A study on the safety, efficacy and immune response following sequential treatment with an anti-sense oligonucleotide against chronic Hepatitis B (CHB) and chronic Hepatitis B targeted immunotherapy (CHB-TI) in CHB patients receiving nucleos(t)ide analogue (NA) therapy.
- Conditions
- Hepatitis B, ChronicTherapeutic area: Diseases [C] - Virus Diseases [C02]
- Registration Number
- CTIS2024-512352-38-00
- Lead Sponsor
- GlaxoSmithKline Biologicals
- Brief Summary
Not available
- Detailed Description
Not available
Recruitment & Eligibility
- Status
- Recruiting
- Sex
- All
- Target Recruitment
- 205
•Participants, who, in the opinion of the investigator, can and will comply with the requirements of the protocol (e.g. completion of the diary cards, return for follow-up visits). •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 HBeAg positive or negative. •Participants who have documented chronic HBV infection =6 months prior to screening and currently stable on 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 Alanine Transaminase (ALT) = 2x upper limit of normal (ULN) (i.e., no ALT >2x ULN) documented in approximately the last 6 months. •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 to participate if they agree 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 oAgree 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 to participate: ?If she is not pregnant or breastfeeding ?AND at least one of the following conditions applies: oIs not a WOCBP oIs 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.
Medical conditions •Clinically significant abnormalities, aside from chronic HBV infection in medical history •Co-infection with: ?Current or past history of Hepatitis C virus (HCV) ?Human immunodeficiency virus (HIV) ?Hepatitis D virus (HDV) •History of or suspected liver cirrhosis and/or evidence of cirrhosis as determined by ?both Aspartate aminotransferase (AST)-Platelet Index (APRI) >2 and FibroSure/FibroTest result >0.7 ?Regardless of APRI or Fibrosure/FibroTest score, if the participant meets one of the following historical criteria, they will be excluded from the study oLiver biopsy (i.e., METAVIR Score F4) oLiver stiffness >12 kPa •FibroScan TE score >9.6 kPa and FibroTest score >0.59 at Screening. •Diagnosed or suspected HCC as evidenced by the following: ?Alpha-fetoprotein concentration =200 ng/mL ?If the screening alpha-fetoprotein concentration is =50 ng/mL and <200 ng/mL, the absence of liver mass must be documented by imaging within 6 months before randomisation. •History of malignancy within the past 5 years with the exception of specific cancers that are cured by surgical resection. •History of vasculitis or presence of symptoms and signs of potential vasculitis. •History of extrahepatic disorders possibly related to HBV immune conditions. •Positive (or borderline positive) Anti-neutrophil cytoplasmic antibody (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 •Fridericia’s QT correction formula (QTcF) =450 msec •Laboratory results as follows: ?Serum albumin <3.5 g/dL ?Glomerular filtration rate (GFR) <60 mL/ min /1.73m2 as calculated by the Chronic Kidney Disease Epidemiologic Collaboration (CKD-EPI) formula ?INR >1.25 ?Platelet count <140x109/L ?Haemoglobin< 10 g/dl ?Total bilirubin >1.25xULN ?Urine albumin to creatinine ratio (ACR) =0.03 mg/mg (or =30 mg/g). •Medical history of hepatic decompensation. •Planned for liver transplantation or previous liver transplantation. •Documented evidence of other currently active cause of hepatitis •Any other clinical condition that, in the opinion of the investigator, might pose additional risk to the participant due to participation in the study. •Major congenital defects, as assessed by the Investigator. •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 (drug, vaccine or medical device) other than the study interventions during the period beginning 30 days before the first dose of study interventions, or their planned use during the study period. •Use of systemic cytotoxic agents, chronic antiviral agents or Chinese herbal medicines which may have activity against HBV within the previous 6 months. •Currently taking, or took within 12 months of screening, any interferon-containing therapy. •Administration of adenovirus/adenovector-based or MVA-based vaccine within the last 12 months, except for adenovirus/adenovector-based Coronavirus Disease 2019 (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 vacc
Study & Design
- Study Type
- Interventional clinical trial of medicinal product
- Study Design
- Not specified
- Primary Outcome Measures
Name Time Method
- Secondary Outcome Measures
Name Time Method