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)

Официальное название

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)

Обзор

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.

Подробное описание

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.

Вмешательства

• Препарат ALG-000184
  300 mg tablet
• Препарат TDF
  300 mg tablet

Первичные конечные точки

• HBeAg positive: HBV DNA <Lower Limit of Quantification [LLOQ] (10 IU/mL, target detected or target not detected) [Срок оценки: 48 weeks]
• HBeAg negative: HBV DNA <Lower Limit of Quantification [LLOQ] (10 IU/mL, target not detected) [Срок оценки: 48 weeks]

Вторичные конечные точки (12)

• Safety and Tolerability [Срок оценки: 96 Weeks]
• HBV DNA levels [Срок оценки: 48 weeks]
• HBV DNA < lower limit of quantification [LLOQ] (target detected or target not detected) [HBeAg positive] [Срок оценки: 48 weeks]
• HBV DNA < Lower Limit of Quantification [LLOQ] (target not detected) [HBeAg negative] [Срок оценки: 48 weeks]
• Change in HBV DNA levels from baseline [Срок оценки: 48 weeks]
• Time to HBV DNA level <Lower Limit of Quantification [LLOQ] [Срок оценки: 96 Weeks]
• Change in HBV RNA levels from baseline [Срок оценки: 48 weeks]
• Time to HBV RNA level <Lower Limit of Quantification [LLOQ] [Срок оценки: 96 Weeks]
• Subjects with abnormal ALT at baseline who have normal ALT at Week 48 [Срок оценки: 48 weeks]
• Emergence of treatment associated mutations in the HBV genome [Срок оценки: 96 Weeks]
• PK parameters of ALG-001075 [Срок оценки: 96 Weeks]
• PK parameters of ALG-001075 [Срок оценки: 96 Weeks]

Критерии участия

Критерии включения

• 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).
• HBeAg-positive and anti-HBeAg (HBeAb) negative (Part 1); or HBeAg-negative (Part 2).
• HBsAg ≥LLOQ.
• HBV DNA ≥20,000 IU/mL.
• 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).

Критерии исключения

• Co-infection with hepatitis A, C, D, E or HIV or any evidence of clinically significant liver disease of non-HBV etiology.
• Positive for anti-HBs antibodies.
• History or current evidence of cirrhosis.
• Liver fibrosis that is classified as Metavir Score ≥F3 liver disease.
• History of, or current evidence of, hepatic decompensation.
• Evidence of hepatocellular carcinoma (HCC) on a liver ultrasound.
• 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
• 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

Критерии приведены из реестра в оригинале (на английском). Окончательную оценку соответствия проводит исследовательский центр.

Здоровые добровольцы: Нет

Дизайн исследования

Распределение

Рандомизированное

Модель

Параллельные группы

Маскирование

Четверное слепое

Основная цель

Лечение

Центры проведения

США · 18 центров

• Aligos Investigational Site — Chandler
• Aligos Investigational Site — Coronado
• Aligos Investigational Site — Garden Grove
• Aligos Investigational Site — Los Angeles
• Aligos Investigational Site — Palo Alto
• Aligos Investigational Site — Pasadena
• Aligos Investigational Site — Rialto
• Aligos Investigational Site — San Francisco
• … и ещё 10 центров

Китай · 7 центров

• Aligos Investigational Sites — Пекин
• Aligos Investigational Site — Changchun
• Aligos Investigational Site — Чэнду
• Aligos Investigational Site — Чунцин
• Aligos Investigational Sites — Гуанчжоу
• Aligos Investigational Site — Нанкин
• Aligos Investigational Sites — Шанхай

Франция · 6 центров

• Aligos Investigational Site — Clichy
• Aligos Investigational Site — Limoges
• Aligos Investigational Site — Nice
• Aligos Investigational Site — Rennes
• Aligos Investigational Site — Rouen
• Aligos Investigational Site — Toulouse

South Korea · 5 центров

• Aligos Investigational Site — Ansan
• Aligos Investigational Site — Busan
• Aligos Investigational Sites — Seoul
• Aligos Investigational Site — Ulsan
• Aligos Investigational Site — Yangsan

Тайвань · 5 центров

• Aligos Investigational Site — Chiayi City
• Aligos Investigational Site — Kaohsiung City
• Aligos Investigational Site — Taichung
• Aligos Investigational Site — Tainan
• Aligos Investigational Site — Taipei

Канада · 4 центра

• Aligos Investigational Site — Edmonton
• Aligos Investigational Site — Ottawa
• Aligos Investigational Site — Toronto
• Aligos Investigational Sites — Vancouver

Болгария · 3 центра

• Aligos Investigational Site — Sliven
• Aligos Investigational Sites — Sofia
• Aligos Investigational Site — Stara Zagora

Великобритания · 3 центра

• Aligos Investigational Site — Glasgow
• Aligos Investigational Site — Leicester
• Aligos Investigational Sites — London

Испания · 2 центра

• Aligos Investigational Site — Barcelona
• Aligos Investigational Site — Pontevedra

Гонконг · 1 центр

• Aligos Investigational Sites — Гонконг

Италия · 1 центр

• Aligos Investigational Site — Milan

Moldova · 1 центр

• Aligos Investigational Site — Chisinau

Новая Зеландия · 1 центр

• Aligos Investigational Site — Auckland

Румыния · 1 центр

• Aligos Investigational Sites — Bucharest

Идентификаторы

NCT: NCT06963710 · ALG-000184-202

Первоисточники (государственные реестры)

• ClinicalTrials.gov (NIH, США)

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