Study of Bulevirtide in Participants Who Have Normal or Impaired Liver Function

A Phase 1, Open-label, Parallel-group, Multiple-dose Study to Evaluate the Pharmacokinetics of Bulevirtide in Participants With Normal and Impaired Hepatic Function

The goals of this study are to measure the amount of bulevirtide (BLV) that gets into the blood stream and how long it takes to get rid of it, measure the effect of BLV on bile acids, and evaluate the safety and tolerability of multiple doses of BLV in participants with normal and impaired hepatic (liver) function.

Study Overview

• Status: Completed
• Conditions: Healthy; Hepatic Impairment
• Intervention / Treatment: Drug: Bulevirtide; Drug: Bulevirtide

• Study Type: Interventional
• Enrollment (Actual): 74
• Phase: Phase 1

Contacts and Locations

Study Locations

• United States
  • California
    • Lake Forest, California, United States, 92630
      • Orange County Research Center
  • Florida
    • Miami, Florida, United States, 33136
      • University of Miami
    • Miami, Florida, United States, 33014
      • Clinical Pharmacology of Miami, LLC
    • Orlando, Florida, United States, 32809
      • Orlando Clinical Research Center
  • Texas
    • San Antonio, Texas, United States, 78215
      • Texas Liver Institute
    • San Antonio, Texas, United States, 78229
      • Pinnacle Clinical Research LLC

Participation Criteria

Eligibility Criteria

• Ages Eligible for Study: 18 years to 79 years (Adult, Older Adult)
• Accepts Healthy Volunteers: Yes

Description

Key Inclusion Criteria:

All individuals:

• Body mass index (BMI) of 18 ≤ BMI ≤ 40 kg/m^2 at screening.
• Have a calculated creatinine clearance (CLcr) of at least 60 mL/min (using the Cockcroft-Gault method) based on serum creatinine and actual body weight as measured at screening.
• Individuals assigned male at birth and individuals assigned female at birth and of childbearing potential who engage in heterosexual intercourse must agree to use protocol-specified method(s) of contraception as described in the protocol.
• Individuals have not donated blood within 56 days of study entry or plasma within 7 days of study entry and must refrain from blood donation from clinic admission, throughout the study period, and continuing for at least 30 days following the last dose of study drug.
• 12-lead electrocardiogram (ECG) evaluations at screening must be without clinically significant abnormalities as assessed by the investigator.
• Aside from hepatic impairment among the individuals with hepatic impairment, the individual must, in the opinion of the investigator, be sufficiently healthy for study participation based upon medical history, physical examination, vital signs, and screening laboratory evaluations.
• Must be willing and able to comply with all study requirements.

Individuals With Hepatic Impairment:

• Have a diagnosis of chronic (> 6 months), stable hepatic impairment (moderate or severe based upon the Child-Pugh-Turcotte (CPT) classification system for moderate or severe hepatic impairment [CPT Class B or C, respectively]) with no clinically significant change in hepatic status (as determined by the investigator) within the 2 months (60 days) prior to screening.

  • Individuals with moderate or severe hepatic impairment must have a score of 7 to 9 or 10 to 15 on the CPT classification system at screening. If an individual's score changes during the study, the score at screening will be used for classification.

• Must meet all of the following laboratory parameters at screening:

  • alanine aminotransferase (ALT) ≤ 10 × upper limit of normal (ULN)
  • aspartate aminotransferase (AST) ≤ 10 × ULN
  • platelets ≥ 25,000/mm^3
  • hemoglobin ≥ 9 g/dL
• Individuals with hepatic impairment who have not been on a stable dose of concomitant medications for at least 4 weeks prior to screening (or 5 half-lives, whichever is longer) and/or for whom dose changes are likely to occur during the study should have their medications reviewed and approved by the sponsor.

Matched Control Individuals With Normal Hepatic Function:

• Have alanine aminotransferase (ALT), aspartate aminotransferase (AST), alkaline phosphatase, international normalized ratio, and total bilirubin at or below the ULN; and albumin above the lower limit of normal at screening and at admission.
• Must be matched for age (± 10 years), sex (assigned at birth), and BMI (± 20%, 18 ≤ BMI ≤ 40 kg/m^2) with an individual in the hepatic impairment group.

Key Exclusion Criteria:

All Individuals:

• Positive serum pregnancy test at screening and at admission.
• Breastfeeding individual.
• Have received any study drug within 30 days prior to study dosing.
• Have current alcohol or substance abuse judged by the investigator to potentially interfere with individual compliance or individual safety, or a positive drug or alcohol test at screening or admission.
• Have poor venous access that limits phlebotomy.
• Have been treated with systemic steroids, immunosuppressant therapies, or chemotherapeutic agents within 3 months prior to screening or is expected to receive these agents during the study.

• Have a history of any of the following:

  • Significant serious skin disease, such as but not limited to rash, food allergy, eczema, psoriasis, or urticaria.
  • Significant drug sensitivity or drug allergy (such as anaphylaxis or hepatoxicity).
  • Known hypersensitivity to the study drugs, their metabolites, or to formulation excipients.
  • Significant cardiac disease (including history of myocardial infarction based on ECG and/or clinical history, any history of ventricular tachycardia, congestive heart failure, or dilated cardiomyopathy with left ventricular ejection fraction ≤ 40%); or a family history of long QT syndrome, or unexplained death in an otherwise healthy individual between the ages of 1 and 30 years.
  • Syncope, palpitations, or unexplained dizziness.
  • Implanted defibrillator or pacemaker.
• Have any serious or active medical or psychiatric illness (including depression).
• Requirement for ongoing therapy with or prior use of any prohibited medications listed in the protocol.

Individuals With Hepatic Impairment:

• Have a positive test result for human immunodeficiency virus (HIV) antibody, hepatitis B surface antigen (HBsAg), or hepatitis C virus (HCV) antibody with detectable HCV ribonucleic acid (RNA) at screening.
• Suspicion of hepatocellular carcinoma (ie, if alpha-fetoprotein > 20 ng/mL at screening).
• Anticipated changes in concomitant medications or dosage used to treat symptoms of hepatic impairment or associated comorbid conditions that could lead to clinically significant changes in medical conditions during the study.
• Use of known hepatotoxic medications, clinical organic anion transporting polypeptide (OATP)1B1/3 inhibitors, or sodium-taurocholate cotransporting polypeptide (NTCP) inhibitors (half-maximal inhibitory concentration (IC50) or kinetic inhibition constant [Ki] < 20 μM).
• Positive test for drugs of abuse, including alcohol at screening or admission, with the exception of opioids and tetrahydrocannabinol (marijuana) under prescription and verified by the investigator as for pain management.

Matched Control Individuals With Normal Hepatic Function:

• Have a positive test result for HIV antibody, HBsAg, or HCV antibody.
• Have a history of liver disease including Gilbert's disease.
• 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 and/or acetaminophen and/or ibuprofen and/or hormonal contraceptive medications.

Note: Other protocol defined Inclusion/Exclusion criteria may apply.

Study Plan

How is the study designed?

Design Details

• Primary Purpose: Treatment
• Allocation: Non-Randomized
• Interventional Model: Parallel Assignment
• Masking: None (Open Label)

Number of Arms

8

Arms and Interventions

Participant Group / Arm	Intervention / Treatment
Experimental: Group A: Bulevirtide (BLV) 2 mg, Moderate Hepatic Impairment; Participants with moderate hepatic impairment will receive BLV 2 mg subcutaneous (SC) injection, once daily for 6 days starting on Day 1.	Drug: Bulevirtide; 2 mg administered via subcutaneous injections.; Other Names: Myrcludex B; Hepcludex®; Drug: Bulevirtide; 10 mg administered via subcutaneous injections.; Other Names: Myrcludex B; Hepcludex®
Experimental: Group A: BLV 2 mg, Matched Control; Control group participants with normal hepatic function matched similar to moderate hepatic impairment participants will receive BLV 2 mg SC injection once daily for 6 days starting on Day 1.	Drug: Bulevirtide; 2 mg administered via subcutaneous injections.; Other Names: Myrcludex B; Hepcludex®; Drug: Bulevirtide; 10 mg administered via subcutaneous injections.; Other Names: Myrcludex B; Hepcludex®
Experimental: Group B: BLV 2 mg, Severe Hepatic Impairment; Participants with severe hepatic impairment will receive BLV 2 mg SC injection, once daily for 6 days starting on Day 1.	Drug: Bulevirtide; 2 mg administered via subcutaneous injections.; Other Names: Myrcludex B; Hepcludex®; Drug: Bulevirtide; 10 mg administered via subcutaneous injections.; Other Names: Myrcludex B; Hepcludex®
Experimental: Group B: BLV 2 mg, Matched Control; Control group participants with normal hepatic function matched similar to moderate hepatic impairment participants will receive BLV 2 mg SC injection once daily for 6 days starting on Day 1.	Drug: Bulevirtide; 2 mg administered via subcutaneous injections.; Other Names: Myrcludex B; Hepcludex®; Drug: Bulevirtide; 10 mg administered via subcutaneous injections.; Other Names: Myrcludex B; Hepcludex®
Experimental: Group C: BLV 10 mg, Moderate Hepatic Impairment; Participants with moderate hepatic impairment will receive BLV 10 mg SC injection, once daily for 6 days starting on Day 1.	Drug: Bulevirtide; 2 mg administered via subcutaneous injections.; Other Names: Myrcludex B; Hepcludex®; Drug: Bulevirtide; 10 mg administered via subcutaneous injections.; Other Names: Myrcludex B; Hepcludex®
Experimental: Group C: BLV 10 mg, Matched Control; Control group participants with normal hepatic function matched similar to moderate hepatic impairment participants will receive BLV 10 mg SC injection once daily for 6 days starting on Day 1.	Drug: Bulevirtide; 2 mg administered via subcutaneous injections.; Other Names: Myrcludex B; Hepcludex®; Drug: Bulevirtide; 10 mg administered via subcutaneous injections.; Other Names: Myrcludex B; Hepcludex®
Experimental: Group D: BLV 10 mg, Severe Hepatic Impairment; Participants with severe hepatic impairment will receive BLV 10 mg SC injection, once daily for 6 days starting on Day 1.	Drug: Bulevirtide; 2 mg administered via subcutaneous injections.; Other Names: Myrcludex B; Hepcludex®; Drug: Bulevirtide; 10 mg administered via subcutaneous injections.; Other Names: Myrcludex B; Hepcludex®
Experimental: Group D: BLV 10 mg, Matched Control; Control group participants with normal hepatic function matched similar to moderate hepatic impairment participants will receive BLV 10 mg SC injection once daily for 6 days starting on Day 1.	Drug: Bulevirtide; 2 mg administered via subcutaneous injections.; Other Names: Myrcludex B; Hepcludex®; Drug: Bulevirtide; 10 mg administered via subcutaneous injections.; Other Names: Myrcludex B; Hepcludex®

What is the study measuring?

Primary Outcome Measures

Outcome Measure	Measure Description	Time Frame
Pharmacokinetic (PK) Parameter: AUCtau of Bulevirtide (BLV)	AUCtau was defined as the area under the concentration versus time curve (AUC) over the dosing interval at steady state.	Day 6: Predose and up to 24 hours postdose
PK Parameter: Cmax,ss of BLV	Cmax,ss was defined as the maximum observed concentration of drug at steady state.	Day 6: Predose and up to 24 hours postdose

Secondary Outcome Measures

Outcome Measure	Measure Description	Time Frame
PK Parameter: AUC0-24h of BLV	AUC0-24h was defined as the partial area under the concentration versus time curve from time zero to time 24 hours.	Day 1: Predose and up to 24 hours postdose
PK Parameter: Tmax of BLV	Tmax was defined as the time (observed time point) of Cmax.	Days 1 and 6: Predose and up to 24 hours postdose
PK Parameter: Cmax of BLV	Cmax was defined as the maximum observed plasma concentration of drug.	Day 1: Predose and up to 24 hours postdose
PK Parameter: t1/2 of BLV	t1/2 was defined as estimate of the terminal elimination half-life of the drug in plasma, calculated by dividing the natural log of 2 by the terminal elimination rate constant (λz).	Day 6: Predose and up to 48 hours postdose
PK Parameter: CLss/F of BLV	CLss/F was defined as the apparent clearance at the steady state (CLss) after administration of the drug: CLss/F = Dose/AUCtau, where "Dose" is the dose of the drug per interval.	Day 6: Predose and up to 48 hours postdose
PK Parameter: Vss/F of BLV	Vss/F was defined as the apparent steady-state volume of distribution of the drug.	Day 6: Predose and up to 48 hours postdose
Pharmacodynamic (PD) Parameter: Ctrough of Total Bile Acids (BA)	Ctrough was defined as the concentration of total BA at the end of the dosing interval.	Predose on Days 2, 3, 4, 5, 7, and 8
PD Parameter: Cmax of Total BA	Cmax was defined as the maximum observed concentration of total BA.	Days 1 and 6: Predose and up to 24 hours postdose
PD Parameter: AUC0-24h of Total BA	AUC0-24 was defined as the partial area under the concentration versus time curve from time "0" to time "24" hours for total BA.	Days 1 and 6: Predose and up to 24 hours postdose
PD Parameter: NetAUC of Total BA	NetAUC was defined as the positive portion of area under the baseline-adjusted biomarker concentration versus time curve over the dosing interval.	Days 1 and 6: Predose and up to 24 hours postdose
PD Parameter: Tmax of Total BA	Tmax was defined as the time (observed time point) of Cmax of total BA.	Days 1 and 6: Predose and up to 24 hours postdose
Percentage of Participants With Treatment-emergent Adverse Events (TEAEs)	TEAEs were defined as any AEs with an onset date on or after the study drug start date and no later than 30 days after permanent discontinuation of study drug and/or any AEs leading to premature discontinuation of study drug. If the AE onset date is the same as the date of study drug start date then the AE onset time must be on or after the study drug start time. If the AE onset time is missing when the start dates were the same, the AE were considered treatment emergent. An AE was any untoward medical occurrence in a clinical study participant administered a study drug that did not necessarily had a causal relationship with the treatment.	First dose date up to Day 6 plus 30 days
Percentage of Participants With Laboratory Abnormalities	Treatment-emergent laboratory abnormalities were defined as values that increase at least 1 toxicity grade from baseline at any postbaseline time point, up to and including the date of last dose of study drug plus 30 days. If the relevant baseline laboratory value is missing, any abnormality of at least Grade 1 observed within the time frame specified above will be considered treatment emergent. Grading categories are determined by Common Terminology Criteria for Adverse Events (CTCAE) version 5.0. Grade 1: mild, Grade 2: moderate, Grade 3: severe or medically significant, Grade 4: life-threatening; Grade 5: Death.	First dose date up to Day 6 plus 30 days

Collaborators and Investigators

• Sponsor: Gilead Sciences
• Investigators: Study Director: Gilead Study Director, Gilead Sciences

Publications and helpful links

General Publications

• Kumar P, Mercier RC, Nieves W, Pan D, Tseng S, Chee GM, et al. Pharmacokinetics, Pharmacodynamics, and Safety of Bulevirtide 2 mg Once Daily for 6 Days in Participants With Moderate and Severe HI and in Matched Control Participants With Normal Hepatic Function. American Association for the Study of Liver Diseases (AASLD); 1154: 15 November 2024
• Parag Kumar, Wildaliz Nieves, David Pan, Steve Tseng, Yuejiao Jiang, Yehong Wang, Ann Qin, Teckla Akinyi, Renee-Claude Mercier. Pharmacokinetics, Pharmacodynamics, and Safety of Bulevirtide 10 mg Once Daily for 6 Days in Participants With Moderate HI and in Matched Control Participants With Normal Hepatic Function. EASL - European Association for the Study of the Liver May 7-10, 2025 Amsterdam the Netherlands

Helpful Links

• Gilead Clinical Trials Website

Study record dates

Study Major Dates

• Study Start (Actual): March 15, 2023
• Primary Completion (Actual): January 10, 2025
• Study Completion (Actual): January 13, 2025

Study Registration Dates

• First Submitted: March 1, 2023
• First Submitted That Met QC Criteria: March 1, 2023
• First Posted (Actual): March 13, 2023

Study Record Updates

• Last Update Posted (Actual): January 26, 2026
• Last Update Submitted That Met QC Criteria: January 8, 2026
• Last Verified: January 1, 2026

More Information

Terms related to this study

• Additional Relevant MeSH Terms: Pathologic Processes; Chronic Disease; Disease Attributes; Infections; RNA Virus Infections; Virus Diseases; Digestive System Diseases; Liver Diseases; Hepatitis, Viral, Human; Hepatitis, Chronic; Hepatitis; Hepatitis D; Hepatitis D, Chronic; bulevirtide; myrcludex-B
• Other Study ID Numbers: GS-US-589-6162; 2022-502054-13-00 (Other Identifier: European Medicines Agency)

Plan for Individual participant data (IPD)

• Plan to Share Individual Participant Data (IPD)?: NO

Drug and device information, study documents

• Studies a U.S. FDA-regulated drug product: Yes
• Studies a U.S. FDA-regulated device product: No