A Study Evaluating Treatment Intensification With ABI-H0731 in Participants With Chronic Hepatitis B Infection on Nucleos(t)Ide Reverse Transcriptase Inhibitors

Assembly Biosciences

Status and phase: Terminated; Phase 2

Conditions: Chronic Hepatitis B

Treatments: Drug: ABI-H0731; Drug: Placebo; Drug: NrtI

Study type: Interventional

Funder types: Industry

Identifiers

NCT04454567

UTN 1111-1251-7136 (Other Identifier)

ABI-H0731-205

Details and patient eligibility

About

This study will explore the safety and antiviral activity of ABI-H0731 when added to a nucleos(t)ide reverse transcriptase inhibitor (NrtI) in participants who are partially virologically suppressed.

Enrollment: 2 patients

Sex: All

Ages: 18 to 65 years old

Volunteers: No Healthy Volunteers

Inclusion criteria

• Body mass index (BMI) 18 to 36 kg/m^2 and a minimum body weight of 45 kg (inclusive)
• In good general health except for chronic hepatitis B (CHB)
• HBeAg positive or HBeAg negative chronic hepatitis B
• HBV DNA >LLOQ using a commercially available assay with LLOQ=20 IU/mL
• On a stable NrtI regimen (ETV, TDF or TAF) for more than 12 months
• Lack of cirrhosis or advanced liver disease

Exclusion criteria

• Current or prior treatment for CHB with lamivudine, telbivudine, adefovir, HBV core inhibitor, or previous treatment with an investigational agent for HBV infection

• Presence of substitutions in the HBV polymerase coding region which may confer reduced susceptibility to NrtIs

• Co-infection with human immunodeficiency virus, hepatitis A virus, hepatitis C virus, hepatitis E virus, or hepatitis D virus

• Females who are lactating or wish to become pregnant during the course of the trial

• History or evidence of advanced liver disease or hepatic decompensation

• Clinically significant cardiac disease including poorly-controlled or unstable hypertension; pulmonary disease; chronic or recurrent renal or urinary tract disease; liver disease other than CHB; 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 trial participation

• History of hepatocellular carcinoma (HCC)

• Exclusionary laboratory parameters at Screening:

  • Platelet count <100,000/mm^3
  • Albumin <lower limit of normal
  • Total bilirubin >1.2 × upper limit of normal (ULN)
  • Direct bilirubin >1.2 × ULN
  • ALT >10 × ULN
  • Serum alpha fetoprotein (AFP) ≥100 ng/mL. If AFP at Screening is >ULN but <100 ng/mL, the participant is eligible if a hepatic imaging trial prior to initiation of study drug reveals no lesions indicative of possible HCC.
  • International Normalized Ratio >1.5 × ULN
  • Glomerular filtration rate <50 mL/min/1.73 m^2 by Chronic Kidney Disease Epidemiology Collaboration equation
  • Any other laboratory abnormality deemed clinically significant by the Sponsor or the Investigator.

Trial design

Primary purpose: Treatment

Allocation: Randomized

Interventional model: Parallel Assignment

Masking: Double Blind

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2 participants in 2 patient groups, including a placebo group

ABI-H0731 + SOC NrtI

Experimental group

Description:

Participants with chronic hepatitis B virus (HBV) infection with partial virologic suppression on NrtI alone will receive ABI-H0731 300 mg once daily plus standard of care (SOC) NrtI for 96 weeks, followed by SOC NrtI alone for an additional 24 weeks (120 weeks total).

Treatment:

Drug: ABI-H0731

Drug: NrtI

Placebo + SOC NrtI

Placebo Comparator group

Description:

Participants with chronic HBV infection with partial virologic suppression on NrtI alone will receive placebo to ABI-H0731 once daily plus SOC NrtI for 48 weeks, followed by ABI-H0731 300 mg once daily plus SOC NrtI for Weeks 48 to 96, followed by SOC NrtI alone for Weeks 96 to 120.

Treatment:

Drug: Placebo

Drug: ABI-H0731

Drug: NrtI