Chronic Hepatitis B Virus Infection MedDRA version: 20.1 Level: PT Classification code 10008910 Term: Chronic hepatitis B System Organ Class: 10021881 - Infections and infestations
Conditions
Interventions
Product Name: Vebicorvir
Product Code: ABI-H0731
Pharmaceutical Form: Tablet
INN or Proposed INN: Vebicorvir
Current Sponsor code: ABI-H0731
Concentration unit: mg milligram(s)
Concentration type: equ
Sponsors
Assembly Biosciences, Inc.
Eligibility
Sex/Gender
All
Inclusion criteria
Inclusion criteria: 1.Willing and able to provide Informed Consent 2. Male or female between the ages 18 and 50 years (inclusive) at Screening 3. Body mass index (BMI) 18 to 36 kg/m2 and a minimum body weight of 45 kg (inclusive) at Screening 4. Female subjects of child-bearing potential (Appendix 2) must be non-pregnant and have a negative serum pregnancy test at Screening and a negative urine pregnancy test at Day 1 predose 5. cHBV defined as HBV infection documented for =6 months prior to Screening 6. Must be HBeAg negative at least 3 months prior to the Screening Visit (historical documentation) AND at the Screening Visit to be eligible 7. Virologically suppressed on NrtI therapy with nonquantifiable HBV DNA for at least 6 months prior to and including Screening 8. On a stable NrtI regimen of entecavir (ETV), tenofovir disoproxil fumarate (TDF), or tenofovir alafenamide (TAF) for >12 months 9. HBsAg =100 IU/mL at Screening 10. Lack of bridging fibrosis or cirrhosis as documented by the following: • Fasting FibroScan® =8 kPa within 3 months prior to Screening (including the Screening visit) or other Sponsor-approved hepatic imaging method within 6 months prior to Screening (eg, Meta-analysis of Histological Data in Viral Hepatitis [METAVIR] F0-F2 or equivalent) or • Liver biopsy results (eg, METAVIR F0-F2 or equivalent) within 1 year prior to Screening If results from liver biopsy and FibroScan® are available, then the diagnostic method reporting the most advanced liver disease will be used to determine eligibility for the study 11. Agreement to comply with protocol-specified contraceptive requirements (Appendix 2) 12. In good general health, except for cHBV, in the opinion of the Investigator 13. Able to take oral medication, be willing to receive subcutaneous injections of AB-729, and in the opinion of the Investigator, be willing to adhere to study treatment and procedures Are the trial subjects under 18? no Number of subjects for this age range: F.1.2 Adults (18-64 years) yes F.1.2.1 Number of subjects for this age range 180 F.1.3 Elderly (>=65 years) no F.1.3.1 Number of subjects for this age range
Exclusion criteria
Exclusion criteria: Subjects who meet any of the following exclusion criteria will not be eligible for Cohort 1 of the study: 1. Co-infection with human immunodeficiency virus (HIV), hepatitis C virus (HCV), hepatitis D virus (HDV), acute hepatitis A virus (HAV), or acute hepatitis E virus (HEV) 2. Females who are lactating or wish to become pregnant during the course of the study 3. History of liver transplant or evidence of advanced liver disease, cirrhosis, or hepatic decompensation (including jaundice, ascites, portal hypertension, gastrointestinal bleeding esophageal varices, hepatic encephalopathy) at any time prior to, or at the time of Screening 4. History of persistent alcohol abuse (alcohol consumption exceeding 2 standard drinks per day on average [1 standard drink=14 grams of alcohol]) or illicit drug abuse within 3 years prior to Screening 5. Clinically significant diseases or conditions, such as cardiac disease, including poorly-controlled or unstable hypertension; pulmonary disease; chronic or recurrent renal or urinary tract disease; liver disease other than cHBV; endocrine disorder; autoimmune disorder; poorly controlled diabetes mellitus; neuromuscular, musculoskeletal, or mucocutaneous conditions requiring frequent treatment, seizure disorders requiring treatment; ongoing infection 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 study participation 6. History of hepatocellular carcinoma (HCC) 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 8. History or presence at Screening of electrocardiogram (ECG) abnormalities deemed clinically significant, in the opinion of the Investigator 9. History of hypersensitivity or idiosyncratic reaction to any components or excipients of the investigational drugs 10. History of any significant food or drug-related allergic reactions such as anaphylaxis or Stevens-Johnson syndrome 11. The following are exclusionary laboratory results at Screening: a. Platelet count 1.2× ULN d. ALT =5× ULN e. Serum alpha fetoprotein (AFP) =100 ng/mL. If AFP at Screening is > ULN but 1.5× ULN g. Estimated creatinine clearance (CrCl) <50 mL/min (using the Cockcroft-Gault method) based on serum creatinine and actual body weight at Screening h. Any other laboratory abnormality deemed clinically significant by the Investigator 12. Current or prior use of prohibited concomitant medications from 28 days prior to Day 1 (Section 6.3.1) 13. Current or prior treatment for cHBV with: • Lamivudine, telbivudine or adefovir (any duration) • HBV core inhibitor (any duration) • siRNA or other oligonucleotide therapeutic (any duration) • Interferon in the 6 months prior to Screening • Any investigational agent for cHBV in the 6 months prior to Screening 14. Participation in another clinical study of a drug or device whereby the last investigational drug/device administration is within 60 days or 5 half-lives prior to the first study drug administration, whichever is longer
Design outcomes
Primary
| Measure | Time frame |
|---|---|
| Main Objective: To evaluate the safety and tolerability of combination treatment with VBR, AB-729, and nucleos(t)ide reverse transcriptase inhibitor (NrtI);Secondary Objective: The secondary objectives of Cohort 1 are: • To evaluate the effect of adding VBR and AB-729 to NrtI on reduction in and loss of HBsAg • To evaluate the effect of adding VBR and AB-729 to NrtI in reducing HBV DNA levels • To evaluate the effect of adding VBR and AB-729 to NrtI in reducing HBV RNA levels • To evaluate the effect of adding VBR and AB-729 to NrtI in reducing other HBV antigens (ie, HBcrAg) • To evaluate the effect of adding VBR and AB-729 to NrtI on HBsAg seroconversion • To evaluate the effect of adding VBR and AB-729 to NrtI on normalization of ALT • To evaluate the off-treatment durability of response to treatment with VBR and AB-729 • To evaluate the PK of VBR and AB-729 when coadministered with NrtI;Primary end point(s): Proportion of subjects with AEs, premature treatment discontinuation due to AEs, and abnormal laboratory results;Timepoint(s) of evaluation of this end point: 48 Weeks | — |
Secondary
| Measure | Time frame |
|---|---|
| Secondary end point(s): The secondary endpoints of Cohort 1 are: • Mean change in log10 HBsAg from Baseline at each timepoint • Proportion of subjects with HBsAg <LLOQ at each timepoint • Proportion of subjects with HBV DNA TND (<5 IU/mL) at Week 48 • Proportion of subjects with HBV RNA <LLOQ at Week 48 • Mean change in log10 HBV RNA from Baseline at each timepoint • Mean change in log10 HBcrAg from Baseline at each timepoint • Proportion of subjects with HBsAg seroconversion at Week 48 • Proportion of subjects with abnormal ALT at Baseline who have normal ALT (by central laboratory and American Association for the Study of Liver Diseases [AASLD] criteria) at each timepoint • Proportion of subjects achieving Treatment Stopping Criteria at end of treatment (EOT) • Proportion of subjects who remain off-treatment at end of study (EOS) • Analysis of VBR and AB-729 drug concentrations, NrtI concentrations may be analyzed, as needed;Timepoint(s) of evaluation of this end point: 48 weeks | — |
Countries
Australia, Bulgaria, Canada, New Zealand
Contacts
Public ContactHeather Berns, Clinical Operation
Assembly Biosciences, Inc.
Outcome results
None listed