Skip to main content
OpenTrials
Completed

NCT Number: NCT05393271

First-Time-in-Human (FTIH) Study to Evaluate the Safety, Tolerability and Pharmacokinetics (PK) of VH4011499 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 VH4011499 in healthy adults. The study will be conducted in 3 parts: Part 1 will investigate single ascending doses (SAD) and Part 2 will investigate multiple ascending doses (MAD). Part 3 will investigate single dose of a new formulation of VH4011499. The transition from SAD to MAD will be based on the assessment of the Safety and Dose Escalation Committee.

Completed

Looking for future studies?

Notify Me

Key information

Conditions

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

Age range

18 year–55 year

Sex eligibility

All sexes

Study type

Interventional

Phase

Phase 1

Primary location

GSK Investigational Site, Las Vegas, Nevada, United States

Loading trial locations.

Who can participate

Healthy volunteers accepted: Yes

Only the study team can determine whether someone qualifies for participation.

Inclusion criteria

  • Participants who are overtly healthy.
  • Participants must have two consecutive Severe Acute Respiratory Syndrome Coronavirus 2 (SARs-CoV-2) Polymerase chain reaction (PCR) negative results prior to dosing.
  • Participants must have body weight > 50 kilograms (kg) and body mass index (BMI) within the range 19-32 kilograms per meter square (kg/m^2).
  • Male or female participants (either of non-childbearing potential or of child-bearing potential and using acceptable contraception).
  • 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.
  • 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 within 7 days (or 14 days if the drug is a potential enzyme inducer) or 5 half-lives (whichever is longer) prior to dosing and for the duration of the study, unless in the opinion of the Investigator and Sponsor, the medication will not interfere with the study medications, procedures, or compromise participant safety.
  • Live vaccine(s) within 1 month prior to screening or plans to receive such vaccines during the study.
  • Exposure to more than 4 investigational products within 12 months prior to dosing.
  • Current enrollment or recent 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 within 14 days.
  • Positive HIV antibody test.
  • Use 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 midazolam, excipients contained therein, benzodiazepines, or drug or other allergy that, contraindicates participation in the study.

Treatment and study plan

VH4011499

Drug

VH4011499 will be administered.

Other names: GSK4011499

Placebo

Drug

Placebo will be administered.

midazolam

Drug

Midazolam will be administered

Primary outcomes

  1. Part 1: Number of Participants With Adverse Events (AEs)

    Time frame: Up to Day 28

    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.

  2. Part 2: Number of Participants With AEs

    Time frame: Up to Day 42

    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.

  3. Part 3: Number of Participants With AEs

    Time frame: Up to Day 28

    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.

  4. Part 1: Number of Participants With AEs by Severity

    Time frame: Up to Day 28

    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.

  5. Part 2: Number of Participants With AEs by Severity

    Time frame: Up to Day 42

    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.

  6. Part 3: Number of Participants With AEs by Severity

    Time frame: Up to Day 28

    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.

  7. Part 2: Number of Participants Discontinuing Treatment Due to AEs

    Time frame: Up to Day 42

    Number of participants who discontinued treatment due to AEs are presented.

  8. Part 1: Absolute Values of Liver Panel Parameters: Direct Bilirubin, Total Bilirubin

    Time frame: Up to Day 28

    Blood samples were collected as assessed by protocol, at specific time points for laboratory analysis of bilirubin.

  9. Part 1: Absolute Values of Liver Panel Parameters: Alanine Aminotransferase (ALT), Alkaline Phosphatase (ALP) and Aspartate Aminotransferase (AST)

    Time frame: Up to Day 28

    Blood samples were collected as assessed by protocol, at specific time points for laboratory analysis of ALT, ALP and AST.

  10. Part 2: Absolute Values of Liver Panel Parameters: Direct Bilirubin, Total Bilirubin

    Time frame: Up to Day 42

    Blood samples were collected as assessed by protocol, at specific time points for laboratory analysis of bilirubin.

  11. Part 2: Absolute Values of Liver Panel Parameters: ALT, ALP and AST

    Time frame: Up to Day 42

    Blood samples were collected as assessed by protocol, at specific time points for laboratory analysis of ALT, ALP and AST

  12. Part 3: Absolute Values of Liver Panel Parameters: Direct Bilirubin, Total Bilirubin

    Time frame: Up to Day 28

    Blood samples were collected as assessed by protocol, at specific time points for laboratory analysis of bilirubin.

  13. Part 3: Absolute Values of Liver Panel Parameters: ALT, ALP and AST

    Time frame: Up to Day 28

    Blood samples were collected as assessed by protocol, at specific time points for laboratory analysis of ALT, ALP and AST

  14. Part 1: Change From Baseline in Liver Panel Parameters: Direct Bilirubin, Total Bilirubin

    Time frame: From Baseline (Day 1) and up to Day 28

    Blood samples were collected as assessed by protocol, at specific time points for laboratory analysis of bilirubin. Change from baseline was calculated by subtracting the baseline value from the post-dose visit value.

  15. Part 1: Change From Baseline in Liver Panel Parameters: ALT, ALP and AST

    Time frame: From Baseline (Day 1) and up to Day 28

    Blood samples were collected as assessed by protocol, at specific time points for laboratory analysis of ALT, ALP and AST. Change from baseline was calculated by subtracting the baseline value from the post-dose visit value.

  16. Part 2: Change From Baseline in Liver Panel Parameters: Direct Bilirubin, Total Bilirubin

    Time frame: From Baseline (Day 1) and up to Day 42

    Blood samples were collected as assessed by protocol, at specific time points for laboratory analysis of 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.

  17. Part 2: Change From Baseline in Liver Panel Parameters: ALT, ALP and AST

    Time frame: From Baseline (Day 1) and up to Day 42

    Blood samples were collected as assessed by protocol, at specific time points for laboratory analysis of ALT, ALP and AST. Change from baseline was calculated by subtracting the baseline value from the post-dose visit value. SD=0.00 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 0.00.

  18. Part 3: Change From Baseline in Liver Panel Parameters: Direct Bilirubin, Total Bilirubin

    Time frame: From Baseline (Day 1) and up to Day 28

    Blood samples were collected as assessed by protocol, at specific time points for laboratory analysis of bilirubin. Change from baseline was calculated by subtracting the baseline value from the post-dose visit value.

  19. Part 3: Change From Baseline in Liver Panel Parameters: ALT, ALP and AST

    Time frame: From Baseline (Day 1) and up to Day 28

    Blood samples were collected as assessed by protocol, at specific time points for laboratory analysis of ALT, ALP and AST. Change from baseline was calculated by subtracting the baseline value from the post-dose visit value.

  20. Part 1: Number of Participants With Maximum Toxicity Grade Increase From Baseline for Liver Panel Parameters

    Time frame: Up to Day 28

    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.

  21. Part 2: Number of Participants With Maximum Toxicity Grade Increase From Baseline for Liver Panel Parameters

    Time frame: Up to Day 42

    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.

  22. Part 3: Number of Participants With Maximum Toxicity Grade Increase From Baseline for Liver Panel Parameters

    Time frame: Up to Day 28

    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.

  23. Part 1: Area Under the Plasma Concentration Time Curve (AUC) From Time Zero to Infinity (0-inf) Following Single Dose Administration of VH4011499

    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.

  24. Part 2: AUC Over a Dosing Interval From Time of Dosing to the Time of the Subsequent Dose (0-t) Following Repeat Dose Administration of VH4011499

    Time frame: At Days 1 and 14 for Part 2 (MAD): VH4011499 200 mg PiB and Part 2 (MAD): VH4011499 400 mg PiB groups, and at Days 2 and 15 for Part 2 (MAD): VH4011499 300 mg + Midazolam 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.

  25. Part 1: Maximum Observed Plasma Concentration (Cmax) Following Single Dose Administration of VH4011499.

    Time frame: At Day 1

    Blood samples were collected as assessed by protocol, at specific time points for PK analysis to determine Cmax.

  26. Part 1: Time to Maximum Observed Plasma Concentration (Tmax) Following Single Dose Administration of VH4011499

    Time frame: At Day 1

    Blood samples were collected as assessed by protocol, at specific time points for PK analysis to determine Tmax.

  27. Part 1: Apparent Terminal Half-life (T1/2) Following Single Dose Administration of VH4011499

    Time frame: At Day 1

    Blood samples were collected as assessed by protocol, at specific time points for PK analysis to determine T1/2.

  28. Part 2: Cmax Following Repeat Dose Administration of VH4011499

    Time frame: At Days 1 and 14 for Part 2 (MAD): VH4011499 200 mg PiB and Part 2 (MAD): VH4011499 400 mg PiB groups, and at Days 2 and 15 for Part 2 (MAD): VH4011499 300 mg + Midazolam PiB group

    Blood samples were collected as assessed by protocol, at specific time points for PK analysis to determine Cmax.

  29. Part 2: Tmax Following Repeat Dose Administration of VH4011499

    Time frame: At Days 1 and 14 for Part 2 (MAD): VH4011499 200 mg PiB and Part 2 (MAD): VH4011499 400 mg PiB groups, and at Days 2 and 15 for Part 2 (MAD): VH4011499 300 mg + Midazolam PiB group

    Blood samples were collected as assessed by protocol, at specific time points for PK analysis to determine Tmax.

  30. Part 2: T1/2 Following Repeat Dose Administration of VH4011499

    Time frame: At Day 14 for Part 2 (MAD): VH4011499 200 mg PiB and Part 2 (MAD): VH4011499 400 mg PiB groups, and at Day 15 for Part 2 (MAD): VH4011499 300 mg + Midazolam PiB group

    Blood samples were collected as assessed by protocol, at specific time points for PK analysis to determine T1/2.

Sponsors and collaborators

Lead sponsor

ViiV Healthcare

Industry

Registry information

Official study title

A Randomized, Double-Blind (Sponsor Unblinded), Placebo-Controlled Study to Evaluate the Safety, Tolerability and Pharmacokinetics of Orally Administered VH4011499 in Healthy Participants

Important dates

Study start
2022
Primary completion
2023
Study completion
2023
First posted
May 26, 2022
Registry last updated
Apr 1, 2025

OpenTrials presents study information sourced from ClinicalTrials.gov. The official registry record should be consulted for the latest information.

View the official ClinicalTrials.gov record (opens in a new tab)

This listing is for discovery and informational purposes only. It is not medical advice, does not guarantee that a study is recruiting, and does not determine eligibility. Contact the study team and a qualified healthcare professional when considering participation.

Related clinical trials

Published trials that share one or more normalized conditions with this study.