Study of AHB-137 in Chronic Hepatitis B (CHB) Participants in North America and Europe Regions

Официальное название

A Phase 2 Multi-center, Randomized, Open-label Study to Assess the Efficacy and Safety of AHB-137 in Nucleos(t)Ide Analogue-treated Participants With Chronic Hepatitis B in the North America and Europe Regions

Обзор

This study is a randomized, open-label, multicenter phase 2 clinical trial to evaluate the efficacy and safety of AHB-137 injection in participants with CHB treated with Nucleos(t)ide Analogue (NAs).

Вмешательства

• Препарат AHB-137
  Subcutaneous injection

Первичные конечные точки

• Proportion of participants with persistent HBsAg < limit of detection (LOD) and HBV DNA < lower limit of quantification (LLOQ) [Срок оценки: 24 Weeks post AHB-137 treatment (Week 48)]

Вторичные конечные точки (12)

• Proportion of participants with HBsAg < LOD and HBV DNA < LLOQ [Срок оценки: Off-treatment follow-up (Week 48 to 72)]
• Proportion of participants with HBsAg < LOD [Срок оценки: Week 72]
• Proportion of participants with HBV DNA < LLOQ [Срок оценки: From baseline through Week 72]
• Proportion of participants with protocol-defined virologic response for HBsAg and HBV DNA post AHB-137 treatment [Срок оценки: 24 weeks post AHB-137 treatment]
• Proportion of participants with protocol-defined virologic response for HBsAg and HBV DNA at weeks 48 and 72 [Срок оценки: 24 weeks post AHB-137 treatment and at Week 72]
• Proportion of participants with protocol-defined virologic response for HBsAg and HBV DNA [Срок оценки: From baseline through end of study (Week 72)]
• Proportion of participants with HBsAg < or ≥ LOD (0.05 IU/mL) and/or HBV DNA < or ≥ LLOQ [Срок оценки: From baseline through end of study (Week 72)]
• Proportion of participants with highly sensitive HBsAg < LOD (0.005 IU/mL) [Срок оценки: From baseline through end of study (Week 72)]
• Proportion of participants with protocol-defined levels of HBsAg [Срок оценки: From baseline through end of study (Week 72)]
• Proportion of participants that meet nucleos(t)ide analog (NA) discontinuation criteria [Срок оценки: Week 48]
• Categorical change from baseline in HBsAg levels, defined as reductions of ≥0.5, ≥1.0, ≥1.5, ≥2.0, or ≥3.0 log₁₀ IU/mL, assessed at each scheduled study visit [Срок оценки: From baseline through end of study (Week 72)]
• Proportion of participants with anti-HBs seroconversion (with hepatitis B surface antibody [HBsAb] > 10 IU/L) [Срок оценки: Weeks 24, 48, and 72]

Критерии участия

Критерии включения

Participants are eligible to be included in the study only if all of the following criteria apply:

• Adults ≥18 years of age and up to 65 years of age (inclusive) at Screening who are able to provide informed consent, comply with study procedures, and agree to discontinue nucleos(t)ide analog (NA) therapy if protocol-defined discontinuation criteria are met.
• Body mass index (BMI) ≤35 kg/m².
• Documented chronic hepatitis B virus (HBV) infection for ≥6 months prior to randomization, defined by hepatitis B surface antigen (HBsAg) positivity or detectable HBV DNA.
• Receiving stable, approved nucleos(t)ide analog (NA) monotherapy for ≥6 months prior to randomization.
• HBV DNA meeting protocol-specified virologic criteria at Screening.
• Hepatitis B surface antigen (HBsAg) level meeting protocol-specified virologic criteria at Screening.
• Alanine aminotransferase (ALT) meeting protocol-specified criteria at Screening.
• Screening electrocardiogram (ECG) without clinically significant abnormalities and with a Fridericia-corrected QT interval (QTcF) ≤450 msec for males or ≤470 msec for females.
• Females of childbearing potential must not be breastfeeding and must have a negative serum pregnancy test at Screening and a negative urine pregnancy test prior to first dose.
• Males and female participants of childbearing potential must agree to use protocol-specified effective contraception during the dosing period and for ≥6 months after the last dose of AHB-137.

Критерии исключения

Participants will be excluded from the study if any of the following criteria apply:

• Clinically significant disease other than chronic hepatitis B virus (HBV) infection.
• Concomitant clinically significant liver disease.
• Any severe infection (other than chronic HBV infection) within 1 month prior to randomization.
• History of immune thrombocytopenia.
• Current suspected liver cirrhosis and/or evidence of cirrhosis by protocol-specified criteria for FibroScan® or equivalent imaging modality (e.g., ultrasound elastography); historical FibroScan® (or equivalent) results with documentation within 6 months from screening is acceptable.
• History of liver cirrhosis defined by liver biopsy or by FibroScan® or equivalent imaging modality using protocol-specified criteria.
• Prior history of, current diagnosis of, or suspected hepatocellular carcinoma (HCC), or alpha-fetoprotein (AFP) ≥20 ng/mL at Screening.
• History of extrahepatic diseases potentially associated with HBV infection.
• Laboratory evidence of active infection with human immunodeficiency virus (HIV), hepatitis C virus (HCV), hepatitis D virus (HDV), or active syphilis. Participants with positive HCV or HDV serology and documented negative HCV RNA or HDV RNA, respectively, are eligible.
• Protocol-specified abnormal laboratory values at Screening.
• History of vasculitis or presence of signs or symptoms suggestive of vasculitis, or history or presence of diseases associated with vasculitis.
• History of malignancy within 5 years prior to Screening, except for adequately treated non-melanoma skin cancer. Participants currently undergoing evaluation for potential malignancy are excluded.
• History of hypersensitivity or allergy to any component of the investigational product (IP).
• Major trauma or major surgery within 3 months prior to Screening, or planned surgery during the study period unless eligibility is confirmed by the Medical Monitor.
• Current alcohol or substance abuse judged by the Investigator to potentially interfere with participant compliance.
• Female participants who are pregnant, breastfeeding, planning pregnancy during the study, or unwilling to refrain from egg donation and/or in vitro fertilization during the study.
• Participation in another clinical trial or receipt of any investigational product prior to first dose in this study within:

• Five half-lives (if known) or twice the duration of biological effect (if known), whichever is longer, or
• Six months, if neither half-life nor duration of effect is known
• Prior treatment with antisense oligonucleotides (ASOs) or small interfering RNA (siRNA)-based therapies.
• Any of the following prior or concomitant therapies:

• Prolonged use of immunomodulators (e.g., corticosteroids, methotrexate), cytotoxic drugs, or biologics (e.g., monoclonal antibodies) within 6 months prior to first IP administration, except for short-term treatment (≤2 weeks) or topical/inhaled corticosteroids
• Interferon therapy within 12 months prior to first dose
• Vaccination within 1 month prior to Screening, except for influenza or SARS-CoV-2 (COVID-19) vaccination or booster
• Current treatment with bulevirtide
• Requirement for long-term regular use of anticoagulants (e.g., warfarin, factor Xa inhibitors) or antiplatelet agents (e.g., clopidogrel or regular aspirin), except for low-dose aspirin.
• Any other condition or circumstance that, in the Investigator's judgment, would make the participant unsuitable for participation in the study.

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

Открытое

Основная цель

Лечение

Центры проведения

США · 4 центра

• Stanford University — Palo Alto
• University of Maryland — Baltimore
• NYU Langone Health — New York
• Texas Liver Institute — San Antonio

Канада · 1 центр

• University of Calgary — Calgary

Франция · 1 центр

• Hôpital Beaujon — Clichy

Италия · 1 центр

• Clinica Mangiagalli — Milan

Испания · 1 центр

• Vall d'Hebron Hospital — Barcelona

Великобритания · 1 центр

• King's College Hospital — London

Идентификаторы

NCT: NCT07654283 · AB-10-8012 · 2025-524159-30-00

Первоисточники (государственные реестры)

• ClinicalTrials.gov (NIH, США)

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