Clinical trial NCT04954859: Long-term Follow-up Study to Evaluate Durability of Treatment Response in Previous Bepirovirsen Study Participants (B-Sure)
Official title: 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
Study type: INTERVENTIONAL
Overall status: RECRUITING
Phase: PHASE2
Conditions: Hepatitis B
Keywords: Bepirovirsen
B-Sure
Nucleos(t)ide
Durability
HBsAg
Functional cure
Lead sponsor: GlaxoSmithKline
Sponsor class: INDUSTRY
First posted: 2021-07-08
Enrollment: 450
Sex: ALL
Minimum age (years): 18
Standard ages: ADULT
OLDER_ADULT
Accepts healthy volunteers: no
Allocation: NON_RANDOMIZED
Intervention model: PARALLEL
Primary purpose: TREATMENT

Brief summary: 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.


Eligibility criteria: 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.

Primary outcomes:
measure: Percentage of Not-on-NA participants without loss of parent study primary outcome (PSPO)
timeFrame: From primary endpoint assessment in the parent study up to Month 57
measure: Percentage of On-NA participants rolling over from studies 209668 and 209348 without loss of functional cure (FC) after NA-cessation in study 206882
timeFrame: From Month 3 up to Month 57
measure: Percentage of On-NA participants rolling over from study 217023 without loss of FC after NA-cessation in study 206882
timeFrame: From Month 3 up to Month 33
measure: Percentage of NA-cessated participants rolling over from studies 202009 and 219288 without loss of FC after NA-cessation in the parent study
timeFrame: From primary endpoint assessment in the parent study up to Month 33
Secondary outcomes:
measure: 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)
timeFrame: Up to Month 57
measure: 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)
timeFrame: Up to Month 57
measure: 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)
timeFrame: Up to Month 57
measure: 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)
timeFrame: Up to Month 57
measure: 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
timeFrame: From primary endpoint assessment in the parent study up to Month 33
measure: 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
timeFrame: Up to Month 57
measure: 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
timeFrame: From date of achieving delayed FC up to Month 57
measure: 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
timeFrame: Up to Month 57
measure: 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
timeFrame: From date of achieving delayed FC up to Month 57
measure: 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
timeFrame: Up to Month 33
measure: 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
timeFrame: From date of achieving delayed treatment response up to Month 33
measure: 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
timeFrame: From Month 3 to Month 57
measure: 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
timeFrame: From Month 3 up to Month 57
measure: 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
timeFrame: From Month 3 up to Month 57
measure: 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
timeFrame: From Month 3 up to Month 57
measure: Percentage of participants with anti-HBs (antibody to HBsAg)
timeFrame: Up to 57 months
measure: Percentage of participants with anti-HBe (antibody to hepatitis B e-antigen [HBeAg])
timeFrame: Up to 57 months
measure: Absolute values for HBsAg, hepatitis B virus (HBV) deoxyribonucleic acid (DNA), HBeAg (logarithm to the base 10 [log10] international units per milliliter [IU/mL])
timeFrame: Up to 57 months
measure: Change from Baseline for HBsAg, HBV DNA, HBeAg (log10 IU/mL)
timeFrame: Baseline (End of Study visit in the parent study) and up to 57 months
measure: Absolute values for hepatitis B core-related antigen (HBcrAg) (kiloUnits per milliliter [kU/mL])
timeFrame: Up to 57 months
measure: Change from Baseline for HBcrAg (kU/mL)
timeFrame: Baseline (End of Study visit in the parent study) and up to 57 months
measure: Absolute values for HBV ribonucleic acid (RNA) (log10 IU/ml)
timeFrame: Up to 57 months
measure: Change from Baseline for HBV RNA (log10 IU/ml)
timeFrame: Baseline (End of Study visit in the parent study) and up to 57 months
measure: Percentage of participants with mutations
timeFrame: Up to 57 months
Other outcomes:
Locations:
city: Sacramento
country: United States
facility: GSK Investigational Site
state: California
city: Boston
country: United States
facility: GSK Investigational Site
state: Massachusetts
city: Detroit
country: United States
facility: GSK Investigational Site
state: Michigan
city: Buenos Aires
country: Argentina
facility: GSK Investigational Site
city: Sliven
country: Bulgaria
facility: GSK Investigational Site
city: Sofia
country: Bulgaria
facility: GSK Investigational Site
city: Calgary
country: Canada
facility: GSK Investigational Site
state: Alberta
city: Victoria
country: Canada
facility: GSK Investigational Site
state: British Columbia
city: Toronto
country: Canada
facility: GSK Investigational Site
state: Ontario
city: Hangzhou
country: China
facility: GSK Investigational Site
city: Shanghai
country: China
facility: GSK Investigational Site
city: Wuhan
country: China
facility: GSK Investigational Site
city: Clichy Cedex
country: France
facility: GSK Investigational Site
city: Strasbourg
country: France
facility: GSK Investigational Site
city: Pokfulam
country: Hong Kong
facility: GSK Investigational Site
city: Milano
country: Italy
facility: GSK Investigational Site
city: Milano
country: Italy
facility: GSK Investigational Site
city: Modena
country: Italy
facility: GSK Investigational Site
city: Hiroshima
country: Japan
facility: GSK Investigational Site
city: Hiroshima
country: Japan
facility: GSK Investigational Site
city: Ishikawa
country: Japan
facility: GSK Investigational Site
city: Kagawa
country: Japan
facility: GSK Investigational Site
city: Kumamoto
country: Japan
facility: GSK Investigational Site
city: Miyagi
country: Japan
facility: GSK Investigational Site
city: Osaka
country: Japan
facility: GSK Investigational Site
city: Tokyo
country: Japan
facility: GSK Investigational Site
city: Tokyo
country: Japan
facility: GSK Investigational Site
city: Ansan-si Gyenggi-do
country: Korea, Republic of
facility: GSK Investigational Site
city: Busan
country: Korea, Republic of
facility: GSK Investigational Site
city: Pusan
country: Korea, Republic of
facility: GSK Investigational Site
city: Seoul
country: Korea, Republic of
facility: GSK Investigational Site
city: Lublin
country: Poland
facility: GSK Investigational Site
city: Craiova Dolj
country: Romania
facility: GSK Investigational Site
city: Galati
country: Romania
facility: GSK Investigational Site
city: Chelyabinsk
country: Russian Federation
facility: GSK Investigational Site
city: Krasnojarsk
country: Russian Federation
facility: GSK Investigational Site
city: Moscow
country: Russian Federation
facility: GSK Investigational Site
city: Novosibirsk
country: Russian Federation
facility: GSK Investigational Site
city: Saint-Petersburg
country: Russian Federation
facility: GSK Investigational Site
city: Samara
country: Russian Federation
facility: GSK Investigational Site
city: St Petersburg
country: Russian Federation
facility: GSK Investigational Site
city: Singapore
country: Singapore
facility: GSK Investigational Site
city: Singapore
country: Singapore
facility: GSK Investigational Site
city: Durban
country: South Africa
facility: GSK Investigational Site
city: Johannesburg
country: South Africa
facility: GSK Investigational Site
city: Madrid
country: Spain
facility: GSK Investigational Site
city: Santander
country: Spain
facility: GSK Investigational Site
city: Bangkok
country: Thailand
facility: GSK Investigational Site
city: Kho Hong Hat Yai
country: Thailand
facility: GSK Investigational Site
city: London
country: United Kingdom
facility: GSK Investigational Site
city: Plymouth
country: United Kingdom
facility: GSK Investigational Site
Study officials:
affiliation: GlaxoSmithKline
name: GSK Clinical Trials
role: STUDY_DIRECTOR
References: