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.
Study Type
INTERVENTIONAL
Allocation
RANDOMIZED
Purpose
TREATMENT
Masking
QUADRUPLE
Enrollment
200
300 mg tablet
300 mg tablet
HBeAg positive: HBV DNA <Lower Limit of Quantification [LLOQ] (10 IU/mL, target detected or target not detected)
HBV DNA \<Lower Limit of Quantification \[LLOQ\] (10 IU/mL, target detected or target not detected) at Week 48
Time frame: 48 weeks
HBeAg negative: HBV DNA <Lower Limit of Quantification [LLOQ] (10 IU/mL, target not detected)
HBV DNA \<Lower Limit of Quantification \[LLOQ\] (10 IU/mL, target not detected) at Week 48
Time frame: 48 weeks
Safety and Tolerability
Number of participants with Treatment Emergent Adverse Events (TEAEs), with abnormal 12-lead electrocardiogram readings and abnormal clinical laboratory results.
Time frame: 96 Weeks
HBV DNA levels
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)
Time frame: 48 weeks
HBV DNA < lower limit of quantification [LLOQ] (target detected or target not detected) [HBeAg positive]
HBV DNA \< Lower Limit of Quantification \[LLOQ\] (target detected or target not detected) at various time points during the first 48 weeks
Time frame: 48 weeks
HBV DNA < Lower Limit of Quantification [LLOQ] (target not detected) [HBeAg negative]
HBV DNA \< Lower Limit of Quantification \[LLOQ\] (target not detected) at various time points during the first 48 weeks
Time frame: 48 weeks
Change in HBV DNA levels from baseline
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Aligos Investigational Site
Chandler, Arizona, United States
RECRUITINGAligos Investigational Site
Coronado, California, United States
RECRUITINGAligos Investigational Site
Garden Grove, California, United States
RECRUITINGAligos Investigational Site
Los Angeles, California, United States
RECRUITINGAligos Investigational Site
Palo Alto, California, United States
RECRUITINGAligos Investigational Site
Pasadena, California, United States
RECRUITINGAligos Investigational Site
Rialto, California, United States
RECRUITINGAligos Investigational Site
San Francisco, California, United States
RECRUITINGAligos Investigational Site
San Jose, California, United States
RECRUITINGAligos Investigational Site
Miami, Florida, United States
RECRUITING...and 47 more locations
Change from baseline in HBV DNA at various time points during the first 48 weeks.
Time frame: 48 weeks
Time to HBV DNA level <Lower Limit of Quantification [LLOQ]
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)
Time frame: 96 Weeks
Change in HBV RNA levels from baseline
Change from baseline in HBV RNA levels at various time points during the first 48 weeks
Time frame: 48 weeks
Time to HBV RNA level <Lower Limit of Quantification [LLOQ]
Time to HBV RNA \< Lower Limit of Quantification \[LLOQ\]
Time frame: 96 Weeks
Subjects with abnormal ALT at baseline who have normal ALT at Week 48
Subjects with abnormal ALT at baseline who have normal ALT at Week 48
Time frame: 48 weeks
Emergence of treatment associated mutations in the HBV genome
Emergence of treatment associated mutations in the HBV genome
Time frame: 96 Weeks
PK parameters of ALG-001075
PK parameters of ALG-001075 including the trough plasma concentration (Ctrough)
Time frame: 96 Weeks
PK parameters of ALG-001075
PK parameters of ALG-001075 including the time to reach the maximum plasma concentration (Tmax)
Time frame: 96 Weeks
PK parameters of ALG-001075
PK parameters of ALG-001075 including the maximum drug concentration (Cmax)
Time frame: 96 Weeks
PK parameters of ALG-001075
PK parameters of ALG-001075 including the minimum drug concentration (Cmin)
Time frame: 96 Weeks
PK parameters of ALG-001075
PK parameters of ALG-001075 including the area under the plasma concentration-time curve steady state (AUCss)
Time frame: 96 Weeks
PK parameters of ALG-001075
PK parameters of ALG-001075 including the half-life
Time frame: 96 Weeks