Clinical trial NCT05458102: Drug-Drug Interaction Study of Vesatolimod in Adults With HIV-1 Who Have Very Low or Undetectable Virus Levels
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)
Study type: INTERVENTIONAL
Overall status: TERMINATED
Phase: PHASE1
Conditions: Human Immunodeficiency Virus Type 1 (HIV-1) Infection
Lead sponsor: Gilead Sciences
Sponsor class: INDUSTRY
First posted: 2022-07-14
Enrollment: 18
Sex: ALL
Minimum age (years): 18
Standard ages: ADULT
OLDER_ADULT
Accepts healthy volunteers: no
Allocation: NON_RANDOMIZED
Intervention model: PARALLEL
Primary purpose: TREATMENT

Brief 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).


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.

Primary outcomes:
measure: Pharmacokinetic (PK) Parameter : AUClast of Vesatolimod (VES)
timeFrame: 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
measure: PK Parameter : AUCinf of VES
timeFrame: 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
measure: PK Parameter : Cmax of VES
timeFrame: 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
measure: PK Parameter : %AUCexp of VES
timeFrame: 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
measure: PK Parameter : Tmax of VES
timeFrame: 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
measure: PK Parameter : Clast of VES
timeFrame: 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
measure: PK Parameter : Tlast of VES
timeFrame: 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
measure: PK Parameter : Lambda z of VES
timeFrame: 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
measure: PK Parameter : t1/2 of VES
timeFrame: 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
measure: PK Parameter : CL/F of VES
timeFrame: 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
measure: PK Parameter : Vz/F of VES
timeFrame: 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
measure: Percentage of Participants Who Experienced Treatment-Emergent Adverse Events (TEAEs)
timeFrame: 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)
measure: Percentage of Participants Who Experienced Treatment-Emergent Laboratory Abnormalities
timeFrame: 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)
Secondary outcomes:
Other outcomes:
Locations:
city: Long Beach
country: United States
facility: Collaborative Neuroscience Research, LLC.
state: California
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: West Palm Beach
country: United States
facility: Triple O Research Institute, P.A.
state: Florida
city: Marlton
country: United States
facility: Hassman Research Institute
state: New Jersey
Study officials:
affiliation: Gilead Sciences
name: Gilead Study Director
role: STUDY_DIRECTOR
References: