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.

Study Overview

• Status: Completed
• Conditions: HIV Infections
• Intervention / Treatment: Drug: Placebo; Drug: VH4004280; Drug: Midazolam

• Study Type: Interventional
• Enrollment (Actual): 73
• Phase: Phase 1

Contacts and Locations

Study Locations

• United States
  • Nevada
    • Las Vegas, Nevada, United States, 89113
      • GSK Investigational Site

Participation Criteria

Eligibility Criteria

• Ages Eligible for Study: 18 years to 55 years (Adult)
• Accepts Healthy Volunteers: Yes

Description

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.

Study Plan

How is the study designed?

Design Details

• Primary Purpose: Treatment
• Allocation: Randomized
• Interventional Model: Sequential Assignment
• Masking: Double

Number of Arms

11

Arms and Interventions

Participant Group / Arm	Intervention / Treatment
Placebo Comparator: 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.	Drug: Placebo; Placebo will be administered.
Experimental: 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.	Drug: VH4004280; VH4004280 will be administered.; Other Names: GSK4004280
Experimental: 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.	Drug: VH4004280; VH4004280 will be administered.; Other Names: GSK4004280
Experimental: 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.	Drug: VH4004280; VH4004280 will be administered.; Other Names: GSK4004280
Experimental: 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.	Drug: VH4004280; VH4004280 will be administered.; Other Names: GSK4004280
Experimental: 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.	Drug: VH4004280; VH4004280 will be administered.; Other Names: GSK4004280
Placebo Comparator: 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.	Drug: Placebo; Placebo will be administered.
Experimental: 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.	Drug: VH4004280; VH4004280 will be administered.; Other Names: GSK4004280
Experimental: 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.	Drug: VH4004280; VH4004280 will be administered.; Other Names: GSK4004280; Drug: Midazolam; Midazolam will be administered
Experimental: 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.	Drug: VH4004280; VH4004280 will be administered.; Other Names: GSK4004280
Experimental: 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.	Drug: VH4004280; VH4004280 will be administered.; Other Names: GSK4004280

What is the study measuring?

Primary Outcome Measures

Outcome Measure	Measure Description	Time Frame
Part 1: Number of Participants With Any Adverse Events (AEs) and by Severity	An AE was defined as any untoward medical occurrence in a participant, temporally associated with the use of a study intervention whether or not considered related to the study intervention. The Division of AIDS (DAIDS) Table for Grading the Severity of Adult and Pediatric AE was used for all AE severity grading, where Grade 1=Mild symptoms causing no or minimal interference with usual social & functional activities with intervention not indicated, 2=Moderate symptoms causing greater than minimal interference with usual social & functional activities with intervention indicated, 3=Severe symptoms causing inability to perform usual social & functional activities with intervention or hospitalization indicated, 4=Potentially life-threatening symptoms causing inability to perform basic self-care functions with intervention indicated to prevent permanent impairment, persistent disability or death, 5=Death.	Up to Day 49
Part 2: Number of Participants With Any AEs and by Severity	The DAIDS Table for Grading the Severity of Adult and Pediatric AE was used for all AE severity grading, where Grade 1=Mild symptoms causing no or minimal interference with usual social & functional activities with intervention not indicated, 2=Moderate symptoms causing greater than minimal interference with usual social & functional activities with intervention indicated, 3=Severe symptoms causing inability to perform usual social & functional activities with intervention or hospitalization indicated, 4=Potentially life-threatening symptoms causing inability to perform basic self-care functions with intervention indicated to prevent permanent impairment, persistent disability or death, 5=Death.	Up to Day 63
Part 3: Number of Participants With Any AEs and by Severity	The DAIDS Table for Grading the Severity of Adult and Pediatric AE was used for all AE severity grading, where Grade 1=Mild symptoms causing no or minimal interference with usual social & functional activities with intervention not indicated, 2=Moderate symptoms causing greater than minimal interference with usual social & functional activities with intervention indicated, 3=Severe symptoms causing inability to perform usual social & functional activities with intervention or hospitalization indicated, 4=Potentially life-threatening symptoms causing inability to perform basic self-care functions with intervention indicated to prevent permanent impairment, persistent disability or death, 5=Death.	Up to Day 49
Part 2: Number of Participants Discontinuing Treatment Due to AEs	Number of participants who discontinued treatment due to AEs are presented.	Up to Day 63
Part 1: Absolute Values of Liver Panel Parameters: Direct Bilirubin and Total Bilirubin	Blood samples were collected as assessed by protocol, at specific time points for laboratory analysis of bilirubin. Standard Deviation (SD)=0.0000 is defined as following: if all participants analyzed for a specific parameter at a specific time point have the same value, then SD is equal with 0.0000.	Up to Day 49
Part 1: Absolute Values of Liver Panel Parameters: Alkaline Phosphatase (ALP), Alanine Aminotransferase (ALT) and Aspartate Aminotransferase (AST)	Blood samples were collected as assessed by protocol, at specific time points for laboratory analysis of ALP, ALT and AST.	Up to Day 49
Part 2: Absolute Values of Liver Panel Parameters: Direct Bilirubin and Total Bilirubin	Blood samples were collected as assessed by protocol, at specific time points for laboratory analysis of bilirubin. Standard Deviation (SD)=0.00000 is defined as following: if all participants analyzed for a specific parameter at a specific time point have the same value, then SD is equal with 0.00000.	Up to Day 63
Part 2: Absolute Values of Liver Panel Parameters: ALP, ALT and AST	Blood samples were collected as assessed by protocol, at specific time points for laboratory analysis of ALP, ALT and AST.	Up to Day 63
Part 3: Absolute Values of Liver Panel Parameters: Direct Bilirubin, Total Bilirubin	Blood samples were collected as assessed by protocol, at specific time points for laboratory analysis of bilirubin.	Up to Day 49
Part 3: Absolute Values of Liver Panel Parameters: ALP, ALT and AST	Blood samples were collected as assessed by protocol, at specific time points for laboratory analysis of ALP, ALT and AST.	Up to Day 49
Part 1: Change From Baseline in Liver Panel Parameters: Direct Bilirubin, Total Bilirubin	Change from baseline was calculated by subtracting the baseline value from the post-dose visit value. Standard Deviation (SD)=0.0000 is defined as following: if all participants analyzed for a specific parameter at a specific time point have the same value, then SD is equal with 0.0000.	From Baseline (Day 1) and up to Day 49
Part 1: Change From Baseline in Liver Panel Parameters: ALP, ALT and AST	Change from baseline was calculated by subtracting the baseline value from the post-dose visit value.	From Baseline (Day 1) and up to Day 49
Part 2: Change From Baseline in Liver Panel Parameters: Direct Bilirubin, Total Bilirubin	Change from baseline was calculated by subtracting the baseline value from the post-dose visit value. Standard Deviation (SD)=0.0000 is defined as following: if all participants analyzed for a specific parameter at a specific time point have the same value, then SD is equal with 0.0000.	From Baseline (Day 1) and up to Day 63
Part 2: Change From Baseline in Liver Panel Parameters: ALP, ALT and AST	Change from baseline was calculated by subtracting the baseline value from the post-dose visit value.	From Baseline (Day 1) and up to Day 63
Part 3: Change From Baseline in Liver Panel Parameters: Direct Bilirubin, Total Bilirubin	Change from baseline was calculated by subtracting the baseline value from the post-dose visit value.	From Baseline (Day 1) and up to Day 49
Part 3: Change From Baseline in Liver Panel Parameters: ALP, ALT and AST	Change from baseline was calculated by subtracting the baseline value from the post-dose visit value.	From Baseline (Day 1) and up to Day 49
Part 1: Number of Participants With Maximum Toxicity Grade Increase From Baseline for Liver Panel Parameters	Blood samples were collected as assessed by protocol, at specific time points for laboratory analysis of the liver panel parameters: ALT, ALP, AST, total bilirubin and direct bilirubin. The number of participants with any grade increase (from grade 1 [mild] to grade 4 [potentially life-threatening]) have been presented.	Up to Day 49
Part 2: Number of Participants With Maximum Toxicity Grade Increase From Baseline for Liver Panel Parameters	Blood samples were collected as assessed by protocol, at specific time points for laboratory analysis of the liver panel parameters: ALT, ALP, AST, total bilirubin and direct bilirubin. The number of participants with any grade increase (from grade 1 [mild] to grade 4 [potentially life-threatening]) have been presented.	Up to Day 63
Part 3: Number of Participants With Maximum Toxicity Grade Increase From Baseline for Liver Panel Parameters	Blood samples were collected as assessed by protocol, at specific time points for laboratory analysis of the liver panel parameters: ALT, ALP, AST, total bilirubin and direct bilirubin. The number of participants with any grade increase (from grade 1 [mild] to grade 4 [potentially life-threatening]) have been presented.	Up to Day 49
Part 1: Area Under the Plasma Concentration Time Curve From Time Zero to Infinity (AUC[0-infinity]) Following Single Dose Administration of VH4004280	Blood samples were collected as assessed by protocol, at specific time points for pharmacokinetic (PK) analysis to determine AUC(0-inf). For AUC, a linear trapezoidal method was employed for all incremental trapezoids arising from increasing concentrations and the logarithmic trapezoidal method was used for those arising from decreasing concentrations. Geometric Coefficient of Variation was expressed in percentages.	At Day 1
Part 2: AUC Over a Dosing Interval From Time of Dosing to the Time of the Subsequent Dose (AUC[0-t]) Following Repeat Dose Administration of VH4004280	Blood samples were collected as assessed by protocol, at specific time points for PK analysis to determine AUC(0-t). For AUC, a linear trapezoidal method was employed for all incremental trapezoids arising from increasing concentrations and the logarithmic trapezoidal method was used for those arising from decreasing concentrations.	At Days 1 and 14 for Part 2 (MAD): VH4004280 100 mg PiB and Part 2 (MAD): VH4004280 350 mg PiB groups, and at Days 2 and 15 for Part 2 (MAD): VH4004280 250 mg + Midazolam (MDZ) PiB group
Part 1: Maximum Observed Plasma Concentration (Cmax) Following Single Dose Administration of VH4004280	Blood samples were collected as assessed by protocol, at specific time points for PK analysis to determine Cmax.	At Day 1
Part 1: Time to Maximum Observed Plasma Concentration (Tmax) Following Single Dose Administration of VH4004280	Blood samples were collected as assessed by protocol, at specific time points for PK analysis to determine Tmax.	At Day 1
Part 1: Apparent Terminal Half-life (T1/2) Following Single Dose Administration of VH4004280	Blood samples were collected as assessed by protocol, at specific time points for PK analysis to determine T1/2.	Day 1 to Day 49
Part 2: Cmax Following Repeat Dose Administration of VH4004280	Blood samples were collected as assessed by protocol, at specific time points for PK analysis to determine Cmax.	At Days 1 and 14 for Part 2 (MAD): VH4004280 100 mg PiB and Part 2 (MAD): VH4004280 350 mg PiB groups, and at Days 2 and 15 for Part 2 (MAD): VH4004280 250 mg + Midazolam (MDZ) PiB group
Part 2: T1/2 Following Repeat Dose Administration of VH4004280	Blood samples were collected as assessed by protocol, at specific time points for PK analysis to determine T1/2.	Day 14 to Day 63 for Part 2 (MAD): VH4004280 100 mg PiB and Part 2 (MAD): VH4004280 350 mg PiB groups, and Day 15 to Day 63 for Part 2 (MAD): VH4004280 250 mg + Midazolam (MDZ) PiB group
Part 2: Tmax Following Repeat Dose Administration of VH4004280	Blood samples were collected as assessed by protocol, at specific time points for PK analysis to determine Tmax.	At Days 1 and 14 for Part 2 (MAD): VH4004280 100 mg PiB and Part 2 (MAD): VH4004280 350 mg PiB groups, and at Days 2 and 15 for Part 2 (MAD): VH4004280 250 mg + Midazolam (MDZ) PiB group

Collaborators and Investigators

• Sponsor: ViiV Healthcare
• Investigators: Study Director: GSK Clinical Trials, ViiV Healthcare

Study record dates

Study Major Dates

• Study Start (Actual): December 13, 2021
• Primary Completion (Actual): June 21, 2023
• Study Completion (Actual): June 21, 2023

Study Registration Dates

• First Submitted: December 6, 2021
• First Submitted That Met QC Criteria: December 6, 2021
• First Posted (Actual): December 20, 2021

Study Record Updates

• Last Update Posted (Actual): July 30, 2025
• Last Update Submitted That Met QC Criteria: July 9, 2025
• Last Verified: July 1, 2025

More Information

Terms related to this study

• Keywords: First-time-in-human; HIV-1 capsid inhibitor; Single ascending doses; Multiple ascending doses; GSK4004280; VH4004280
• Additional Relevant MeSH Terms: Blood-Borne Infections; Urogenital Diseases; Genital Diseases; Immune System Diseases; Infections; RNA Virus Infections; Virus Diseases; Communicable Diseases; Sexually Transmitted Diseases, Viral; Sexually Transmitted Diseases; Lentivirus Infections; Retroviridae Infections; Immunologic Deficiency Syndromes; HIV Infections; Physiological Effects of Drugs; Molecular Mechanisms of Pharmacological Action; Anesthetics; Central Nervous System Depressants; Neurotransmitter Agents; Adjuvants, Anesthesia; Hypnotics and Sedatives; Anti-Anxiety Agents; Tranquilizing Agents; Psychotropic Drugs; Anesthetics, Intravenous; Anesthetics, General; GABA Modulators; GABA Agents; Midazolam
• Other Study ID Numbers: 217058

Plan for Individual participant data (IPD)

• Plan to Share Individual Participant Data (IPD)?: YES
• IPD Plan Description: Sponsor will assess requests from qualified researchers for anonymized individual patient-level data and related study documents. Data sharing is subject to certain criteria, conditions, and exceptions. For further information, refer to https://www.viiv-studyregister.com/documents/About_ViiV_Patient_Level_Data_Sharing_Final_25Sep2023.pdf.
• IPD Sharing Time Frame: IPD will be made available within 6 months of publishing the results of the primary endpoints, key secondary endpoints and safety data of the study.
• IPD Sharing Access Criteria: Access is provided after a research proposal is submitted and has received approval from the Independent Review Panel and after a Data Sharing Agreement is in place. Access is provided for an initial period of 12 months but an extension can be granted, when justified, for up to another 12 months.
• IPD Sharing Supporting Information Type: STUDY_PROTOCOL; SAP; ICF; CSR

Drug and device information, study documents

• Studies a U.S. FDA-regulated drug product: Yes
• Studies a U.S. FDA-regulated device product: No