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
试验速览
- 阶段
- 2 期
- 状态
- 进行中（未招募）
- 入组人数
- 360
- 试验地点
- 164
- 主要终点
- Percentage of Not-on-NA participants without loss of parent study primary outcome (PSPO)
研究概览
简要总结
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.
研究设计
- 研究类型
- Interventional
- 分配方式
- Non Randomized
- 干预模型
- Parallel
- 主要目的
- Treatment
- 盲法
- None
入排标准
- 年龄范围
- 18 Years 至 —（Adult, Older Adult）
- 性别
- All
- 接受健康志愿者
- 否
入选标准
- •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
- •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
- •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
- •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
- •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
- •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
- •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
- •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.
排除标准
- •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.
研究组 & 干预措施
Not-on-NA participants
Participants rolling over from study 209668 who have not received nucleos(t)ide analogue (NA) therapy during the parent study and remain off NAs will be included in this 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. No study treatment will be administered in this study.
干预措施: Bepirovirsen (Drug)
On-NA participants
Participants rolling over from studies 209668, 209348, 212602, 202009, 219288, and 217023 who entered the parent study on stable NA therapy and remained on NA therapy for the duration of the treatment and follow-up periods in the parent study will be included in this arm. NA cessation will occur at 3 months in 206882 for eligible and willing participants. Participants will be followed up for 33 months. Participants rolling over from studies 209668 and 209348 who stopped NA treatment and are maintaining either FC or a partial response at Month 33, and remaining off NA treatment, will be eligible to be followed up for an additional 2 years. No study treatment will be administered in this study.
干预措施: Bepirovirsen (Drug)
NA-cessated participants
Participants rolling over from studies 202009 and 219288 who have stopped NA treatment during the parent study will be included in this arm. Participants will be followed up for 33 months. No study treatment will be administered in this study.
干预措施: Bepirovirsen (Drug)
NA-cessated participants
Participants rolling over from studies 202009 and 219288 who have stopped NA treatment during the parent study will be included in this arm. Participants will be followed up for 33 months. No study treatment will be administered in this study.
干预措施: Placebo (Drug)
Not-on-NA participants
Participants rolling over from study 209668 who have not received nucleos(t)ide analogue (NA) therapy during the parent study and remain off NAs will be included in this 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. No study treatment will be administered in this study.
干预措施: Placebo (Drug)
On-NA participants
Participants rolling over from studies 209668, 209348, 212602, 202009, 219288, and 217023 who entered the parent study on stable NA therapy and remained on NA therapy for the duration of the treatment and follow-up periods in the parent study will be included in this arm. NA cessation will occur at 3 months in 206882 for eligible and willing participants. Participants will be followed up for 33 months. Participants rolling over from studies 209668 and 209348 who stopped NA treatment and are maintaining either FC or a partial response at Month 33, and remaining off NA treatment, will be eligible to be followed up for an additional 2 years. No study treatment will be administered in this study.
干预措施: Placebo (Drug)
结局指标
主要结局
Percentage of Not-on-NA participants without loss of parent study primary outcome (PSPO)
时间窗: From primary endpoint assessment in the parent study up to Month 57
NA indicates nucleos(t)ide analogue (NA).
Percentage of On-NA participants rolling over from studies 209668 and 209348 without loss of functional cure (FC) after NA-cessation in study 206882
时间窗: 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
时间窗: 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
时间窗: From primary endpoint assessment in the parent study up to Month 33
次要结局
- 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)(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)(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)(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)(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(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(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(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(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(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(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(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(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(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(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(From Month 3 up to Month 57)
- Percentage of participants with anti-HBs (antibody to HBsAg)(Up to 57 months)
- Percentage of participants with anti-HBe (antibody to hepatitis B e-antigen [HBeAg])(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])(Up to 57 months)
- Change from Baseline for HBsAg, HBV DNA, HBeAg (log10 IU/mL)(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])(Up to 57 months)
- Change from Baseline for HBcrAg (kU/mL)(Baseline (End of Study visit in the parent study) and up to 57 months)
- Absolute values for HBV ribonucleic acid (RNA) (log10 IU/ml)(Up to 57 months)
- Change from Baseline for HBV RNA (log10 IU/ml)(Baseline (End of Study visit in the parent study) and up to 57 months)
- Percentage of participants with mutations(Up to 57 months)