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

GlaxoSmithKline (GSK)

Status and phase: Enrolling; Phase 2

Conditions: Hepatitis B

Treatments: Drug: Placebo; Drug: Bepirovirsen

Study type: Interventional

Funder types: Industry

Identifiers

NCT04954859

2023-506867-33 (Other Identifier)

206882

Details and patient eligibility

About

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.

Enrollment: 450 estimated patients

Sex: All

Ages: 18+ years old

Volunteers: No Healthy Volunteers

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.

Trial design

Primary purpose: Treatment

Allocation: Non-Randomized

Interventional model: Parallel Assignment

Masking: None (Open label)

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450 participants in 3 patient groups

Not-on-NA participants

Experimental group

Description:

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.

Treatment:

Drug: Bepirovirsen

Drug: Placebo

On-NA participants

Experimental group

Description:

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.

Treatment:

Drug: Bepirovirsen

Drug: Placebo

NA-cessated participants

Experimental group

Description:

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.

Treatment:

Drug: Bepirovirsen

Drug: Placebo