TerminatedNCT05458102Updated Dec 3, 2024Results posted

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

A Phase 1 interventional study of Vesatolimod and Cobicistat in Human Immunodeficiency Virus Type 1 (HIV-1) Infection, sponsored by Gilead Sciences. Terminated at 5 sites in United States. Open to participants aged 18 Years and older. Per ClinicalTrials.gov, last updated 2024-12-03.

Sponsored by Gilead Sciences · Phase 1, Interventional, and Treatment

Why this study was terminated

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

Phase: Phase 1
Study type: Interventional
Enrollment: 18
Allocation: Non-randomized
Ages: 18 Years and older
Sex: All

Study 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).

Conditions studied

Human Immunodeficiency Virus Type 1 (HIV-1) Infection

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In context

Acquired Immunodeficiency Syndrome

2,040 studies on the registry are indexed under Acquired Immunodeficiency Syndrome; 272 are open to participants now.

This study's enrollment of 18 is below the median of 105 across 1,543 interventional studies indexed under Acquired Immunodeficiency Syndrome.

Browse Acquired Immunodeficiency Syndrome studies →

Lead sponsor

Gilead Sciences is the lead sponsor of 680 studies on the registry; 24 are open to participants now.

Of its 259 completed or terminated interventional studies of FDA-regulated products, 249 (96%) have results posted.

Counted across the registry records on this site, refreshed daily.

Who can participate

Ages eligible: 18 Years and older
Sexes eligible: All
Accepts healthy volunteers: No

Eligibility criteria

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 (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
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.

Study design

Phase: Phase 1
Primary purpose: Treatment
Allocation: Non-randomized
Intervention model: Parallel assignment
Masking: None (open label)
Enrollment: 18 participants (actual)

Study arms

Experimental
Cohort 1: Vesatolimod + Cobicistat + Voriconazole
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.
Drug: Vesatolimod · Drug: Cobicistat · Drug: Voriconazole
Experimental
Cohort 2: Vesatolimod + Rifabutin
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.
Drug: Vesatolimod · Drug: Rifabutin

Interventions

DrugVesatolimod
Administered orally
Also known as: GS-9620
DrugCobicistat
Administered orally
Also known as: Tybost®
DrugVoriconazole
Administered orally
Also known as: Vfend®
DrugRifabutin
Administered orally
Also known as: Mycobutin®

What researchers measure

Primary outcomes

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.
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
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.
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
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.
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
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.
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
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.
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
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.
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
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.
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
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.
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
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.
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
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.
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
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.
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
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.
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)
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.
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)

Results

Posted Dec 3, 2024

Participant flow

Participants were enrolled at study sites in the United States.

Participant flow — Overall Study
Milestone	Cohort 1: Vesatolimod + Cobicistat + Voriconazole	Cohort 2: Vesatolimod + Rifabutin
Started	16	2
Completed	11	2
Not completed	5	0
Withdrew: Withdrew consent	2	0
Withdrew: Adverse event	1	0
Withdrew: Enrolled but never treated	1	0
Withdrew: Protocol violation	1	0

Outcome measures

PrimaryPharmacokinetic (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.

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
Reported as:: Mean · h*pg/mL

Pharmacokinetic (PK) Parameter : AUClast of Vesatolimod (VES)
h*pg/mL	Cohort 1: Vesatolimod 2 mg	Cohort 1: Vesatolimod 2 mg + Cobicistat 150 mg	Cohort 1: Vesatolimod 2 mg + Voriconazole 200 mg	Cohort 2: Vesatolimod 6 mg	Cohort 2: Vesatolimod 6 mg + Rifabutin 300 mg
Pharmacokinetic (PK) Parameter : AUClast of Vesatolimod (VES)	13500 ± 9500	61900 ± 35400	14600 ± 11000	16400 ± 17900	86300 ± 16000

Statistical analysis

Cohort 1: Vesatolimod 2 mg vs Cohort 1: Vesatolimod 2 mg + Cobicistat 150 mg · Geometric least-squares mean ratio: 560 · 90% CI 414 to 757Parametric (normal theory) mixed-effects ANOVA model was fitted to the natural log-transformed values of the PK parameter under evaluation.
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 189Parametric (normal theory) mixed-effects ANOVA model was fitted to the natural log-transformed values of the PK parameter under evaluation.

PrimaryPK 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.

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
Reported as:: Mean · h*pg/mL

PK Parameter : AUCinf of VES
h*pg/mL	Cohort 1: Vesatolimod 2 mg	Cohort 1: Vesatolimod 2 mg + Cobicistat 150 mg	Cohort 1: Vesatolimod 2 mg + Voriconazole 200 mg	Cohort 2: Vesatolimod 6 mg	Cohort 2: Vesatolimod 6 mg + Rifabutin 300 mg
PK Parameter : AUCinf of VES	17600 ± 9220	68000 ± 36600	17800 ± 11600	—	88000 ± 16800

Statistical analysis

Cohort 1: Vesatolimod 2 mg vs Cohort 1: Vesatolimod 2 mg + Cobicistat 150 mg · Geometric least-squares mean ratio: 433 · 90% CI 347 to 540Parametric (normal theory) mixed-effects ANOVA model was fitted to the natural log-transformed values of the PK parameter under evaluation.
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 150Parametric (normal theory) mixed-effects ANOVA model was fitted to the natural log-transformed values of the PK parameter under evaluation.

PrimaryPK 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.

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
Reported as:: Mean · pg/mL

PK Parameter : Cmax of VES
pg/mL	Cohort 1: Vesatolimod 2 mg	Cohort 1: Vesatolimod 2 mg + Cobicistat 150 mg	Cohort 1: Vesatolimod 2 mg + Voriconazole 200 mg	Cohort 2: Vesatolimod 6 mg	Cohort 2: Vesatolimod 6 mg + Rifabutin 300 mg
PK Parameter : Cmax of VES	1130 ± 1020	6930 ± 4650	1020 ± 895	944 ± 928	22200 ± 7780

Statistical analysis

Cohort 1: Vesatolimod 2 mg vs Cohort 1: Vesatolimod 2 mg + Cobicistat 150 mg · Geometric least-squares mean ratio: 752 · 90% CI 525 to 1080Parametric (normal theory) mixed-effects ANOVA model was fitted to the natural log-transformed values of the PK parameter under evaluation.
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 172Parametric (normal theory) mixed-effects ANOVA model was fitted to the natural log-transformed values of the PK parameter under evaluation.

PrimaryPK 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.

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
Reported as:: Mean · percentage of AUCexp

PK Parameter : %AUCexp of VES
percentage of AUCexp	Cohort 1: Vesatolimod 2 mg	Cohort 1: Vesatolimod 2 mg + Cobicistat 150 mg	Cohort 1: Vesatolimod 2 mg + Voriconazole 200 mg	Cohort 2: Vesatolimod 6 mg	Cohort 2: Vesatolimod 6 mg + Rifabutin 300 mg
PK Parameter : %AUCexp of VES	14.6 ± 6.97	6.16 ± 3.91	14.7 ± 6.75	—	1.92 ± 0.602

PrimaryPK 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.

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
Reported as:: Median · hours

PK Parameter : Tmax of VES
hours	Cohort 1: Vesatolimod 2 mg	Cohort 1: Vesatolimod 2 mg + Cobicistat 150 mg	Cohort 1: Vesatolimod 2 mg + Voriconazole 200 mg	Cohort 2: Vesatolimod 6 mg	Cohort 2: Vesatolimod 6 mg + Rifabutin 300 mg
PK Parameter : Tmax of VES	3.03 (1.50 to 6.00)	1.52 (1.50 to 2.48)	2.50 (1.00 to 3.10)	5.13 (4.18 to 6.07)	1.28 (1.05 to 1.50)

Statistical analysis

Cohort 1: Vesatolimod 2 mg vs Cohort 1: Vesatolimod 2 mg + Cobicistat 150 mg · Geometric least-squares mean ratio: 68.5 · 90% CI 45.5 to 103Parametric (normal theory) mixed-effects ANOVA model was fitted to the natural log-transformed values of the PK parameter under evaluation.
Cohort 1: Vesatolimod 2 mg vs Cohort 1: Vesatolimod 2 mg + Voriconazole 200 mg · Geometric least-squares mean ratio: 65.4 · 90% CI 42.5 to 101Parametric (normal theory) mixed-effects ANOVA model was fitted to the natural log-transformed values of the PK parameter under evaluation.

PrimaryPK 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.

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
Reported as:: Mean · pg/mL

PK Parameter : Clast of VES
pg/mL	Cohort 1: Vesatolimod 2 mg	Cohort 1: Vesatolimod 2 mg + Cobicistat 150 mg	Cohort 1: Vesatolimod 2 mg + Voriconazole 200 mg	Cohort 2: Vesatolimod 6 mg	Cohort 2: Vesatolimod 6 mg + Rifabutin 300 mg
PK Parameter : Clast of VES	84.2 ± 19.4	103 ± 42.2	74.2 ± 17.4	75.9 ± 30.5	74.3 ± 27.2

PrimaryPK 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.

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
Reported as:: Median · hours

PK Parameter : Tlast of VES
hours	Cohort 1: Vesatolimod 2 mg	Cohort 1: Vesatolimod 2 mg + Cobicistat 150 mg	Cohort 1: Vesatolimod 2 mg + Voriconazole 200 mg	Cohort 2: Vesatolimod 6 mg	Cohort 2: Vesatolimod 6 mg + Rifabutin 300 mg
PK Parameter : Tlast of VES	48.0 (24.1 to 72.0)	72.0 (71.7 to 96.0)	48.0 (24.3 to 96.0)	59.8 (24.0 to 95.5)	72.0 (72.0 to 72.0)

PrimaryPK 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.

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
Reported as:: Median · per hour

PK Parameter : Lambda z of VES
per hour	Cohort 1: Vesatolimod 2 mg	Cohort 1: Vesatolimod 2 mg + Cobicistat 150 mg	Cohort 1: Vesatolimod 2 mg + Voriconazole 200 mg	Cohort 2: Vesatolimod 6 mg	Cohort 2: Vesatolimod 6 mg + Rifabutin 300 mg
PK Parameter : Lambda z of VES	0.0381 (0.0310 to 0.0528)	0.0310 (0.0252 to 0.0425)	0.0321 (0.0241 to 0.0561)	—	0.0442 (0.0400 to 0.0485)

PrimaryPK 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.

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
Reported as:: Median · hours

PK Parameter : t1/2 of VES
hours	Cohort 1: Vesatolimod 2 mg	Cohort 1: Vesatolimod 2 mg + Cobicistat 150 mg	Cohort 1: Vesatolimod 2 mg + Voriconazole 200 mg	Cohort 2: Vesatolimod 6 mg	Cohort 2: Vesatolimod 6 mg + Rifabutin 300 mg
PK Parameter : t1/2 of VES	18.4 (13.1 to 22.3)	22.4 (16.7 to 27.6)	21.6 (12.4 to 28.7)	—	15.8 (14.3 to 17.4)

Statistical analysis

Cohort 1: Vesatolimod 2 mg vs Cohort 1: Vesatolimod 2 mg + Cobicistat 150 mg · Geometric least-squares mean ratio: 120 · 90% CI 104 to 138Parametric (normal theory) mixed-effects ANOVA model was fitted to the natural log-transformed values of the PK parameter under evaluation.
Cohort 1: Vesatolimod 2 mg vs Cohort 1: Vesatolimod 2 mg + Voriconazole 200 mg · Geometric least-squares mean ratio: 111 · 90% CI 95.4 to 128Parametric (normal theory) mixed-effects ANOVA model was fitted to the natural log-transformed values of the PK parameter under evaluation.

PrimaryPK 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.

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
Reported as:: Mean · L/h

PK Parameter : CL/F of VES
L/h	Cohort 1: Vesatolimod 2 mg	Cohort 1: Vesatolimod 2 mg + Cobicistat 150 mg	Cohort 1: Vesatolimod 2 mg + Voriconazole 200 mg	Cohort 2: Vesatolimod 6 mg	Cohort 2: Vesatolimod 6 mg + Rifabutin 300 mg
PK Parameter : CL/F of VES	156 ± 92.9	42.4 ± 28.5	176 ± 137	—	69.4 ± 13.3

PrimaryPK 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.

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
Reported as:: Mean · L

PK Parameter : Vz/F of VES
L	Cohort 1: Vesatolimod 2 mg	Cohort 1: Vesatolimod 2 mg + Cobicistat 150 mg	Cohort 1: Vesatolimod 2 mg + Voriconazole 200 mg	Cohort 2: Vesatolimod 6 mg	Cohort 2: Vesatolimod 6 mg + Rifabutin 300 mg
PK Parameter : Vz/F of VES	3480 ± 1530	1320 ± 1100	4330 ± 2220	—	1560 ± 86.7

PrimaryPercentage 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.

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)
Reported as:: Number · percentage of participants

Percentage of Participants Who Experienced Treatment-Emergent Adverse Events (TEAEs)
percentage of participants	Cohort 1: Vesatolimod 2 mg	Cohort 1: Cobicistat 150 mg	Cohort 1: Vesatolimod 2 mg + Cobicistat 150 mg	Cohort 1: Voriconazole 400 mg	Cohort 1: Voriconazole 200 mg	Cohort 1: Vesatolimod 2 mg + Voriconazole 200 mg	Cohort 2: Vesatolimod 6 mg	Cohort 2: Rifabutin 300 mg	Cohort 2: Vesatolimod 6 mg + Rifabutin 300 mg
Percentage of Participants Who Experienced Treatment-Emergent Adverse Events (TEAEs)	13.3	38.5	0	36.4	9.1	9.1	0	50.0	50.0

PrimaryPercentage 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.

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)
Reported as:: Number · percentage of participants

Percentage of Participants Who Experienced Treatment-Emergent Laboratory Abnormalities
percentage of participants	Cohort 1: Vesatolimod 2 mg	Cohort 1: Cobicistat 150 mg	Vesatolimod 2 mg + Cobicistat 150 mg	Cohort 1: Voriconazole 400 mg	Cohort 1: Voriconazole 200 mg	Vesatolimod 2 mg + Voriconazole 200 mg	Cohort 2: Vesatolimod 6 mg	Cohort 2: Rifabutin 300 mg	Vesatolimod 6 mg + Rifabutin 300 mg
Percentage of Participants Who Experienced Treatment-Emergent Laboratory Abnormalities	35.7	53.8	—	—	63.6	—	50.0	100.0	—

Adverse events

Collected over Adverse Events and All-cause mortality: Up to 77 days for Cohort 1 and up to 54 days for Cohort 2. Non-serious events are listed at a 5% frequency threshold.

Adverse event summary by group
Group	Deaths	Serious	Other
Cohort 1: Vesatolimod 2 mg	0/15 (0%)	0/15 (0%)	2/15 (13.3%)
Cohort 1: Cobicistat 150 mg	0/13 (0%)	0/13 (0%)	5/13 (38.5%)
Cohort 1: Vesatolimod 2 mg + Cobicistat 150 mg	0/13 (0%)	0/13 (0%)	0/13 (0%)
Cohort 1: Voriconazole 400 mg	0/11 (0%)	0/11 (0%)	4/11 (36.4%)
Cohort 1: Voriconazole 200 mg	0/11 (0%)	0/11 (0%)	1/11 (9.1%)
Cohort 1: Vesatolimod 2 mg + Voriconazole 200 mg	0/11 (0%)	0/11 (0%)	1/11 (9.1%)
Cohort 1: No Treatment	0/1 (0%)	—	—
Cohort 2: Vesatolimod 6 mg	0/2 (0%)	0/2 (0%)	0/2 (0%)
Cohort 2: Rifabutin 300 mg	0/2 (0%)	0/2 (0%)	1/2 (50%)
Cohort 2: Vesatolimod 6 mg + Rifabutin 300 mg	0/2 (0%)	0/2 (0%)	1/2 (50%)

Most frequent other events

Showing 10 of 20

Most frequent other events
Event	Cohort 1: Vesatolimod 2 mg	Cohort 1: Cobicistat 150 mg	Cohort 1: Vesatolimod 2 mg + Cobicistat 150 mg	Cohort 1: Voriconazole 400 mg	Cohort 1: Voriconazole 200 mg	Cohort 1: Vesatolimod 2 mg + Voriconazole 200 mg	Cohort 1: No Treatment	Cohort 2: Vesatolimod 6 mg	Cohort 2: Rifabutin 300 mg	Cohort 2: Vesatolimod 6 mg + Rifabutin 300 mg
Decreased appetiteMetabolism and nutrition disorders	0/15	1/13	0/13	0/11	0/11	0/11	—	0/2	1/2	0/2
DiarrhoeaGastrointestinal disorders	0/15	0/13	0/13	0/11	0/11	0/11	—	0/2	1/2	0/2
ChillsGeneral disorders	0/15	0/13	0/13	0/11	0/11	0/11	—	0/2	0/2	1/2
FatigueGeneral disorders	0/15	0/13	0/13	0/11	0/11	0/11	—	0/2	0/2	1/2
PyrexiaGeneral disorders	0/15	0/13	0/13	0/11	0/11	0/11	—	0/2	0/2	1/2
CoughRespiratory, thoracic and mediastinal disorders	0/15	0/13	0/13	0/11	0/11	0/11	—	0/2	1/2	0/2
HypertensionVascular disorders	0/15	0/13	0/13	0/11	0/11	0/11	—	0/2	0/2	1/2
TachycardiaCardiac disorders	0/15	0/13	0/13	0/11	0/11	0/11	—	0/2	0/2	1/2
Cytokine release syndromeImmune system disorders	0/15	0/13	0/13	0/11	0/11	0/11	—	0/2	0/2	1/2
PhotopsiaEye disorders	0/15	0/13	0/13	2/11	0/11	0/11	—	0/2	0/2	0/2

Baseline characteristics

The Safety Analysis Set included all enrolled participants who received at least 1 dose of study drug.

Age, Categorical
Age, Categorical(Participants)	Cohort 1: Vesatolimod + Cobicistat + Voriconazole	Cohort 2: Vesatolimod + Rifabutin	Total
<=18 years	0	0	0
Between 18 and 65 years	14	2	16
>=65 years	1	0	1

Age, Continuous
Age, Continuous(years)	Cohort 1: Vesatolimod + Cobicistat + Voriconazole	Cohort 2: Vesatolimod + Rifabutin	Total
Mean	47 ± 14.5	45 ± 14.8	47 ± 14.0

Sex: Female, Male
Sex: Female, Male(Participants)	Cohort 1: Vesatolimod + Cobicistat + Voriconazole	Cohort 2: Vesatolimod + Rifabutin	Total
Female	2	0	2
Male	13	0	13

Ethnicity (NIH/OMB)
Ethnicity (NIH/OMB)(Participants)	Cohort 1: Vesatolimod + Cobicistat + Voriconazole	Total
Hispanic or Latino	3	3
Not Hispanic or Latino	12	12
Unknown or Not Reported	0	0

Race (NIH/OMB)
Race (NIH/OMB)(Participants)	Cohort 1: Vesatolimod + Cobicistat + Voriconazole	Total
American Indian or Alaska Native	1	1
Asian	2	2
Native Hawaiian or Other Pacific Islander	0	0
Black or African American	10	10
White	2	2
More than one race	0	0
Unknown or Not Reported	0	0

Region of Enrollment
Region of Enrollment(Participants)	Cohort 1: Vesatolimod + Cobicistat + Voriconazole	Cohort 2: Vesatolimod + Rifabutin	Total
United States	15	2	17

Study locations

5 sites

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

References and documents

Study documents

Study protocol · Dec 12, 2022
Statistical analysis plan · Jan 19, 2024

Documents are hosted by the registry — open the source record to download them.

Individual participant data

Plan to share: No

Updates

Tracking since Sep 25, 2026

No changes since tracking began. The registry record was last updated on Dec 3, 2024, before this site started recording changes on Sep 25, 2026. Its history is on ClinicalTrials.gov ↗

Registry details

Key details

Study ID: NCT05458102
Lead sponsor: Gilead Sciences
Responsible party: Sponsor
First posted: Jul 14, 2022
Start date: Aug 19, 2022
Primary completion: May 1, 2023
Completion: May 1, 2023
Results posted: Dec 3, 2024
Last update: Dec 3, 2024

Study contacts

Gilead Study Director

study director · Gilead Sciences

Oversight

Data monitoring committee: No
FDA-regulated drug: Yes
FDA-regulated device: No

View the source record on ClinicalTrials.gov ↗

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