A Study to Investigate Safety, Tolerability, and Pharmacokinetics (PK) of VH4524184 and the Potential for Changes in Cytochrome P450 3A (CYP3A) Activity

NCT05631704 | Completed Phase 1 FDA Drug

• 1 other identifier: 218803
• Study Type: interventional
• Target: 84
• Locations: 1 country
• Sites: 1

Brief Summary

This study is designed to investigate the safety, tolerability and PK of VH4524184 (GSK4524184) and the potential of VH4524184 to inhibit or induce CYP3A activity in healthy participants.

Conditions

HIV Infections

Keywords

First-time-in-human; GSK4524184; Healthy volunteers; Multiple Ascending Dose; Single Ascending Dose; VH4524184

Outcome Measures

Primary Outcomes (32)

• Part 1: Number of participants with serious adverse events (SAE) and non-serious adverse events (non-SAE)

  Up to 4 weeks

• Part 2: Number of participants with SAE and non-SAE

  Up to 6.5 weeks

• Part 3: Number of participants with SAE and non-SAE

  Up to 6.5 weeks

• Part 1: Number of participants with adverse events based on severity

  Up to 4 weeks

• Part 2: Number of participants with adverse events by severity

  Up to 6.5 weeks

• Part 3: Number of participants with adverse events based on severity

  Up to 6.5 weeks

• Part 1: Percentage of participants who discontinue treatment due to adverse events (AE)

  Up to 4 weeks

• Part 2: Percentage of participants who discontinue treatment due to AE

  Up to 6.5 weeks

• Part 3: Percentage of participants who discontinue treatment due to AE

  Up to 6.5 weeks

• Part 1: Change from Baseline in Aspartate aminotransferase (AST), Alanine aminotransferase (ALT) and Alkaline phosphatase (ALP) (International units per liter)

  Baseline (Day 1) and up to 4 weeks

• Part 2: Change from Baseline in AST, ALT and ALP (International units per liter)

  Baseline (Day 1) and up to 6.5 weeks

• Part 3: Change from Baseline in AST, ALT and ALP (International units per liter)

  Baseline (Day 1) and up to 6.5 weeks

• Part 1: Change from Baseline in Total bilirubin and Direct bilirubin (Micromoles per liter)

  Baseline (Day 1) and up to 4 weeks

• Part 2: Change from Baseline in Total bilirubin and Direct bilirubin (Micromoles per liter)

  Baseline (Day 1) and up to 6.5 weeks

• Part 3: Change from Baseline in Total bilirubin and Direct bilirubin (Micromoles per liter)

  Baseline (Day 1) and up to 6.5 weeks

• Part 1: Change from Baseline in Prothrombin time and Partial Thromboplastin Time (Seconds)

  Baseline (Day 1) and up to 4 weeks

• Part 2: Change from Baseline in Prothrombin time and Partial Thromboplastin Time (Seconds)

  Baseline (Day 1) and up to 6.5 weeks

• Part 3: Change from Baseline in Prothrombin time and Partial Thromboplastin Time (Seconds)

  Baseline (Day 1) and up to 6.5 weeks

• Part 1: Change from Baseline in International normalized ratio (INR) (Ratio)

  Baseline (Day 1) and up to 4 weeks

• Part 2: Change from Baseline in INR (Ratio)

  Baseline (Day 1) and up to 6.5 weeks

• Part 3: Change from Baseline in INR (Ratio)

  Baseline (Day 1) and up to 6.5 weeks

• Part 1: Number of participants with maximum toxicity grade increase from Baseline in liver panel laboratory parameters; AST, ALT, ALP, Total bilirubin, Direct bilirubin, Prothrombin time, Partial Thromboplastin Time and INR

  Baseline (Day 1) and up to 4 weeks

• Part 2: Number of participants with maximum toxicity grade increase from Baseline in liver panel laboratory parameters; AST, ALT, ALP, Total bilirubin, Direct bilirubin, Prothrombin time, Partial Thromboplastin Time and INR

  Baseline (Day 1) and up to 6.5 weeks

• Part 3: Number of participant with maximum toxicity grade increase from Baseline in liver panel laboratory parameters; AST, ALT, ALP, Total bilirubin, Direct bilirubin, Prothrombin time, Partial Thromboplastin Time and INR

  Baseline (Day 1) and up to 6.5 weeks

• Part 1: Area under the plasma-concentration time curve from zero (pre-dose) extrapolated to infinite time (AUC[0-infinity]) following dosing of VH4524184

  Up to 4 weeks

• Part 2: Area under the plasma concentration-time curve from zero (pre-dose) to the end of the dosing interval at steady state (AUC[0-tau]) following dosing of VH4524184

  Up to 6.5 weeks

• Part 1: Maximum observed plasma drug concentration (Cmax) following dosing of VH4524184

  Up to 4 weeks

• Part 2: Cmax following dosing of VH4524184

  Up to 6.5 weeks

• Part 1: Time to maximum observed plasma drug concentration (tmax) following dosing of VH4524184

  Up to 4 weeks

• Part 2: Tmax following dosing of VH4524184

  Up to 6.5 weeks

• Part 1: Apparent terminal half-life (t1/2) following dosing of VH4524184

  Up to 4 weeks

• Part 2: T1/2 following dosing of VH4524184

  Up to 6.5 weeks

Secondary Outcomes (3)

• Part 1: Number of participants with treatment emergent Grade 3 or Grade 4 laboratory abnormalities

  Up to 4 weeks

• Part 2: Number of participants with treatment emergent Grade 3 or Grade 4 laboratory abnormalities

  Up to 6.5 weeks

• Part 3: Number of participants with treatment emergent Grade 3 or Grade 4 laboratory abnormalities

  Up to 6.5 weeks

Study Arms (19)

Part 1: Cohort 1: Participants receiving VH4524184 DL1

EXPERIMENTAL

Eligible participants will receive VH4524184 Dose Level 1 (DL1) during Cohort 1 of Part 1 of the study.

Drug: VH4524184

Part 1: Cohort 1: Participants receiving Placebo

PLACEBO COMPARATOR

Eligible participants will receive Placebo matching VH4524184 DL1 during Cohort 1 of Part 1 of the study.

Drug: Placebo

Part 1: Cohort 2: Participants receiving VH4524184 DL2

EXPERIMENTAL

Eligible participants will receive VH4524184 DL2 during Cohort 2 of Part 1 of the study.

Drug: VH4524184

Part 1: Cohort 2: Participants receiving Placebo

PLACEBO COMPARATOR

Eligible participants will receive Placebo matching VH4524184 DL2 during Cohort 2 of Part 1 of the study.

Drug: Placebo

Part 1: Cohort 3: Participants receiving VH4524184 DL3

EXPERIMENTAL

Eligible participants will receive VH4524184 DL3 during Cohort 3 of Part 1 of the study.

Drug: VH4524184

Part 1: Cohort 3: Participants receiving Placebo

PLACEBO COMPARATOR

Eligible participants will receive Placebo matching VH4524184 DL3 during Cohort 3 of Part 1 of the study.

Drug: Placebo

Part 1: Cohort 4: Participants receiving VH4524184 DL4

EXPERIMENTAL

Eligible participants will receive VH4524184 DL4 during Cohort 4 of Part 1 of the study.

Drug: VH4524184

Part 1: Cohort 4: Participants receiving Placebo

PLACEBO COMPARATOR

Eligible participants will receive Placebo matching VH4524184 DL4 during Cohort 4 of Part 1 of the study.

Drug: Placebo

Part 1: Cohort 5: Participants receiving VH4524184 DL5

EXPERIMENTAL

Eligible participants will receive VH4524184 DL5 during Cohort 5 (optional) of Part 1 of the study.

Drug: VH4524184

Part 1: Cohort 5: Participants receiving Placebo

PLACEBO COMPARATOR

Eligible participants will receive Placebo matching VH4524184 DL5 during Cohort 5 (optional) of Part 1 of the study.

Drug: Placebo

Part 1: Cohort 6: Participants receiving VH4524184 DL6

EXPERIMENTAL

Eligible participants will receive VH4524184 DL6 during Cohort 6 (optional) of Part 1 of the study.

Drug: VH4524184

Part 1: Cohort 6: Participants receiving Placebo

PLACEBO COMPARATOR

Eligible participants will receive Placebo matching VH4524184 DL6 during Cohort 6 (optional) of Part 1 of the study.

Drug: Placebo

Part 2: Cohort 7: Participants receiving VH4524184 RL1

EXPERIMENTAL

Eligible participants will receive VH4524184 Repeat dose Level 1 (RL1) during Cohort 7 (Part 2) of the study.

Drug: VH4524184

Part 2: Cohort 7: Participants receiving Placebo

PLACEBO COMPARATOR

Eligible participants will receive Placebo matching VH4524184 RL1 during Cohort 7 (Part 2) of the study.

Drug: Placebo

Part 2: Cohort 8: Participants receiving VH4524184 RL2

EXPERIMENTAL

Eligible participants will receive VH4524184 RL2 during Cohort 8 (Part 2) of the study. If Cohort 8 is the highest Part 2 dose cohort, participants may also receive midazolam probe before and following repeat dose administration of VH4524184

Drug: VH4524184; Drug: Midazolam

Part 2: Cohort 8: Participants receiving Placebo

PLACEBO COMPARATOR

Eligible participants will receive Placebo matching VH4524184 RL2 during Cohort 8 (Part 2) of the study. If Cohort 8 is the highest Part 2 dose cohort, participants may also receive midazolam probe before and following repeat dose administration of Placebo matching VH4524184.

Drug: Midazolam; Drug: Placebo

Part 2: Cohort 9: Participants receiving VH4524184 RL3

EXPERIMENTAL

Eligible participants will receive VH4524184 RL3 during Cohort 9 (Part 2) (optional) of the study. If Cohort 9 is the highest Part 2 dose cohort, participants may also receive midazolam probe before and following repeat dose administration of VH4524184.

Drug: VH4524184; Drug: Midazolam

Part 2: Cohort 9: Participants receiving Placebo

PLACEBO COMPARATOR

Eligible participants will receive Placebo matching VH4524184 RL3 during Cohort 9 (Part 2) (optional) of the study. If Cohort 9 is the highest Part 2 dose cohort, participants may also receive midazolam probe before and following repeat dose administration of Placebo matching VH4524184.

Drug: Midazolam; Drug: Placebo

Part 3: Cohort 10: VH4524184 Fasted/ VH4524184 Fed

EXPERIMENTAL

Eligible participants will receive VH4524184 under fasted condition in Treatment Period 1 followed by VH4524184 under fed condition in Treatment Period 2 during Cohort 10 (Part 3) of the study. Treatment Periods will be separated by a washout period.

Drug: VH4524184

Interventions

VH4524184 DRUG

VH4524184 will be administered.

Part 1: Cohort 1: Participants receiving VH4524184 DL1; Part 1: Cohort 2: Participants receiving VH4524184 DL2; Part 1: Cohort 3: Participants receiving VH4524184 DL3; Part 1: Cohort 4: Participants receiving VH4524184 DL4; Part 1: Cohort 5: Participants receiving VH4524184 DL5; Part 1: Cohort 6: Participants receiving VH4524184 DL6; Part 2: Cohort 7: Participants receiving VH4524184 RL1; Part 2: Cohort 8: Participants receiving VH4524184 RL2; Part 2: Cohort 9: Participants receiving VH4524184 RL3; Part 3: Cohort 10: VH4524184 Fasted/ VH4524184 Fed

Midazolam DRUG

Midazolam will be administered in the highest dose cohort in Part 2 (Cohorts 8 or 9).

Part 2: Cohort 8: Participants receiving Placebo; Part 2: Cohort 8: Participants receiving VH4524184 RL2; Part 2: Cohort 9: Participants receiving Placebo; Part 2: Cohort 9: Participants receiving VH4524184 RL3

Placebo DRUG

Placebo will be administered.

Part 1: Cohort 1: Participants receiving Placebo; Part 1: Cohort 2: Participants receiving Placebo; Part 1: Cohort 3: Participants receiving Placebo; Part 1: Cohort 4: Participants receiving Placebo; Part 1: Cohort 5: Participants receiving Placebo; Part 1: Cohort 6: Participants receiving Placebo; Part 2: Cohort 7: Participants receiving Placebo; Part 2: Cohort 8: Participants receiving Placebo; Part 2: Cohort 9: Participants receiving Placebo

Eligibility Criteria

• Age: 18 Years - 50 Years
• Sex: all
• Healthy Volunteers: Yes
• Age Groups: Adult (18-64)

You may qualify if:

• Participant must be 18 to 50 years of age.
• Participants who are overtly healthy.
• Body weight \>=50.0 kilograms (kg) (110 pounds \[lbs\]) for men and \>=45.0 kg (99 lbs) for women and body mass index within the range 18.5 to 32.0 kilograms per meter square (kg/m\^2) (inclusive).
• Male or female. Male Participants: No contraceptive restrictions for male participants. Female Participants: A female participant (female sex assigned at birth) is eligible to participate if she is not pregnant, or breastfeeding and is not physically able to have a baby.

You may not qualify if:

• History or presence of clinical condition that could significantly alter how medicines are absorbed, broken down or eliminated from the body; be risky to the participant, or make it difficult to interpret the data from the study.
• Pre-existing clinically relevant gastro-intestinal disorders.
• Abnormal blood pressure.
• Certain blood or other cancers within the past 5 years.
• Breast cancer within the past 10 years
• Current or chronic history of liver disease or liver or bile tract abnormalities (with the exception of Gilbert's syndrome or asymptomatic gallstones).
• QT interval corrected for heart rate according to Fridericia's formula (QTcF) \>450 milliseconds (msec).
• Medical history of cardiac arrhythmias or cardiac disease or a family and personal history of long QT syndrome.
• History of seizure
• Any known or suspected pre-existing psychiatric condition, including depression, anxiety and insomnia/sleep disturbances.
• Any positive (abnormal) response to the Columbia Suicide Severity Rating Scale (CSSRS).
• Past or intended use of over-the-counter or prescription medication 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.
• Receipt of any live vaccine(s) or vaccines against Coronavirus disease 2019 (Covid-19) within 28 days prior to screening or plans to receive such vaccines during the study.
• Exposure to more than 4 new investigational products (including long-acting investigational products) within 12 months prior to the first dosing day.
• Current enrollment or past participation in another investigational study in which an investigational intervention (e.g., drug, human blood product, monoclonal antibody, vaccine, invasive device) was administered within the last 30 days, 5 half-lives or twice the duration of the biological effect of the investigational product (whichever is longer) before signing of consent (OR screening) any other clinical study.

Sponsors & Collaborators

• ViiV Healthcare: lead

Study Sites (1)

GSK Investigational Site

Baltimore, Maryland, 21225, United States

Location

Related Publications (1)

• Rogg L, Underwood M, Hanan N, Castillo-Mancilla JR, Kahl L, Halliday F, Ghita GL, Jeffrey JL, Byrne S, Onodera T, Horton J, Gartland M. Phase 1 Evaluation of VH4524184, a Third-Generation Integrase Strand Transfer Inhibitor With an Enhanced Resistance Profile. Clin Infect Dis. 2025 Oct 6;81(3):510-520. doi: 10.1093/cid/ciaf135.

  PMID: 40117383 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

Study Officials

• GSK Clinical Trials

  ViiV Healthcare

  STUDY DIRECTOR

Study Design

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

Model Details: Participants will receive escalating doses of VH4524184 or placebo in Part 1 and Part 2 of the study. In Part 3, participants will receive VH4524184 under fasted and fed conditions.

Study Record Dates

• First Submitted: November 18, 2022
• First Posted: November 30, 2022
• Study Start: December 2, 2022
• Primary Completion: July 27, 2023
• Study Completion: July 27, 2023
• Last Updated: December 29, 2025

Record last verified: 2025-12

Data Sharing

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

Locations

US (1)