Impact of bepirovirsen on immune response in chronic hepatitis B patients
| ISRCTN | ISRCTN11489455 |
|---|---|
| DOI | https://doi.org/10.1186/ISRCTN11489455 |
| ClinicalTrials.gov (NCT) | Nil known |
| Clinical Trials Information System (CTIS) | Nil known |
| Protocol serial number | Nil known |
| Sponsor | Chang Gung Memorial Hospital |
| Funder | GlaxoSmithKline Research & Development Ltd |
- Submission date
- 30/10/2025
- Registration date
- 30/10/2025
- Last edited
- 30/10/2025
- Recruitment status
- Recruiting
- Overall study status
- Ongoing
- Condition category
- Infections and Infestations
Plain English summary of protocol
Background and study aims
This study is looking at how the immune system reacts to a potential new treatment for chronic hepatitis B called Bepirovirsen. Researchers want to understand why some people respond better to the treatment than others, especially those who continue to have lower levels of the virus after treatment. To do this, they’ll study stored blood samples from people who took part in an earlier clinical trial called B-Well.
Who can participate?
No new participants are needed for this study. It will only use samples from people who already took part in the previous trial and gave permission for their samples to be used in future research.
What does the study involve?
There is no involvement required from participants. The study will use previously collected and anonymised blood samples, so no one will be contacted or asked to do anything new.
What are the possible benefits and risks of participating?
Since no new participation is required, there are no direct risks or benefits for individuals. However, the research could help improve future treatments for hepatitis B by helping scientists understand how the immune system responds to Bepirovirsen.
Where is the study run from?
Chang Gung Memorial Hospital in Taiwan.
When is the study starting and how long is it expected to run for?
October 2025 ti October 2027.
Who is funding the study?
GlaxoSmithKline Research & Development Ltd.
Who is the main contact?
Professor Wen-Juei (Rachel) Jeng, rachel.jeng@gmail.com
Contact information
Public, Scientific, Principal investigator
Department of Gastroenterology and Hepatology, Chang Gung Memorial Hospital, Linkou Medical Center, No. 5, Fuxing Street, Guishan District
Taoyuan
33305
Taiwan
 ORCID ID |
0000-0002-3706-1259 |
|---|---|
| Phone | +886-3-3281200 ext 8107 |
| m7197@cgmh.org.tw |
Public, Scientific, Principal investigator
Department of Gastroenterology and Hepatology, Chang Gung Memorial Hospital, Linkou Medical Center, No. 5, Fuxing Street, Guishan District
Taoyuan
33305
Taiwan
| Phone | +886-3-3281200 ext 8107 |
|---|---|
| chunyenlin@gmail.com |
Study information
| Primary study design | Observational |
|---|---|
| Study design | Observational single-centre retrospective cohort sub-study |
| Secondary study design | Retrospective sub-study |
| Study type | Participant information sheet |
| Scientific title | The impact of bepirovirsen on host HBV-specific immune response in relation to HBsAg decline and its durability |
| Study objectives | To explore the changes in HBV-specific T-cell phenotype during Bepirovirsen administration and their association with HBsAg decline and durability. Secondary objectives include investigating (1) changes in innate-like CD8⁺ T cells and their relationship with ALT elevation, (2) phenotype alterations in monocytes, and (3) plasma cytokine patterns (IL-12, IL-15, IL-18) during treatment. |
| Ethics approval(s) |
Approved 17/07/2025, Chang Gung Medical Foundation Institutional Review Board (199, Tung Hwa North Road, Taipei, 10507, Taiwan; +886-3-3196200; irb@cgmh.org.tw), ref: 202500942B0 |
| Health condition(s) or problem(s) studied | Chronic Hepatitis B (CHB) infection; functional cure; HBsAg seroclearance; immune reconstitution after Bepirovirsen. |
| Intervention | Drug (interventional parent trial with Bepirovirsen); this sub-study is observational using biological samples. Brief methodology of the parent trial: The parent trial is a Phase 2b randomized controlled study (B-Well) evaluating Bepirovirsen, an antisense oligonucleotide (ASO) targeting all HBV mRNAs. -Design: 1:3 randomization (Bepirovirsen 300 mg vs placebo). -Dose and duration: Participants receive weekly subcutaneous injections of 300 mg Bepirovirsen for 24 weeks, followed by a 24-week off-treatment observation period. -Comparator: Placebo administered on the same schedule. -Population: Chronic hepatitis B (CHB) patients with long-term nucleos(t)ide analogue (Nuc) suppression. -Sub-study (current project): Retrospective observational analysis of immunologic changes in 20 participants (10 cross-sectional and 10 longitudinal) from the B-Well cohort to evaluate Bepirovirsen’s impact on HBV-specific and innate-like T-cell responses and cytokine signatures. |
| Intervention type | Other |
| Primary outcome measure(s) |
HBV-specific CD8 T-cell phenotype measured using multicolor flow cytometry (Symphony) and single-cell RNA sequencing of PBMC samples at baseline (before IP/placebo), Week 7–10, Week 21–23 (end of IP treatment), and Week 40–46 (24 weeks post-treatment follow-up) |
| Key secondary outcome measure(s) |
1. Innate-like CD8 T-cell frequency and activation status (CD38⁺HLA-DR⁺ CD8 T cells) measured by flow cytometry and scRNA-seq at baseline, Week 7–10, Week 21–23 and Week 40–46. |
| Completion date | 29/10/2027 |
Eligibility
| Participant type(s) | Patient |
|---|---|
| Age group | Adult |
| Lower age limit | 18 Years |
| Sex | All |
| Target sample size at registration | 20 |
| Total final enrolment | 20 |
| Key inclusion criteria | 1. Adults with chronic hepatitis B enrolled in the Bepirovirsen-based B-Well trial 2. Provided informed consent for optional immunologic sub-study 3. Available peripheral blood mononuclear cell (PBMC) and plasma samples collected at predefined time points |
| Key exclusion criteria | 1. Hemoglobin < 10 g/dL 2. Withdrawal of consent for B-Well sub-study 3. Insufficient sample quality or quantity for immune analysis |
| Date of first enrolment | 31/10/2025 |
| Date of final enrolment | 11/10/2027 |
Locations
Countries of recruitment
- Taiwan
Study participating centre
Taoyuan
33305
Taiwan
Results and Publications
| Individual participant data (IPD) Intention to share | Yes |
|---|---|
| IPD sharing plan summary | Available on request |
| IPD sharing plan | De-identified data will be shared in aggregated form with GlaxoSmithKline Research & Development Ltd and may be made available to qualified researchers upon reasonable request, following institutional and IRB approval. No individual-level identifiers will be released publicly. |
Study outputs
| Output type | Details | Date created | Date added | Peer reviewed? | Patient-facing? |
|---|---|---|---|---|---|
| Participant information sheet | Participant information sheet | 11/11/2025 | 11/11/2025 | No | Yes |
| Protocol file | version 1.1 | 07/07/2025 | 30/10/2025 | No | No |
Additional files
Editorial Notes
30/10/2025: Trial's existence confirmed by Chang Gung Medical Foundation Institutional Review Board.
