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

• Status: Not yet recruiting
• Trial end date: 2023-05-01
• Target enrollment: 0
• Participant gender: All

Summary

The primary objectives of this study are to evaluate 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 vesatolimod (VES) pharmacokinetics (PK) and to evaluate safety in virologically suppressed adults with HIV-1 on antiretroviral therapy (ART).

• Phase: Phase 1
• Accepts Healthy Volunteers?: No

Details

• Lead Sponsor: Gilead Sciences
• Treatments: Cobicistat; Rifabutin; Vesatolimod; Voriconazole

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: bictegravir (BIC), dolutegravir (DTG), raltegravir (RAL), or doravirine (DORI) + nucleoside reverse transcriptase inhibitor (NRTIs)

• Cohort 2: DTG/abacavir (ABC)/lamivudine (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.

• Have a positive test result for hepatitis B virus (HBV) surface antigen (HBsAg), or hepatitis C virus (HCV) antibody at screening.

• 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.

• 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.