Status:
COMPLETED
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
Lead Sponsor:
GlaxoSmithKline
Conditions:
Hepatitis B, Chronic
Eligibility:
All Genders
18-65 years
Phase:
PHASE2
Brief Summary
This study will assess the safety, efficacy and immune response following the sequential treatment of GlaxoSmithKline's (GSK) ASO compound (GSK3228836) and CHB-TI (GSK3528869A) in participants 18 to 6...
Detailed Description
The study follow-up period was reduced from 2 years post last dose to at least 1 year post last dose, with Visit Treatment 2-Day 505 defined as the last visit of the study. For participants who comple...
Eligibility Criteria
Inclusion
- Inclusion criteria:
- 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 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 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 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.
- 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:
- Is not a WOCBP
- 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.
- Exclusion criteria:
- 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 prior the study.
- 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 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 months (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 months before the first dose of study interventions or planned administration during the study
- Chronic administration of immunosuppressants or other immune-modifying drugs within 3 months prior to the first study intervention (e.g. prednisone equivalent \>=20 mg/day; \>=10 mg/day applicable in Germany only). Inhaled and topical steroids are allowed.
- Participants for whom immunosuppressive treatment is not advised.
- Treatment with nephrotoxic drugs or competitors of renal excretion within 2 months prior to Screening or planned during the study.
- Participants requiring anti-coagulation therapies.
- Prior/Concurrent clinical study experience
- Concurrently participating in another clinical study, at any time during the study period, in which the participant has been/will be exposed to an investigational/a non-investigational intervention.
- Previous participation in clinical trials with administration of either GSK3228836 or GSK3528869A.
- Previous participation in a clinical study in which he/she has received an investigational product within the following time period prior to the first dosing day in the current study: 5 half-lives or twice the duration of the biological effect of the study treatment or 90 days.
- Prior treatment with any other oligonucleotide/siRNA within 12 months prior to the first dosing day.
- Other exclusions:
- Pregnant or lactating female.
- Female planning to become pregnant/to discontinue contraceptive precautions.
- Any study personnel or their immediate dependents, family, or household members.
- History of/sensitivity to GSK3228836, or components thereof, or a history of drug or other allergy that contraindicates their participation.
Exclusion
Key Trial Info
Start Date :
March 22 2022
Trial Type :
INTERVENTIONAL
Allocation :
ACTUAL
End Date :
August 5 2025
Estimated Enrollment :
174 Patients enrolled
Trial Details
Trial ID
NCT05276297
Start Date
March 22 2022
End Date
August 5 2025
Last Update
December 30 2025
Active Locations (51)
Enter a location and click search to find clinical trials sorted by distance.
1
GSK Investigational Site
Edegem, Belgium, 2650
2
GSK Investigational Site
Sliven, Bulgaria, 8800
3
GSK Investigational Site
Sofia, Bulgaria, 1407
4
GSK Investigational Site
Sofia, Bulgaria, 1431