Drug-Drug Interaction Study of Vesatolimod in Adults With HIV-1 Who Have Very Low or Undetectable Virus Levels

Human Immunodeficiency Virus Type 1 (HIV-1) Infection Clinical Trial

Official title:

A Phase 1, Open-label, Multicohort Study to Evaluate the Impact of Inhibitors and Inducers of Cytochrome P450 Enzyme (CYP)3A, P-glycoprotein (P-gp), and Breast Cancer Resistant Protein (BCRP) on the Pharmacokinetics (PK) of Vesatolimod (VES) in Virologically Suppressed Adults With HIV-1 on Antiretroviral Therapy (ART)

Clinical Trial Details — Status: Terminated

Administrative data

• NCT number: NCT05458102
• Other study ID #: GS-US-382-1587
• Status: Terminated
• Phase: Phase 1
• Start date: August 19, 2022
• Est. completion date: October 13, 2023

Study information

• Verified date: November 2023
• Source: Gilead Sciences
• Contact: n/a
• Is FDA regulated: No
• Study type: Interventional

Clinical Trial Summary

The goal of this clinical study is to learn more about the impact of cobicistat (COBI) (P-glycoprotein (P-gp), breast cancer resistance protein (BCRP), and strong cytochrome P450 enzyme [CYP]3A inhibitor), voriconazole (VOR) (strong CYP3A inhibitor), and rifabutin (RFB) (moderate CYP3A inducer) on the study drug, vesatolimod (VES), in people with HIV-1 on antiretroviral therapy (ART).

Recruitment information / eligibility

• Status: Terminated
• Enrollment: 18
• Est. completion date: October 13, 2023
• Est. primary completion date: October 13, 2023
• Accepts healthy volunteers: No
• Gender: All
• Age group: 18 Years and older

Eligibility

Key Inclusion Criteria:

• On an antiretroviral therapy (ART) regimen for at least 6 consecutive months, with no change in the ART regimen within 2 months prior to screening. Permitted ARTs are as follows:

• Cohort 1: A regimen of (BIC, DTG, RAL, or DOR) plus Nucleoside Reverse Transcriptase Inhibitors (NRTIs). Examples of acceptable regimens include BIC/emtricitabine/tenofovir, DTG/ABC/3TC, DTG/3TC, DTG + emtricitabine/tenofovir, or DOR/3TC/tenofovir

• Cohort 2: A DTG-based regimen is required (DTG/ABC/3TC), (DTG/3TC), or (DTG + NRTIs)

• Plasma HIV-1 RNA levels less than 50 copies/mL at screening

• Have normal hematologic function with an absolute neutrophil count greater than or equal to 1.5 × 10^9/L, platelets greater than or equal to 150 × 10^9/L; hemoglobin greater than or equal to 10.5 g/dL for females and greater than or equal to 11.5 g/dL for males

• Clusters of differentiation (CD) 4 T cell count greater than or equal to 350 cells/µL

• Aspartate aminotransferase (AST) and alanine aminotransferase (ALT) less than or equal to 2.5 x upper limit of normal (ULN) and total bilirubin less than or equal to 1.5 mg/dL, or normal direct bilirubin and creatinine less than or equal to 1.25 x ULN

• 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 and upon admission

• Individuals assigned female at birth and of childbearing potential who engage in heterosexual intercourse must agree to use protocol-specified method(s) of contraception

• Must be willing and able to comply with all study requirements and available to complete the study schedule of assessments

• In the judgment of the investigator, be in good general health, based on review of the results from a screening visit

Key Exclusion Criteria:

• Have received any study drug within 30 days prior to study dosing

• Participation in any other clinical study (including observation studies) without prior approval from the sponsor is prohibited while participating in this study

• 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 baseline

• No Evidence of chronic hepatitis B virus (HBV) infection (defined as positive hepatitis B surface antigen [HBsAg] and/or positive HBV core antibody with positive reflex HBV DNA polymerase chain reaction (PCR)). Note: positive HBV core antibody with negative reflex HBV DNA PCR results are acceptable

• No Evidence of active hepatitis C virus (HCV) infection (defined as positive hepatitis C antibody and HCV RNA above lower limit of quantitation). Note: positive anti-HCV antibody and negative HCV PCR results are acceptable

• Acute febrile illness within 35 days prior to Day 1

• 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

• Received any vaccine or immunomodulatory medication within 4 weeks prior to screening. Elective vaccination (eg, flu shot, hepatitis A or B vaccine) during the course of the study will require prior approval from the sponsor

• Coronavirus disease of 2019 (COVID-19) vaccinations are allowed, with the requirement that they should not be administered within 7 ± 2 days of receiving VES

• 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

• Autoimmune disease

• Significant cardiac disease 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

• Liver disease, including Gilbert syndrome

• Severe peptic ulcer disease requiring prolonged (= 6 months) medical treatment

• Medical or surgical treatment that permanently altered gastric absorption (eg, gastric or intestinal surgery). A history of cholecystectomy is not exclusionary

• Have any serious or active medical or psychiatric illness (including depression) that, in the opinion of the investigator, would interfere with individual treatment, assessment, or compliance with the protocol

• For Cohort 1, individuals with CYP2C19 genotype of CYP2C19*2/*2, CYP2C19*2/*3, or CYP2C19*3/*3

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

Related Conditions & MeSH terms

• Acquired Immunodeficiency Syndrome
• HIV Infections
• Human Immunodeficiency Virus Type 1 (HIV-1) Infection

Intervention

Drug:
• Vesatolimod
Administered orally
• Cobicistat
Administered orally
• Voriconazole
Administered orally
• Rifabutin
Administered orally

Locations

Country	Name	City	State
United States	Collaborative Neuroscience Research, LLC.	Long Beach	California
United States	Hassman Research Institute	Marlton	New Jersey
United States	Advanced Pharma, CR, LLC.	Miami	Florida
United States	Clinical Pharmacology of Miami, LLC.	Miami	Florida
United States	Triple O Research Institute, P.A.	West Palm Beach	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 : AUClast of Vesatolimod (VES)	AUClast is defined as an area under the concentration versus time curve from time zero to the last quantifiable concentration.	Predose up to 96 hours postdose
Primary	PK Parameter : AUCinf of VES	AUCinf is defined as an area under the concentration versus time curve extrapolated to infinite time, calculated as AUClast + (Clast/Lambda z).	Predose up to 96 hours postdose
Primary	PK Parameter : Cmax of VES	Cmax is defined as the maximum observed concentration of drug.	Predose up to 96 hours postdose
Primary	PK Parameter : %AUCexp of VES	%AUCexp is defined as the percentage of AUC extrapolated between AUClast and AUCinf.	Predose up to 96 hours postdose
Primary	PK Parameter : Tmax of VES	Tmax is defined as the time (observed time point) of Cmax.	Predose up to 96 hours postdose
Primary	PK Parameter : Clast of VES	Clast is defined as the last observed quantifiable concentration of the drug.	Predose up to 96 hours postdose
Primary	PK Parameter : Tlast of VES	Tlast is defined as the time (observed time point) of Clast.	Predose up to 96 hours postdose
Primary	PK Parameter : Lambda z of VES	Lambda z is defined as the terminal elimination rate constant, estimated by linear regression of the terminal elimination phase of the log concentration of drug versus time curve of the drug.	Predose up to 96 hours postdose
Primary	PK Parameter : t1/2 of VES	t1/2 is defined as the terminal elimination half-life.	Predose up to 96 hours postdose
Primary	PK Parameter : CL/F of VES	CL/F is defined as an apparent oral clearance.	Predose up to 96 hours postdose
Primary	PK Parameter : Vz/F of VES	Vz/F is defined as an apparent volume of distribution of the drug.	Predose up to 96 hours postdose
Primary	Percentage of Participants Experiencing Treatment-Emergent Adverse Events (TEAEs)		First dose date up to Week 7 plus 30 days
Primary	Percentage of Participants Experiencing Treatment-Emergent Graded Laboratory Abnormalities		First dose date up to Week 7 plus 30 days

External Links

•   Gilead Clinical Trials Website