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Trial details imported from ClinicalTrials.gov

For full trial details, please see the original record at https://clinicaltrials.gov/study/NCT06537414




Registration number
NCT06537414
Ethics application status
Date submitted
1/08/2024
Date registered
5/08/2024

Titles & IDs
Public title
A Study of Sequential Therapy With Daplusiran/Tomligisiran (DAP/TOM) Followed by Bepirovirsen in Participants Living With Chronic Hepatitis B (CHB)
Scientific title
A Phase 2b, Multi-centre, Randomized, Partially Placebo-controlled, Double-blind Study to Investigate the Safety and Efficacy of Sequential Therapy With Daplusiran/Tomligisiran Followed by Bepirovirsen in Participants With Chronic Hepatitis B Virus on Background Nucleos(t)Ide Analogue Therapy (B-United)
Secondary ID [1] 0 0
218309
Universal Trial Number (UTN)
Trial acronym
B-UNITED
Linked study record

Health condition
Health condition(s) or problem(s) studied:
Chronic Hepatitis B Virus Infection 0 0
Hepatitis B 0 0
Condition category
Condition code
Infection 0 0 0 0
Other infectious diseases
Oral and Gastrointestinal 0 0 0 0
Other diseases of the mouth, teeth, oesophagus, digestive system including liver and colon

Intervention/exposure
Study type
Interventional
Description of intervention(s) / exposure
Treatment: Drugs - Daplusiran/Tomligisiran Dose Level 1
Treatment: Drugs - Daplusiran/Tomligisiran Dose Level 2
Treatment: Drugs - Bepirovirsen
Treatment: Drugs - Placebo

Experimental: Treatment Arm 1A: DAP/TOM + Bepirovirsen - Participants with high Hepatitis B surface antigen (HBsAg) level will receive dose level 1 of DAP/TOM in Treatment Stage 1. After DAP/TOM Treatment, eligible participants will receive bepirovirsen in Treatment Stage 2. All participants will continue background NA treatment throughout these treatment stages. After bepirovirsen Treatment Stage, participants will be observed during the NA Only Stage, while maintaining background NA treatment. Eligible participants will then discontinue background NA treatment.

Experimental: Treatment Arm 1B: DAP/TOM + Bepirovirsen - Participants with high HBsAg level will receive dose level 2 of DAP/TOM in Treatment Stage 1. After DAP/TOM treatment, eligible participants will receive bepirovirsen in Treatment Stage 2. All participants will continue background NA treatment throughout these treatment stages. After bepirovirsen Treatment Stage, participants will be observed during the NA Only Stage, while maintaining background NA treatment. Eligible participants will then discontinue background NA treatment.

Experimental: Treatment Arm 2A: DAP/TOM + Bepirovirsen - Participants with low HBsAg level will receive dose level 1 of DAP/TOM in Treatment Stage 1. After DAP/TOM treatment, eligible participants will receive bepirovirsen in Treatment Stage 2. All participants will continue background NA treatment throughout these treatment stages. After bepirovirsen Treatment Stage, participants will be observed during the NA Only Stage, while maintaining background NA treatment. Eligible participants will then discontinue background NA treatment.

Experimental: Treatment Arm 2B: DAP/TOM + Bepirovirsen - Participants with low HBsAg level will receive dose level 2 of DAP/TOM in Treatment Stage 1. After DAP/TOM treatment, eligible participants will receive bepirovirsen in Treatment Stage 2. All participants will continue background NA treatment throughout these treatment stages. After bepirovirsen Treatment Stage, participants will be observed during the NA Only Stage, while maintaining background NA treatment. Eligible participants will then discontinue background NA treatment.

Experimental: Treatment Arm 2C: Placebo + Bepirovirsen - Participants with low HBsAg level will receive Placebo in Treatment Stage 1. After Placebo treatment, eligible participants will receive bepirovirsen in Treatment Stage 2. All participants will continue background NA treatment throughout these treatment stages. After bepirovirsen Treatment Stage, participants will be observed during the NA Only Stage, while maintaining background NA treatment. Eligible participants will then discontinue background NA treatment.


Treatment: Drugs: Daplusiran/Tomligisiran Dose Level 1
Daplusiran/Tomligisiran dose level 1 will be administered

Treatment: Drugs: Daplusiran/Tomligisiran Dose Level 2
Daplusiran/Tomligisiran dose level 2 will be administered

Treatment: Drugs: Bepirovirsen
Bepirovirsen will be administered

Treatment: Drugs: Placebo
Placebo will be administered
Intervention code [1] 0 0
Treatment: Drugs
Comparator / control treatment
Control group

Outcomes
Primary outcome [1] 0 0
Number of participants achieving functional cure
Timepoint [1] 0 0
Up to 100 Weeks
Secondary outcome [1] 0 0
Number of participants achieving functional cure with high Baseline HBsAg level
Timepoint [1] 0 0
Up to 100 Weeks
Secondary outcome [2] 0 0
Number of participants achieving functional cure with low Baseline HBsAg level
Timepoint [2] 0 0
Up to 100 Weeks
Secondary outcome [3] 0 0
Number of participants achieving functional cure with low Baseline HBsAg level compared against placebo + bepirovirsen arm
Timepoint [3] 0 0
Up to 100 Weeks
Secondary outcome [4] 0 0
Number of participants with undetected HBsAg and HBV DNA <LLOQ
Timepoint [4] 0 0
Up to 48 Weeks

Eligibility
Key inclusion criteria
* Age: At least 18 years of age at the time of signing the informed consent.
* Documented chronic HBV infection >=6 months prior to Screening AND currently receiving stable NA therapy defined as receiving an NA regimen form at least 6 months prior to Screening and with no planned changes to their stable regimen over the duration of the study.
* Plasma or serum HBsAg concentration >100 international units per milliliter (IU/mL)
* Plasma or serum HBV DNA concentration must be adequately suppressed, defined as plasma or serum HBV DNA <90 IU/mL.
* Alanine aminotransferase <=2* upper limit of normal (ULN)
* Participants who are willing and able to cease their NA treatment in accordance with the protocol.
* Male and Female
Minimum age
18 Years
Maximum age
No limit
Sex
Both males and females
Can healthy volunteers participate?
No
Key exclusion criteria
* Clinically significant abnormalities, aside from chronic HBV infection in medical history (e.g., moderate-severe liver disease other than chronic HBV, acute coronary syndrome within 6 months of screening, major surgery within 3 months of screening, significant/unstable cardiac disease, uncontrolled diabetes, bleeding diathesis coagulopathy) or clinically significant physical examination findings.
* Coinfection with Hepatitis C (cured <12 months at the time of screening), Human immunodeficiency virus or hepatitis D virus.
* History of or suspected liver cirrhosis and/or evidence of cirrhosis.
* Diagnosed or suspected hepatocellular carcinoma.
* History of malignancy within the past 5 years with the exception of specific cancers that are cured by surgical resection (example, skin cancer). Participants under evaluation for possible malignancy are not eligible.
* History of vasculitis or presence of symptoms and signs of potential vasculitis (e.g., vasculitic rash, skin ulceration, repeated blood detected in urine without identified cause), current or history of an autoimmune condition or history/presence of other diseases that may be associated with vasculitis condition (example, systemic lupus erythematosus, rheumatoid arthritis, relapsing polychondritis, mononeuritis multiplex).
* History of extrahepatic disorders possibly related to HBV immune conditions (example, nephrotic syndrome, any type of glomerulonephritis, polyarteritis nodosa, cryoglobulinemia, uncontrolled hypertension).
* History of alcohol or drug abuse/dependence:
* Currently taking, or took within 3 months of screening, any immunosuppressing drugs (example, prednisone), other than a short course of therapy (<=2 weeks) or topical/inhaled steroid use.
* Participants, to whom immunosuppressive treatment (including therapeutic doses of steroids) is contraindicated, should not be considered for enrollment in the study.
* Currently taking, or has taken within 6 months of Screening, any interferon-containing therapy.
* Participants requiring anti-coagulation therapies (example, warfarin, Factor Xa inhibitors) or anti-platelet agents (like clopidogrel or aspirin) unless treatment can safely be discontinued throughout duration of Investigational medicinal product (IMP) treatment, by the discretion of the investigator. Occasional use is permitted.
* Prior hepatitis B treatment with bepirovirsen, DAP/TOM, or another oligonucleotide or small interfering ribonucleic acid (RNA) (siRNA).
* Prior non-hepatitis B treatment with an oligonucleotide or siRNA within 12 months prior to the first dosing day.
* Fridericia's QT correction formula (QTcF) >=450 millisecond (msec) (if single electrocardiogram [ECG] at screening shows QTcF >=450 msec, a mean of triplicate measurements should be used to confirm that participant meets exclusion criterion).
* History of/sensitivity to bepirovirsen, DAP/TOM or components thereof or a history of drug or other allergy that, in the opinion of the investigator or Medical Monitor, contraindicates their participation
* Participants who do not wish to discontinue taking NA therapy for their chronic HBV infection.

Study design
Purpose of the study
Treatment
Allocation to intervention
Randomised controlled trial
Procedure for enrolling a subject and allocating the treatment (allocation concealment procedures)
Methods used to generate the sequence in which subjects will be randomised (sequence generation)
Masking / blinding
Blinded (masking used)
Who is / are masked / blinded?
The people receiving the treatment/s


The people analysing the results/data
Intervention assignment
Other
Other design features
Phase
Phase 2
Type of endpoint/s
Statistical methods / analysis

Recruitment
Recruitment status
Recruiting
Data analysis
Reason for early stopping/withdrawal
Other reasons
Date of first participant enrolment
Anticipated
Actual
11/11/2024
Date of last participant enrolment
Anticipated
Actual
Date of last data collection
Anticipated
29/10/2027
Actual
Sample size
Target
280
Accrual to date
Final
Recruitment in Australia
Recruitment state(s)
NSW,VIC
Recruitment hospital [1] 0 0
GSK Investigational Site - Camperdown
Recruitment hospital [2] 0 0
GSK Investigational Site - Westmead
Recruitment hospital [3] 0 0
GSK Investigational Site - Fitzroy
Recruitment postcode(s) [1] 0 0
2050 - Camperdown
Recruitment postcode(s) [2] 0 0
2145 - Westmead
Recruitment postcode(s) [3] 0 0
3065 - Fitzroy
Recruitment outside Australia
Country [1] 0 0
United States of America
State/province [1] 0 0
California
Country [2] 0 0
United States of America
State/province [2] 0 0
Minnesota
Country [3] 0 0
United States of America
State/province [3] 0 0
New York
Country [4] 0 0
United States of America
State/province [4] 0 0
Pennsylvania
Country [5] 0 0
Belgium
State/province [5] 0 0
Bruxelles
Country [6] 0 0
Belgium
State/province [6] 0 0
Edegem
Country [7] 0 0
Belgium
State/province [7] 0 0
Gent
Country [8] 0 0
Brazil
State/province [8] 0 0
Aracaju
Country [9] 0 0
Brazil
State/province [9] 0 0
Curitiba
Country [10] 0 0
Brazil
State/province [10] 0 0
Manaus
Country [11] 0 0
Brazil
State/province [11] 0 0
Sao Paulo
Country [12] 0 0
Canada
State/province [12] 0 0
Alberta
Country [13] 0 0
Canada
State/province [13] 0 0
Ontario
Country [14] 0 0
Canada
State/province [14] 0 0
Quebec
Country [15] 0 0
China
State/province [15] 0 0
Beijing
Country [16] 0 0
China
State/province [16] 0 0
Chengdu
Country [17] 0 0
China
State/province [17] 0 0
Guangzhou
Country [18] 0 0
China
State/province [18] 0 0
Shanghai
Country [19] 0 0
China
State/province [19] 0 0
Zhenjiang
Country [20] 0 0
France
State/province [20] 0 0
Clichy Cedex
Country [21] 0 0
France
State/province [21] 0 0
CrEteil cedex
Country [22] 0 0
France
State/province [22] 0 0
Limoges cedex
Country [23] 0 0
France
State/province [23] 0 0
Lyon
Country [24] 0 0
France
State/province [24] 0 0
Marseille
Country [25] 0 0
France
State/province [25] 0 0
Toulouse Cedex 9
Country [26] 0 0
Germany
State/province [26] 0 0
Berlin
Country [27] 0 0
Germany
State/province [27] 0 0
Essen
Country [28] 0 0
Germany
State/province [28] 0 0
Hannover
Country [29] 0 0
Germany
State/province [29] 0 0
Leipzig
Country [30] 0 0
Germany
State/province [30] 0 0
Muenster
Country [31] 0 0
Greece
State/province [31] 0 0
Athens
Country [32] 0 0
Hong Kong
State/province [32] 0 0
Pokfulam
Country [33] 0 0
Hong Kong
State/province [33] 0 0
Shatin
Country [34] 0 0
Italy
State/province [34] 0 0
Bergamo
Country [35] 0 0
Italy
State/province [35] 0 0
Firenze
Country [36] 0 0
Italy
State/province [36] 0 0
Milano
Country [37] 0 0
Italy
State/province [37] 0 0
Modena
Country [38] 0 0
Italy
State/province [38] 0 0
Napoli
Country [39] 0 0
Italy
State/province [39] 0 0
Padova
Country [40] 0 0
Italy
State/province [40] 0 0
Pisa
Country [41] 0 0
Italy
State/province [41] 0 0
Roma
Country [42] 0 0
Italy
State/province [42] 0 0
Torino
Country [43] 0 0
Japan
State/province [43] 0 0
Chiba
Country [44] 0 0
Japan
State/province [44] 0 0
Hokkaido
Country [45] 0 0
Japan
State/province [45] 0 0
Hyogo
Country [46] 0 0
Japan
State/province [46] 0 0
Kagawa
Country [47] 0 0
Japan
State/province [47] 0 0
Kumamoto
Country [48] 0 0
Japan
State/province [48] 0 0
Osaka
Country [49] 0 0
Japan
State/province [49] 0 0
Tokyo
Country [50] 0 0
Japan
State/province [50] 0 0
Yamanashi
Country [51] 0 0
Korea, Republic of
State/province [51] 0 0
Ansan
Country [52] 0 0
Korea, Republic of
State/province [52] 0 0
Busan
Country [53] 0 0
Korea, Republic of
State/province [53] 0 0
Pusan
Country [54] 0 0
Korea, Republic of
State/province [54] 0 0
Seoul
Country [55] 0 0
New Zealand
State/province [55] 0 0
Auckland
Country [56] 0 0
New Zealand
State/province [56] 0 0
Papatoetoe Auckland
Country [57] 0 0
Singapore
State/province [57] 0 0
Singapore
Country [58] 0 0
South Africa
State/province [58] 0 0
Johannesburg
Country [59] 0 0
South Africa
State/province [59] 0 0
Reiger Park
Country [60] 0 0
South Africa
State/province [60] 0 0
Soweto Johannesburg
Country [61] 0 0
Spain
State/province [61] 0 0
Barcelona
Country [62] 0 0
Spain
State/province [62] 0 0
Leon
Country [63] 0 0
Spain
State/province [63] 0 0
Madrid
Country [64] 0 0
Spain
State/province [64] 0 0
Salamanca
Country [65] 0 0
Spain
State/province [65] 0 0
Santander
Country [66] 0 0
Spain
State/province [66] 0 0
Valencia
Country [67] 0 0
Taiwan
State/province [67] 0 0
Kaohsiung City
Country [68] 0 0
Taiwan
State/province [68] 0 0
Kaohsiung
Country [69] 0 0
Taiwan
State/province [69] 0 0
Taichung
Country [70] 0 0
Taiwan
State/province [70] 0 0
Tau-Yuan
Country [71] 0 0
United Kingdom
State/province [71] 0 0
London
Country [72] 0 0
United Kingdom
State/province [72] 0 0
Middlesbrough

Funding & Sponsors
Primary sponsor type
Commercial sector/industry
Name
GlaxoSmithKline
Address
Country

Ethics approval
Ethics application status

Summary
Brief summary
Trial website
Trial related presentations / publications
Public notes

Contacts
Principal investigator
Name 0 0
GSK Clinical Trials
Address 0 0
GlaxoSmithKline
Country 0 0
Phone 0 0
Fax 0 0
Email 0 0
Contact person for public queries
Name 0 0
US GSK Clinical Trials Call Center
Address 0 0
Country 0 0
Phone 0 0
877-379-3718
Fax 0 0
Email 0 0
GSKClinicalSupportHD@gsk.com
Contact person for scientific queries

Data sharing statement
Will individual participant data (IPD) for this trial be available (including data dictionaries)?
Yes
What data in particular will be shared?
Qualified researchers may request access to anonymized individual patient-level data (IPD) and related study documents of the eligible studies via the Data Sharing Portal. Details on GSK's data sharing criteria can be found at: https://www.gsk.com/en-gb/innovation/trials/data-transparency/

Supporting document/s available: Study protocol, Statistical analysis plan (SAP), Informed consent form (ICF), Clinical study report (CSR)
When will data be available (start and end dates)?
Anonymized IPD will be made available within 6 months of publication of primary, key secondary and safety results for studies in product with approved indication(s) or terminated asset(s) across all indications.
Available to whom?
Anonymized IPD is shared with researchers whose proposals are approved by an Independent Review Panel and after a Data Sharing Agreement is in place. Access is provided for an initial period of 12 months but an extension may be granted, when justified, for up to 6 months.
Available for what types of analyses?
How or where can data be obtained?
IPD available at link: https://www.gsk.com/en-gb/innovation/trials/data-transparency/


What supporting documents are/will be available?

No Supporting Document Provided



Results publications and other study-related documents

No documents have been uploaded by study researchers.


Results not provided in https://clinicaltrials.gov/study/NCT06537414