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

Primary Purpose

Chronic Hepatitis D Infection

Status
Recruiting
Phase
Phase 1
Locations
United States
Study Type
Interventional
Intervention
Bulevirtide
Sponsored by
Gilead Sciences
About
Eligibility
Locations
Arms
Outcomes
Full info

About this trial

This is an interventional treatment trial for Chronic Hepatitis D Infection

Eligibility Criteria

18 Years - 79 Years (Adult, Older Adult)All SexesAccepts Healthy Volunteers

Key Inclusion Criteria: All individuals: Body mass index (BMI) of at least 19 and no greater than 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, α-fetoprotein, 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%, 19 ≤ BMI ≤ 40 kg/m^2) with a 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. Severe peptic ulcer disease, gastroesophageal reflux disease, or other gastric acid hypersecretory conditions requiring prolonged (≥ 6 months) medical treatment. 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.

Sites / Locations

  • Orange County Research CenterRecruiting
  • Clinical Pharmacology of Miami, LLCRecruiting
  • Orlando Clinical Research CenterRecruiting
  • Texas Liver InstituteRecruiting
  • Pinnacle Clinical Research LLCRecruiting

Arms of the Study

Arm 1

Arm 2

Arm 3

Arm Type

Experimental

Experimental

Experimental

Arm Label

Bulevirtide (BLV), Moderate Hepatic Impairment

BLV, Severe Hepatic Impairment

BLV, Normal Hepatic Function (Matched Control Participants)

Arm Description

Participants with moderate hepatic impairment will receive BLV 2 mg injection once daily for 6 days starting on Day 1. Following completion and evaluation of pharmacokinetics (PK) and safety data, additional participant groups and BLV doses may be initiated.

Participants with severe hepatic impairment will receive BLV 2 mg injection once daily for 6 days starting on Day 1. Following completion and evaluation of PK and safety data, additional participant groups and BLV doses may be initiated.

Participants with normal hepatic function will receive BLV 2 mg once daily for 6 days.

Outcomes

Primary Outcome Measures

Pharmacokinetic (PK) Parameter: AUCtau of Bulevirtide (BLV)
AUCtau is defined as the area under the concentration versus time curve over the dosing interval at steady state.
PK Parameter: Cmax,ss of BLV
Cmax,ss is defined as the maximum observed concentration of drug at steady state.

Secondary Outcome Measures

PK Parameter: AUC0-24h of BLV
AUC0-24h is defined as the partial area under the concentration versus time curve from time zero to time 24 hours.
PK Parameter: Tmax of BLV
Tmax is defined as the time (observed time point) of Cmax.
PK Parameter: Cmax of BLV
Cmax is defined as the maximum observed concentration of drug.
PK Parameter: t1/2 of BLV
t1/2 is defined as the terminal elimination half-life.
PK Parameter: CLss/F of BLV
CLss/F is defined as the apparent oral clearance at steady state.
PK Parameter: Vss/Fv of BLV
Vss/F is defined as the apparent steady-state volume of distribution of the drug.
PK Parameter: Ctrough of Total Bile Acid (BA)
Ctrough is defined as the concentration of total BA at the end of the dosing interval.
PK Parameter: Cmax of Total BA
Cmax is defined as the maximum observed concentration of total BA.
PK Parameter: AUC0-24h of Total BA
AUC0-24 is defined as the concentration of total BA over time between time 0 hour and time 24 hours.
PK Parameter: Tmax of Total BA
Tmax is defined as the time (observed time point) of Cmax of total BA.
Percentage of Participants with Treatment-emergent Adverse Events
Percentage of Participants with Laboratory Abnormalities

Full Information

First Posted
March 1, 2023
Last Updated
October 5, 2023
Sponsor
Gilead Sciences
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1. Study Identification

Unique Protocol Identification Number
NCT05765344
Brief Title
Study of Bulevirtide in Participants Who Have Normal or Impaired Liver Function
Official Title
A Phase 1, Open-label, Parallel-group, Multiple-dose Study to Evaluate the Pharmacokinetics of Bulevirtide in Participants With Normal and Impaired Hepatic Function
Study Type
Interventional

2. Study Status

Record Verification Date
October 2023
Overall Recruitment Status
Recruiting
Study Start Date
March 15, 2023 (Actual)
Primary Completion Date
February 2025 (Anticipated)
Study Completion Date
February 2025 (Anticipated)

3. Sponsor/Collaborators

Responsible Party, by Official Title
Sponsor
Name of the Sponsor
Gilead Sciences

4. Oversight

Studies a U.S. FDA-regulated Drug Product
Yes
Studies a U.S. FDA-regulated Device Product
No
Data Monitoring Committee
No

5. Study Description

Brief Summary
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.

6. Conditions and Keywords

Primary Disease or Condition Being Studied in the Trial, or the Focus of the Study
Chronic Hepatitis D Infection

7. Study Design

Primary Purpose
Treatment
Study Phase
Phase 1
Interventional Study Model
Parallel Assignment
Masking
None (Open Label)
Allocation
Non-Randomized
Enrollment
72 (Anticipated)

8. Arms, Groups, and Interventions

Arm Title
Bulevirtide (BLV), Moderate Hepatic Impairment
Arm Type
Experimental
Arm Description
Participants with moderate hepatic impairment will receive BLV 2 mg injection once daily for 6 days starting on Day 1. Following completion and evaluation of pharmacokinetics (PK) and safety data, additional participant groups and BLV doses may be initiated.
Arm Title
BLV, Severe Hepatic Impairment
Arm Type
Experimental
Arm Description
Participants with severe hepatic impairment will receive BLV 2 mg injection once daily for 6 days starting on Day 1. Following completion and evaluation of PK and safety data, additional participant groups and BLV doses may be initiated.
Arm Title
BLV, Normal Hepatic Function (Matched Control Participants)
Arm Type
Experimental
Arm Description
Participants with normal hepatic function will receive BLV 2 mg once daily for 6 days.
Intervention Type
Biological
Intervention Name(s)
Bulevirtide
Other Intervention Name(s)
Hepcludex®, Myrcludex B
Intervention Description
Administered via subcutaneous injections.
Primary Outcome Measure Information:
Title
Pharmacokinetic (PK) Parameter: AUCtau of Bulevirtide (BLV)
Description
AUCtau is defined as the area under the concentration versus time curve over the dosing interval at steady state.
Time Frame
Day 6: Predose and up to 24 hours postdose
Title
PK Parameter: Cmax,ss of BLV
Description
Cmax,ss is defined as the maximum observed concentration of drug at steady state.
Time Frame
Day 6: Predose and up to 24 hours postdose
Secondary Outcome Measure Information:
Title
PK Parameter: AUC0-24h of BLV
Description
AUC0-24h is defined as the partial area under the concentration versus time curve from time zero to time 24 hours.
Time Frame
Day 1: Predose and up to 24 hours postdose
Title
PK Parameter: Tmax of BLV
Description
Tmax is defined as the time (observed time point) of Cmax.
Time Frame
Days 1 and 6: Predose and up to 24 hours postdose
Title
PK Parameter: Cmax of BLV
Description
Cmax is defined as the maximum observed concentration of drug.
Time Frame
Day 1: Predose and up to 24 hours postdose
Title
PK Parameter: t1/2 of BLV
Description
t1/2 is defined as the terminal elimination half-life.
Time Frame
Day 1: Predose and up to 24 hours postdose; Day 6: Predose and up to 48 hours postdose
Title
PK Parameter: CLss/F of BLV
Description
CLss/F is defined as the apparent oral clearance at steady state.
Time Frame
Day 6: Predose and up to 48 hours postdose
Title
PK Parameter: Vss/Fv of BLV
Description
Vss/F is defined as the apparent steady-state volume of distribution of the drug.
Time Frame
Day 6: Predose and up to 48 hours postdose
Title
PK Parameter: Ctrough of Total Bile Acid (BA)
Description
Ctrough is defined as the concentration of total BA at the end of the dosing interval.
Time Frame
Day 2 up to Day 5 (predose), Day 7, and Day 8
Title
PK Parameter: Cmax of Total BA
Description
Cmax is defined as the maximum observed concentration of total BA.
Time Frame
Days 1 and 6: Predose and up to 24 hours postdose
Title
PK Parameter: AUC0-24h of Total BA
Description
AUC0-24 is defined as the concentration of total BA over time between time 0 hour and time 24 hours.
Time Frame
Days 1 and 6: Predose and up to 24 hours postdose
Title
PK Parameter: Tmax of Total BA
Description
Tmax is defined as the time (observed time point) of Cmax of total BA.
Time Frame
Days 1 and 6: Predose and up to 24 hours postdose
Title
Percentage of Participants with Treatment-emergent Adverse Events
Time Frame
First dose date up to 6 days plus 7 days
Title
Percentage of Participants with Laboratory Abnormalities
Time Frame
First dose date up to 6 days plus 7 days

10. Eligibility

Sex
All
Minimum Age & Unit of Time
18 Years
Maximum Age & Unit of Time
79 Years
Accepts Healthy Volunteers
Accepts Healthy Volunteers
Eligibility Criteria
Key Inclusion Criteria: All individuals: Body mass index (BMI) of at least 19 and no greater than 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, α-fetoprotein, 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%, 19 ≤ BMI ≤ 40 kg/m^2) with a 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. Severe peptic ulcer disease, gastroesophageal reflux disease, or other gastric acid hypersecretory conditions requiring prolonged (≥ 6 months) medical treatment. 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.
Central Contact Person:
First Name & Middle Initial & Last Name or Official Title & Degree
Gilead Clinical Study Information Center
Phone
1-833-445-3230 (GILEAD-0)
Email
GileadClinicalTrials@gilead.com
Overall Study Officials:
First Name & Middle Initial & Last Name & Degree
Gilead Study Director
Organizational Affiliation
Gilead Sciences
Official's Role
Study Director
Facility Information:
Facility Name
Orange County Research Center
City
Tustin
State/Province
California
ZIP/Postal Code
92780
Country
United States
Individual Site Status
Recruiting
Facility Name
Clinical Pharmacology of Miami, LLC
City
Miami
State/Province
Florida
ZIP/Postal Code
33014
Country
United States
Individual Site Status
Recruiting
Facility Name
Orlando Clinical Research Center
City
Orlando
State/Province
Florida
ZIP/Postal Code
32809
Country
United States
Individual Site Status
Recruiting
Facility Name
Texas Liver Institute
City
San Antonio
State/Province
Texas
ZIP/Postal Code
78215
Country
United States
Individual Site Status
Recruiting
Facility Name
Pinnacle Clinical Research LLC
City
San Antonio
State/Province
Texas
ZIP/Postal Code
78229
Country
United States
Individual Site Status
Recruiting

12. IPD Sharing Statement

Plan to Share IPD
No
Links:
URL
https://www.gileadclinicaltrials.com/study/?id=GS-US-589-6162
Description
Gilead Clinical Trials Website

Learn more about this trial

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

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