HIV InfectionsPhase 1NCT05163522

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

A Phase 1 study testing VH4004280 and Midazolam in people with HIV Infections, run by ViiV Healthcare at 1 site in United States.

Completed

Finished. The study has ended and is not enrolling. Results may be posted on the official record.

Official record

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Trial 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… Read more about this study

Who is it for?: Ages 18 to 55 yearsHealthy volunteers can take part
Conditions the study is for: HIV Infections
What is being tested?: VH4004280 and Midazolam
Type of treatment: Pill or oral medicine
Could I receive a placebo?: Yes, some participants may receive a placebo
How many people: 73 participants
Where: 1 siteUnited States
Study dates: 13 Dec 2021to 21 Jun 2023
Phase: Phase 1
Are there results?: Yes, posted in the registrySummary in the doctors' view

Key requirements

Who can take part, as listed by the sponsor. Only the study team can confirm whether you are eligible, so take this list to your doctor.

Ages 18 to 55 years
All sexes
Healthy volunteers accepted
Adult

Who may be able to join

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.

Who cannot join

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.

Show all 18Show fewer

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.

Trial locations and contacts

1 site in 1 country.

United States1 site

GSK Investigational Site
Las Vegas, Nevada, 89113

Other trials in United States

About this study

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

Conditions: HIV Infections
Being tested: VH4004280, Placebo, Midazolam
Keywords: First-time-in-human, GSK4004280, VH4004280, HIV-1 capsid inhibitor, Single ascending doses, Multiple ascending doses
Medical subject headings: HIV Infections

What participants receive

What participants receive. In a randomised study each person is assigned to one group by chance.

VH4004280Drug
Also called GSK4004280
VH4004280 will be administered.
PlaceboDrug
Placebo will be administered.
MidazolamDrug
Midazolam will be administered

Study groups in NCT05163522
Study group	Role	What they receive
Part 1 Single Ascending Dose (SAD): Placebo Powder-in-bottle (PiB)	Placebo comparator	Healthy participants were given a single oral dose of placebo on Day 1 and were followed up to approximately Day 49. Receives: Drug: Placebo
Part 1 (SAD): VH4004280 10 mg PiB	Experimental	Healthy participants were given a single oral dose of 10 mg VH4004280 PiB on Day 1 and were followed up to approximately Day 49. Receives: Drug: VH4004280
Part 1 (SAD): VH4004280 50 mg PiB	Experimental	Healthy participants were given a single oral dose of 50 mg VH4004280 PiB on Day 1 and were followed up to approximately Day 49. Receives: Drug: VH4004280
Part 1 (SAD): VH4004280 150 mg PiB	Experimental	Healthy participants were given a single oral dose of 150 mg VH4004280 PiB on Day 1 and were followed up to approximately Day 49. Receives: Drug: VH4004280
Part 1 (SAD): VH4004280 450 mg PiB	Experimental	Healthy participants were given a single oral dose of 450 mg VH4004280 PiB on Day 1 and were followed up to approximately Day 49. Receives: Drug: VH4004280
Part 1 (SAD): VH4004280 900 mg PiB	Experimental	Healthy participants were given a single oral dose of 900 mg VH4004280 PiB on Day 1 and were followed up to approximately Day 49. Receives: Drug: VH4004280
Part 2 Multiple Ascending Dose (MAD): Placebo PiB	Placebo comparator	Healthy participants were given a dose of placebo once daily (QD) for a 14-day period and were followed up to approximately Day 63. Receives: Drug: Placebo
Part 2 (MAD): VH4004280 100 mg PiB	Experimental	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. Receives: Drug: VH4004280
Part 2 (MAD): VH4004280 250 mg + Midazolam (MDZ) PiB	Experimental	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. Receives: Drug: VH4004280; Drug: Midazolam
Part 2 (MAD): VH4004280 350 mg PiB	Experimental	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. Receives: Drug: VH4004280
Part 3 (Single dose): VH4004280 450 mg tablet	Experimental	Healthy participants were given a single oral dose of VH4004280 450 mg tablet at Day 1 and were followed up to approximately Day 49. Receives: Drug: VH4004280

What is being measured

The primary outcome is the main question the study is designed to answer.

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.
Measured: 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.
Measured: 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.
Measured: 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.
Measured: 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.
Measured: 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.
Measured: 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.
Measured: 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.
Measured: 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.
Measured: 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.
Measured: 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.
Measured: 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.
Measured: 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.
Measured: 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.
Measured: 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.
Measured: 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.
Measured: 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.
Measured: 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.
Measured: 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.
Measured: 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.
Measured: 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.
Measured: 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.
Measured: 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.
Measured: 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.
Measured: 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.
Measured: 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.
Measured: 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.
Measured: 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

Timeline

From the start of the study to its completion; the mark is today. Estimated dates are the sponsor’s plan.

13 Dec 202121 Jun 2023

First posted20 Dec 2021
Study start13 Dec 2021
Primary completion21 Jun 2023
Study completion21 Jun 2023

Resources

Official record on ClinicalTrials.govThe registry entry this page is built from, with its full change history.
Posted resultsParticipant flow, outcome measures and adverse events reported by the sponsor.
Publications (1)Papers the sponsor has linked to this study.
Other trials for HIV InfectionsStudies of the same condition, open and under way.
More trials run by ViiV HealthcareThe sponsor's other registered studies.
What the trial phases meanHow a treatment moves from first tests in people to approval.

More details

For doctors and researchers: how the study is designed, who runs it, and its registry IDs.

Study design

Study type: Interventional
Phase: Phase 1
Primary purpose: Treatment
Allocation: Randomised
Intervention model: Sequential
Masking: Double blind
Who is masked: Participant, Investigator
Enrolment: 73 participants (actual)

IDs, dates and publications

ClinicalTrials.gov ID: NCT05163522
Sponsor's protocol ID: 217058
Status last verified: Jul 2025
First submitted: 6 Dec 2021
Last updated: 30 Jul 2025
Results posted: Yes, on ClinicalTrials.gov
Data monitoring committee: No
FDA-regulated drug: Yes
FDA-regulated device: No
Individual data sharing: Yes: 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.

Publications

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.
PubMed 40287607

Want to know more?

The sponsor has not listed a contact. The official record may have more details.

Talk to your doctor first and take this page with you. Only the study team can confirm whether you can join.

Questions to ask the study team

What is the study trying to find out?
What would I need to do, and how often would I visit?
Could I receive a placebo instead of the treatment?
What are the possible risks and benefits for me?
Will it cost me anything? Are travel or time paid for?
Can I keep seeing my own doctor during the study?
What happens when the study ends?

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Study at a glance

From the registry record, last updated by the sponsor on 30 Jul 2025. Recruitment status is as the sponsor reported it: confirm with the study team.

Official title: A Randomized, Double-Blind (Sponsor Unblinded), Placebo-Controlled Study to Evaluate the Safety, Tolerability and Pharmacokinetics of Orally Administered VH4004280 in Healthy Participants
ClinicalTrials.gov ID: NCT05163522
Acronym / sponsor ID: 217058
Conditions: HIV Infections
Keywords: First-time-in-human, GSK4004280, VH4004280, HIV-1 capsid inhibitor, Single ascending doses, Multiple ascending doses
Phase: Phase 1
Study type: Interventional
Recruitment status: Completed
Enrolment: 73 participants (actual)
Lead sponsor: ViiV HealthcareIndustry (pharma, biotech, devices)
Study start: 13 Dec 2021 (actual)
Primary completion: 21 Jun 2023 (actual)
Study completion: 21 Jun 2023 (actual)
First posted: 20 Dec 2021 (actual)
Results: Posted 30 Jul 2025

Clinical summary

The research question as the sponsor registered it. This describes what the study plans to test, not what it found.

Study design

Primary purpose: Treatment
Allocation: Randomised
Intervention model: Sequential
Masking: Double blind (participant, investigator)
Number of arms: 11

Arm	Type	Receives
Part 1 Single Ascending Dose (SAD): Placebo Powder-in-bottle (PiB)	Placebo comparator	Drug: PlaceboHealthy participants were given a single oral dose of placebo on Day 1 and were followed up to approximately Day 49.
Part 1 (SAD): VH4004280 10 mg PiB	Experimental	Drug: VH4004280Healthy participants were given a single oral dose of 10 mg VH4004280 PiB on Day 1 and were followed up to approximately Day 49.
Part 1 (SAD): VH4004280 50 mg PiB	Experimental	Drug: VH4004280Healthy participants were given a single oral dose of 50 mg VH4004280 PiB on Day 1 and were followed up to approximately Day 49.
Part 1 (SAD): VH4004280 150 mg PiB	Experimental	Drug: VH4004280Healthy participants were given a single oral dose of 150 mg VH4004280 PiB on Day 1 and were followed up to approximately Day 49.
Part 1 (SAD): VH4004280 450 mg PiB	Experimental	Drug: VH4004280Healthy participants were given a single oral dose of 450 mg VH4004280 PiB on Day 1 and were followed up to approximately Day 49.
Part 1 (SAD): VH4004280 900 mg PiB	Experimental	Drug: VH4004280Healthy participants were given a single oral dose of 900 mg VH4004280 PiB on Day 1 and were followed up to approximately Day 49.
Part 2 Multiple Ascending Dose (MAD): Placebo PiB	Placebo comparator	Drug: PlaceboHealthy participants were given a dose of placebo once daily (QD) for a 14-day period and were followed up to approximately Day 63.
Part 2 (MAD): VH4004280 100 mg PiB	Experimental	Drug: VH4004280Healthy participants were given a dose of 100 mg VH4004280 PiB QD for a 14-day period and were followed up to approximately Day 63.
Part 2 (MAD): VH4004280 250 mg + Midazolam (MDZ) PiB	Experimental	Drug: VH4004280, Drug: MidazolamHealthy 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.
Part 2 (MAD): VH4004280 350 mg PiB	Experimental	Drug: VH4004280Healthy participants were given a dose of 350 mg VH4004280 PiB QD for a 14-day period and were followed up to approximately Day 63.
Part 3 (Single dose): VH4004280 450 mg tablet	Experimental	Drug: VH4004280Healthy participants were given a single oral dose of VH4004280 450 mg tablet at Day 1 and were followed up to approximately Day 49.

Who may qualify

Ages: 18 to 55 years
Sex: All
Healthy volunteers: Accepted
Age groups: Adult

Key inclusion criteria (4 listed)

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.

Key exclusion criteria (18 listed)

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.

Eligibility is decided by the study team after screening; this overview does not establish that a patient qualifies. Full inclusion and exclusion criteria.

Interventions

Intervention	Type	Arms
VH4004280Also: GSK4004280VH4004280 will be administered.	Drug	Part 1 (SAD): VH4004280 10 mg PiB, Part 1 (SAD): VH4004280 150 mg PiB, Part 1 (SAD): VH4004280 450 mg PiB, Part 1 (SAD): VH4004280 50 mg PiB, Part 1 (SAD): VH4004280 900 mg PiB, Part 2 (MAD): VH4004280 100 mg PiB, Part 2 (MAD): VH4004280 250 mg + Midazolam (MDZ) PiB, Part 2 (MAD): VH4004280 350 mg PiB, Part 3 (Single dose): VH4004280 450 mg tablet
PlaceboPlacebo will be administered.	Drug	Part 1 Single Ascending Dose (SAD): Placebo Powder-in-bottle (PiB), Part 2 Multiple Ascending Dose (MAD): Placebo PiB
MidazolamMidazolam will be administered	Drug	Part 2 (MAD): VH4004280 250 mg + Midazolam (MDZ) PiB

Primary outcome

Part 1: Number of Participants With Any Adverse Events (AEs) and by Severity
Time frame: Up to Day 49
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.
Part 2: Number of Participants With Any AEs and by Severity
Time frame: Up to Day 63
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.
Part 3: Number of Participants With Any AEs and by Severity
Time frame: Up to Day 49
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.
Part 2: Number of Participants Discontinuing Treatment Due to AEs
Time frame: Up to Day 63
Number of participants who discontinued treatment due to AEs are presented.
Part 1: Absolute Values of Liver Panel Parameters: Direct Bilirubin and Total Bilirubin
Time frame: Up to Day 49
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.
Part 1: Absolute Values of Liver Panel Parameters: Alkaline Phosphatase (ALP), Alanine Aminotransferase (ALT) and Aspartate Aminotransferase (AST)
Time frame: Up to Day 49
Blood samples were collected as assessed by protocol, at specific time points for laboratory analysis of ALP, ALT and AST.
Part 2: Absolute Values of Liver Panel Parameters: Direct Bilirubin and Total Bilirubin
Time frame: Up to Day 63
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.
Part 2: Absolute Values of Liver Panel Parameters: ALP, ALT and AST
Time frame: Up to Day 63
Blood samples were collected as assessed by protocol, at specific time points for laboratory analysis of ALP, ALT and AST.
Part 3: Absolute Values of Liver Panel Parameters: Direct Bilirubin, Total Bilirubin
Time frame: Up to Day 49
Blood samples were collected as assessed by protocol, at specific time points for laboratory analysis of bilirubin.
Part 3: Absolute Values of Liver Panel Parameters: ALP, ALT and AST
Time frame: Up to Day 49
Blood samples were collected as assessed by protocol, at specific time points for laboratory analysis of ALP, ALT and AST.
Part 1: Change From Baseline in Liver Panel Parameters: Direct Bilirubin, Total Bilirubin
Time frame: From Baseline (Day 1) and up to Day 49
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.
Part 1: Change From Baseline in Liver Panel Parameters: ALP, ALT and AST
Time frame: From Baseline (Day 1) and up to Day 49
Change from baseline was calculated by subtracting the baseline value from the post-dose visit value.
Part 2: Change From Baseline in Liver Panel Parameters: Direct Bilirubin, Total Bilirubin
Time frame: From Baseline (Day 1) and up to Day 63
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.
Part 2: Change From Baseline in Liver Panel Parameters: ALP, ALT and AST
Time frame: From Baseline (Day 1) and up to Day 63
Change from baseline was calculated by subtracting the baseline value from the post-dose visit value.
Part 3: Change From Baseline in Liver Panel Parameters: Direct Bilirubin, Total Bilirubin
Time frame: From Baseline (Day 1) and up to Day 49
Change from baseline was calculated by subtracting the baseline value from the post-dose visit value.
Part 3: Change From Baseline in Liver Panel Parameters: ALP, ALT and AST
Time frame: From Baseline (Day 1) and up to Day 49
Change from baseline was calculated by subtracting the baseline value from the post-dose visit value.
Part 1: Number of Participants With Maximum Toxicity Grade Increase From Baseline for Liver Panel Parameters
Time frame: Up to Day 49
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.
Part 2: Number of Participants With Maximum Toxicity Grade Increase From Baseline for Liver Panel Parameters
Time frame: Up to Day 63
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.
Part 3: Number of Participants With Maximum Toxicity Grade Increase From Baseline for Liver Panel Parameters
Time frame: Up to Day 49
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.
Part 1: Area Under the Plasma Concentration Time Curve From Time Zero to Infinity (AUC[0-infinity]) Following Single Dose Administration of VH4004280
Time frame: At Day 1
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.
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
Time frame: 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
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.
Part 1: Maximum Observed Plasma Concentration (Cmax) Following Single Dose Administration of VH4004280
Time frame: At Day 1
Blood samples were collected as assessed by protocol, at specific time points for PK analysis to determine Cmax.
Part 1: Time to Maximum Observed Plasma Concentration (Tmax) Following Single Dose Administration of VH4004280
Time frame: At Day 1
Blood samples were collected as assessed by protocol, at specific time points for PK analysis to determine Tmax.
Part 1: Apparent Terminal Half-life (T1/2) Following Single Dose Administration of VH4004280
Time frame: Day 1 to Day 49
Blood samples were collected as assessed by protocol, at specific time points for PK analysis to determine T1/2.
Part 2: Cmax Following Repeat Dose Administration of VH4004280
Time frame: 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
Blood samples were collected as assessed by protocol, at specific time points for PK analysis to determine Cmax.
Part 2: T1/2 Following Repeat Dose Administration of VH4004280
Time frame: 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
Blood samples were collected as assessed by protocol, at specific time points for PK analysis to determine T1/2.
Part 2: Tmax Following Repeat Dose Administration of VH4004280
Time frame: 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
Blood samples were collected as assessed by protocol, at specific time points for PK analysis to determine Tmax.

Results and safety

Results posted to the registry on 30 Jul 2025, as reported by the sponsor. Figures are copied from the record, not re-analysed. Full results on ClinicalTrials.gov.

Participant flow

Group	Started	Completed
Part 1 Single Ascending Dose (SAD): Placebo Powder-in-bottle (PiB)	10	10
Part 1 (SAD): VH4004280 10 mg PiB	6	6
Part 1 (SAD): VH4004280 50 mg PiB	7	6
Part 1 (SAD): VH4004280 150 mg PiB	6	6
Part 1 (SAD): VH4004280 450 mg PiB	6	6
Part 1 (SAD): VH4004280 900 mg PiB	6	6
Part 2 Multiple Ascending Dose (MAD): Placebo PiB	6	6
Part 2 (MAD): VH4004280 100 mg PiB	6	6
Part 2 (MAD): VH4004280 250 mg + Midazolam (MDZ) PiB	8	8
Part 2 (MAD): VH4004280 350 mg PiB	6	6
Part 3 (Single Dose): VH4004280 450 mg Tablet	6	6

Primary outcome: Part 1: Number of Participants With Any Adverse Events (AEs) and by Severity

Time frame: Up to Day 49. Count of participants. Unit: Participants

Measure	Part 1 Single Ascending Dose (SAD): Placebo Powder-in-bottle (PiB) n = 10	Part 1 (SAD): VH4004280 10 mg PiB n = 6	Part 1 (SAD): VH4004280 50 mg PiB n = 7	Part 1 (SAD): VH4004280 900 mg PiB n = 6
Any AEs	4	2	3	1
Grade 1 AEs	3	2	3	1
Grade 2 AEs	0	0	0	0
Grade 3 AEs	1	0	0	0
Grade 4 AEs	0	0	0	0
Grade 5 AEs	0	0	0	0

Population analysed: The analysis was performed on the Safety Set which included all enrolled participants in Part 1 (SAD) who received 1 full dose of study treatment. The participants were analyzed according to the treatment they actually received.

Primary outcome: Part 2: Number of Participants With Any AEs and by Severity

Time frame: Up to Day 63. Count of participants. Unit: Participants

Measure	Part 2 Multiple Ascending Dose (MAD): Placebo PiB n = 6	Part 2 (MAD): VH4004280 100 mg PiB n = 6	Part 2 (MAD): VH4004280 250 mg + Midazolam (MDZ) PiB n = 8	Part 2 (MAD): VH4004280 350 mg PiB n = 6
Any AEs	3	4	7	4
Grade 1 AEs	3	4	4	2
Grade 2 AEs	0	0	3	0
Grade 3 AEs	0	0	0	1
Grade 4 AEs	0	0	0	1
Grade 5 AEs	0	0	0	0

Population analysed: The analysis was performed on the Safety Set which included all enrolled participants in Part 2 (MAD) who received at least 1 full or partial dose of study treatment. The participants were analyzed according to the treatment they actually received.

Primary outcome: Part 3: Number of Participants With Any AEs and by Severity

Time frame: Up to Day 49. Count of participants. Unit: Participants

Measure	Part 3 (Single Dose): VH4004280 450 mg Tablet n = 6
Any AEs	3
Grade 1 AEs	2
Grade 2 AEs	0
Grade 3 AEs	1
Grade 4 AEs	0
Grade 5 AEs	0

Population analysed: The analysis was performed on the Safety Set which included all enrolled participants in Part 3 (Single Dose) who received 1 single dose of study treatment. The participants were analyzed according to the treatment they actually received.

Primary outcome: Part 2: Number of Participants Discontinuing Treatment Due to AEs

Time frame: Up to Day 63. Count of participants. Unit: Participants

Measure	Part 2 Multiple Ascending Dose (MAD): Placebo PiB n = 6	Part 2 (MAD): VH4004280 100 mg PiB n = 6	Part 2 (MAD): VH4004280 250 mg + Midazolam (MDZ) PiB n = 8	Part 2 (MAD): VH4004280 350 mg PiB n = 6
Value	0	0	0	0

Adverse events

Time frame: All cause mortality, serious adverse events (SAEs) and non-SAEs were collected up to a 49-day period following VH4004280 or placebo (i.e.: Day 49 for Parts 1 and 3, and Day 63 for Part 2).. Other adverse events reported at 5% frequency or more

Group	Serious adverse events	Other adverse events	Deaths
Part 1 Single Ascending Dose (SAD): Placebo Powder-in-bottle (PiB)	0 of 10 (0%)	4 of 10 (40%)	0 of 10
Part 1 (SAD): VH4004280 10 mg PiB	0 of 6 (0%)	2 of 6 (33.3%)	0 of 6
Part 1 (SAD): VH4004280 50 mg PiB	0 of 7 (0%)	3 of 7 (42.9%)	0 of 7
Part 1 (SAD): VH4004280 150 mg PiB	0 of 6 (0%)	0 of 6 (0%)	0 of 6
Part 1 (SAD): VH4004280 450 mg PiB	0 of 6 (0%)	0 of 6 (0%)	0 of 6
Part 1 (SAD): VH4004280 900 mg PiB	0 of 6 (0%)	1 of 6 (16.7%)	0 of 6
Part 2 Multiple Ascending Dose (MAD): Placebo PiB	0 of 6 (0%)	3 of 6 (50%)	0 of 6
Part 2 (MAD): VH4004280 100 mg PiB	0 of 6 (0%)	4 of 6 (66.7%)	0 of 6
Part 2 (MAD): VH4004280 250 mg + Midazolam (MDZ) PiB	0 of 8 (0%)	7 of 8 (87.5%)	0 of 8
Part 2 (MAD): VH4004280 350 mg PiB	0 of 6 (0%)	4 of 6 (66.7%)	0 of 6
Part 3 (Single Dose): VH4004280 450 mg Tablet	0 of 6 (0%)	3 of 6 (50%)	0 of 6

Loading the posted results from ClinicalTrials.gov…

Research links

Official record on ClinicalTrials.govLast updated by the sponsor 30 Jul 2025.
Posted resultsParticipant flow, baseline, all outcome measures and adverse events.
Derived from this study: PubMed 40287607Thakkar 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.
Individual participant dataSharing planned: Yes. 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.

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Referral and contact

AzTrials does not enrol participants or take referrals. Contact the study team or a site listed below; they decide who can take part. This study is not recruiting at the moment.

GSK Clinical Trials study director

ViiV Healthcare

1 site in 1 country: see every site and its status.

Questions about this trial

What is this clinical trial studying?

A Phase 1 study testing VH4004280 and Midazolam in people with HIV Infections, run by ViiV Healthcare at 1 site in United States.

The full registered description is in the About this study section and the official record.

Who may be eligible to take part?

The sponsor lists 4 inclusion and 18 exclusion criteria. Eligibility is decided by the study team after screening, so read the full criteria and contact a listed site.

Is this clinical trial currently recruiting?

The record says: finished, as of the sponsor's last update on 30 Jul 2025. Status can change between updates, so confirm with the study contact before making plans.

Where is the study taking place?

The record lists 1 site in United States. Whether a site is taking part right now should be confirmed with that site. See every site.

What are the possible benefits and risks?

They depend on the study and the treatment, and no study can promise a benefit. Some participants in this study may receive a placebo. The study team explains the known risks during informed consent, before anyone joins; the record itself does not list them.

What does this phase mean?

Phase 1 studies test a treatment in a small group of people for the first time or in a new way, mainly to check safety and find the right dose.

Not every study follows the same path, and some studies (observational studies, device studies) have no phase.

Are results available for this study?

Yes. Results are posted in the registry (first posted 30 Jul 2025). A summary is in the For doctors view, and the full results are on ClinicalTrials.gov.

How can a doctor refer a patient or contact the research team?

The record lists no contact. The official record names the sponsor, who can be asked directly. AzTrials does not enrol participants or take referrals.

What does the primary outcome measure?

Part 1: Number of Participants With Any Adverse Events (AEs) and by Severity (time frame: Up to Day 49). The study lists 27 primary outcomes in all. It is what the study was designed to measure, not a finding.

Where can I read the original study information?

On the ClinicalTrials.gov record for NCT05163522, which also lists 1 linked publication.

Does a listing mean the treatment is approved or proven to work?

No. A listing means the study is registered. It does not show that the treatment is safe, works, or is approved by a regulator.

How often is this information updated?

AzTrials copies changed records from ClinicalTrials.gov every night and reloads the whole registry every week. The sponsor last updated this record on 30 Jul 2025.