A Multicenter, Randomized, Double-Blind, Placebo-controlled Study to Assess the Efficacy and Safety of Treatment with Bepirovirsen in Participants living with Human Immunodeficiency Virus and Chronic Hepatitis B Virus Infection on Antiretroviral Treatment

Overview

Sponsor-declared trial summary

Key facts

Sponsor

Glaxosmithkline Research & Development Limited

Participant type

Patients

Age range

18-64 years, 65+ years

Gender

Male and Female

Therapeutic area

Diseases [C] - Virus Diseases [C02]

Trial duration

11 Feb 2025 → ongoing

Decision date (initial)

2025-01-15

Transition trial

No

Low-intervention

No

Rare-disease indication

No

Vulnerable population

Yes

Trial design

CTIS Part I — objectives, methods, condition coding

Main objective

Scope: Efficacy, Safety

To assess the treatment effect of 24 weeks bepirovirsen with loading doses to achieve a Hepatitis B Virus (HBV) virologic response 36 weeks off study treatment in participants with chronic Human Immunodeficiency Virus (HIV)/HBV coinfection on HBV and HIV active Antiretroviral treatment (ART) with Baseline HBV surface antigen (HBsAg) less than or equal to (<=)3000 International units (IU)/ milliLiter (mL).

Secondary objectives 1

1. To assess the treatment effect of 24 weeks bepirovirsen with loading doses to achieve an HBV virologic response at scheduled end of treatment in participants with chronic HIV/HBV coinfection on HBV and HIV active ART with baseline HBsAg <=3000 IU/mL

Conditions and MedDRA coding

Hepatitis B

Study design 1 period

Regulatory references

Scientific advice from competent authorities

Food And Drug Administration

EMA paediatric investigation plan (PIP)

EMEA-003082-PIP01-21

Plan to share IPD

Yes

IPD plan description

"GSK will assess requests from qualified researchers for anonymized individual patient-level data (IPD) and related study documents. Data sharing is subject to certain criteria, conditions, and exceptions. For further information, refer to https://www.gsk-studyregister.com. IPD Sharing Access Criteria: 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. IPD Sharing Time Frame: 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 asset(s) with development terminated across all indications."

Eligibility criteria

Principal inclusion / exclusion criteria as submitted by sponsor

Inclusion criteria 7

1. Documented chronic HBV infection and documented HIV-1 infection greater than equal to (>=)12 months prior to screening
2. Must be on uninterrupted ART containing at least Tenofovir disoproxil (TDF) or Tenofovir alafenamide (TAF) plus Lamivudine (3TC) or Emtricitabine (FTC) for greater than (>)12 months, with no planned changes to the stable regimen over the duration of the study o Switch in ART is permitted >=6 months prior to Screening for reasons not related to loss of HIV or HBV control (e.g., change in formulary, tolerability, side effects)
3. Documented evidence of at least 2 plasma HIV-1 Ribonucleic acid (RNA) measurements <50 copies/mL are required in the 12 months prior to Screening: 1 within 6 to 12 months prior to screening and 1 within 6 months prior to Screening
4. Plasma or serum HBV DNA concentration must be adequately suppressed, defined as plasma or serum HBV DNA <90 IU/mL
5. Plasma HIV-1 RNA concentration must be undetectable, defined as plasma HIV 1 RNA <50 copies/mL
6. Cluster of differentiation 4 (CD4) count >=350 cells/Cubic Millimeters (mm3)
7. Alanine aminotransferase (ALT) <=2 times Upper limit of normal (ULN)

Exclusion criteria 16

1. History of or suspected liver cirrhosis and/or evidence of cirrhosis. Diagnosed or suspected Hepatocellular carcinoma (HCC)
2. History of extrahepatic disorders possibly related to HBV immune conditions (e.g., nephrotic syndrome, any type of glomerulonephritis, polyarteritis nodosa, cryoglobulinemia, uncontrolled hypertension)
3. Coinfection with: a. Hepatitis C virus (HCV) with positive HCV antibody and detectable HCV RNA at Screening I. HCV treatment should have completed >12 months prior to Screening b. Hepatitis D virus (HDV) defined as positive or equivocal HDV antibody regardless of HDV RNA level
4. Clinically significant abnormalities, aside from HIV-1 infection and chronic HBV infection in medical history (e.g., moderate severe liver disease other than chronic HBV/HIV, 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
5. Untreated syphilis infection (positive Rapid plasma reagin [RPR] at Screening without clear documentation of treatment) are excluded unless they complete treatment during the screening period and 7 days prior to randomization
6. 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
7. 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)
8. Participants who in the investigator’s judgment, have a significant risk of suicide or self-harm
9. Alcohol or drug abuse/dependence
10. 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
11. Participants to whom immunosuppressive treatment, including therapeutic doses of steroids, is contraindicated should not be considered for enrolment in the study
12. Currently taking, or has taken within 12 months of Screening, any interferon containing therapy
13. Participants requiring anti coagulation therapies (e.g., warfarin, Factor Xa inhibitors) or anti platelet agents (including but not limited to clopidogrel or aspirin) unless treatment can safely be discontinued throughout duration of study intervention, by the discretion of the investigator. Occasional use is permitted.
14. Treatment with an HIV-1 immunotherapeutic vaccine within 90 days of screening
15. Prior treatment with any oligonucleotide or Small interfering ribonucleic acid (siRNA) within 12 months prior to the first dosing day
16. Prior treatment with bepirovirsen

Endpoints

Primary and secondary outcome measures (English text)

Primary endpoints 1

1. Percentage of participants achieving HBsAg not detected and HBV Deoxyribonucleic acid (DNA) less than (<) Lower limit of quantification (LLOQ) at 36 weeks after scheduled end of study treatment in absence of rescue medication

Secondary endpoints 1

1. Percentage of participants achieving HBsAg not detected and HBV DNA

Investigational products

Investigational medicinal products (IMPs), comparators, placebo, auxiliary

Test 1

Placebo 1

Sponsors and contacts

Sponsor organisations, regulatory contacts, third parties

Glaxosmithkline Research & Development Limited

Sponsor organisation

Glaxosmithkline Research & Development Limited

Address

G S K House, 980 Great West Road 980 Great West Road

City

Brentford

Postcode

TW8 9GS

Country

United Kingdom

Scientific contact point

Organisation

Glaxosmithkline Research & Development Limited

Contact name

EU GSK Clinical Trials Call Center

Public contact point

Organisation

Glaxosmithkline Research & Development Limited

Contact name

EU GSK Clinical Trials Call Center

Third parties 18

Locations

3 EU/EEA countries · 18 investigational sites

By country

Investigational sites

Country notifications

Trial-start, recruitment-start, end and early-termination notifications submitted per Member State

Results and documents

Annex IV summary of results, Annex V layperson summary, and all documents registered in CTIS for this trial

Documents 36 files

Public protocol annexes, IB summaries, regulatory submissions and post-authorisation documents registered in CTIS.

Application history

5 submissions — initial application plus substantial / non-substantial modifications