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

NCT05163522 | Completed Phase 1 Results FDA Drug

• 1 other identifier: 217058
• Study Type: interventional
• Target: 73
• Locations: 1 country
• Sites: 1

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

Keywords

First-time-in-human; GSK4004280; VH4004280; HIV-1 capsid inhibitor; Single ascending doses; Multiple ascending doses

Outcome Measures

Primary Outcomes (27)

• 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

Study Arms (11)

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.

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.

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.

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.

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.

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.

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.

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.

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.

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.

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.

Drug: VH4004280

Interventions

VH4004280 DRUG

VH4004280 will be administered.

Also known as: GSK4004280

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

Placebo DRUG

Placebo will be administered.

Part 1 Single Ascending Dose (SAD): Placebo Powder-in-bottle (PiB); Part 2 Multiple Ascending Dose (MAD): Placebo PiB

Midazolam DRUG

Midazolam will be administered

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

Eligibility Criteria

• Age: 18 Years - 55 Years
• Sex: all
• Healthy Volunteers: Yes
• Age Groups: Adult (18-64)

You may qualify if:

• 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.

You may not qualify if:

• 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.

Sponsors & Collaborators

• ViiV Healthcare: lead

Study Sites (1)

GSK Investigational Site

Las Vegas, Nevada, 89113, United States

Location

Related Publications (1)

• 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.

  PMID: 40287607 DERIVED

MeSH Terms

Conditions

HIV Infections

Interventions

Midazolam

Condition Hierarchy (Ancestors)

Blood-Borne Infections; Communicable Diseases; Infections; Sexually Transmitted Diseases, Viral; Sexually Transmitted Diseases; Lentivirus Infections; Retroviridae Infections; RNA Virus Infections; Virus Diseases; Genital Diseases; Urogenital Diseases; Immunologic Deficiency Syndromes; Immune System Diseases

Intervention Hierarchy (Ancestors)

Benzodiazepines; Benzazepines; Heterocyclic Compounds, 2-Ring; Heterocyclic Compounds, Fused-Ring; Heterocyclic Compounds

Results Point of Contact

• Title: GSK Response Center
• Organization: ViiV Healthcare

GSKClinicalSupportHD@gsk.com

866-435-7343

Study Officials

• GSK Clinical Trials

  ViiV Healthcare

  STUDY DIRECTOR

Publication Agreements

• PI is Sponsor Employee: No
• Restriction Type: OTHER
• Restrictive Agreement: Yes

Study Design

• Study Type: interventional
• Phase: phase 1
• Allocation: RANDOMIZED
• Masking: DOUBLE
• Who Masked: PARTICIPANT, INVESTIGATOR
• Masking Details: This is a double-blind (sponsor unblinded) study.
• Purpose: TREATMENT
• Intervention Model: SEQUENTIAL
• Sponsor Type: INDUSTRY
• Responsible Party: SPONSOR

Study Record Dates

• First Submitted: December 6, 2021
• First Posted: December 20, 2021
• Study Start: December 13, 2021
• Primary Completion: June 21, 2023
• Study Completion: June 21, 2023
• Last Updated: July 30, 2025
• Results First Posted: July 30, 2025

Record last verified: 2025-07

Data Sharing

• IPD Sharing: Will share
• Shared Documents: STUDY PROTOCOL, SAP, ICF, CSR
• 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.
• 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.

Locations

US (1)