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

NCT ID: NCT05163522

Last Updated: 2025-07-30

Basic Information

• Recruitment Status: COMPLETED
• Clinical Phase: PHASE1
• Total Enrollment: 73 participants
• Study Classification: INTERVENTIONAL
• Study Start Date: 2021-12-13
• Study Completion Date: 2023-06-21

Brief Summary

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.

Conditions

HIV Infections

Study Design

• Allocation Method: RANDOMIZED
• Intervention Model: SEQUENTIAL
• Primary Study Purpose: TREATMENT
• Blinding Strategy: DOUBLE

Study Groups

Part 1 Single Ascending Dose (SAD): Placebo Powder-in-bottle (PiB)

Healthy participants were given a single oral dose of placebo on Day 1 and were followed up to approximately Day 49.

Group Type: PLACEBO_COMPARATOR

Placebo

Intervention Type: DRUG

Placebo will be administered.

Part 1 (SAD): VH4004280 10 mg PiB

Healthy participants were given a single oral dose of 10 mg VH4004280 PiB on Day 1 and were followed up to approximately Day 49.

Group Type: EXPERIMENTAL

VH4004280

Intervention Type: DRUG

VH4004280 will be administered.

Part 1 (SAD): VH4004280 50 mg PiB

Healthy participants were given a single oral dose of 50 mg VH4004280 PiB on Day 1 and were followed up to approximately Day 49.

Group Type: EXPERIMENTAL

VH4004280

Intervention Type: DRUG

VH4004280 will be administered.

Part 1 (SAD): VH4004280 150 mg PiB

Healthy participants were given a single oral dose of 150 mg VH4004280 PiB on Day 1 and were followed up to approximately Day 49.

Group Type: EXPERIMENTAL

VH4004280

Intervention Type: DRUG

VH4004280 will be administered.

Part 1 (SAD): VH4004280 450 mg PiB

Healthy participants were given a single oral dose of 450 mg VH4004280 PiB on Day 1 and were followed up to approximately Day 49.

Group Type: EXPERIMENTAL

VH4004280

Intervention Type: DRUG

VH4004280 will be administered.

Part 1 (SAD): VH4004280 900 mg PiB

Healthy participants were given a single oral dose of 900 mg VH4004280 PiB on Day 1 and were followed up to approximately Day 49.

Group Type: EXPERIMENTAL

VH4004280

Intervention Type: DRUG

VH4004280 will be administered.

Part 2 Multiple Ascending Dose (MAD): Placebo PiB

Healthy participants were given a dose of placebo once daily (QD) for a 14-day period and were followed up to approximately Day 63.

Group Type: PLACEBO_COMPARATOR

Placebo

Intervention Type: DRUG

Placebo will be administered.

Part 2 (MAD): VH4004280 100 mg PiB

Healthy participants were given a dose of 100 mg VH4004280 PiB QD for a 14-day period and were followed up to approximately Day 63.

Group Type: EXPERIMENTAL

VH4004280

Intervention Type: DRUG

VH4004280 will be administered.

Part 2 (MAD): VH4004280 250 mg + Midazolam (MDZ) PiB

Healthy participants were given a dose of 250 mg VH4004280 PiB QD for a 14-day period, and a single dose of Midazolam on days 1, 2, and 15, and were followed up to approximately Day 63.

Group Type: EXPERIMENTAL

VH4004280

Intervention Type: DRUG

VH4004280 will be administered.

Midazolam

Intervention Type: DRUG

Midazolam will be administered

Part 2 (MAD): VH4004280 350 mg PiB

Healthy participants were given a dose of 350 mg VH4004280 PiB QD for a 14-day period and were followed up to approximately Day 63.

Group Type: EXPERIMENTAL

VH4004280

Intervention Type: DRUG

VH4004280 will be administered.

Part 3 (Single dose): VH4004280 450 mg tablet

Healthy participants were given a single oral dose of VH4004280 450 mg tablet at Day 1 and were followed up to approximately Day 49.

Group Type: EXPERIMENTAL

VH4004280

Intervention Type: DRUG

VH4004280 will be administered.

Interventions

VH4004280

VH4004280 will be administered.

Intervention Type: DRUG

Placebo

Placebo will be administered.

Intervention Type: DRUG

Midazolam

Midazolam will be administered

Intervention Type: DRUG

Other Intervention Names

GSK4004280

Eligibility Criteria

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.

• Minimum Eligible Age: 18 Years
• Maximum Eligible Age: 55 Years
• Eligible Sex: ALL
• Accepts Healthy Volunteers: Yes

Sponsors

ViiV Healthcare

INDUSTRY

Sponsor Role: lead

Responsible Party

Responsibility Role: SPONSOR

Principal Investigators

GSK Clinical Trials

Role: STUDY_DIRECTOR

ViiV Healthcare

Locations

GSK Investigational Site

Las Vegas, Nevada, United States

Countries

United States

References

Thakkar N, Griesel R, Pierce A, Bainbridge V, Shepherd B, Angelis K, Tomlinson A, Gandhi Y, Brimhall D, Anderson D, Andrews S, Acuipil C, McCoig C, Baker M, Benn P. Clinical Pharmacokinetics and Safety of a New HIV-1 Capsid Inhibitor, VH4004280, After Oral Administration in Adults Without HIV. Infect Dis Ther. 2025 Jun;14(6):1313-1326. doi: 10.1007/s40121-025-01154-x. Epub 2025 Apr 26.

Reference Type: DERIVED

PMID: 40287607 (View on PubMed)

Provided Documents

Document Type: Study Protocol

View Document

Document Type: Statistical Analysis Plan

View Document

Other Identifiers

217058

Identifier Type: -

Identifier Source: org_study_id