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
- Interventions
- Registration Number
- NCT06963710
- Lead Sponsor
- Aligos Therapeutics
- 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.
Recruitment & Eligibility
- Status
- NOT_YET_RECRUITING
- Sex
- All
- Target Recruitment
- 200
-
Male or female between 18 and 65 years of age, with body mass index (BMI) of 18.0 to 35.0 kg/m2.
-
HBeAg-positive and anti-HBeAg (HBeAb) negative (Part 1); or HBeAg-negative (Part 2).
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HBsAg ≥100 IU/mL.
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HBV DNA ≥20,000 IU/mL.
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A history of a clinical diagnosis of chronic HBV infection AND an ALT values of ≤8×ULN during screening.
-
Must have the following chronic hepatitis B virus infection treatment status at screening:
- 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
- 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
-
Co-infection with hepatitis A, C, D, E or HIV or any evidence of clinically significant liver disease of non-HBV etiology.
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Positive for anti-HBs antibodies.
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History or current evidence of cirrhosis.
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Liver fibrosis that is classified as Metavir Score ≥F3 liver disease.
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History of, or current evidence of, hepatic decompensation.
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Evidence of hepatocellular carcinoma (HCC) on a liver ultrasound.
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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
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Exclusionary screening laboratory values include:
- Aspartate aminotransferase (AST) >8×ULN,
- Bilirubin (total, direct) >1.2×ULN (unless Gilbert's syndrome is suspected)
- International Normalization Ratio (INR) >1.2×ULN
Study & Design
- Study Type
- INTERVENTIONAL
- Study Design
- PARALLEL
- Arm && Interventions
Group Intervention Description ALG-000184 ALG-000184 Orally for 48 weeks followed by open-label treatment with ALG-000184 for 48 weeks. TDF TDF Orally for 48 weeks followed by open-label treatment with ALG-000184 for 48 weeks.
- Primary Outcome Measures
Name Time Method HBeAg positive: HBV DNA <Lower Limit of Quantification [LLOQ] (10 IU/mL, target detected or target not detected) 48 weeks HBV DNA \<Lower Limit of Quantification \[LLOQ\] (10 IU/mL, target detected or target not detected) at Week 48
HBeAg negative: HBV DNA <Lower Limit of Quantification [LLOQ] (10 IU/mL, target not detected) 48 weeks HBV DNA \<Lower Limit of Quantification \[LLOQ\] (10 IU/mL, target not detected) at Week 48
- Secondary Outcome Measures
Name Time Method Change in HBV DNA levels from baseline 48 weeks Change from baseline in HBV DNA at various time points during the first 48 weeks.
Time to HBV DNA level <Lower Limit of Quantification [LLOQ] 96 Weeks Time to HBV DNA \< Lower Limit of Quantification \[LLOQ\] (target detected or target not detected) (HBeAg positive) and HBV DNA \< Lower Limit of Quantification \[LLOQ\] (target not detected) (HBeAg negative)
Change in HBV RNA levels from baseline 48 weeks Change from baseline in HBV RNA levels at various time points during the first 48 weeks
Time to HBV RNA level <Lower Limit of Quantification [LLOQ] 96 Weeks Time to HBV RNA \< Lower Limit of Quantification \[LLOQ\]
Subjects with abnormal ALT at baseline who have normal ALT at Week 48 48 weeks Subjects with abnormal ALT at baseline who have normal ALT at Week 48
Emergence of treatment associated mutations in the HBV genome 96 Weeks Emergence of treatment associated mutations in the HBV genome
PK parameters of ALG-001075 96 Weeks PK parameters of ALG-001075 including the half-life
HBV DNA < lower limit of quantification [LLOQ] (target detected or target not detected) [HBeAg positive] 48 weeks HBV DNA \< Lower Limit of Quantification \[LLOQ\] (target detected or target not detected) at various time points during the first 48 weeks
HBV DNA < Lower Limit of Quantification [LLOQ] (target not detected) [HBeAg negative] 48 weeks HBV DNA \< Lower Limit of Quantification \[LLOQ\] (target not detected) at various time points during the first 48 weeks
Safety and Tolerability 96 Weeks Number of participants with Treatment Emergent Adverse Events (TEAEs), with abnormal 12-lead electrocardiogram readings and abnormal clinical laboratory results.
HBV DNA levels 48 weeks Categorized by HBV DNA ≥ Lower Limit of Quantification \[LLOQ\], HBV DNA \<Lower Limit of Quantification \[LLOQ\] (target detected), and HBV DNA \< Lower Limit of Quantification \[LLOQ\] (target not detected)