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

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: EUCTR2021-005139-22-HU
• Lead Sponsor: GlaxoSmithKline Research & Development Limited

Brief Summary

Not available

Detailed Description

Not available

Study Timeline

• Results First Posted: 1900-01-01
• Study Start: 2022-12-14
• Last Update Posted: 20 February 2023

Recruitment & Eligibility

• Status: Authorised-recruitment may be ongoing or finished
• Sex: All
• Target Recruitment: 534

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 must be HBeAg negative at screening.
3.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
4.Plasma or serum HBsAg concentration >100 IU/mL, but no greater than 3000 IU/mL
5.Plasma or serum HBV DNA concentration must be adequately suppressed, defined as plasma or serum HBV DNA <90 IU/mL
6.Alanine aminotransferase (ALT) =2 x ULN
7.Participants who are willing and able to cease their NA treatment in accordance with the protocol.

Sex and Contraceptive/Barrier Requirements
8.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 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 8.2.5).
•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
9.Capable of giving signed informed consent as described in Section 10.1 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 454
F.1.3 Elderly (>=65 years) yes
F.1.3.1 Number of subjects for this age range 80

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 or coagulopathy) or physical examination
2.Co-infection with:
a.Current history of Hepatitis C infection or participants that have been cured for <12 months at the time of screening
b.Human immunodeficiency virus (HIV)
c.Hepatitis D virus
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 participant meets 1 of the following criteria documented from their medical history, they will be excluded from the study
•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
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) 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 treatment, including therapeutic doses of steroids is contraindicated, should not be considered for enrolment in the study.
11.Currently taking, or HAS TAKEN within 12 months of Screening, any interferon containing therapy.
12.Participants requiring anti-coagulation therapies (e.g., warfarin, Factor Xa inhibitors) or anti-platelet agents (like clopidogrel or aspirin) unless treatment can safely be discontinued throughout dura

Study & Design

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