A phase 2, single-blinded, randomised, controlled multi-country study to evaluate the safety, reactogenicity, efficacy and immune response following sequential treatment with an anti-sense oligonucleotide (ASO) against chronic Hepatitis B (CHB) followed by chronic Hepatitis B targeted immunotherapy (CHB-TI) in CHB patients receiving nucleos(t)ide analogue (NA) therapy. - TH HBV ASO-001

GlaxoSmithKline Biologicals0 个研究点目标入组 174 人开始时间: 2021年11月3日最近更新: 2024年5月21日

适应症

试验速览

阶段: 1 期
状态: 进行中（未招募）
发起方: GlaxoSmithKline Biologicals
入组人数: 174

研究概览入排标准研究者记录与标识符相似试验

研究概览

简要总结

暂无简介。

研究设计

研究类型: Interventional clinical trial of medicinal product

入排标准

性别: All

入选标准

•Participants, who, in the opinion of the investigator, can and will comply with the requirements of the protocol.
•Written or witnessed/thumb printed informed consent obtained from the participant prior to performance of any study-specific procedure.
•A male or female between, and including, 18 and 65 years of age at the time of signing of the informed consent (except for South Korea, where a male or female between, and including, 19 and 65 years of age at the time of signing of the informed consent can participate in the study).
•Participants who are Hepatitis B envelop antigen (HBeAg) positive or negative.
•Participants who have documented chronic HBV infection =6 months prior to screening and currently receiving stable NA therapy defined as no changes to their nucleos(t)ide regimen from at least 6 months prior to screening and with no planned changes to the stable regimen over the duration of the study.
•CHB patient, under and adherent to treatment with a NA with high barrier to resistance (e.g. entecavir, tenofovir disoproxil fumarate and tenofovir alafenamide).
•Participants with ALT = 2x upper limit of normal (ULN) documented in approximately the last 6 months (i.e., no ALT >2x ULN).
•Participants with plasma or serum HBsAg concentration >100 IU/mL.
•Participants must be adequately suppressed, defined as plasma or serum HBV DNA <90 IU/mL.
•A male participant is eligible if he agrees to the following during the intervention period and for at least 90 days after the last dose of study intervention
•- Refrain from donating sperm
•- AND be abstinent from heterosexual intercourse as their preferred and usual lifestyle (abstinent on a long-term and persistent basis) and agree to remain abstinent OR Must agree to use contraception/barrier as detailed below
•o Agree to use a male condom [and should also be advised of the benefit for a female partner to use a highly effective method of contraception as a condom may break or leak] when having sexual intercourse with a woman of childbearing potential (WOCBP) who is not currently pregnant
•A female participant is eligible:
•- If she is not pregnant or breastfeeding
•- AND at least one of the following conditions applies:
•o Is not a WOCBP
•o Is a WOCBP and using a contraceptive method that is highly effective (with a failure rate of <1% per year), preferably with low user dependency during the intervention period and for at least 90 days after the last dose of study treatment.
•A WOCBP must have a negative highly sensitive pregnancy test (urine or serum as required by local regulations) within 24 hours before the first dose of study intervention.
•Are the trial subjects under 18? no
•Number of subjects for this age range:
•F.1.2 Adults (18-64 years) yes
•F.1.2.1 Number of subjects for this age range 180
•F.1.3 Elderly (>=65 years) yes
•F.1.3.1 Number of subjects for this age range 4

排除标准

•Medical conditions
•Clinically significant abnormalities, aside from chronic HBV infection
•Co-infection with: Current or past history of HCV,HIV,HDV
•History of or suspected liver cirrhosis and/or evidence of cirrhosis as determined by
•-both AST-Platelet Index (APRI) >2 and FibroSure/FibroTest result >0.7
•-Liver biopsy (METAVIR Score F4) or Liver stiffness >12 kPa
•FibroScan TE score >9.6 kPa and FibroTest score >0.59 at Screening
•Diagnosed or suspected HCC
•History of
•-malignancy within the past 5 years except of specific
•cancers that are cured by surgical resection
•-vasculitis or presence of symptoms and signs of potential vasculitis
•-extrahepatic disorders possibly related to HBV immune conditions
•Positive (or borderline positive) ANCA at screening
•Low C3/C4 at screening AND evidence of past history or current manifestations of vasculitic/inflammatory/autoimmune conditions
•History of alcohol or drug abuse/dependence
•QTcF =450 msec
•Laboratory results as follows:
•-Serum albumin<3.5 g/dL
•-GFR<60 mL/min/1.73m^2
•-INR>1.25
•-PLT count<140x10^9/L
•-HGB<10 g/dl
•-T Bil>1.25xULN unless considered as clinically not significant by the Investigator
•-ACR=0.03 mg/mg
•Medical history of hepatic decompensation
•Planned or previous liver transplantation
•Documented evidence of other currently active cause of hepatitis
•Any other clinical condition that might pose additional risk to the participant due to participation in the study
•Major congenital defects
•Recurrent history or uncontrolled neurological disorders or seizures
•History of any reaction or hypersensitivity likely to be exacerbated by any component of the study intervention(s)
•Prior/Concomitant therapy
•Use of any investigational or non-registered product other than the study interventions within 30 days before the first dose of study interventions, or their planned use during the study
•Use of systemic cytotoxic agents, chronic antiviral agents or Chinese herbal medicines which may have activity against HBV within 6 months (M) prior the study
•Currently taking, or took within 12 M of screening, any interferon-containing therapy
•Administration of adenovirus/adenovector-based or MVA-based vaccine within the last 12 M, except for adenovirus/adenovector-based COVID-19 vaccines that could be administered up to 30 days prior to the first study vaccine dose (applicable for all patients except for the patients in France) OR Administration of adenovirus/adenovector-based or MVA-based vaccine within the last 12 M (applicable for the patients in France only)
•Planned administration/administration of a vaccine not foreseen by the study protocol within 14 days before the first dose and/or 30 days after the last dose of study intervention administration, with the exception of influenza vaccine that may be given at any time except within a 7-day period before or after each dose and COVID-19 vaccine that may be given at any time except within a 30-day period before or after each vaccine dose apart from COVID-19 mRNA based-vaccines that may be administered any time except for the period of 14 days before and 30 days after each study vaccine dose
•Administration of:
•-long-acting immune-modifying drugs at any time during the study
•-immunoglobulins and/or any blood products or plasma derivatives
•within 3 M before the first dose of study interventions or planned administration during the study
•Chronic administration of immunosuppressants or other immune-modifying drugs within 3 M prior to the first st

研究者

发起方

GlaxoSmithKline Biologicals

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