A Phase 2b Study Evaluating Oral VH4524184 Regimens in Treatment Naïve Persons With HIV-1 (INNOVATE Study)

Exclusion Criteria24

• Participants who are breastfeeding or plan to breastfeed during the study.
• Participants with acute HIV infection, evidenced by acute retroviral syndrome (e.g., fever, malaise, fatigue, etc.) and/or evidence of recent (within 3 months) documented viremia without antibody production and/or evidence of recent (within 3 months) documented seroconversion.
• Any evidence of an active Centres for Disease Control and Prevention (CDC) Stage 3 disease \[CDC 2014\], except cutaneous Kaposi's sarcoma not requiring systemic therapy during the study. Historical CD4+ cell counts less than 200 cells/µL are not exclusionary.
• Unstable liver disease known biliary abnormalities (with the exception of Gilbert's syndrome or asymptomatic gallstones or otherwise stable chronic liver disease per investigator assessment).
• History of cirrhosis with or without viral hepatitis co-infection.
• Participants with HCV co-infection will be excluded from the study.
• Individuals who are co-infected with HIV and HBV will be excluded Participants diagnosed with syphilis at Screening (i.e., positive syphilis testing) should be treated as per local guidelines and will be eligible to enroll at any time regardless of the stage of disease.
• Uncontrolled malignancy is excluded, whereas participants who have controlled malignancies may be included in agreement between the investigator and the ViiV Healthcare medical monitor.
• Any pre-existing physical, or mental condition (including alcohol or drug abuse) which, in the opinion of the investigator (with or without psychiatric evaluation) or the ViiV Healthcare medical monitor, may interfere with the participant's ability to comply with the dosing schedule and/or protocol evaluations or which may compromise the safety of the participant.
• Any condition which, in the opinion of the investigator or the ViiV Healthcare medical monitor, that may interfere with the absorption, distribution, metabolism or excretion of the study interventions or render the participant unable to take oral medication and normal gastrointestinal anatomy or motility or hepatic and/or renal function
• Clinically significant CV disease, as defined by history/evidence of congestive heart failure, symptomatic arrhythmia, angina/ischemia, coronary artery bypass grafting surgery or percutaneous transluminal coronary angioplasty or any clinically significant cardiac disease.
• Participants receiving any protocol-prohibited medication and who are unwilling or unable to switch to an alternate medication.
• History of sensitivity to any of the study medications, or their components or drugs of their class, or a history of drug or other allergy that, in the opinion of the investigator or ViiV Healthcare medical monitor, contraindicates their participation.
• Current or anticipated need for chronic anti-coagulation with the exception of the use of low dose acetylsalicylic acid (≤325 mg) or hereditary coagulation and platelet disorders such as hemophilia or Von Willebrand Disease.
• Treatment with any of the following agents within 60 days of Screening: radiation therapy, cytotoxic chemotherapeutic agents, any systemic immune suppressant.
• Treatment with immunomodulating agents (such as systemic corticosteroids, interleukins, interferons) or any agent with known anti-HIV activity (such as hydroxyurea or foscarnet) within 30 days of Day 1.
• Treatment with an HIV-1 immunotherapeutic vaccine within 90 days of Screening.
• Exposure to an approved vaccine within 14 days prior to Day 1.
• Current enrollment or past participation within the last 30 days before signing of consent in any other clinical study involving an investigational study intervention or any other type of medical research
• Participants with known or suspected presence of virologic resistance mutations as defined by the Stanford HIV Drug Resistance Database to INSTIs or NRTIs. This determination will be based on local virologic resistance testing, either at Screening or within the 3 months prior to Screening. ViiV Healthcare clinical virologist and/or ViiV Healthcare medical monitor will verify eligibility to this criterion prior to Day 1.
• Creatinine clearance (eGFR) of \<60 mL/min/1.73 m2 via CKD-EPI race neutral method \[Delgado, 2021\].
• ALT \>3 times the upper limit of normal (ULN). A single repeat of ALT is allowed within a single screening period to determine eligibility.
• Any Grade 4 laboratory abnormality at screening, except for a Grade 4 CPK and lipid abnormalities (e.g., total cholesterol, triglycerides, etc.) will exclude a participant from the study unless the investigator can provide a compelling explanation for the laboratory result(s) and has the assent of the ViiV Healthcare medical monitor. A single repeat of any lab abnormality is allowed within a single screening period to determine eligibility.
• Any acute laboratory abnormality at screening which, in the opinion of the investigator, should preclude participation in the study of an investigational compound.