Phase 3 Study of Bepirovirsen in Nucleos(t)ide Analogue-treated Participants with Chronic Hepatitis B (B-Well 2)

Phase 1

• Conditions: Chronic Hepatitis B infection; MedDRA version: 20.1Level: PTClassification code 10008910Term: Chronic hepatitis BSystem Organ Class: 10021881 - Infections and infestations; Therapeutic area: Diseases [C] - Virus Diseases [C02]

• Registration Number: EUCTR2022-002268-53-DE
• Lead Sponsor: GSK & Development Limited

Brief Summary

Not available

Detailed Description

Not available

Study Timeline

• Results First Posted: 1900-01-01
• Study Start: 2022-10-20
• Last Update Posted: 28 August 2023

Recruitment & Eligibility

• Status: Authorised-recruitment may be ongoing or finished
• Sex: All
• Target Recruitment: 900

Inclusion Criteria

Participants are eligible to be included in the study only if all of the
following criteria apply:
Age
1.At least 18 years of age at the time of signing the informed consent (if
country/site age requirements for consent differ, the more stringent
[e.g., higher age] restriction will be required for that country/site).

Type of Participant and Disease Characteristics
2.Participants who have documented chronic HBV infection =6 months prior to Screening AND
•Currently receiving stable NA therapy defined as no changes to their NA regimen from at least 6 months prior to Screening and with no planned changes to the stable regimen over the duration of the study
3.Plasma or serum HBsAg concentration >100 IU/mL, and HBsAg
concentration =than 3000 IU/mL
4.Plasma or serum HBV DNA concentration must be adequately
suppressed, defined as plasma or serum HBV DNA <90 IU/mL
5.Alanine aminotransferase (ALT) =2 x ULN
6.Participants who are willing and able to cease their NA treatment in
accordance with the protocol.

Sex and Contraceptive/Barrier Requirements
7.Male and/or female
a.There are no contraceptive requirements for male participants.
b.A female participant is eligible to participate if she is not pregnant or breastfeeding, and 1 of the following conditions applies:
•Is a woman of non childbearing potential (WONCBP) as defined in
Section 10.4
OR
Is a WOCBP and using a contraceptive method (for a period of 28 days prior to enrollment [first dose of study drug]) that is highly effective (with a failure rate of <1% per year), preferably with low user dependency, as described in Appendix 4 during the study intervention period and for at least 7 days after the last dose of study intervention up to Week 25 and agrees not to donate eggs (ova, oocytes) for the purpose of reproduction during this period. The investigator should evaluate the potential for contraceptive method failure (e.g., noncompliance, recently initiated) in relationship to the first dose of study intervention.
A WOCBP must have a negative highly sensitive pregnancy test (urine or serum as required by local regulations) within 24 hours before the first dose of study intervention (see Section 8.3.5).
•If a urine test cannot be confirmed as negative (e.g., an ambiguous
result), a serum pregnancy test is required. In such cases, the
participant must be excluded from participation if the serum pregnancy result is positive.
The investigator is responsible for review of medical history, menstrual history, and recent sexual activity to decrease the risk for inclusion of a woman with an early undetected pregnancy

Informed Consent
8.Capable of giving signed informed consent as described in Section 9.1 which includes compliance with the requirements and restrictions listed in the ICF and in this protocol.
Are the trial subjects under 18? no
Number of subjects for this age range:
F.1.2 Adults (18-64 years) yes
F.1.2.1 Number of subjects for this age range 738
F.1.3 Elderly (>=65 years) yes
F.1.3.1 Number of subjects for this age range 162

Exclusion Criteria

Participants are excluded from the study if any of the following criteria apply:
Medical Conditions
1.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
2.Co-infection with:
a. Hepatitis C infection or participants that have been cured for <12
months at the time of screening (defined as having been HCV RNA
negative for <12 months)
b.Human immunodeficiency virus (HIV)
c.Hepatitis D virus defined as HDV antibody positive
3.History of or suspected liver cirrhosis and/or evidence of cirrhosis as determined by
a.Both APRI >2 and FibroSure/FibroTest result >0.7
•If only 1 parameter (APRI or FibroSure/FibroTest) result is positive, a
discussion with the Medical Monitor is required before inclusion in study is permitted
b.Regardless of APRI of Fibrosure/FibroTest score, if the participants
has historic record of either/both liver biopsy or liver stiffness
measurements in their medical records and meets 1 of the following
criteria, they will be excluded from the study (note: it is not required to perform liver biopsy or liver stiffness measurement for screening if the patient has not had the assessments)
•Liver biopsy (i.e., Metavir Score F4)
•Liver stiffness >12 kPa
4.Diagnosed or suspected hepatocellular carcinoma as evidenced by the
following
a.Alpha-fetoprotein concentration =200 ng/mL
b.If the screening alpha fetoprotein concentration is =50 ng/mL and
<200 ng/mL, the absence of liver mass must be documented by imaging within 6 months before randomization. You may reach out to the Medical Monitor to discuss eligibility.
5.History of malignancy within the past 5 years with the exception of
specific cancers that are cured by surgical resection (e.g., skin cancer).
Participants under evaluation for possible malignancy are not eligible.
6.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 (e.g., systemic lupus erythematosus, rheumatoid arthritis, relapsing polychondritis, mononeuritis multiplex)
7.History of extrahepatic disorders possibly related to HBV immune
conditions (e.g., nephrotic syndrome, any type of glomerulonephritis,
polyarteritis nodosa, cryoglobulinemia, uncontrolled hypertension)
8.History of alcohol or drug abuse/dependence
a.Current alcohol use as judged by investigator to potentially interfere
with participant compliance
b.History of or current drug abuse/dependence as judged by the
investigator to potentially interfere with participant compliance
i.Refers to illicit drugs and substances with abuse potential. Medications that are used by the participant as directed, whether over-the-counter or through prescription, are acceptable and would not meet the exclusion criteria
Prior/Concomitant Therapy
9.Currently taking, or took within 3 months of screening, any
immunosuppressing drugs (e.g., prednisone), other than a short course of therapy (=2 weeks) or topical/inhaled steroid use.
10.Participants to whom immnosuppressive treatme

Study & Design

• Study Type: Interventional clinical trial of medicinal product
• Study Design: Not specified