Study Details

OVERVIEW

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)

PROTOCOL 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).

Participation Requirements

Age

18 Years +

Sex

All

Healthy Volunteers

Medical Condition

Human Immunodeficiency Virus Type 1 (HIV-1) Infection

Gender

N/A

Date

August 2022 - October 2023

Study Type

Interventional

Study Phase

Phase 1

Product

Vesatolimod, Cobicistat, Voriconazole, Rifabutin

Eligibility Information

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

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.

Locations

Locations (5)

Collaborative Neuroscience Research, LLC.

Long Beach, California, United States, 90806

Clinical Pharmacology of Miami, LLC.

Miami, Florida, United States, 33014

Advanced Pharma, CR, LLC.

Miami, Florida, United States, 33147

Triple O Research Institute, P.A.

West Palm Beach, Florida, United States, 33407

Hassman Research Institute

Marlton, New Jersey, United States, 08054

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