BEPIROVIRSEN SODIUM for Chronic hepatitis B | HIV infection

Stratification factors

• HBsAg level (>100 IU/mL to ≤1000 IU/mL or >1000 IU/mL to ≤3000 IU/mL)
• HBeAg status (positive or negative)

Inclusion criteria

• {"criterion_text":"- Documented chronic HBV infection and documented HIV-1 infection greater than equal to (>=)12 months prior to screening\n- 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\tSwitch 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)\n- 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\n- Plasma or serum HBV DNA concentration must be adequately suppressed, defined as plasma or serum HBV DNA <90 IU/mL\n- Plasma HIV-1 RNA concentration must be undetectable, defined as plasma HIV 1 RNA <50 copies/mL\n- Cluster of differentiation 4 (CD4) count >=350 cells/Cubic Millimeters (mm3)\n- Alanine aminotransferase (ALT) <=2 times Upper limit of normal (ULN)"}

Exclusion criteria

• {"criterion_text":"- History of or suspected liver cirrhosis and/or evidence of cirrhosis. Diagnosed or suspected Hepatocellular carcinoma (HCC)\n- 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\n- Participants to whom immunosuppressive treatment, including therapeutic doses of steroids, is contraindicated should not be considered for enrolment in the study\n- Currently taking, or has taken within 12 months of Screening, any interferon containing therapy\n- 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.\n- Treatment with an HIV-1 immunotherapeutic vaccine within 90 days of screening\n- Prior treatment with any oligonucleotide or Small interfering ribonucleic acid (siRNA) within 12 months prior to the first dosing day\n- Prior treatment with bepirovirsen\n- History of extrahepatic disorders possibly related to HBV immune conditions (e.g., nephrotic syndrome, any type of glomerulonephritis, polyarteritis nodosa, cryoglobulinemia, uncontrolled hypertension)\n- Coinfection with: a.\tHepatitis C virus (HCV) with positive HCV antibody and detectable HCV RNA at Screening I.\tHCV treatment should have completed >12 months prior to Screening b.\tHepatitis D virus (HDV) defined as positive or equivocal HDV antibody regardless of HDV RNA level\n- 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\n- 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\n- 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\n- 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)\n- Participants who in the investigator’s judgment, have a significant risk of suicide or self-harm\n- Alcohol or drug abuse/dependence"}

Primary endpoints

• {"endpoint_text":"- 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","definition_or_measurement_approach":"Proportion of participants with HBsAg reported as not detected and HBV DNA below the assay LLOQ measured at 36 weeks after scheduled end of study treatment; assessed in absence of rescue medication."}

Secondary endpoints

• {"endpoint_text":"- Percentage of participants achieving HBsAg not detected and HBV DNA ","definition_or_measurement_approach":"Proportion of participants achieving HBsAg not detected and HBV DNA < LLOQ at the scheduled end of treatment in the absence of rescue medication (end of treatment timepoint)."}

Methods

• K1_Recruitment arrangements (document title present in CTIS documents) - recruitment arrangements document (associated with specific Member State applications)
• K2_Flyer (document title present) - participant-facing flyer material
• K2_Poster / K2_GP Poster - poster materials for recruitment
• K2_HCP Letter - healthcare professional invitation/notification letter
• K2_Patient Letter / K2_Participant letter - direct patient invitation letters
• K2_Tri-Fold Brochure - informational brochure for participants
• K2_Patient Letter_redacted and related materials (multiple language/redacted versions present)

Spain

Earliest CTIS Part Ii Submission Date

16-10-2024

Latest Decision Or Authorization Date

10-12-2025

Processing Time Days

420

Number Of Sites

6

Number Of Participants

16

France

Earliest CTIS Part Ii Submission Date

03-12-2024

Latest Decision Or Authorization Date

28-11-2025

Processing Time Days

360

Number Of Sites

7

Number Of Participants

15

Italy

Earliest CTIS Part Ii Submission Date

18-12-2024

Latest Decision Or Authorization Date

23-03-2026

Processing Time Days

460

Number Of Sites

6

Number Of Participants

20

Primary sponsor

Full Name

Glaxosmithkline Research & Development Limited

Organisation Type

Pharmaceutical company

Country Of Registered Address

United Kingdom

Contract research organisations

Name

Sermes CRO

Responsibilities

Patient fee reimbursement

Third parties

• {"country":"France","full_name":"Fm Richard Et Associes","duties_or_roles":"Reimbursement of patient fees and compensation / Payment of biological exams performed outside the sites","organisation_type":"Non-Pharmaceutical company"}
• {"country":"United States","full_name":"Corevitas LLC","duties_or_roles":"7","organisation_type":"Pharmaceutical company"}
• {"country":"Spain","full_name":"Alcura Health Espana S.A.","duties_or_roles":"Medicine product destruction","organisation_type":"Pharmaceutical company"}
• {"country":"Belgium","full_name":"Universitair Ziekenhuis Gent","duties_or_roles":"4","organisation_type":"Hospital/Clinic/Other health care facility"}
• {"country":"United Kingdom","full_name":"Labcorp Early Development Laboratories Limited","duties_or_roles":"4","organisation_type":"Pharmaceutical company"}
• {"country":"United States","full_name":"Monogram Biosciences Inc.","duties_or_roles":"4","organisation_type":"Pharmaceutical company"}
• {"country":"France","full_name":"Creapharm Clinical Supplies","duties_or_roles":"14","organisation_type":"Pharmaceutical company"}
• {"country":"United States","full_name":"Greenphire LLC","duties_or_roles":"Travel reimbursement and Travel organization","organisation_type":"Non-Pharmaceutical company"}
• {"country":"United States","full_name":"Infinity Biologix LLC","duties_or_roles":"4","organisation_type":"Pharmaceutical company"}
• {"country":"United Kingdom","full_name":"Biocair International Limited","duties_or_roles":"14","organisation_type":"Pharmaceutical company"}
• {"country":"United States","full_name":"Eresearchtechnology Inc.","duties_or_roles":"7","organisation_type":"Pharmaceutical company"}
• {"country":"United States","full_name":"WCG Clinical Inc.","duties_or_roles":"10","organisation_type":"Pharmaceutical company"}
• {"country":"Spain","full_name":"Sermes CRO","duties_or_roles":"Patient fee reimbursement","organisation_type":"Pharmaceutical company"}
• {"country":"France","full_name":"Cerba","duties_or_roles":"4","organisation_type":"Laboratory/Research/Testing facility"}
• {"country":"United States","full_name":"Acetaminophen Toxicity Diagnostics LLC","duties_or_roles":"4","organisation_type":"Laboratory/Research/Testing facility"}
• {"country":"Belgium","full_name":"PPD Global Central Labs","duties_or_roles":"4","organisation_type":"Pharmaceutical company"}
• {"country":"Denmark","full_name":"Nordic Bioscience A/S","duties_or_roles":"4","organisation_type":"Pharmaceutical company"}
• {"country":"Belgium","full_name":"Cerba Research","duties_or_roles":"4","organisation_type":"Laboratory/Research/Testing facility"}