---|---|
| Main Objective: To evaluate the potential for ABI-H0731 to increase the rapidity of HBV DNA loss in HBeAg-positive CHB subjects by initiating treatment with ABI-H0731 + ETV in subjects who are not yet on treatment for CHB, as measured by timing and magnitude of change in serum HBV DNA from Baseline;Secondary Objective: To evaluate the safety and tolerability of ABI-H0731 when added to ETV therapy as initial therapy for HBeAg-positive CHB subjects To confirm a lack of drug-drug interactions between ETV and ABI H0731 To evaluate the potential for emergence of resistance, if any, to ABI-H0731 in combination with ETV therapy ;Primary end point(s): The primary efficacy endpoint will be change in mean log10 HBV DNA from Baseline (Day 1) to Week 12 or Week 24 on ABI-H0731 + ETV as compared to placebo + ETV | — |
Secondary
| Measure | Time frame |
|---|---|
| Secondary end point(s): Secondary endpoints will be: • Number of subjects with adverse events, premature discontinuations, abnormal safety laboratory results, ECG, or vital signs • Subjects with abnormal alanine aminotransferase (ALT) at Baseline who have normal ALT at Week 24 on ABI-H0731 + ETV as compared to placebo + ETV • Percent of subjects with a decline in viral DNA to below limit of quantitation (LOQ; on ABI-H0731 + ETV as compared to placebo + ETV) at end of treatment • Median time to viral suppression, defined as HBV DNA <20 IU/mL, on ABI-H0731 + ETV as compared to placebo + ETV • Emergence of resistant HBV variants, if any • Drug concentrations: o Trough levels and (in subjects where optional samples are available) trough to peak ratios of ABI-H0731 on ABI-H0731 + ETV o Trough levels and (in subjects where optional samples are available) trough to peak ratios of ETV on ABI-H0731 + ETV therapy as compared with placebo + ETV | — |
Countries
Canada, Hong Kong, New Zealand, United Kingdom, United States
Contacts
Public ContactEric Ruby
Assembly Biosciences
Outcome results
None listed