Objective stated in the ClinicalTrials.gov record

“This is a global multi-center, long-term follow-up study to assess durability of efficacy, as measured by maintenance of treatment response from the parent study, in participants who participated in a previous bepirovirsen study and achieved a complete or partial response.” (opens the source at this quote in a new tab)

Official title in the ClinicalTrials.gov record

“A Prospective, Multi-Centre Study (B-Sure) to Evaluate Long-Term Durability of Treatment Response in Chronic Hepatitis B Participants With and Without Nucleos(t)Ide Therapy Who Have Participated in a Previous Bepirovirsen Treatment Study” (opens the source at this quote in a new tab)

Aim stated on the first annual report poster

“B-Sure (NCT04954859) was initiated to generate long-term data on the durability of response in participants with a complete or partial response after bepirovirsen treatment and included an option for NA cessation for On-NA participants.” (opens the source at this quote in a new tab)

Durability follow-up described in the B-Clear publications

“Durability of response is being investigated in the B-Sure trial (ClinicalTrials.gov number, NCT04954859), which will follow participants for an additional 33 months and includes criteria for stopping NA therapy.” (opens the source at this quote in a new tab)

Durability follow-up described in the company release of B-Clear results

“Longer term durability of response will be investigated in the B-Sure trial which will follow participants for an additional 33 months and includes criteria for stopping NA therapy with the possibility to demonstrate functional cure in patients who successfully stop all medication and continue to demonstrate no serologic evidence of HBsAg or HBV DNA.” (opens the source at this quote in a new tab)

Study dates and status in the ClinicalTrials.gov record

Field	Registry value
Study start (actual)	“2021-12-14”
Primary completion (estimated)	“2029-01-24”
Study completion (estimated)	“2029-01-24”
First posted	“2021-07-08”
Last update posted	“2026-06-24”
Status	“Active, not recruiting”
Other study IDs	“206882”
EU CT number	“2023-506867-33”

Number of locations in the ClinicalTrials.gov record

“This study has 163 locations” (opens the source at this quote in a new tab)

Congress presentations of interim data

“Presented at the European Association for the Study of the Liver (EASL) Congress, Vienna, Austria, 21–24 June 2023” (opens the source at this quote in a new tab)

“EASL 2025 | 7–10 May 2025 | Amsterdam, The Netherlands” (opens the source at this quote in a new tab)

Design details in the ClinicalTrials.gov record

Field	Registry value
Study type	“Interventional”
Phase	“Phase 2”
Primary purpose	“Treatment”
Allocation	“Non-Randomized”
Interventional model	“Parallel Assignment”
Masking	“None (Open Label)”

Parent studies and participant categories

“Eligible participants will be enrolled in this study after completing the end of study (EoS) visit in the respective parent bepirovirsen studies (studies B-Clear [209668: NCT04449029], B-Together [209348: NCT04676724], B-Fine [212602: NCT04544956], B-Well 1 [202009: NCT05630807], B-Well 2 [219288: NCT05630820], and TH HBV ASO-001 [217023: NCT05276297]). Participants will be categorized as Not-on-NA, NA-cessated, or On-NA based on their nucleos(t)ide analogue (NA) status in the parent study. No further treatment with bepirovirsen will be administered in this study.” (opens the source at this quote in a new tab)

Follow-up duration by arm

“Participants will be followed up for 33 months. Participants maintaining either functional cure (FC) or a partial response off NA treatment at Month 33 will be eligible to be followed up for an additional 2 years.” (opens the source at this quote in a new tab)
“NA cessation will occur at 3 months in 206882 for eligible and willing participants.” (opens the source at this quote in a new tab)

Response categories and follow-up schedule: B-Clear responders

“The B-Sure study recruited B-Clear study responders (CR or PR at the end of the B-Clear study) for long-term follow-up” (opens the source at this quote in a new tab)
“CR was defined as HBsAg and HBV DNA <LLOQ” (opens the source at this quote in a new tab)
“PR was defined as HBsAg <100 IU/mL and HBV DNA <LLOQ” (opens the source at this quote in a new tab)
“Following entry into B-Sure, Not-on-NA participants were followed up at Months 3, 9, 15, 21, 27 and 33 (Figure 1). This is the third data review, with a cut-off date of 9 September 2024” (opens the source at this quote in a new tab)

Follow-up schedule after nucleos(t)ide analogue cessation: B-Clear On-NA responders

“On-NA participants, if eligible, discontinued NAs 3 months after entry into B-Sure and were followed every 2 weeks in the first month after NA cessation, then every month in the next 3 months, and every 3 months up to Month 15. Subsequently, they were monitored every 6 months up to Month 33” (opens the source at this quote in a new tab)

Durability assessment in the first annual report

“The durability of the response was assessed as follows: Not-on-NA: Time from achieving complete response to loss of response; On-NA: Time from NA cessation to loss of complete response.” (opens the source at this quote in a new tab)
“Adverse events (AEs) were recorded at each visit to assess safety.” (opens the source at this quote in a new tab)

General inclusion and exclusion criteria in the ClinicalTrials.gov record

“Participants who enter the study on stable NA are willing and able to cease their NA treatment in accordance with the NA cessation schedule.” (opens the source at this quote in a new tab)
“Participants who have/or are currently participating in another non-GSK interventional clinical study exploring HBV treatment since completing their treatment with bepirovirsen.” (opens the source at this quote in a new tab)

Inclusion criteria for participants rolling over from B-Clear, B-Together, and B-Fine

“Participants who have previously received at least one dose of bepirovirsen AND” (opens the source at this quote in a new tab)
“Achieved the PSPO in the parent study and who maintained a response until the End of Study (EoS) visit in their parent study (defined as complete responders to bepirovirsen from the parent study) OR” (opens the source at this quote in a new tab)
“Demonstrated hepatitis B virus surface antigen (HBsAg) reduction greater than or equal to (≥) 1.0 log10 international units per milliliter (IU/mL) from parent study Baseline with HBsAg levels less than (<) 100 IU/mL and HBV deoxyribonucleic acid (DNA) < lower limit of quantification (LLOQ) for 24 weeks after the actual end of treatment regimen, in the absence of rescue medication and maintained until their EoS visit in the parent study.” (opens the source at this quote in a new tab)

Inclusion criteria for participants rolling over from B-Well 1 and B-Well 2

“NA cessated at Week 48 in parent study and achieved at least HBsAg <1 IU/ml and HBV DNA <LLOQ at the EOS visit (Week 96) in the parent study OR” (opens the source at this quote in a new tab)
“Achieved NA cessation criteria at Week 48 in parent study but have not stopped NA treatment, and are maintaining at least HBsAg <1 IU/ml and HBV DNA <LLOQ at EOS visit (Week 72) of parent study OR” (opens the source at this quote in a new tab)
“Did not achieve NA cessation criteria in parent study but achieved at least HBsAg <1 IU/ml and HBV DNA <LLOQ at EOS visit (Week 72) of parent study.” (opens the source at this quote in a new tab)

Criteria for nucleos(t)ide analogue discontinuation and restart: B-Clear On-NA responders

“Participants could discontinue NA if they meet all of the following criteria: a) If a CR: achieve the B-Clear primary outcome and maintain a CR without reversion (HBsAg ≥LLOQ or HBV DNA ≥LLOQ confirmed by 2 consecutive visits at 1 week [±3 days] apart) in the absence of rescue medication up to 3 months into B-Sure (excluding blips)” (opens the source at this quote in a new tab)
“b) have stable NA treatment for 3 months into B-Sure; c) have ALT <1.25xULN at 2.5 months into B-Sure.” (opens the source at this quote in a new tab)
“Participants could resume NA treatment if they meet any of the following criteria: a) HBV DNA >20000 IU/mL; b) HBV DNA >2000 IU/mL after 2 sequential lab results confirmed within 1 week (±3 days) from the date of first result (with or without ALT elevation)” (opens the source at this quote in a new tab)

Age, sex, and healthy volunteers in the ClinicalTrials.gov record

Field	Registry value
Ages eligible for study	“18 Years and older (Adult, Older Adult )”
Sexes eligible for study	“All”
Accepts healthy volunteers	“No”

No study treatment administered

“No study treatment will be administered in this study.” (opens the source at this quote in a new tab)
“No study drug will be administered in this study. Eligible participants who received prior treatment with bepirovirsen in the parent studies will be included.” (opens the source at this quote in a new tab)
“No study drug will be administered in this study. Eligible participants who received prior treatment with placebo in the parent studies (209668, 202009, and 219288) will be included to maintain the blind in the still ongoing parent studies.” (opens the source at this quote in a new tab)

Nucleos(t)ide analogue cessation 3 months after entry

“On-NA participants, if eligible, will cease NA 3 months after entry into B-Sure and be followed more intensively.” (opens the source at this quote in a new tab)

Primary outcome measures in the ClinicalTrials.gov record

Primary outcome measure	Time frame
“Percentage of Not-on-NA participants without loss of parent study primary outcome (PSPO)”	“From primary endpoint assessment in the parent study up to Month 57”
“Percentage of On-NA participants rolling over from studies 209668 and 209348 without loss of functional cure (FC) after NA-cessation in study 206882”	“From Month 3 up to Month 57”
“Percentage of On-NA participants rolling over from study 217023 without loss of FC after NA-cessation in study 206882”	“From Month 3 up to Month 33”
“Percentage of NA-cessated participants rolling over from studies 202009 and 219288 without loss of FC after NA-cessation in the parent study”	“From primary endpoint assessment in the parent study up to Month 33”

Functional cure as the optimal endpoint

“is regarded as the optimal treatment endpoint for chronic HBV infection, but is rarely achieved with current standard-of-care NA therapies” (opens the source at this quote in a new tab)
“Functional cure, defined as sustained HBsAg loss and HBV DNA <LLOQ for 24 weeks off all treatment” (opens the source at this quote in a new tab)

Time off treatment required before a response counts as functional cure: Not-on-NA participants

“Participants maintaining a CR at Month 3 (i.e. at least 9 months off bepirovirsen, allowing for a 3-month washout period” (opens the source at this quote in a new tab)

Time off treatment required before a response counts as functional cure: On-NA participants

“Participants maintaining a CR at Month 9 (i.e. 6 months post NA cessation and 15–18 months off bepirovirsen) achieved functional cure” (opens the source at this quote in a new tab)

Functional cure rarely achieved with nucleos(t)ide analogues: first annual report

“Functional cure, defined as the loss of hepatitis B surface antigen (HBsAg) and hepatitis B virus (HBV) DNA after treatment cessation,1,2 is rarely (<5%) achieved with current standard of care nucleos(t)ide analogue (NA) therapies.” (opens the source at this quote in a new tab)
“Red box: equivalent to functional cure, all Not-on-NA patients have at least 36 weeks off all treatment (allowing for bepirovirsen wash out), all On-NA participants have at least 24 weeks off NA therapy.” (opens the source at this quote in a new tab)

Secondary outcome measures: relapse, retreatment, and delayed functional cure

“Percentage of On-NA and NA-cessated participants with PSPO in the parent study who have virologic relapse or use of any rescue medication after NA cessation (in either parent study or study 206682)” (opens the source at this quote in a new tab)
“Percentage of On-NA and NA-cessated participants with PSPO in the parent study who receive NA retreatment after NA cessation (in either parent study or study 206682)” (opens the source at this quote in a new tab)
“Percentage of Not-on-NA participants with a partial response in the parent study and a delayed FC in study 206882 in absence of rescue medication after end of treatment in the parent study” (opens the source at this quote in a new tab)
“Percentage of participants with mutations” (opens the source at this quote in a new tab)

Planned enrollment in the ClinicalTrials.gov record

“Enrollment (Estimated)” (opens the source at this quote in a new tab)
“360” (opens the source at this quote in a new tab)

B-Clear complete responders enrolled: first annual report

“From B-Clear, 13/16 On-NA and 12/16 Not-on-NA complete responders enrolled into B-Sure.” (opens the source at this quote in a new tab)
“In the Phase 2b, randomised, B-Clear study (NCT04449029), 32 participants on and not on NA therapy (On-NA and Not-on-NA) achieved a complete response (modified primary endpoint: HBsAg <0.05 IU/mL and HBV DNA level <20 IU/mL [<lower limit of quantification; LLOQ]) maintained for 24 weeks after planned end of bepirovirsen treatment, in the absence of newly initiated antiviral treatment [rescue medication]).” (opens the source at this quote in a new tab)

B-Clear Not-on-NA responders enrolled: third report

“From the B-Clear Not-on-NA participants, 11 CRs and 5 PRs enrolled into B-Sure (Table 1).” (opens the source at this quote in a new tab)

B-Clear On-NA responders enrolled: third report

“From the B-Clear On-NA participants, 14 CRs and 26 PRs enrolled into B-Sure” (opens the source at this quote in a new tab)

Complete responders by the modified primary outcome: first annual report

“This analysis presents the first annual report from the B-Sure study in B-Clear complete responders (according to the modified primary outcome).” (opens the source at this quote in a new tab)
“Two participants each in the On-NA and Not-on-NA populations missed the primary endpoint but were included using the modified primary endpoint due to a HBsAg ‘blip’ during B-Clear.” (opens the source at this quote in a new tab)

Participants enrolled in error and excluded from the flow analysis: Not-on-NA

“One non-responder from B-Clear was enrolled into B-Sure; this participant did not meet eligibility criteria but was enrolled in error” (opens the source at this quote in a new tab)
“One non-responder from B-Clear was enrolled into B-Sure in error and was excluded from the flow diagram” (opens the source at this quote in a new tab)

Participants enrolled in error and reclassification after blips: On-NA

“Four non-responders from B-Clear were enrolled into B-Sure; these participants did not meet eligibility criteria but were enrolled in error” (opens the source at this quote in a new tab)
“Further consideration of how to handle blips has led to the re-classification of individual participants at the end of the parent study, and therefore the data presented here are different than that previously shared within the abstract” (opens the source at this quote in a new tab)

Disposition of B-Clear On-NA complete responders: first annual report

“69% (9/13) participants ceased NA as per protocol.” (opens the source at this quote in a new tab)
“8% (1/13) withdrew prior to NA cessation due to commitments” (opens the source at this quote in a new tab)
“23% (3/13) were not eligible to cease NA (2 did not meet protocol defined criteria for cessation due to detectable HBsAg and 1 due to investigator discretion despite HBsAg <0.05 IU/mL)” (opens the source at this quote in a new tab)
“Mean duration between B-Clear end-of-study and entry into B-Sure: 102 days (range 94–113).” (opens the source at this quote in a new tab)

Time from B-Clear end of study to B-Sure entry: Not-on-NA, first annual report

“Mean duration between B-Clear end-of-study and entry into B-Sure: 84 days (range 0–105).” (opens the source at this quote in a new tab)

Disposition of B-Clear Not-on-NA responders: third report

“As of the data cut-off date, these participants were continuing the trial” (opens the source at this quote in a new tab)
“Two PR participants started NA treatment after B-Sure enrolment” (opens the source at this quote in a new tab)

Disposition of B-Clear On-NA responders: third report

“As of the data cut-off date, 38/40 (95%) participants were continuing the trial” (opens the source at this quote in a new tab)
“Of the 14 CRs, 10 (71%) discontinued NAs 3 months into B-Sure” (opens the source at this quote in a new tab)
“Of the 26 PRs, 22 (85%) discontinued NAs 3 months after rollover into B-Sure” (opens the source at this quote in a new tab)
“Due to safety, HBsAg reversion, and/or investigator error” (opens the source at this quote in a new tab)
“Due to safety of participant and/or investigator discretion based on lab results” (opens the source at this quote in a new tab)

B-Clear complete responders enrolled in B-Sure: first annual report

Characteristic at B-Clear baseline	On-NA (N=13)	Not-on-NA (N=12)
Male, n (%)	“12 (92)”	“7 (58)”
Age, mean (SD) years	“53.20 (10.01)”	“43.80 (9.96)”
B-Clear arm 1, n (%)	“7 (54)”	“7 (58)”
B-Clear arm 2, n (%)	“5 (38)”	“4 (33)”
B-Clear arm 3, n (%)	“1 (8)”	“1 (8)”
HBeAg negative, n (%)	“10 (77)”	“12 (100)”
HBeAg positive, n (%)	“3 (23)”	“0”
HBsAg 1000 IU/mL or less, n (%)	“9 (69)”	“7 (58)”
HBsAg more than 1000 to 3000 IU/mL, n (%)	“3 (23)”	“3 (25)”
HBsAg more than 3000 IU/mL, n (%)	“1 (8)”	“2 (17)”

B-Clear Not-on-NA participants enrolled in B-Sure: third report

Characteristic at B-Clear baseline	All participants (N=17)
Age, mean (SD) years	“44.1 (10.4)”
B-Clear arm 1, n (%)	“9 (53)”
B-Clear arm 2, n (%)	“6 (35)”
B-Clear arm 3, n (%)	“2 (12)”
B-Clear arm 4, n (%)	“0 (0)”
HBeAg negative, n (%)	“17 (100)”
HBsAg 1000 IU/mL or less, n (%)	“9 (53)”
HBsAg more than 1000 to 3000 IU/mL, n (%)	“4 (24)”
HBsAg more than 3000 IU/mL, n (%)	“4 (24)”
HBV DNA 4 log10 IU/mL or less, n (%)	“7 (41)”
HBV DNA more than 4 to 6 log10 IU/mL, n (%)	“9 (53)”
HBV DNA more than 6 log10 IU/mL, n (%)	“1 (6)”

B-Clear On-NA participants enrolled in B-Sure: third report

Characteristic at B-Clear baseline	All participants (N=44)
Age, mean (SD) years	“53.8 (11.4)”
B-Clear arm 1, n (%)	“21 (48)”
B-Clear arm 2, n (%)	“15 (34)”
B-Clear arm 3 or arm 4, n (%) each	“4 (9)”
Probable duration of chronic HBV infection less than 10 years, n (%)	“11 (25)”
Probable duration 10 to less than 20 years, n (%)	“14 (32)”
Probable duration 20 years or more, n (%)	“19 (43)”
HBeAg negative, n (%)	“34 (77)”
HBeAg positive, n (%)	“10 (23)”
HBsAg more than 100 to 1000 IU/mL, n (%)	“32 (73)”
HBsAg more than 1000 to 3000 IU/mL, n (%)	“10 (23)”
HBsAg more than 3000 IU/mL, n (%)	“2 (5)”

Durability in B-Clear Not-on-NA responders: third report

“Of the 11 CR participants, 8 (73%) maintained a CR at Month 3, thus achieving functional cure (Figure 2). All 8 participants maintained functional cure at 21 months of B-Sure” (opens the source at this quote in a new tab)
“All 6 participants with Month 27 data (i.e. 33–36 months off-bepirovirsen) had maintained functional cure at this timepoint” (opens the source at this quote in a new tab)
“For PR participants, 1/5 maintained a PR at 3 months; this response was maintained to Month 27 of B-Sure (Figure 2)” (opens the source at this quote in a new tab)
“One participant subsequently had seroclearance by Month 15 (Figure 3)” (opens the source at this quote in a new tab)
“Only 6 of the 8 CRs had reached the 27-month follow-up timepoint at the data cut” (opens the source at this quote in a new tab)

Durability in B-Clear On-NA responders after nucleos(t)ide analogue cessation: third report

“Of the 14 CRs, 10 (71%) discontinued NAs 3 months into B-Sure; of these, 8 (80%) achieved functional cure 6 months post NA cessation and all 8 maintained functional cure up to 18 months” (opens the source at this quote in a new tab)
“Of the 2 participants who did not achieve functional cure at 6 months post NA cessation, 1 had restarted NA therapy by 24 months post NA cessation” (opens the source at this quote in a new tab)
“Of the 26 PRs, 22 (85%) discontinued NAs 3 months after rollover into B-Sure; of these, 2 (9%) achieved functional cure and were maintaining functional cure for up to 18 months. Five out of 22 (23%) maintained PR status at 6 months post NA cessation; of these, 2 maintained to 24 months post NA cessation; the 3 losses of PR were due to HBV DNA reversion” (opens the source at this quote in a new tab)
“Among 22 PRs who discontinued NAs, 13 had restarted NA therapy by 24 months post NA cessation” (opens the source at this quote in a new tab)

Durability in B-Clear complete responders: first annual report

“Of the 9 participants with ≥3 months of follow-up within B-Sure, 78% (7/9) maintained response (Figure 2). No participant met NA restart criteria.” (opens the source at this quote in a new tab)
“Of the 3 participants with ≥9 months of follow-up within B-Sure, 100% (3/3) maintained response (≥15–18 months after end of bepirovirsen).” (opens the source at this quote in a new tab)
“Of the 7 participants who ceased NA and had ≥6 months of follow-up within B-Sure, 86% (6/7) maintained response 3 months post NA cessation (Figure 3).” (opens the source at this quote in a new tab)
“Of the 4 participants who ceased NA and had ≥9 months of follow-up within B-Sure, 100% (4/4) maintained response 6 months post NA cessation; no participants restarted NAs.” (opens the source at this quote in a new tab)
“In this global, long-term, follow-up study, 7 participants (n=4 On-NA and n=3 Not-on-NA) demonstrated HBsAg and HBV DNA loss 15–18 months post bepirovirsen cessation.” (opens the source at this quote in a new tab)

Sub-analysis of B-Together responders announced for AASLD 2025 (no figures released)

“Phase II B-Sure study sub-analysis shows durability of functional cure in chronic hepatitis B (CHB) patients treated with bepirovirsen and pegylated interferon (Peg-IFN)” (opens the source at this quote in a new tab)
“Data will be presented from a sub-analysis from the B-Sure phase II study, evaluating the achievement and duration of a functional cure in CHB patients who responded to treatment with bepirovirsen followed by Peg-IFN, a type of immune-boosting therapy.” (opens the source at this quote in a new tab)

Adverse events in B-Clear complete responders: first annual report

n (%)	On-NA (N=13)	Not-on-NA (N=12)
Any adverse events	“6 (46)”	“2 (17)”
Mild	“5 (38)”	“0”
Moderate	“1 (8)”	“2 (17)”
Adverse events related to previous treatment in B-Clear	“0”	“0”
Any serious adverse events	“0”	“0”

No latent adverse drug effect: first annual report

“There were no safety signals that suggested a latent adverse drug effect following use of bepirovirsen (Table 2).” (opens the source at this quote in a new tab)

ALT increases after nucleos(t)ide analogue cessation: B-Clear On-NA responders, third report

“After stopping bepirovirsen, there were no safety signals that suggested a latent adverse drug effect following use of bepirovirsen” (opens the source at this quote in a new tab)
“AEs of increased ALT were reported in 1 (2%) participant pre-NA cessation (mild severity) and 3 (7%) participants post NA cessation (2 mild, 1 moderate severity)” (opens the source at this quote in a new tab)
“Of the 34 participants who discontinued NAs, 5 had ALT ≥2 × ULN” (opens the source at this quote in a new tab)
“One participant who restarted NA therapy had ALT >5 × ULN; no other participants had ALT >5 × ULN” (opens the source at this quote in a new tab)

Safety in B-Clear Not-on-NA responders: third report

“After stopping bepirovirsen, there were no safety signals that suggested a latent adverse drug effect following treatment with bepirovirsen” (opens the source at this quote in a new tab)

Summary: study limitations

B-Sure is open-label and non-randomized and enrolls only participants who responded in a parent study, so it has no comparator group and its durability estimates describe responders. As of October 2026, the B-Sure results available for B-Clear participants are congress posters with small denominators: 13 On-NA and 12 Not-on-NA complete responders in the first annual report, and 44 On-NA and 17 Not-on-NA enrolled participants in the third report. The first report's authors stated that the data should be interpreted with caution owing to low participant numbers. In the third report, participants were reclassified after reconsideration of how to handle blips, 1 Not-on-NA and 4 On-NA non-responders were enrolled in error, and only 6 of the 8 Not-on-NA participants with functional cure had reached Month 27 at the 9 September 2024 data cut-off. The ClinicalTrials.gov record has no posted results, and its estimated primary completion date is 24 January 2029.

Small numbers stated by the authors of the first annual report

“These data provide early evidence on the durability of response observed with bepirovirsen, although they should be interpreted with caution due to low participant numbers. The B-Sure study will continue to evaluate the durability of bepirovirsen response up to 33 months and data will be published when available.” (opens the source at this quote in a new tab)

Benefit in partial responders not yet established

“Clinical benefits (i.e. reduced HBsAg and HBV DNA) were particularly evident in participants who achieved a CR in the parent study. The potential benefits in participants with a PR are being further analysed” (opens the source at this quote in a new tab)

Open-label, non-randomized design in the ClinicalTrials.gov record

Field	Registry value
Allocation	“Non-Randomized”
Masking	“None (Open Label)”
Results	“No Results Posted”