First-Time-in-Human (FTIH) Study to Evaluate the Safety, Tolerability and Pharmacokinetics (PK) of VH4011499 in Healthy Participants

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

Study Overview

• Status: Completed
• Conditions: HIV Infections
• Intervention / Treatment: Drug: VH4011499; Drug: Placebo; 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
  • Texas
    • Austin, Texas, United States, 78744
      • GSK Investigational Site

Participation Criteria

Eligibility Criteria

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

Description

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.

Study Plan

How is the study designed?

Design Details

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

Number of Arms

7

Arms and Interventions

Participant Group / Arm	Intervention / Treatment
Experimental: Part 1 (SAD): Participants receiving VH4011499	Drug: VH4011499; VH4011499 will be administered.; Other Names: GSK4011499
Placebo Comparator: Part 1 (SAD): Participants receiving placebo	Drug: Placebo; Placebo will be administered.
Experimental: Part 2 (MAD) Drug-Drug Interaction (DDI) cohort: Participants receiving VH4011499 + Midazolam	Drug: VH4011499; VH4011499 will be administered.; Other Names: GSK4011499; Drug: Midazolam; Midazolam will be administered
Placebo Comparator: Part 2 (MAD) DDI cohort: Participants receiving placebo + Midazolam	Drug: Placebo; Placebo will be administered.; Drug: Midazolam; Midazolam will be administered
Experimental: Part 2 (MAD) Non DDI cohort: Participants receiving VH4011499	Drug: VH4011499; VH4011499 will be administered.; Other Names: GSK4011499
Placebo Comparator: Part 2 (MAD) Non DDI cohort: Participants receiving placebo	Drug: Placebo; Placebo will be administered.
Experimental: Part 3 (Single dose): Participants receiving VH4011499 (new formulation)	Drug: VH4011499; VH4011499 will be administered.; Other Names: GSK4011499

What is the study measuring?

Primary Outcome Measures

Outcome Measure	Time Frame
Part 1: Number of participants with adverse events (AEs)	Up to Day 28
Part 2: Number of participants with AEs	Up to Day 42
Part 1: Number of participants with AEs by severity	Up to Day 28
Part 2: Number of participants with AEs by severity	Up to Day 42
Part 1: Absolute values of liver panel parameters: Direct bilirubin, total bilirubin (Micromoles per liter)	Up to Day 28
Part 1: Absolute values of liver panel parameters: Alanine aminotransferase (ALT), Alkaline phosphatase (ALP) and Aspartate aminotransferase (AST) (International units per Liter)	Up to Day 28
Part 2: Absolute values of liver panel parameters: Direct bilirubin, total bilirubin (Micromoles per liter)	Up to Day 42
Part 1: Change from Baseline in liver panel parameters: Direct bilirubin, total bilirubin (Micromoles per liter)	Baseline (Day 1) and up to Day 28
Part 1: Change from Baseline in liver panel parameters: ALT, ALP and AST (International units per Liter)	Baseline (Day 1) and up to Day 28
Part 2: Change from Baseline in liver panel parameters: Direct bilirubin, total bilirubin (Micromoles per liter)	Baseline (Day 1) and up to Day 42
Part 2: Change from Baseline in liver panel parameters: ALT, ALP and AST (International units per Liter)	Baseline (Day 1) and up to Day 42
Part 1: Percentage of participants with maximum toxicity grade increase from Baseline for liver panel parameters	Up to Day 28
Part 2: Percentage of participants with maximum toxicity grade increase from Baseline for liver panel parameters	Up to Day 42
Part 1: Area under the plasma concentration time curve from time zero to infinity (AUC[0-infinity]) following single dose administration of VH4011499	Up to Day 28
Part 2: Area under the plasma concentration time curve over a dosing interval from time of dosing to the time of the subsequent dose (AUC[0-tau]) following repeat dose administration of VH4011499	Up to Day 42
Part 1: Maximum observed plasma concentration (Cmax) following single dose administration of VH4011499	Up to Day 28
Part 1: Time to maximum observed plasma concentration (Tmax) and Apparent terminal half-life (T1/2) following single dose administration of VH4011499 (Hours)	Up to Day 28
Part 2: Cmax following repeat dose administration of VH4011499	Up to Day 42
Part 2: Tmax and T1/2 following repeat dose administration of VH4011499 (Hours)	Up to Day 42
Part 3: Number of participants with AEs	Up to Day 28
Part 3: Number of participants with AEs by severity	Up to Day 28
Part 2: Percentage of participants discontinuing treatment due to AEs	Up to Day 42
Part 2: Absolute values of liver panel parameters: ALT, ALP and AST (International units per Liter)	Up to Day 42
Part 3: Absolute values of liver panel parameters: Direct bilirubin, total bilirubin (Micromoles per liter)	Up to Day 28
Part 3: Absolute values of liver panel parameters: ALT, ALP and AST (International units per Liter)	Up to Day 28
Part 3: Change from Baseline in liver panel parameters: Direct bilirubin, total bilirubin (Micromoles per liter)	Baseline (Day 1) and up to Day 28
Part 3: Change from Baseline in liver panel parameters: ALT, ALP and AST (International units per Liter)	Baseline (Day 1) and up to Day 28
Part 3: Percentage of participants with maximum toxicity grade increase from Baseline for liver panel parameters	Up to Day 28

Collaborators and Investigators

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

Study record dates

Study Major Dates

• Study Start (Actual): May 27, 2022
• Primary Completion (Actual): April 24, 2023
• Study Completion (Actual): April 24, 2023

Study Registration Dates

• First Submitted: May 23, 2022
• First Submitted That Met QC Criteria: May 23, 2022
• First Posted (Actual): May 26, 2022

Study Record Updates

• Last Update Posted (Actual): July 6, 2023
• Last Update Submitted That Met QC Criteria: July 4, 2023
• Last Verified: July 1, 2023

More Information

Terms related to this study

• Keywords: GSK4011499; VH4011499; First-time-in-human; HIV-1 capsid inhibitor; Single ascending doses; Multiple ascending doses; Drug-drug Interaction
• Additional Relevant MeSH Terms: RNA Virus Infections; Virus Diseases; Infections; Blood-Borne Infections; Communicable Diseases; Sexually Transmitted Diseases, Viral; Sexually Transmitted Diseases; Lentivirus Infections; Retroviridae Infections; Immunologic Deficiency Syndromes; Immune System Diseases; Urogenital Diseases; Genital Diseases; HIV Infections; Physiological Effects of Drugs; Neurotransmitter Agents; Molecular Mechanisms of Pharmacological Action; Central Nervous System Depressants; Anesthetics, Intravenous; Anesthetics, General; Anesthetics; Tranquilizing Agents; Psychotropic Drugs; Hypnotics and Sedatives; Adjuvants, Anesthesia; Anti-Anxiety Agents; GABA Modulators; GABA Agents; Midazolam
• Other Study ID Numbers: 218490

Plan for Individual participant data (IPD)

• Plan to Share Individual Participant Data (IPD)?: YES
• IPD Plan Description: Qualified researchers may request access to anonymized individual patient-level data (IPD) and related study documents of the eligible studies via the Data Sharing Portal. Details on GSK's data sharing criteria can be found at: https://www.gsk.com/en-gb/innovation/trials/data-transparency/
• IPD Sharing Time Frame: Anonymized IPD will be made available within 6 months of publication of primary, key secondary and safety results for studies in product with approved indication(s) or terminated asset(s) across all indications.
• IPD Sharing Access Criteria: Anonymized IPD is shared with researchers whose proposals are approved by an 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 may be granted, when justified, for up to 6 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
• product manufactured in and exported from the U.S.: No