a study evaluating the efficacy and safety of alg-000184 compared with tenofovir disoproxil fumarate in untreated hbeag-positive and hbeag- negative adult subjects with chronic hepatitis b (b-supreme)

Conditions: Chronic Hepatitis B Infection

Summary: this is a phase 2 study to evaluate efficacy and safety of 48 weeks of oral once daily monotherapy with alg-000184 versus tenofovir disproxil fumarate (tdf) for chronic hbv infection.

this is a randomized, double-blind, active-controlled, multicenter phase 2 study to evaluate the efficacy and safety of 48 weeks of oral (po) once daily (qd) monotherapy with alg-000184 versus tdf in treatment naive (tn) or currently not treated (cnt) hbeag-positive and hbeag-negative subjects with chronic hbv infection (inclusive of chronic infection and/or chronic hepatitis). a total of approximately 200 eligible subjects will be enrolled across 2 study parts. part 1 will be an evaluation of hbeag-positive subjects with chronic hbv infection and part 2 will be an evaluation of hbeag-negative subjects with chronic hbv infection. each study part will consist of a main study and an exploratory liver biopsy sub-study. following the 48-week double-blind dosing period (week 48), all participating subjects (in parts 1 and 2) will be allowed to roll over into a 48 week (i.e., week 48-96) open-label treatment extension period where they will all receive alg-000184 monotherapy.

Eligibility criteria:
key inclusion criteria: 1. male or female between 18 and 65 years of age, with body mass index (bmi) of 18.0 to 35.0 kg/m2. 2. hbeag-positive and anti-hbeag (hbeab) negative (part 1); or hbeag-negative (part 2). 3. hbsag ≥100 iu/ml. 4. hbv dna ≥20,000 iu/ml. 5. a history of a clinical diagnosis of chronic hbv infection and an alt values of ≤8×uln during screening. 6. must have the following chronic hepatitis b virus infection treatment status at screening: 1. have never received treatment with hbv antiviral medicines (na, interferon) or investigational anti-hbv agents including a cam \[i.e., treatment naïve (tn) subjects\], or 2. have not been on treatment with approved (na, interferon) or investigational hbv antiviral medicines (e.g., antisense oligonucleotides or small interfering rnas) within 6 months or 5 half-lives (whichever is longer) prior to randomization (i.e., currently not treated (cnt) subjects). key exclusion criteria: 1. co-infection with hepatitis a, c, d, e or hiv or any evidence of clinically significant liver disease of non-hbv etiology. 2. positive for anti-hbs antibodies. 3. history or current evidence of cirrhosis. 4. liver fibrosis that is classified as metavir score ≥f3 liver disease. 5. history of, or current evidence of, hepatic decompensation. 6. evidence of hepatocellular carcinoma (hcc) on a liver ultrasound. 7. having received an investigational medicinal product or device within 4 weeks (or 5 half-lives, whichever is longer) before the planned first dose of study drug 8. exclusionary screening laboratory values include: 1. aspartate aminotransferase (ast) \>8×uln, 2. bilirubin (total, direct) \>1.2×uln (unless gilbert's syndrome is suspected) 3. international normalization ratio (inr) \>1.2×uln

Keywords: capsid assembly modulators cams chb hbv chronic hepatitis b hepatitis b infection hepatitis b