Long-term Follow-up Study to Evaluate Durability of Treatment Response in Previous Bepirovirsen Study Participants (B-Sure)

Phase 2RecruitingNCT04954859

GlaxoSmithKline450 enrolled

Overview

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. 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.

Study Type

INTERVENTIONAL

Allocation

NON_RANDOMIZED

Purpose

TREATMENT

Masking

NONE

Enrollment

450

Conditions

Hepatitis B

Interventions

Eligibility

Sex: ALLMin age: 18 Years

Medical Language ↔ Plain English

Inclusion criteria: * Participants who enter the study on stable NA are willing and able to cease their NA treatment in accordance with the NA cessation schedule. * Capable of giving informed consent. For participants rolling over from 209668 (B-Clear), 209348 (B-Together), and 212602 (B-Fine): * Participants who have previously received at least one dose of bepirovirsen AND 1. 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 2. 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. For participants rolling over from 202009 (B-Well1) and 219288 (B-Well 2): * Participants who have previously received at least 1 dose of bepirovirsen (or matching placebo where appropriate) AND 1. 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 2. 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 3. 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. For participants rolling over from 217023 (TH HBV ASO-001): * Participants who have previously received at least 1 dose of bepirovirsen AND 1. Achieved HBsAg \<1 IU/ml and HBV DNA \<LLOQ in parent study at Week 66 (ASO12 arm) or Week 78 (ASO 24 arm) and are maintaining HBsAg \< 1 IU/ml and HBV DNA \<LLOQ, at the EOS study visit \[Week 133 ASO12 arm), or Week 145 (ASO24 arm)\] in parent study OR 2. Did not achieve HBsAg \<1 IU/ml and HBV DNA \<LLOQ in parent study at Week 66 (ASO12 arm) or Week 78 (ASO24 arm) but have achieved HBsAg \< 1 IU/ml and HBV DNA \< LLOQ by the EOS visit (Week 133 (ASO12 arm) or Week 145 (ASO24 arm)) in the parent study. Exclusion Criteria: * Participants who have/or are currently participating in another non-GSK interventional clinical study exploring HBV treatment since completing their treatment with bepirovirsen. * Any condition which, in the opinion of the investigator or Medical Monitor, contraindicates their participation in this study.

Locations (51)

GSK Investigational Site

Sacramento, California, United States

RECRUITING

GSK Investigational Site

Boston, Massachusetts, United States

RECRUITING

GSK Investigational Site

Detroit, Michigan, United States

RECRUITING

GSK Investigational Site

Buenos Aires, Argentina

Outcomes

Primary Outcomes

Percentage of Not-on-NA participants without loss of parent study primary outcome (PSPO)

NA indicates nucleos(t)ide analogue (NA).

Time frame: 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

Time frame: 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

Time frame: 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

Time frame: From primary endpoint assessment in the parent study up to Month 33

Secondary Outcomes

Percentage of On-NA and NA-cessated participants with PSPO in the parent study who have hepatitis B surface antigen (HBsAg) reversion or use of any rescue medication after NA cessation (in either parent study or study 206682)

Time frame: Up to Month 57

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)

Time frame: Up to Month 57

Percentage of On-NA and NA-cessated participants with PSPO in the parent study who have clinical relapse or use of any rescue medication after NA cessation (in either parent study or study 206682)

Time frame: Up to Month 57

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)

Time frame: Up to Month 57

Percentage of On-NA participants with PSPO in the parent study, who continue NA treatment in study 206882, and have no loss of treatment response

Time frame: From primary endpoint assessment in the parent study up to Month 33

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

Time frame: Up to Month 57

Time to loss of FC from time of achieving delayed FC in Not-on-NA participants with a partial response in the parent study and a delayed FC in study 206882

Time frame: From date of achieving delayed FC up to Month 57

Percentage of On-NA participants with a partial response in the parent study, who discontinue NA treatment in study 206882, and have a delayed FC in 206882 in absence of rescue medication after end of treatment in the parent study

Time frame: Up to Month 57

Time to loss of FC in On-NA participants who achieve a partial response in the parent study, discontinue NA treatment in study 206882 and achieve delayed FC in 206882

Time frame: From date of achieving delayed FC up to Month 57

Percentage of On-NA participants with a partial response in the parent study, who do not discontinue NA treatment in study 206882, and have a delayed treatment response in 206882 in absence of rescue medication after end of treatment in the parent study

Time frame: Up to Month 33

Time to loss of treatment response in On-NA participants who achieve a partial response in the parent study, do not discontinue NA treatment in study 206882 and have a delayed treatment response in 206882

Time frame: From date of achieving delayed treatment response up to Month 33

Percentage of On-NA participants with a partial response in the parent study, who discontinue NA treatment in study 206882, and have HBsAg loss in the absence of any rescue medication after NA cessation in 206882

Time frame: From Month 3 to Month 57

Percentage of On-NA participants with a partial response in the parent study, who discontinue NA treatment in study 206882, and have virologic relapse or use of any rescue medication after NA cessation in 206882

Time frame: From Month 3 up to Month 57

Percentage of On-NA participants with a partial response in the parent study, who discontinue NA treatment in study 206882, and have clinical relapse or use of any rescue medication after NA cessation in 206882

Time frame: From Month 3 up to Month 57

Percentage of On-NA participants with a partial response in the parent study, who discontinue NA treatment in study 206882 and have use of any rescue medication after NA cessation in 206882

Time frame: From Month 3 up to Month 57

Percentage of participants with anti-HBs (antibody to HBsAg)

Time frame: Up to 57 months

Percentage of participants with anti-HBe (antibody to hepatitis B e-antigen [HBeAg])

Time frame: Up to 57 months

Absolute values for HBsAg, hepatitis B virus (HBV) deoxyribonucleic acid (DNA), HBeAg (logarithm to the base 10 [log10] international units per milliliter [IU/mL])

Time frame: Up to 57 months

Change from Baseline for HBsAg, HBV DNA, HBeAg (log10 IU/mL)

Time frame: Baseline (End of Study visit in the parent study) and up to 57 months

Absolute values for hepatitis B core-related antigen (HBcrAg) (kiloUnits per milliliter [kU/mL])

Time frame: Up to 57 months

Change from Baseline for HBcrAg (kU/mL)

Time frame: Baseline (End of Study visit in the parent study) and up to 57 months

Absolute values for HBV ribonucleic acid (RNA) (log10 IU/ml)

Time frame: Up to 57 months

Change from Baseline for HBV RNA (log10 IU/ml)

Time frame: Baseline (End of Study visit in the parent study) and up to 57 months

Percentage of participants with mutations

Time frame: Up to 57 months

Central Contacts

US GSK Clinical Trials Call Center

CONTACT

877-379-3718 GSKClinicalSupportHD@gsk.com

EU GSK Clinical Trials Call Center

CONTACT

+44 (0) 20 89904466 GSKClinicalSupportHD@gsk.com