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

Chronic Hepatitis D Infection Clinical Trial

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

Clinical Trial Details — Status: Recruiting

Administrative data

• NCT number: NCT05760300
• Other study ID #: GS-US-589-6160
• Secondary ID: 2022-502054-13-0
• Status: Recruiting
• Phase: Phase 1
• Start date: March 15, 2023
• Est. completion date: May 2026

Study information

• Verified date: May 2024
• Source: Gilead Sciences
• Contact: Gilead Clinical Study Information Center
• Phone: 1-833-445-3230 (GILEAD-0)
• Email: GileadClinicalTrials[@]gilead.com
• Is FDA regulated: No
• Study type: Interventional

Clinical Trial 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.

Recruitment information / eligibility

• Status: Recruiting
• Enrollment: 80
• Est. completion date: May 2026
• Est. primary completion date: May 2026
• Accepts healthy volunteers: Accepts Healthy Volunteers
• Gender: All
• Age group: 18 Years to 79 Years

Eligibility

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

Related Conditions & MeSH terms

• Chronic Hepatitis D Infection
• Hepatitis D
• Hepatitis D, Chronic
• Renal Insufficiency

Intervention

Drug:
• Bulevirtide (BLV)
Administered via subcutaneous (SC) injections

Locations

Country	Name	City	State
United States	Massachusetts General Hospital - Renal Associates Clinic	Boston	Massachusetts
United States	Velocity Clinical Research, New Smyrna Beach	Edgewater	Florida
United States	Advanced Pharma CR, LLC	Miami	Florida
United States	Clinical Pharmacology of Miami, LLC	Miami	Florida
United States	Floridian Clinical Research, LLC	Miami Lakes	Florida
United States	Panax Clinical Research	Miami Lakes	Florida
United States	Nucleus Network	Saint Paul	Minnesota
United States	Global Clinical Professionals Research	Saint Petersburg	Florida
United States	Genesis Clinical Research, LLC	Tampa	Florida

Sponsors (1)

Lead Sponsor	Collaborator
Gilead Sciences

Country where clinical trial is conducted

United States, 

Outcome

Type	Measure	Description	Time frame	Safety issue
Primary	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.	Day 6: Predose up to 24 hours postdose
Primary	PK Parameter: Cmax ss of BLV	Cmax is defined as the maximum observed concentration of drug at steady state.	Day 6: Predose up to 24 hours postdose
Secondary	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.	Day 1: Predose up to 24 hours postdose
Secondary	PK Parameter: Cmax of BLV	Cmax is defined as the maximum observed concentration of drug.	Day 1: Predose up to 24 hours postdose
Secondary	PK Parameter: Tmax of BLV	Tmax is defined as the time (observed time point) of Cmax.	Day 1 and Day 6: Predose up to 24 hours postdose
Secondary	PK Parameter: t1/2 of BLV	t1/2 is defined as the estimate of the terminal elimination half-life of the drug.	Day 1: Predose up to 24 hours postdose and Day 6: Predose up to 48 hours postdose
Secondary	PK Parameter: CLss/F of BLV	CLss/F is defined as the apparent clearance at steady state.	Day 6: Predose up to 48 hours postdose
Secondary	PK Parameter: Vss/F of BLV	Vss/F is defined as the apparent volume of distribution at steady state.	Day 6: Predose up to 48 hours postdose
Secondary	PK Parameter: Ctrough of Total Bile Acids (BA)	Ctrough is defined as the concentration of total BA at the end of the dosing interval.	Day 2 and Day 5 (predose), Day 7, and Day 8
Secondary	PK Parameter: Cmax of Total BA	Cmax is defined as the maximum observed concentration of total BA.	Day 1 and Day 6: Predose up to 24 hours postdose
Secondary	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.	Day 1 and Day 6: Predose up to 24 hours postdose
Secondary	PK Parameter: Tmax of Total BA	Tmax is defined as the time (observed time point) of Cmax of total BA.	Day 1 and Day 6: Predose up to 24 hours postdose
Secondary	Percentage of Participants With Treatment-Emergent Adverse Events		First dose date up to 6 days plus 7 days
Secondary	Percentage of Participants With Laboratory Abnormalities		First dose date up to 6 days plus 7 days

External Links

•   Gilead Clinical Trials Website