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

Primary Purpose

Chronic Hepatitis D Infection

Status
Recruiting
Phase
Phase 1
Locations
United States
Study Type
Interventional
Intervention
Bulevirtide (BLV)
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 ≥ 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. Key Exclusion Criteria: 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 Note: Other protocol defined Inclusion/Exclusion criteria may apply

Sites / Locations

  • Velocity Clinical Research, New Smyrna BeachRecruiting
  • Floridian Clinical Research, LLCRecruiting
  • Clinical Pharmacology of Miami, LLCRecruiting
  • Advanced Pharma CR, LLCRecruiting
  • Genesis Clinical Research, LLCRecruiting
  • Nucleus NetworkRecruiting

Arms of the Study

Arm 1

Arm 2

Arm Type

Experimental

Experimental

Arm Label

Group A: Bulevirtide (BLV), Severe Renal Impaired Participants

Group A: BLV, Normal Renal Function (Matched Control Participants)

Arm Description

Participants with severe renal impairment will receive BLV 2 mg once daily for 6 days. Following completion and evaluation of pharmacokinetics (PK) and safety data from all participants in Group A, additional participant groups (Groups B, C, and D) and BLV doses (2 mg or 10 mg) may be initiated.

Participants with normal renal function will receive BLV 2 mg once daily for 6 days. Following completion and evaluation of PK and safety data from all participants in Group A, additional participant groups (Groups B, C, and D) and BLV doses (2 mg or 10 mg) may be initiated.

Outcomes

Primary Outcome Measures

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

Secondary Outcome Measures

PK Parameter: AUC0-24 of BLV
AUC0-24 is defined as the concentration of drug over time between time 0 hour and time 24 hours.
PK Parameter: Cmax of BLV
Cmax is defined as the maximum observed concentration of drug.
PK Parameter: Tmax of BLV
Tmax is defined as the time (observed time point) of Cmax.
PK Parameter: t1/2 of BLV
t1/2 is defined as the estimate of the terminal elimination half-life of the drug.
PK Parameter: CLss/F of BLV
CLss/F is defined as the apparent clearance at steady state.
PK Parameter: Vss/F of BLV
Vss/F is defined as the apparent volume of distribution at steady state.
PK Parameter: Ctrough of Total Bile Acids (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: AUC0-24 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
February 27, 2023
Last Updated
October 13, 2023
Sponsor
Gilead Sciences
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1. Study Identification

Unique Protocol Identification Number
NCT05760300
Brief Title
A Multiple-Dose Study of Bulevirtide in Participants With Normal and Impaired Renal Function
Official Title
A Phase 1 Open-Label, Parallel-Design, Multiple-Dose Study to Evaluate the Pharmacokinetics, Pharmacodynamics, and Safety of Bulevirtide in Participants With Normal and Impaired Renal 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
May 2026 (Anticipated)
Study Completion Date
May 2026 (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 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.

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
80 (Anticipated)

8. Arms, Groups, and Interventions

Arm Title
Group A: Bulevirtide (BLV), Severe Renal Impaired Participants
Arm Type
Experimental
Arm Description
Participants with severe renal impairment will receive BLV 2 mg once daily for 6 days. Following completion and evaluation of pharmacokinetics (PK) and safety data from all participants in Group A, additional participant groups (Groups B, C, and D) and BLV doses (2 mg or 10 mg) may be initiated.
Arm Title
Group A: BLV, Normal Renal Function (Matched Control Participants)
Arm Type
Experimental
Arm Description
Participants with normal renal function will receive BLV 2 mg once daily for 6 days. Following completion and evaluation of PK and safety data from all participants in Group A, additional participant groups (Groups B, C, and D) and BLV doses (2 mg or 10 mg) may be initiated.
Intervention Type
Drug
Intervention Name(s)
Bulevirtide (BLV)
Other Intervention Name(s)
Hepcludex®, Myrcludex B
Intervention Description
Administered via subcutaneous (SC) injections
Primary Outcome Measure Information:
Title
Pharmacokinetic (PK) Parameter: AUCtau of Bulevirtide (BLV)
Description
AUCtau is defined as area under the concentration versus time curve over the dosing interval at steady state.
Time Frame
Day 6: Predose up to 24 hours postdose
Title
PK Parameter: Cmax ss of BLV
Description
Cmax is defined as the maximum observed concentration of drug at steady state.
Time Frame
Day 6: Predose up to 24 hours postdose
Secondary Outcome Measure Information:
Title
PK Parameter: AUC0-24 of BLV
Description
AUC0-24 is defined as the concentration of drug over time between time 0 hour and time 24 hours.
Time Frame
Day 1: Predose 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 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
Day 1 and Day 6: Predose up to 24 hours postdose
Title
PK Parameter: t1/2 of BLV
Description
t1/2 is defined as the estimate of the terminal elimination half-life of the drug.
Time Frame
Day 1: Predose up to 24 hours postdose and Day 6: Predose up to 48 hours postdose
Title
PK Parameter: CLss/F of BLV
Description
CLss/F is defined as the apparent clearance at steady state.
Time Frame
Day 6: Predose up to 48 hours postdose
Title
PK Parameter: Vss/F of BLV
Description
Vss/F is defined as the apparent volume of distribution at steady state.
Time Frame
Day 6: Predose up to 48 hours postdose
Title
PK Parameter: Ctrough of Total Bile Acids (BA)
Description
Ctrough is defined as the concentration of total BA at the end of the dosing interval.
Time Frame
Day 2 and 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
Day 1 and Day 6: Predose up to 24 hours postdose
Title
PK Parameter: AUC0-24 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
Day 1 and Day 6: Predose 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
Day 1 and Day 6: Predose 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 ≥ 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. Key Exclusion Criteria: 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 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
Velocity Clinical Research, New Smyrna Beach
City
Edgewater
State/Province
Florida
ZIP/Postal Code
32132
Country
United States
Individual Site Status
Recruiting
Facility Name
Floridian Clinical Research, LLC
City
Miami Lakes
State/Province
Florida
ZIP/Postal Code
33016
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
Advanced Pharma CR, LLC
City
Miami
State/Province
Florida
ZIP/Postal Code
33147
Country
United States
Individual Site Status
Recruiting
Facility Name
Genesis Clinical Research, LLC
City
Tampa
State/Province
Florida
ZIP/Postal Code
33603
Country
United States
Individual Site Status
Recruiting
Facility Name
Nucleus Network
City
Saint Paul
State/Province
Minnesota
ZIP/Postal Code
55114
Country
United States
Individual Site Status
Recruiting

12. IPD Sharing Statement

Plan to Share IPD
No
Links:
URL
https://www.gileadclinicaltrials.com/study?nctid=NCT05760300
Description
Gilead Clinical Trials Website

Learn more about this trial

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

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