Clinical trial NCT06963710: 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)
Official title: A Randomized, Double-Blind, Active-Controlled Multicenter Phase 2 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 Virus Infection (B-SUPREME)
Study type: INTERVENTIONAL
Overall status: NOT_YET_RECRUITING
Phase: PHASE2
Conditions: Chronic Hepatitis B Infection
Keywords: Capsid Assembly Modulators
CAMs
CHB
HBV
Chronic Hepatitis B
Hepatitis B Infection
Hepatitis B
Lead sponsor: Aligos Therapeutics
Sponsor class: INDUSTRY
First posted: 2025-05-09
Enrollment: 200
Sex: ALL
Minimum age (years): 18
Maximum age (years): 65
Standard ages: ADULT
OLDER_ADULT
Accepts healthy volunteers: no
Allocation: RANDOMIZED
Intervention model: PARALLEL
Primary purpose: TREATMENT

Brief 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.

Detailed description: 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

Primary outcomes:
measure: HBeAg positive: HBV DNA <Lower Limit of Quantification [LLOQ] (10 IU/mL, target detected or target not detected)
timeFrame: 48 weeks
measure: HBeAg negative: HBV DNA <Lower Limit of Quantification [LLOQ] (10 IU/mL, target not detected)
timeFrame: 48 weeks
Secondary outcomes:
measure: Safety and Tolerability
timeFrame: 96 Weeks
measure: HBV DNA levels
timeFrame: 48 weeks
measure: HBV DNA < lower limit of quantification [LLOQ] (target detected or target not detected) [HBeAg positive]
timeFrame: 48 weeks
measure: HBV DNA < Lower Limit of Quantification [LLOQ] (target not detected) [HBeAg negative]
timeFrame: 48 weeks
measure: Change in HBV DNA levels from baseline
timeFrame: 48 weeks
measure: Time to HBV DNA level <Lower Limit of Quantification [LLOQ]
timeFrame: 96 Weeks
measure: Change in HBV RNA levels from baseline
timeFrame: 48 weeks
measure: Time to HBV RNA level <Lower Limit of Quantification [LLOQ]
timeFrame: 96 Weeks
measure: Subjects with abnormal ALT at baseline who have normal ALT at Week 48
timeFrame: 48 weeks
measure: Emergence of treatment associated mutations in the HBV genome
timeFrame: 96 Weeks
measure: PK parameters of ALG-001075
timeFrame: 96 Weeks
measure: PK parameters of ALG-001075
timeFrame: 96 Weeks
measure: PK parameters of ALG-001075
timeFrame: 96 Weeks
measure: PK parameters of ALG-001075
timeFrame: 96 Weeks
measure: PK parameters of ALG-001075
timeFrame: 96 Weeks
measure: PK parameters of ALG-001075
timeFrame: 96 Weeks
Other outcomes:
measure: Change in levels of various HBV antigens at various time points from Baseline
timeFrame: 96 Weeks
measure: Histologic, virologic, immunologic and/or PK-related endpoints
timeFrame: 96 Weeks
Locations:
Study officials:
References: