Chronic Hepatitis B Infection
Conditions
Keywords
Capsid Assembly Modulators, CAMs, CHB, HBV, Chronic Hepatitis B, Hepatitis B Infection, Hepatitis B
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.
Interventions
DRUGALG-000184
300 mg tablet
DRUGTDF
300 mg tablet
Sponsors
Aligos Therapeutics
Study design
Allocation
RANDOMIZED
Intervention model
PARALLEL
Primary purpose
TREATMENT
Masking
QUADRUPLE (Subject, Caregiver, Investigator, Outcomes Assessor)
Eligibility
Sex/Gender
ALL
Age
18 Years to 65 Years
Healthy volunteers
No
Inclusion 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 (or minimun age by local regulatory requirements). 2. HBeAg-positive and anti-HBeAg (HBeAb) negative (Part 1); or HBeAg-negative (Part 2). 3. HBsAg ≥LLOQ. 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
Design outcomes
Primary
| Measure | Time frame | Description |
|---|---|---|
| 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
| Measure | Time frame | Description |
|---|---|---|
| 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) |
| 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 |
| 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 trough plasma concentration (Ctrough) |
Countries
Bulgaria, Canada, China, France, Hong Kong, Italy, Moldova, New Zealand, Romania, South Korea, Spain, Taiwan, United Kingdom, United States
Outcome results
None listed