First-Time-in-Human (FTIH) Study to Evaluate the Safety, Tolerability and Pharmacokinetics (PK) of VH4004280 in Healthy Participants

A Randomized, Double-Blind (Sponsor Unblinded), Placebo-Controlled Study to Evaluate the Safety, Tolerability and Pharmacokinetics of Orally Administered VH4004280 in Healthy Participants

This FTIH study aims to evaluate the safety, tolerability and PK of the novel investigational Human immunodeficiency virus (HIV)-1 capsid inhibitor VH4004280 in healthy adults. The study will be conducted in 3 parts: Part 1 will investigate single ascending doses (SAD), Part 2 will investigate multiple ascending doses and drug-drug interaction (MAD/MAD DDI) Part 3 will investigate single dose relative bioavailability (RBA) of a new formulation of VH4004280.

Inclusion criteria:

• Participant must be 18 to 55 years of age inclusive.
• Participants who are overtly healthy.
• Male or female participants of non-childbearing potential.
• Capable of giving signed informed consent.

Exclusion criteria:

• History or presence of cardiovascular, respiratory, hepatic, renal, gastrointestinal, endocrine, hematological, neurological or psychiatric disorders capable of significantly altering the absorption, metabolism, or elimination of drugs; constituting a risk when taking the study drug or interfering with the interpretation of data.
• Abnormal blood pressure.
• Symptomatic herpes zoster.
• Evidence of active or latent tuberculosis (TB).
• Lymphoma, leukemia, or any malignancy within the past 5 years except for basal cell or squamous epithelial carcinomas of the skin that have been resected with no evidence of metastatic disease for 3 years.
• Breast cancer within the past 10 years.
• Current or chronic history of liver disease or known hepatic or biliary abnormalities (with the exception of Gilbert's syndrome or asymptomatic gallstones).
• QT interval corrected for heart rate according to Fridericia's formula (QTcF) greater than (>)450 milliseconds (msec).
• Past or intended use of over-the-counter or prescription medication including herbal medications.
• Live vaccine(s) within 1 month prior to screening or plans to receive such vaccines during the study.
• Exposure to more than 4 new investigational products within 12 months prior to the first dosing day.
• Current enrollment or past participation in another investigational study.
• ALT >1.5 times upper limit of normal (ULN), total bilirubin >1.5 times ULN, and/or estimated serum creatinine clearance less than 60 milliliters per minute.
• History of or current infection with hepatitis B or hepatitis C.
• Positive Severe Acute Respiratory Syndrome Coronavirus 2 (SARS-CoV-2) test, having signs and symptoms, or having contact with known Coronavirus Disease-2019 (COVID-19) positive person/s.
• Positive HIV antibody test.
• User of tobacco or nicotine-containing products, regular alcohol consumption and/or regular use of known drugs of abuse.
• Sensitivity to the study drug, or components thereof.