Clinical trial NCT05760300: 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
Overall status: COMPLETED
Phase: PHASE1
Conditions: Chronic Hepatitis D Infection
Lead sponsor: Gilead Sciences
Sponsor class: INDUSTRY
First posted: 2023-03-08
Enrollment: 41
Sex: ALL
Minimum age (years): 18
Maximum age (years): 79
Standard ages: ADULT
OLDER_ADULT
Accepts healthy volunteers: yes
Allocation: NON_RANDOMIZED
Intervention model: PARALLEL
Primary purpose: TREATMENT

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.


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

Primary outcomes:
measure: Pharmacokinetic (PK) Parameter: AUCtau of Bulevirtide (BLV)
timeFrame: Day 6: Predose up to 24 hours postdose
measure: PK Parameter: Cmax ss of BLV
timeFrame: Day 6: Predose up to 24 hours postdose
Secondary outcomes:
measure: PK Parameter: AUC0-24 of BLV
timeFrame: Day 1: Predose up to 24 hours postdose
measure: PK Parameter: Cmax of BLV
timeFrame: Day 1: Predose up to 24 hours postdose
measure: PK Parameter: Tmax of BLV
timeFrame: Day 1 and Day 6: Predose up to 24 hours postdose
measure: PK Parameter: t1/2 of BLV
timeFrame: Day 1: Predose up to 24 hours postdose and Day 6: Predose up to 48 hours postdose
measure: PK Parameter: CLss/F of BLV
timeFrame: Day 6: Predose up to 48 hours postdose
measure: PK Parameter: Vss/F of BLV
timeFrame: Day 6: Predose up to 48 hours postdose
measure: PK Parameter: Ctrough of Total Bile Acids (BA)
timeFrame: Day 2 and Day 5 (predose), Day 7, and Day 8
measure: PK Parameter: Cmax of Total BA
timeFrame: Day 1 and Day 6: Predose up to 24 hours postdose
measure: PK Parameter: AUC0-24 of Total BA
timeFrame: Day 1 and Day 6: Predose up to 24 hours postdose
measure: PK Parameter: Tmax of Total BA
timeFrame: Day 1 and Day 6: Predose up to 24 hours postdose
measure: Percentage of Participants With Treatment-Emergent Adverse Events
timeFrame: First dose date up to 6 days plus 7 days
measure: Percentage of Participants With Laboratory Abnormalities
timeFrame: First dose date up to 6 days plus 7 days
Other outcomes:
Locations:
city: Edgewater
country: United States
facility: Velocity Clinical Research, New Smyrna Beach
state: Florida
city: Miami Lakes
country: United States
facility: Panax Clinical Research
state: Florida
city: Miami Lakes
country: United States
facility: Floridian Clinical Research, LLC
state: Florida
city: Miami
country: United States
facility: Clinical Pharmacology of Miami, LLC
state: Florida
city: Miami
country: United States
facility: Advanced Pharma CR, LLC
state: Florida
city: Saint Petersburg
country: United States
facility: Global Clinical Professionals Research
state: Florida
city: Tampa
country: United States
facility: Genesis Clinical Research, LLC
state: Florida
city: Boston
country: United States
facility: Massachusetts General Hospital - Renal Associates Clinic
state: Massachusetts
city: Saint Paul
country: United States
facility: Nucleus Network
state: Minnesota
Study officials:
affiliation: Gilead Sciences
name: Gilead Study Director
role: STUDY_DIRECTOR
References: