Human Immunodeficiency Virus Type 1 (HIV-1) InfectionPhase 1NCT05458102

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

A Phase 1 study testing Vesatolimod, Cobicistat and Voriconazole in people with Human Immunodeficiency Virus Type 1 (HIV-1) Infection, run by Gilead Sciences at 5 sites in United States.

Terminated

Stopped early. The study ended before it was planned to and will not resume.

Official record

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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… Read more about this study

Who is it for?: Ages 18 years and older
Conditions the study is for: Human Immunodeficiency Virus Type 1 (HIV-1) Infection
What is being tested?: Vesatolimod, Cobicistat and Voriconazole
Type of treatment: Pill or oral medicine
Could I receive a placebo?: No, everyone receives an active treatment
How many people: 18 participants
Where: 5 sitesUnited States
Study dates: 19 Aug 2022to 1 May 2023
Phase: Phase 1
Are there results?: Yes, posted in the registrySummary in the doctors' view

Key requirements

Who can take part, as listed by the sponsor. Only the study team can confirm whether you are eligible, so take this list to your doctor.

Ages 18 years and older
All sexes
No healthy volunteers
Adult, Older adult

Who may be able to join

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 (bictegravir [BIC], dolutegravir [DTG], raltegravir [RAL], or doravirine [DOR]) plus Nucleoside Reverse Transcriptase Inhibitors (NRTIs). Examples of acceptable regimens include BIC/emtricitabine/tenofovir, DTG/ abacavir (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

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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

Who cannot join

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

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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.

Trial locations and contacts

5 sites in 1 country.

City, postcode or hospital

5 sites in 1 country

United States5 sites

Collaborative Neuroscience Research, LLC.
Long Beach, California, 90806
Hassman Research Institute
Marlton, New Jersey, 08054
Clinical Pharmacology of Miami, LLC.
Miami, Florida, 33014
Advanced Pharma, CR, LLC.
Miami, Florida, 33147
Triple O Research Institute, P.A.
West Palm Beach, Florida, 33407

Other trials in United States

About this study

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

Conditions: Human Immunodeficiency Virus Type 1 (HIV-1) Infection
Being tested: Vesatolimod, Cobicistat, Voriconazole, Rifabutin
Medical subject headings: Acquired Immunodeficiency Syndrome, Infections

What participants receive

What participants receive. In a randomised study each person is assigned to one group by chance.

VesatolimodDrug
Also called GS-9620
Administered orally
CobicistatDrug
Also called Tybost®
Administered orally
VoriconazoleDrug
Also called Vfend®
Administered orally
RifabutinDrug
Also called Mycobutin®
Administered orally

Study groups in NCT05458102
Study group	Role	What they receive
Cohort 1: Vesatolimod + Cobicistat + Voriconazole	Experimental	Participants will receive a single dose of vesatolimod (VES) 2 mg on Day 1 of Period 1. In Period 2, participants will receive cobicistat (COBI) 150 mg once daily on Days 1 to 5 along with a single dose of VES 2 mg on Day 2. In Period 3, participants will receive a loading dose of voriconazole (VOR) 400 mg twice daily on Day 1, then VOR 200 mg twice daily on Days 2 to 6, and a single dose of VES 2 mg in the morning on Day 3. There will be a washout period of 7 to 14 days between treatments in Period 1 Day 1 and Period 2 Day 1 and a washout period of 14 to 21 days between treatments in Period 2 Day 5 and Period 3 Day 1. Receives: Drug: Vesatolimod; Drug: Cobicistat; Drug: Voriconazole
Cohort 2: Vesatolimod + Rifabutin	Experimental	Participants will receive a single dose of VES 6 mg on Day 1. In Period 2, participants will receive Rifabutin (RFB) 300 mg once daily on Days 1 to 9 along with a single dose of VES 6 mg on Day 6. There will be a washout period of 7 to 14 days between treatments in Period 1 Day 1 and Period 2 Day 1. Receives: Drug: Vesatolimod; Drug: Rifabutin

What is being measured

The primary outcome is the main question the study is designed to answer.

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.
Cohort 1 Period 1 Day 1: Day 1 from Baseline; Cohort 1 Period 2 Day 2: Up to Day 17 from Baseline; Cohort 1 Period 3 Day 3: Up to Day 44 from Baseline; Cohort 2 Period 1 Day 1: Day 1 from Baseline; Cohort 2 Period 2 Day 6: Up to Day 21 from Baseline.
Measured: Pre-dose and 0.25, 0.5, 1, 1.5, 2, 2.5, 3, 4, 6, 8, 12, 24, 48, 72, and 96 hours post-dose for Cohort 1 on Period 1 Day 1, Period 2 Day 2, and Period 3 Day 3; and for Cohort 2 on Period 1 Day 1 and Period 2 Day 6
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).
Cohort 1 Period 1 Day 1: Day 1 from Baseline; Cohort 1 Period 2 Day 2: Up to Day 17 from Baseline; Cohort 1 Period 3 Day 3: Up to Day 44 from Baseline; Cohort 2 Period 1 Day 1: Day 1 from Baseline; Cohort 2 Period 2 Day 6: Up to Day 21 from Baseline.
Measured: Pre-dose and 0.25, 0.5, 1, 1.5, 2, 2.5, 3, 4, 6, 8, 12, 24, 48, 72, and 96 hours post-dose for Cohort 1 on Period 1 Day 1, Period 2 Day 2, and Period 3 Day 3; and for Cohort 2 on Period 1 Day 1 and Period 2 Day 6
PK Parameter : Cmax of VES
Cmax is defined as the maximum observed concentration of drug.
Cohort 1 Period 1 Day 1: Day 1 from Baseline; Cohort 1 Period 2 Day 2: Up to Day 17 from Baseline; Cohort 1 Period 3 Day 3: Up to Day 44 from Baseline; Cohort 2 Period 1 Day 1: Day 1 from Baseline; Cohort 2 Period 2 Day 6: Up to Day 21 from Baseline.
Measured: Pre-dose and 0.25, 0.5, 1, 1.5, 2, 2.5, 3, 4, 6, 8, 12, 24, 48, 72, and 96 hours post-dose for Cohort 1 on Period 1 Day 1, Period 2 Day 2, and Period 3 Day 3; and for Cohort 2 on Period 1 Day 1 and Period 2 Day 6
PK Parameter : %AUCexp of VES
%AUCexp is defined as the percentage of AUC extrapolated between AUClast and AUCinf, calculated as ([AUCinf-AUClast]/AUCinf)*100.
Cohort 1 Period 1 Day 1: Day 1 from Baseline; Cohort 1 Period 2 Day 2: Up to Day 17 from Baseline; Cohort 1 Period 3 Day 3: Up to Day 44 from Baseline; Cohort 2 Period 1 Day 1: Day 1 from Baseline; Cohort 2 Period 2 Day 6: Up to Day 21 from Baseline.
Measured: Pre-dose and 0.25, 0.5, 1, 1.5, 2, 2.5, 3, 4, 6, 8, 12, 24, 48, 72, and 96 hours post-dose for Cohort 1 on Period 1 Day 1, Period 2 Day 2, and Period 3 Day 3; and for Cohort 2 on Period 1 Day 1 and Period 2 Day 6
PK Parameter : Tmax of VES
Tmax is defined as the time (observed time point) of Cmax.
Cohort 1 Period 1 Day 1: Day 1 from Baseline; Cohort 1 Period 2 Day 2: Up to Day 17 from Baseline; Cohort 1 Period 3 Day 3: Up to Day 44 from Baseline; Cohort 2 Period 1 Day 1: Day 1 from Baseline; Cohort 2 Period 2 Day 6: Up to Day 21 from Baseline.
Measured: Pre-dose and 0.25, 0.5, 1, 1.5, 2, 2.5, 3, 4, 6, 8, 12, 24, 48, 72, and 96 hours post-dose for Cohort 1 on Period 1 Day 1, Period 2 Day 2, and Period 3 Day 3; and for Cohort 2 on Period 1 Day 1 and Period 2 Day 6
PK Parameter : Clast of VES
Clast is defined as the last observed quantifiable concentration of the drug.
Cohort 1 Period 1 Day 1: Day 1 from Baseline; Cohort 1 Period 2 Day 2: Up to Day 17 from Baseline; Cohort 1 Period 3 Day 3: Up to Day 44 from Baseline; Cohort 2 Period 1 Day 1: Day 1 from Baseline; Cohort 2 Period 2 Day 6: Up to Day 21 from Baseline.
Measured: Pre-dose and 0.25, 0.5, 1, 1.5, 2, 2.5, 3, 4, 6, 8, 12, 24, 48, 72, and 96 hours post-dose for Cohort 1 on Period 1 Day 1, Period 2 Day 2, and Period 3 Day 3; and for Cohort 2 on Period 1 Day 1 and Period 2 Day 6
PK Parameter : Tlast of VES
Tlast is defined as the time (observed time point) of Clast.
Cohort 1 Period 1 Day 1: Day 1 from Baseline; Cohort 1 Period 2 Day 2: Up to Day 17 from Baseline; Cohort 1 Period 3 Day 3: Up to Day 44 from Baseline; Cohort 2 Period 1 Day 1: Day 1 from Baseline; Cohort 2 Period 2 Day 6: Up to Day 21 from Baseline.
Measured: Pre-dose and 0.25, 0.5, 1, 1.5, 2, 2.5, 3, 4, 6, 8, 12, 24, 48, 72, and 96 hours post-dose for Cohort 1 on Period 1 Day 1, Period 2 Day 2, and Period 3 Day 3; and for Cohort 2 on Period 1 Day 1 and Period 2 Day 6
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.
Cohort 1 Period 1 Day 1: Day 1 from Baseline; Cohort 1 Period 2 Day 2: Up to Day 17 from Baseline; Cohort 1 Period 3 Day 3: Up to Day 44 from Baseline; Cohort 2 Period 1 Day 1: Day 1 from Baseline; Cohort 2 Period 2 Day 6: Up to Day 21 from Baseline.
Measured: Pre-dose and 0.25, 0.5, 1, 1.5, 2, 2.5, 3, 4, 6, 8, 12, 24, 48, 72, and 96 hours post-dose for Cohort 1 on Period 1 Day 1, Period 2 Day 2, and Period 3 Day 3; and for Cohort 2 on Period 1 Day 1 and Period 2 Day 6
PK Parameter : t1/2 of VES
t1/2 is defined as the terminal elimination half-life.
Cohort 1 Period 1 Day 1: Day 1 from Baseline; Cohort 1 Period 2 Day 2: Up to Day 17 from Baseline; Cohort 1 Period 3 Day 3: Up to Day 44 from Baseline; Cohort 2 Period 1 Day 1: Day 1 from Baseline; Cohort 2 Period 2 Day 6: Up to Day 21 from Baseline.
Measured: Pre-dose and 0.25, 0.5, 1, 1.5, 2, 2.5, 3, 4, 6, 8, 12, 24, 48, 72, and 96 hours post-dose for Cohort 1 on Period 1 Day 1, Period 2 Day 2, and Period 3 Day 3; and for Cohort 2 on Period 1 Day 1 and Period 2 Day 6
PK Parameter : CL/F of VES
CL/F is defined as an apparent oral clearance.
Cohort 1 Period 1 Day 1: Day 1 from Baseline; Cohort 1 Period 2 Day 2: Up to Day 17 from Baseline; Cohort 1 Period 3 Day 3: Up to Day 44 from Baseline; Cohort 2 Period 1 Day 1: Day 1 from Baseline; Cohort 2 Period 2 Day 6: Up to Day 21 from Baseline.
Measured: Pre-dose and 0.25, 0.5, 1, 1.5, 2, 2.5, 3, 4, 6, 8, 12, 24, 48, 72, and 96 hours post-dose for Cohort 1 on Period 1 Day 1, Period 2 Day 2, and Period 3 Day 3; and for Cohort 2 on Period 1 Day 1 and Period 2 Day 6
PK Parameter : Vz/F of VES
Vz/F is defined as an apparent volume of distribution of the drug.
Cohort 1 Period 1 Day 1: Day 1 from Baseline; Cohort 1 Period 2 Day 2: Up to Day 17 from Baseline; Cohort 1 Period 3 Day 3: Up to Day 44 from Baseline; Cohort 2 Period 1 Day 1: Day 1 from Baseline; Cohort 2 Period 2 Day 6: Up to Day 21 from Baseline.
Measured: Pre-dose and 0.25, 0.5, 1, 1.5, 2, 2.5, 3, 4, 6, 8, 12, 24, 48, 72, and 96 hours post-dose for Cohort 1 on Period 1 Day 1, Period 2 Day 2, and Period 3 Day 3; and for Cohort 2 on Period 1 Day 1 and Period 2 Day 6
Percentage of Participants Who Experienced Treatment-Emergent Adverse Events (TEAEs)
An adverse event (AE) is any untoward medical occurrence in a clinical study participant administered a study drug that does not necessarily have a causal relationship with the treatment. An AE can, therefore, be any unfavorable and/or unintended sign, symptom, or disease temporally associated with the use of a study drug, whether or not considered related to the study drug. Adverse events may also include pretreatment or posttreatment complications that occur as a result of protocol-specified procedures, or special situations. TEAES included all AEs began on or after the study drug start date.
Measured: First dose date up to last dose date plus 30 days (up to 77 days for Cohort 1, and up to 54 days for Cohort 2)
Percentage of Participants Who Experienced Treatment-Emergent Laboratory Abnormalities
A treatment-emergent laboratory abnormality was defined as an increase of at least 1 toxicity grade from predose at any time postdose. Data for participants with post baseline toxicity grade 1 or higher is reported.
Measured: First dose date up to last dose date plus 30 days (up to 77 days for Cohort 1, and up to 54 days for Cohort 2)

Timeline

From the start of the study to its completion; the mark is today. Estimated dates are the sponsor’s plan.

19 Aug 20221 May 2023

First posted14 Jul 2022
Study start19 Aug 2022
Primary completion1 May 2023
Study completion1 May 2023

Why it stopped: Sponsor's decision to change the clinical development plan of this molecule. This decision is not based on efficacy or safety concerns.

Resources

Official record on ClinicalTrials.govThe registry entry this page is built from, with its full change history.
Posted resultsParticipant flow, outcome measures and adverse events reported by the sponsor.
Publications (1)Papers the sponsor has linked to this study.
Other trials for Human Immunodeficiency Virus Type 1 (HIV-1) InfectionStudies of the same condition, open and under way.
More trials run by Gilead SciencesThe sponsor's other registered studies.
What the trial phases meanHow a treatment moves from first tests in people to approval.

More details

For doctors and researchers: how the study is designed, who runs it, and its registry IDs.

Study design

Study type: Interventional
Phase: Phase 1
Primary purpose: Treatment
Allocation: Non-randomised
Intervention model: Parallel groups
Masking: None (open label)
Enrolment: 18 participants (actual)

IDs, dates and publications

ClinicalTrials.gov ID: NCT05458102
Sponsor's protocol ID: GS-US-382-1587
Status last verified: Oct 2024
First submitted: 11 Jul 2022
Last updated: 3 Dec 2024
Results posted: Yes, on ClinicalTrials.gov
Data monitoring committee: No
FDA-regulated drug: Yes
FDA-regulated device: No
Individual data sharing: No

Publications

Zheng Y, Wire M, Omange RW, deVries CR, Zhang L, Chen B, Huang SSY, Cruz K, Hassman H, Osiyemi O, Rondon JC, Lim D, West S, Wen A, Wallin JJ, SenGupta D, Cai Y. The Effects of Cobicistat and Voriconazole on the Safety, Pharmacokinetics, and Pharmacodynamics of the TLR7 Agonist Vesatolimod in People with HIV. Infect Dis Ther. 2025 Nov;14(11):2535-2549. doi: 10.1007/s40121-025-01227-x. Epub 2025 Sep 15.
PubMed 40952649

Want to know more?

The sponsor has not listed a contact. The official record may have more details.

Talk to your doctor first and take this page with you. Only the study team can confirm whether you can join.

Questions to ask the study team

What is the study trying to find out?
What would I need to do, and how often would I visit?
Could I receive a placebo instead of the treatment?
What are the possible risks and benefits for me?
Will it cost me anything? Are travel or time paid for?
Can I keep seeing my own doctor during the study?
What happens when the study ends?

See locations

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Study at a glance

From the registry record, last updated by the sponsor on 3 Dec 2024. Recruitment status is as the sponsor reported it: confirm with the study team.

Official title: A Phase 1, Open-label, Multicohort Study to Evaluate the Impact of Inhibitors and Inducers of Cytochrome P450 Enzyme (CYP)3A and/or P-glycoprotein (P-gp) on the Pharmacokinetics (PK) of Vesatolimod (VES) in Virologically Suppressed Adults With HIV-1 on Antiretroviral Therapy (ART)
ClinicalTrials.gov ID: NCT05458102
Acronym / sponsor ID: GS-US-382-1587
Conditions: Human Immunodeficiency Virus Type 1 (HIV-1) Infection
Phase: Phase 1
Study type: Interventional
Recruitment status: TerminatedReason stopped: Sponsor's decision to change the clinical development plan of this molecule. This decision is not based on efficacy or safety concerns.
Enrolment: 18 participants (actual)
Lead sponsor: Gilead SciencesIndustry (pharma, biotech, devices)
Study start: 19 Aug 2022 (actual)
Primary completion: 1 May 2023 (actual)
Study completion: 1 May 2023 (actual)
First posted: 14 Jul 2022 (actual)
Results: Posted 3 Dec 2024

Clinical summary

The research question as the sponsor registered it. This describes what the study plans to test, not what it found.

Study design

Primary purpose: Treatment
Allocation: Non-randomised
Intervention model: Parallel groups
Masking: None (open label)
Number of arms: 2

Arm	Type	Receives
Cohort 1: Vesatolimod + Cobicistat + Voriconazole	Experimental	Drug: Vesatolimod, Drug: Cobicistat, Drug: VoriconazoleParticipants will receive a single dose of vesatolimod (VES) 2 mg on Day 1 of Period 1. In Period 2, participants will receive cobicistat (COBI) 150 mg once daily on Days 1 to 5 along with a single dose of VES 2 mg on Day 2. In Period 3, participants will receive a loading dose of voriconazole (VOR) 400 mg twice daily on Day 1, then VOR 200 mg twice daily on Days 2 to 6, and a single dose of VES 2 mg in the morning on Day 3. There will be a washout period of 7 to 14 days between treatments in Period 1 Day 1 and Period 2 Day 1 and a washout period of 14 to 21 days between treatments in Period 2 Day 5 and Period 3 Day 1.
Cohort 2: Vesatolimod + Rifabutin	Experimental	Drug: Vesatolimod, Drug: RifabutinParticipants will receive a single dose of VES 6 mg on Day 1. In Period 2, participants will receive Rifabutin (RFB) 300 mg once daily on Days 1 to 9 along with a single dose of VES 6 mg on Day 6. There will be a washout period of 7 to 14 days between treatments in Period 1 Day 1 and Period 2 Day 1.

Who may qualify

Ages: 18 years and older
Sex: All
Healthy volunteers: Not accepted
Age groups: Adult, Older adult

Key inclusion criteria (11 listed)

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:
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

Key exclusion criteria (23 listed)

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

Eligibility is decided by the study team after screening; this overview does not establish that a patient qualifies. Full inclusion and exclusion criteria.

Interventions

Intervention	Type	Arms
VesatolimodAlso: GS-9620Administered orally	Drug	Cohort 1: Vesatolimod + Cobicistat + Voriconazole, Cohort 2: Vesatolimod + Rifabutin
CobicistatAlso: Tybost®Administered orally	Drug	Cohort 1: Vesatolimod + Cobicistat + Voriconazole
VoriconazoleAlso: Vfend®Administered orally	Drug	Cohort 1: Vesatolimod + Cobicistat + Voriconazole
RifabutinAlso: Mycobutin®Administered orally	Drug	Cohort 2: Vesatolimod + Rifabutin

Primary outcome

Pharmacokinetic (PK) Parameter : AUClast of Vesatolimod (VES)
Time frame: Pre-dose and 0.25, 0.5, 1, 1.5, 2, 2.5, 3, 4, 6, 8, 12, 24, 48, 72, and 96 hours post-dose for Cohort 1 on Period 1 Day 1, Period 2 Day 2, and Period 3 Day 3; and for Cohort 2 on Period 1 Day 1 and Period 2 Day 6
AUClast is defined as an area under the concentration versus time curve from time zero to the last quantifiable concentration. Cohort 1 Period 1 Day 1: Day 1 from Baseline; Cohort 1 Period 2 Day 2: Up to Day 17 from Baseline; Cohort 1 Period 3 Day 3: Up to Day 44 from Baseline; Cohort 2 Period 1 Day 1: Day 1 from Baseline; Cohort 2 Period 2 Day 6: Up to Day 21 from Baseline.
PK Parameter : AUCinf of VES
Time frame: Pre-dose and 0.25, 0.5, 1, 1.5, 2, 2.5, 3, 4, 6, 8, 12, 24, 48, 72, and 96 hours post-dose for Cohort 1 on Period 1 Day 1, Period 2 Day 2, and Period 3 Day 3; and for Cohort 2 on Period 1 Day 1 and Period 2 Day 6
AUCinf is defined as an area under the concentration versus time curve extrapolated to infinite time, calculated as AUClast + (Clast/Lambda z). Cohort 1 Period 1 Day 1: Day 1 from Baseline; Cohort 1 Period 2 Day 2: Up to Day 17 from Baseline; Cohort 1 Period 3 Day 3: Up to Day 44 from Baseline; Cohort 2 Period 1 Day 1: Day 1 from Baseline; Cohort 2 Period 2 Day 6: Up to Day 21 from Baseline.
PK Parameter : Cmax of VES
Time frame: Pre-dose and 0.25, 0.5, 1, 1.5, 2, 2.5, 3, 4, 6, 8, 12, 24, 48, 72, and 96 hours post-dose for Cohort 1 on Period 1 Day 1, Period 2 Day 2, and Period 3 Day 3; and for Cohort 2 on Period 1 Day 1 and Period 2 Day 6
Cmax is defined as the maximum observed concentration of drug. Cohort 1 Period 1 Day 1: Day 1 from Baseline; Cohort 1 Period 2 Day 2: Up to Day 17 from Baseline; Cohort 1 Period 3 Day 3: Up to Day 44 from Baseline; Cohort 2 Period 1 Day 1: Day 1 from Baseline; Cohort 2 Period 2 Day 6: Up to Day 21 from Baseline.
PK Parameter : %AUCexp of VES
Time frame: Pre-dose and 0.25, 0.5, 1, 1.5, 2, 2.5, 3, 4, 6, 8, 12, 24, 48, 72, and 96 hours post-dose for Cohort 1 on Period 1 Day 1, Period 2 Day 2, and Period 3 Day 3; and for Cohort 2 on Period 1 Day 1 and Period 2 Day 6
%AUCexp is defined as the percentage of AUC extrapolated between AUClast and AUCinf, calculated as ([AUCinf-AUClast]/AUCinf)*100. Cohort 1 Period 1 Day 1: Day 1 from Baseline; Cohort 1 Period 2 Day 2: Up to Day 17 from Baseline; Cohort 1 Period 3 Day 3: Up to Day 44 from Baseline; Cohort 2 Period 1 Day 1: Day 1 from Baseline; Cohort 2 Period 2 Day 6: Up to Day 21 from Baseline.
PK Parameter : Tmax of VES
Time frame: Pre-dose and 0.25, 0.5, 1, 1.5, 2, 2.5, 3, 4, 6, 8, 12, 24, 48, 72, and 96 hours post-dose for Cohort 1 on Period 1 Day 1, Period 2 Day 2, and Period 3 Day 3; and for Cohort 2 on Period 1 Day 1 and Period 2 Day 6
Tmax is defined as the time (observed time point) of Cmax. Cohort 1 Period 1 Day 1: Day 1 from Baseline; Cohort 1 Period 2 Day 2: Up to Day 17 from Baseline; Cohort 1 Period 3 Day 3: Up to Day 44 from Baseline; Cohort 2 Period 1 Day 1: Day 1 from Baseline; Cohort 2 Period 2 Day 6: Up to Day 21 from Baseline.
PK Parameter : Clast of VES
Time frame: Pre-dose and 0.25, 0.5, 1, 1.5, 2, 2.5, 3, 4, 6, 8, 12, 24, 48, 72, and 96 hours post-dose for Cohort 1 on Period 1 Day 1, Period 2 Day 2, and Period 3 Day 3; and for Cohort 2 on Period 1 Day 1 and Period 2 Day 6
Clast is defined as the last observed quantifiable concentration of the drug. Cohort 1 Period 1 Day 1: Day 1 from Baseline; Cohort 1 Period 2 Day 2: Up to Day 17 from Baseline; Cohort 1 Period 3 Day 3: Up to Day 44 from Baseline; Cohort 2 Period 1 Day 1: Day 1 from Baseline; Cohort 2 Period 2 Day 6: Up to Day 21 from Baseline.
PK Parameter : Tlast of VES
Time frame: Pre-dose and 0.25, 0.5, 1, 1.5, 2, 2.5, 3, 4, 6, 8, 12, 24, 48, 72, and 96 hours post-dose for Cohort 1 on Period 1 Day 1, Period 2 Day 2, and Period 3 Day 3; and for Cohort 2 on Period 1 Day 1 and Period 2 Day 6
Tlast is defined as the time (observed time point) of Clast. Cohort 1 Period 1 Day 1: Day 1 from Baseline; Cohort 1 Period 2 Day 2: Up to Day 17 from Baseline; Cohort 1 Period 3 Day 3: Up to Day 44 from Baseline; Cohort 2 Period 1 Day 1: Day 1 from Baseline; Cohort 2 Period 2 Day 6: Up to Day 21 from Baseline.
PK Parameter : Lambda z of VES
Time frame: Pre-dose and 0.25, 0.5, 1, 1.5, 2, 2.5, 3, 4, 6, 8, 12, 24, 48, 72, and 96 hours post-dose for Cohort 1 on Period 1 Day 1, Period 2 Day 2, and Period 3 Day 3; and for Cohort 2 on Period 1 Day 1 and Period 2 Day 6
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. Cohort 1 Period 1 Day 1: Day 1 from Baseline; Cohort 1 Period 2 Day 2: Up to Day 17 from Baseline; Cohort 1 Period 3 Day 3: Up to Day 44 from Baseline; Cohort 2 Period 1 Day 1: Day 1 from Baseline; Cohort 2 Period 2 Day 6: Up to Day 21 from Baseline.
PK Parameter : t1/2 of VES
Time frame: Pre-dose and 0.25, 0.5, 1, 1.5, 2, 2.5, 3, 4, 6, 8, 12, 24, 48, 72, and 96 hours post-dose for Cohort 1 on Period 1 Day 1, Period 2 Day 2, and Period 3 Day 3; and for Cohort 2 on Period 1 Day 1 and Period 2 Day 6
t1/2 is defined as the terminal elimination half-life. Cohort 1 Period 1 Day 1: Day 1 from Baseline; Cohort 1 Period 2 Day 2: Up to Day 17 from Baseline; Cohort 1 Period 3 Day 3: Up to Day 44 from Baseline; Cohort 2 Period 1 Day 1: Day 1 from Baseline; Cohort 2 Period 2 Day 6: Up to Day 21 from Baseline.
PK Parameter : CL/F of VES
Time frame: Pre-dose and 0.25, 0.5, 1, 1.5, 2, 2.5, 3, 4, 6, 8, 12, 24, 48, 72, and 96 hours post-dose for Cohort 1 on Period 1 Day 1, Period 2 Day 2, and Period 3 Day 3; and for Cohort 2 on Period 1 Day 1 and Period 2 Day 6
CL/F is defined as an apparent oral clearance. Cohort 1 Period 1 Day 1: Day 1 from Baseline; Cohort 1 Period 2 Day 2: Up to Day 17 from Baseline; Cohort 1 Period 3 Day 3: Up to Day 44 from Baseline; Cohort 2 Period 1 Day 1: Day 1 from Baseline; Cohort 2 Period 2 Day 6: Up to Day 21 from Baseline.
PK Parameter : Vz/F of VES
Time frame: Pre-dose and 0.25, 0.5, 1, 1.5, 2, 2.5, 3, 4, 6, 8, 12, 24, 48, 72, and 96 hours post-dose for Cohort 1 on Period 1 Day 1, Period 2 Day 2, and Period 3 Day 3; and for Cohort 2 on Period 1 Day 1 and Period 2 Day 6
Vz/F is defined as an apparent volume of distribution of the drug. Cohort 1 Period 1 Day 1: Day 1 from Baseline; Cohort 1 Period 2 Day 2: Up to Day 17 from Baseline; Cohort 1 Period 3 Day 3: Up to Day 44 from Baseline; Cohort 2 Period 1 Day 1: Day 1 from Baseline; Cohort 2 Period 2 Day 6: Up to Day 21 from Baseline.
Percentage of Participants Who Experienced Treatment-Emergent Adverse Events (TEAEs)
Time frame: First dose date up to last dose date plus 30 days (up to 77 days for Cohort 1, and up to 54 days for Cohort 2)
An adverse event (AE) is any untoward medical occurrence in a clinical study participant administered a study drug that does not necessarily have a causal relationship with the treatment. An AE can, therefore, be any unfavorable and/or unintended sign, symptom, or disease temporally associated with the use of a study drug, whether or not considered related to the study drug. Adverse events may also include pretreatment or posttreatment complications that occur as a result of protocol-specified procedures, or special situations. TEAES included all AEs began on or after the study drug start date.
Percentage of Participants Who Experienced Treatment-Emergent Laboratory Abnormalities
Time frame: First dose date up to last dose date plus 30 days (up to 77 days for Cohort 1, and up to 54 days for Cohort 2)
A treatment-emergent laboratory abnormality was defined as an increase of at least 1 toxicity grade from predose at any time postdose. Data for participants with post baseline toxicity grade 1 or higher is reported.

Results and safety

Results posted to the registry on 3 Dec 2024, as reported by the sponsor. Figures are copied from the record, not re-analysed. Full results on ClinicalTrials.gov.

Participant flow

Group	Started	Completed
Cohort 1: Vesatolimod + Cobicistat + Voriconazole	16	11
Cohort 2: Vesatolimod + Rifabutin	2	2

Primary outcome: Pharmacokinetic (PK) Parameter : AUClast of Vesatolimod (VES)

Time frame: Pre-dose and 0.25, 0.5, 1, 1.5, 2, 2.5, 3, 4, 6, 8, 12, 24, 48, 72, and 96 hours post-dose for Cohort 1 on Period 1 Day 1, Period 2 Day 2, and Period 3 Day 3; and for Cohort 2 on Period 1 Day 1 and Period 2 Day 6. Mean (Standard Deviation). Unit: h*pg/mL

Measure	Cohort 1: Vesatolimod 2 mg n = 15	Cohort 1: Vesatolimod 2 mg + Cobicistat 150 mg n = 13	Cohort 1: Vesatolimod 2 mg + Voriconazole 200 mg n = 11	Cohort 2: Vesatolimod 6 mg n = 2	Cohort 2: Vesatolimod 6 mg + Rifabutin 300 mg n = 2
Value	13500 (9500)	61900 (35400)	14600 (11000)	16400 (17900)	86300 (16000)

Cohort 1: Vesatolimod 2 mg vs Cohort 1: Vesatolimod 2 mg + Cobicistat 150 mg: Geometric Least-squares Mean Ratio: 560 (90% CI 414 to 757)
Cohort 1: Vesatolimod 2 mg vs Cohort 1: Vesatolimod 2 mg + Voriconazole 200 mg: Geometric Least-squares Mean Ratio: 137 (90% CI 99.5 to 189)

Population analysed: The VES PK Analysis Set included participants who received at least 1 dose of VES and had at least 1 nonmissing PK concentration value.

Primary outcome: PK Parameter : AUCinf of VES

Measure	Cohort 1: Vesatolimod 2 mg n = 13	Cohort 1: Vesatolimod 2 mg + Cobicistat 150 mg n = 12	Cohort 1: Vesatolimod 2 mg + Voriconazole 200 mg n = 10	Cohort 2: Vesatolimod 6 mg n = 0	Cohort 2: Vesatolimod 6 mg + Rifabutin 300 mg n = 2
Value	17600 (9220)	68000 (36600)	17800 (11600)	–	88000 (16800)

Cohort 1: Vesatolimod 2 mg vs Cohort 1: Vesatolimod 2 mg + Cobicistat 150 mg: Geometric Least-squares Mean Ratio: 433 (90% CI 347 to 540)
Cohort 1: Vesatolimod 2 mg vs Cohort 1: Vesatolimod 2 mg + Voriconazole 200 mg: Geometric Least-squares Mean Ratio: 118 (90% CI 93.5 to 150)

Population analysed: Participants in the VES PK Analysis Set with available data were analyzed. Data for Cohort 2 Vesatolimod 6mg are not reported due to participant's confidentiality reasons as there was only 1 participant in this cohort.

Primary outcome: PK Parameter : Cmax of VES

Measure	Cohort 1: Vesatolimod 2 mg n = 15	Cohort 1: Vesatolimod 2 mg + Cobicistat 150 mg n = 13	Cohort 1: Vesatolimod 2 mg + Voriconazole 200 mg n = 11	Cohort 2: Vesatolimod 6 mg n = 2	Cohort 2: Vesatolimod 6 mg + Rifabutin 300 mg n = 2
Value	1130 (1020)	6930 (4650)	1020 (895)	944 (928)	22200 (7780)

Cohort 1: Vesatolimod 2 mg vs Cohort 1: Vesatolimod 2 mg + Cobicistat 150 mg: Geometric Least-squares Mean Ratio: 752 (90% CI 525 to 1080)
Cohort 1: Vesatolimod 2 mg vs Cohort 1: Vesatolimod 2 mg + Voriconazole 200 mg: Geometric Least-squares Mean Ratio: 118 (90% CI 80.3 to 172)

Population analysed: Participants in the VES PK Analysis Set were analyzed.

Primary outcome: PK Parameter : %AUCexp of VES

Measure	Cohort 1: Vesatolimod 2 mg n = 13	Cohort 1: Vesatolimod 2 mg + Cobicistat 150 mg n = 12	Cohort 1: Vesatolimod 2 mg + Voriconazole 200 mg n = 10	Cohort 2: Vesatolimod 6 mg n = 0	Cohort 2: Vesatolimod 6 mg + Rifabutin 300 mg n = 2
Value	14.6 (6.97)	6.16 (3.91)	14.7 (6.75)	–	1.92 (0.602)

Adverse events

Time frame: Adverse Events and All-cause mortality: Up to 77 days for Cohort 1 and up to 54 days for Cohort 2. Other adverse events reported at 5% frequency or more

Group	Serious adverse events	Other adverse events	Deaths
Cohort 1: Vesatolimod 2 mg	0 of 15 (0%)	2 of 15 (13.3%)	0 of 15
Cohort 1: Cobicistat 150 mg	0 of 13 (0%)	5 of 13 (38.5%)	0 of 13
Cohort 1: Vesatolimod 2 mg + Cobicistat 150 mg	0 of 13 (0%)	0 of 13 (0%)	0 of 13
Cohort 1: Voriconazole 400 mg	0 of 11 (0%)	4 of 11 (36.4%)	0 of 11
Cohort 1: Voriconazole 200 mg	0 of 11 (0%)	1 of 11 (9.1%)	0 of 11
Cohort 1: Vesatolimod 2 mg + Voriconazole 200 mg	0 of 11 (0%)	1 of 11 (9.1%)	0 of 11
Cohort 1: No Treatment	0 of 0	0 of 0	0 of 1
Cohort 2: Vesatolimod 6 mg	0 of 2 (0%)	0 of 2 (0%)	0 of 2
Cohort 2: Rifabutin 300 mg	0 of 2 (0%)	1 of 2 (50%)	0 of 2
Cohort 2: Vesatolimod 6 mg + Rifabutin 300 mg	0 of 2 (0%)	1 of 2 (50%)	0 of 2

Loading the posted results from ClinicalTrials.gov…

Research links

Official record on ClinicalTrials.govLast updated by the sponsor 3 Dec 2024.
Posted resultsParticipant flow, baseline, all outcome measures and adverse events.
Derived from this study: PubMed 40952649Zheng Y, Wire M, Omange RW, deVries CR, Zhang L, Chen B, Huang SSY, Cruz K, Hassman H, Osiyemi O, Rondon JC, Lim D, West S, Wen A, Wallin JJ, SenGupta D, Cai Y. The Effects of Cobicistat and Voriconazole on the Safety, Pharmacokinetics, and Pharmacodynamics of the TLR7 Agonist Vesatolimod in People with HIV. Infect Dis Ther. 2025 Nov;14(11):2535-2549. doi: 10.1007/s40121-025-01227-x. Epub 2025 Sep 15.
Gilead Clinical Trials WebsiteLink provided by the sponsor.
Individual participant dataSharing planned: No

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Referral and contact

AzTrials does not enrol participants or take referrals. Contact the study team or a site listed below; they decide who can take part. This study is not recruiting at the moment.

Gilead Study Director study director

Gilead Sciences

5 sites in 1 country: see every site and its status.

Questions about this trial

What is this clinical trial studying?

A Phase 1 study testing Vesatolimod, Cobicistat and Voriconazole in people with Human Immunodeficiency Virus Type 1 (HIV-1) Infection, run by Gilead Sciences at 5 sites in United States.

The full registered description is in the About this study section and the official record.

Who may be eligible to take part?

The sponsor lists 11 inclusion and 23 exclusion criteria. Eligibility is decided by the study team after screening, so read the full criteria and contact a listed site.

Is this clinical trial currently recruiting?

The record says: stopped early, as of the sponsor's last update on 3 Dec 2024. Status can change between updates, so confirm with the study contact before making plans.

Where is the study taking place?

The record lists 5 sites in United States. Whether a site is taking part right now should be confirmed with that site. See every site.

What are the possible benefits and risks?

They depend on the study and the treatment, and no study can promise a benefit. The study team explains the known risks during informed consent, before anyone joins; the record itself does not list them.

What does this phase mean?

Phase 1 studies test a treatment in a small group of people for the first time or in a new way, mainly to check safety and find the right dose.

Not every study follows the same path, and some studies (observational studies, device studies) have no phase.

Are results available for this study?

Yes. Results are posted in the registry (first posted 3 Dec 2024). A summary is in the For doctors view, and the full results are on ClinicalTrials.gov.

How can a doctor refer a patient or contact the research team?

The record lists no contact. The official record names the sponsor, who can be asked directly. AzTrials does not enrol participants or take referrals.

What does the primary outcome measure?

Pharmacokinetic (PK) Parameter : AUClast of Vesatolimod (VES) (time frame: Pre-dose and 0.25, 0.5, 1, 1.5, 2, 2.5, 3, 4, 6, 8, 12, 24, 48, 72, and 96 hours post-dose for Cohort 1 on Period 1 Day 1, Period 2 Day 2, and Period 3 Day 3; and for Cohort 2 on Period 1 Day 1 and Period 2 Day 6). The study lists 13 primary outcomes in all. It is what the study was designed to measure, not a finding.

Where can I read the original study information?

On the ClinicalTrials.gov record for NCT05458102, which also lists 1 linked publication.

Does a listing mean the treatment is approved or proven to work?

No. A listing means the study is registered. It does not show that the treatment is safe, works, or is approved by a regulator.

How often is this information updated?

AzTrials copies changed records from ClinicalTrials.gov every night and reloads the whole registry every week. The sponsor last updated this record on 3 Dec 2024.