Bepirovirsen blood levels in adults with moderate or severe kidney disease

A Phase 1, Open-Label, Single-Dose, Parallel Group, 2-Part Study to Evaluate the Pharmacokinetics of Bepirovirsen in Adult Participants With Severe or Moderate Renal Impairment Compared to Matched Healthy Control Participants

This study will test how a single dose of bepirovirsen is absorbed and cleared from the blood in adults with moderate or severe kidney disease compared with healthy adults.

Quick facts

• Phase: Phase 1
• Study type: Interventional
• Enrollment: 32 (estimated)
• Ages: 18 Years to 80 Years
• Sex: All
• Sponsor: GlaxoSmithKline (Industry-sponsored)
• Locations: 1 site (Tampa, Florida)
• Trial ID: NCT07168356 on ClinicalTrials.gov

What this trial studies

This two-part Phase 1 study gives a single dose of bepirovirsen to all participants and measures blood concentrations over time to characterize pharmacokinetics. Participants are grouped by kidney function: severe renal impairment (eGFR <30 ml/min), moderate renal impairment (eGFR 30–59 ml/min), and healthy controls with normal kidney function. The study compares how much drug gets into the bloodstream and how long it remains there across these groups. The trial is conducted at a GSK investigational site in Tampa, Florida.

Who should consider this trial

Good fit: Adults 18–80 years old who weigh at least 50 kg with BMI 19–40 and who either have moderate (eGFR 30–59 ml/min) or severe (eGFR <30 ml/min) renal impairment, or are healthy volunteers with normal renal function, are eligible.

Not a fit: People with kidney disease due to vasculitis or glomerulonephritis, pregnant or breastfeeding women, those under 18, or those outside the weight/BMI limits are not eligible and would not benefit from participation.

Why it matters

Potential benefit: If blood levels differ in people with kidney disease, the results could support dose adjustments or monitoring recommendations to improve safety and effectiveness.

How similar studies have performed: Pharmacokinetic studies of antisense oligonucleotides in renal impairment have been performed, but published data specifically for bepirovirsen are limited.

Eligibility criteria

Inclusion Criteria:

* Age 18 to 80 years, inclusive
* Body weight greater than or equal to 50 kilograms (kg) and body mass index (BMI) within the range 19 to 40 kilograms per square meter (kg/m\^2).
* Males and females may participate. Female participants must not be pregnant or breastfeeding, and must be of non-childbearing potential, or agree to use a highly effective method of contraception.
* Capable of giving signed informed consent Additional inclusion criteria for renal impairment groups (Group 1 and Group 2)
* Severe renal impairment \[estimated glomerular filtration rate (eGFR) adjusted for actual body surface area (BSA) less than 30 milliliters per minute (ml/min); Group 1\] or moderate renal impairment \[eGFR adjusted for actual BSA between 30 and 59 ml/min; Group 2\], from any cause other than vasculitis or glomerulonephritis Additional inclusion criteria for healthy control participants with normal renal function (Group 3)
* Healthy, based on medical evaluation including medical history, physical examination, laboratory tests, and electrocardiogram (ECG).
* Normal renal function (eGFR adjusted for actual BSA greater than or equal to 90 ml/min)

Exclusion Criteria:

* Any medical condition that could affect the absorption, metabolism, or elimination of drugs, increase the risk of taking part in the study, or interfere with interpretation of the study data.
* History of vasculitis or any type of glomerulonephritis
* Use of creatine-containing supplements within 30 days of screening or intended use during the study.
* Current enrolment in another interventional study, or past participation in a study where an investigational medicine, vaccine or device was administered if, at the time of consent, it is within 5 half-lives or twice the duration of the biological effect (whichever is longer) of the product given in the previous study.
* Received any oligonucleotide or small interfering ribonucleic acid (siRNA) within the past 12 months.
* Exposure to more than 4 investigational products within the past 12 months.
* A positive blood test for hepatitis B, hepatitis C, or human immunodeficiency virus (HIV).
* Average weekly alcohol intake of greater than 14 drinks for males or greater than 7 drinks for females.
* Current substance misuse or dependence, or a previous history of substance misuse or dependence that could interfere with ability to participate in the study.

Additional exclusion criteria for renal impairment groups (Group 1 and Group 2)

* History of renal transplantation or anticipated renal transplant during the study.
* On dialysis or likely to require dialysis during the study.
* Positive drug or alcohol screen (unless because of prescribed medication). Additional exclusion criterion for healthy control group (Group 3)
* Positive drug or alcohol screen.
* Urine albumin-to-creatinine ratio (uACR) \> 0.3 mg/mg (300 mg/g).

Where this trial is running

Tampa, Florida

• GSK Investigational Site — Tampa, Florida, United States (Recruiting)

Study contacts

• Study coordinator: US GSK Clinical Trials Call Center

Conditions Hepatitis B; Bepirovirsen; Pharmacokinetics; Severe renal impairment; Moderate renal impairment; Healthy participants; Renal function; Kidney disease