A Multiple-Dose Study of Bulevirtide in Participants With Normal and Impaired Renal Function

NCT05760300 | Completed Phase 1 Results FDA Drug

• 2 other identifiers: GS-US-589-61602022-502054-13-00
• Study Type: interventional
• Target: 41
• Locations: 1 country
• Sites: 9

Brief Summary

The goals of this study are to compare the amount of study drug, bulevirtide (BLV), that gets into the bloodstream and how long it takes for the body to eliminate it, measure the effect of BLV on bile acids, and evaluate the safety and tolerability of multiple doses of BLV in participants with normal or impaired renal (kidney) function.

Conditions

Chronic Hepatitis D Infection

Outcome Measures

Primary Outcomes (2)

• Pharmacokinetic (PK) Parameter for Bulevirtide (BLV): AUCtau

  AUCtau is defined as the area under the concentration versus time curve over the dosing interval at steady state at Day 6.

  Day 6: Predose (≤ 30 minutes before dose), 0.5, 1, 1.5, 2, 3, 4, 6, 9, 12, and 24 hours postdose

• PK Parameter for BLV: Cmax ss

  Cmax is defined as the maximum observed concentration of drug at steady state at Day 6.

  Day 6: Predose (≤ 30 minutes before dose), 0.5, 1, 1.5, 2, 3, 4, 6, 9, 12, and 24 hours postdose

Secondary Outcomes (11)

• PK Parameter for BLV: AUC0-24

  Day 1: Predose (≤ 30 minutes before dose), 0.5, 1, 1.5, 2, 3, 4, 6, 9, 12, and 24 hours postdose

• PK Parameter for BLV: Cmax

  Day 1: Predose (≤ 30 minutes before dose), 0.5, 1, 1.5, 2, 3, 4, 6, 9, 12, and 24 hours postdose

• PK Parameter for BLV: Tmax

  Day 1: Predose (≤ 30 minutes before dose), 0.5, 1, 1.5, 2, 3, 4, 6, 9, 12, and 24 hours postdose; Day 6: Predose (≤ 30 minutes before dose), 0.5, 1, 1.5, 2, 3, 4, 6, 9, 12, 24, and 48 hours postdose

• PK Parameter for BLV: t1/2

  Day 1: Predose (≤ 30 minutes before dose), 0.5, 1, 1.5, 2, 3, 4, 6, 9, 12, and 24 hours postdose; Day 6: Predose (≤ 30 minutes before dose), 0.5, 1, 1.5, 2, 3, 4, 6, 9, 12, 24, and 48 hours postdose

• PK Parameter for BLV: CLss/F

  Day 6: Predose (≤ 30 minutes before dose), 0.5, 1, 1.5, 2, 3, 4, 6, 9, 12, 24, and 48 hours postdose

Study Arms (4)

Group A: BLV 2 mg (Severe RI Group)

EXPERIMENTAL

Participants with severe renal impairment (RI) \[estimated glomerular filtration rate (eGFR) ≥ 15 to ≤ 29 mL/min/1.73 m\^2\] will receive bulevirtide (BLV) 2 mg, administered subcutaneously (SC), once daily (QD), for 6 days.

Drug: Bulevirtide (BLV)

Group A: BLV 2 mg (Matched Control)

EXPERIMENTAL

Participants with normal renal function (matched control group) \[eGFR ≥ 90 mL/min/1.73 m\^2\] will receive BLV 2 mg, administered SC, QD, for 6 days.

Drug: Bulevirtide (BLV)

Group B: BLV 10 mg (Severe RI Group)

EXPERIMENTAL

Participants with severe RI \[eGFR ≥ 15 to ≤ 29 mL/min/1.73 m\^2\] will receive BLV 10 mg, administered SC, QD, for 6 days.

Drug: Bulevirtide (BLV)

Group B: BLV 10 mg (Matched Control)

EXPERIMENTAL

Participants with normal renal function (matched control group) \[eGFR ≥ 90 mL/min/1.73 m\^2\] will receive BLV 10 mg, administered SC, QD, for 6 days.

Drug: Bulevirtide (BLV)

Interventions

Bulevirtide (BLV) DRUG

Administered via subcutaneous (SC) injections

Also known as: Hepcludex®, Myrcludex B

Group A: BLV 2 mg (Matched Control); Group A: BLV 2 mg (Severe RI Group); Group B: BLV 10 mg (Matched Control); Group B: BLV 10 mg (Severe RI Group)

Eligibility Criteria

• Age: 18 Years - 79 Years
• Sex: all
• Healthy Volunteers: Yes
• Age Groups: Adult (18-64), Older Adult (65+)

You may qualify if:

• All Individuals:
• Body mass index (BMI) of at least ≥ 18.0 kg/m\^2 and ≤ 40.0 kg/m\^2 at screening.
• No clinically significant abnormalities on electrocardiogram (ECG)
• No known Liver Disease (Aspartate Aminotransferase (AST) and Alanine Aminotransferase (ALT)) ≤ 3 x upper limit of normal (ULN) at screening.
• Individuals with Renal Impairment (RI):
• Have RI classification at screening that has been unchanged during the 90 days prior to study drug dosing.
• Estimated Glomerular Filtration Rate (eGFR) must be the following (using the Chronic Kidney Disease Epidemiology Collaboration (CKD-EPI) equation (Inker 2021)) based on serum creatinine as measured at the screening evaluation:
• Severe RI (Groups A and B): eGFR ≥ 15 to ≤ 29 mL/min/1.73 m\^2
• Moderate RI (Group C): eGFR ≥ 30 to ≤ 59 mL/min/1.73 m\^2
• Mild RI (Group D): eGFR ≥ 60 to ≤ 89 mL/min/1.73 m\^2
• Hemoglobin ≥ 9 g/dL at screening.
• Individuals with cardiovascular disease, hypertension, diabetes mellitus, hyperlipidemia, hypothyroidism, osteoporosis, and many others) may be included provided that these diseases/conditions are clinically stable.
• Matched Control Individuals:
• Have an eGFR of at least 90 mL/min/1.73 m\^2 (using the CKD-EPI equation) based on serum creatinine as measured at screening evaluation.
• Matched for sex, age (± 10 years), and BMI (± 20%, 18.0 ≤ BMI ≤ 40.0 kg/m\^2) with the respective participant in the RI group.

You may not qualify if:

• All Individuals:
• Positive human immunodeficiency virus (HIV) test, hepatitis B surface antigen (HBsAg), or hepatitis C virus (HCV) antibody with detectable HCV viral ribonucleic acid (RNA) at screening.
• Have any serious or active medical or psychiatric illness (including depression) that, in the opinion of the investigator, would interfere with participant treatment, assessment, or compliance with the protocol.
• Individuals with RI:
• Recent history of reception of any blood or blood products or history of major bleeding within 4 weeks of dosing.
• Positive test for drugs of abuse, including alcohol at screening or admission, with the exception of opioids and tetrahydrocannabinol (THC, marijuana) under prescription and verified by the investigator as for pain management.
• Received treatment with trimethoprim or cimetidine or tenofovir prodrugs (tenofovir disoproxil fumarate (TDF) or tenofovir alafenamide (TAF)) (affects elimination of creatinine) or with competitors of renal tubular excretion (eg, probenecid, chronic high-dose nonsteroidal anti-inflammatory drugs) within 28 days of Day -1.
• Received known nephrotoxic drugs (eg, aminoglycosides, amphotericin B, vancomycin, cidofovir, foscarnet, cisplatin, pentamidine, cyclosporine, tacrolimus, herbal remedies (eg, compounds with aristolochic acid)) within 28 days of Day -1.
• Individuals requiring or anticipated to require dialysis within 90 days of study entry.
• Serum albumin concentration \<25 g/L.
• Uncontrolled treated/untreated hypertension (defined as a mean of 3 repeated measurements for systolic blood pressure ≥180 mmHg and/or diastolic blood pressure ≥110 mmHg); current or documented history of repeated clinically significant hypotension or severe episodes of orthostatic hypotension (systolic blood pressure \<90 mmHg and/or diastolic blood pressure \<50 mmHg).
• Matched Control Individuals:
• Have taken any prescription medications or over-the-counter medications, including herbal products, within 28 days prior to start of study drug dosing, with the exception of vitamins

Sponsors & Collaborators

• Gilead Sciences: lead

Study Sites (9)

Velocity Clinical Research, New Smyrna Beach

Edgewater, Florida, 32132, United States

Location

Clinical Pharmacology of Miami, LLC

Miami, Florida, 33014, United States

Location

Advanced Pharma CR, LLC

Miami, Florida, 33147, United States

Location

Panax Clinical Research

Miami Lakes, Florida, 33014, United States

Location

Floridian Clinical Research, LLC

Miami Lakes, Florida, 33016, United States

Location

Global Clinical Professionals Research

St. Petersburg, Florida, 33705, United States

Location

Genesis Clinical Research, LLC

Tampa, Florida, 33603, United States

Location

Massachusetts General Hospital - Renal Associates Clinic

Boston, Massachusetts, 02114, United States

Location

Nucleus Network

Saint Paul, Minnesota, 55114, United States

Location

Related Publications (2)

• Yehong Wang, Renee-Claude Mercier, Wildaliz Nieves, David Pan, Carrie Nielson, SteveTseng, Xu Zhang, Ann Qin, Parag Kumar. Pharmacokinetics, Pharmacodynamics, and Safety of Bulevirtide 2 mg Once Daily for 6 Days in Participants with Severe Renal Impairment and in Matched Control Participants with Normal Renal Function. The Liver Meeting, American Association for the Study of Liver Diseases; November 15-19, 2024; San Diego, CA. Abstract #1194.

  BACKGROUND

• Yehong Wang, Renee-Claude Mercier, Wildaliz Nieves, Carolina Machado, Steve Tseng, Yuejiao Jiang, Ann Qin, Teckla Akinyi, Parag Kumar, WED-313 Pharmacokinetics, pharmacodynamics, and safety of bulevirtide 10 mg once daily for 6 days in participants with severe renal impairment and in matched control participants with normal renal function, Journal of Hepatology, Volume 82, Supplement 1, 2025, Page S824 (https://doi.org/10.1016/S0168-8278(25)02119-1).

  BACKGROUND

Related Links

• Gilead Clinical Trials Website

MeSH Terms

Interventions

bulevirtide; myrcludex-B

Results Point of Contact

• Title: Gilead Clinical Study Information Center
• Organization: Gilead Sciences

GileadClinicalTrials@gilead.com

1-833-445-3230 (GILEAD-0)

Study Officials

• Gilead Study Director

  Gilead Sciences

  STUDY DIRECTOR

Publication Agreements

• PI is Sponsor Employee: No
• Restriction Type: OTHER
• Restrictive Agreement: Yes

Study Design

• Study Type: interventional
• Phase: phase 1
• Allocation: NON RANDOMIZED
• Masking: NONE
• Purpose: TREATMENT
• Intervention Model: PARALLEL
• Sponsor Type: INDUSTRY
• Responsible Party: SPONSOR

Study Record Dates

• First Submitted: February 27, 2023
• First Posted: March 8, 2023
• Study Start: March 15, 2023
• Primary Completion: July 18, 2024
• Study Completion: July 23, 2024
• Last Updated: September 18, 2025
• Results First Posted: September 18, 2025

Record last verified: 2025-08

Data Sharing

• IPD Sharing: Will not share

Locations

US (9)