VH4524184 Proof-of-Concept in Treatment-Naïve Adults Living With HIV-1

A Phase 2a, Randomized, Double-Blind (Sponsor Unblinded), Placebo-Controlled, Study to Investigate the Antiviral Effect, Safety, Tolerability and Pharmacokinetics of VH4524184 in HIV-1 Infected Treatment Naïve Adults

The purpose of this study is to evaluate the safety, tolerability, ability of VH4524184 when given alone to reduce the amount of HIV (viral load) in people with HIV-1 infection who have never received antiretroviral therapy (treatment-naïve). Data from this study will be used to decide how VH4524184 can be best included in a full-treatment regimen for HIV-1 in the future.

Study Overview

• Status: Completed
• Conditions: HIV Infections
• Intervention / Treatment: Drug: VH4524184; Drug: Antiretroviral therapy; Drug: Matching Placebo

• Study Type: Interventional
• Enrollment (Actual): 22
• Phase: Phase 2

Contacts and Locations

Study Locations

• Argentina
  • Buenos Aires, Argentina, C1425AGC
    • GSK Investigational Site
  • Buenos Aires, Argentina, C1202
    • GSK Investigational Site
  • Ciudad Autonoma De Bueno, Argentina, C1405CKC
    • GSK Investigational Site
• Canada
  • Quebec
    • Montreal, Quebec, Canada, H4A 3J1
      • GSK Investigational Site
    • Quebec City, Quebec, Canada, G1V 4G2
      • GSK Investigational Site
• Italy
  • Milano, Italy, 20162
    • GSK Investigational Site
• Spain
  • Barcelona, Spain, 08003
    • GSK Investigational Site
  • Barcelona, Spain, 08026
    • GSK Investigational Site
  • Elche Alicante, Spain, 03203
    • GSK Investigational Site
  • Madrid, Spain, 28020
    • GSK Investigational Site
  • Murcia, Spain, 30003
    • GSK Investigational Site
  • Valencia, Spain, 46026
    • GSK Investigational Site
• United States
  • California
    • Bakersfield, California, United States, 93301
      • GSK Investigational Site
    • Los Angeles, California, United States, 90027
      • GSK Investigational Site
    • West Hollywood, California, United States, 90046
      • GSK Investigational Site
  • Florida
    • DeLand, Florida, United States, 32720
      • GSK Investigational Site
    • Orlando, Florida, United States, 32803
      • GSK Investigational Site

Participation Criteria

Eligibility Criteria

• Ages Eligible for Study: Adult; Older Adult
• Accepts Healthy Volunteers: No

Description

Inclusion Criteria:

• Participant must be 18 to 65 years of age inclusive at the time of signing the informed consent.
• Participants who are overtly healthy (other than HIV infection) as determined by the Investigator or medically qualified designee based on a medical evaluation including medical history, physical examination, laboratory tests, and cardiac monitoring.
• Positive HIV antibody test
• Documented HIV infection and Screening plasma HIV-1 RNA ≥ 3,000 copies/mL. A single repeat of this test is allowed within a single Screening period to determine eligibility.
• Screening CD4+ T-cell count ≥200 cells/mm3
• Treatment-naïve: No antiretrovirals (ARVs, in combination or monotherapy) received after the diagnosis of HIV-1 infection.
• HIV Pre-exposure or post-exposure prophylaxis: No prior use of any INSTI (including cabotegravir) for HIV pre-exposure or post-exposure prophylaxis.
• Body weight ≥50.0 kg (110 lbs.) for men and ≥45.0 kg (99 lbs) for women and BMI within the range 18.5-31.0 kg/m2 (inclusive - applies to males and females).
• A participant of childbearing potential must have a negative serum hCG test at screening, and negative urine hCG test at Day 1, before the first dose of study intervention.
• If a urine test cannot be confirmed as negative (e.g. ambiguous result), a serum pregnancy test is required. In such cases, the participant must be excluded from participation if the serum pregnancy result is positive.
• The Investigator is responsible for review of medical history, menstrual history, and recent sexual activity to decrease risk for inclusion of a female with an early undetected pregnancy.
• Capable of giving signed informed consent
• Participant must be willing and able to start standard-of-care ART as selected with the investigator on Study Day 10.

Exclusion Criteria:

• Participants with primary HIV infection. Any evidence of an active CDC Stage 3 disease, except cutaneous Kaposi's sarcoma not requiring systemic therapy during the study. Untreated syphilis infection [positive RPR at screen] without documentation of treatment. Ongoing malignancy other than cutaneous Kaposi's sarcoma, basal cell carcinoma, or resected, non-invasive cutaneous squamous cell carcinoma, or cervical, anal or penile intraepithelial neoplasia; or other localized malignancies
• Any pre-existing physical or mental condition which, in the opinion of the Investigator, may interfere with the participant's ability to comply with the dosing schedule and/or protocol evaluations or which may compromise the safety of the participant.
• Any history of significant underlying psychiatric disorder, or a clinical assessment of suicidality based on the responses on the eCSSRS.
• Any history of major depressive disorder with or without suicidal features, or anxiety disorders, that required medical intervention (pharmacologic or not) such as hospitalization or other inpatient treatment and/or chronic (>6 months) outpatient treatment.
• Current or chronic history of liver disease or known hepatic or biliary abnormalities (with the exception of Gilbert's syndrome or asymptomatic gallstones).
• Medical history of cardiac arrhythmias or cardiac disease or a family or personal history of long QT syndrome or sudden cardiac death. Treatment with immunomodulating agents (such as systemic corticosteroids, interleukins, interferons) or any agent with known anti-HIV activity (such as hydroxyurea or foscarnet) within 30 days of study drug administration.
• 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. Specific medications listed in Section 6.9.1 may be allowed.
• Participants who require concomitant medications known to be associated with a prolonged QTc.
• Participants receiving any protocol-prohibited medication(s) and who are unwilling or unable to switch to an alternate medication).
• The participant has ever received an investigational HIV vaccine (immunotherapeutic or immunomodulatory).
• Exposure to an experimental drug or experimental vaccine within either 30 days, 5 half-lives of the test agent, or twice the duration of the biological effect of the test agent, whichever is longer, prior to the first dose of study intervention.
• Participation in the study would result in donation of blood in excess of 500 mL within 56 days.
• Exposure to more than four new investigational drugs or vaccines within 12 months prior to the first dosing day.
• Current enrollment or past participation 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 in any other clinical study involving an investigational study intervention or any other type of medical research.

Diagnostic Assessments

• Presence of HBsAg or HBcAb at screening
• Positive Hepatitis C antibody test result at Screening
• Positive Hepatitis C RNA test result at Screening.
• Creatinine clearance (eGFR) of < 60 mL/min/1.73 m2 using CKD-EPI equation (2021).

Study Plan

How is the study designed?

Design Details

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

Number of Arms

4

Arms and Interventions

Participant Group / Arm	Intervention / Treatment
Experimental: VH4524184 Dose 1; Participants received VH4524184, administered as Dose 1 (low dose) on Day 1, Day 4, and Day 7. On Day 10, participants began open-label standard-of-care (SOC) antiretroviral therapy (ART), which was selected by the investigator and locally sourced. Participants were monitored weekly until Day 38.	Drug: VH4524184; VH4524184 was administered as tablets orally at Day 1.; Drug: Antiretroviral therapy; Antiretroviral therapy was administered as available and as per investigator's recommendation.
Experimental: VH4524184 Dose 2; Participants received VH4524184, administered as Dose 2 (medium dose) on Day 1, Day 4, and Day 7. On Day 10, participants began open-label SOC ART, which was selected by the investigator and locally sourced. Participants were monitored weekly until Day 38.	Drug: VH4524184; VH4524184 was administered as tablets orally at Day 1.; Drug: Antiretroviral therapy; Antiretroviral therapy was administered as available and as per investigator's recommendation.
Experimental: VH4524184 Dose 3; Participants received VH4524184, administered as Dose 3 (high dose) on Day 1, Day 4, and Day 7. On Day 10, participants began open-label SOC ART, which was selected by the investigator and locally sourced. Participants were monitored weekly until Day 38.	Drug: VH4524184; VH4524184 was administered as tablets orally at Day 1.; Drug: Antiretroviral therapy; Antiretroviral therapy was administered as available and as per investigator's recommendation.
Placebo Comparator: Placebo; Participants received matching Placebo to the study intervention on Day 1, Day 4, and Day 7. On Day 10, participants began open-label SOC ART, which was selected by the investigator and locally sourced. Participants were monitored weekly until Day 38.	Drug: Antiretroviral therapy; Antiretroviral therapy was administered as available and as per investigator's recommendation.; Drug: Matching Placebo; VH4524184 Matching Placebo was administered as tablets orally at Day 1.

What is the study measuring?

Primary Outcome Measures

Outcome Measure	Measure Description	Time Frame
Monotherapy: Maximum Change From Baseline in Plasma Human Immunodeficiency Virus-1 (HIV-1) Ribonucleic Acid (RNA)	Plasma samples were collected for the quantitative analysis of plasma HIV-1 RNA. The maximum change from baseline was calculated by determining the largest change from baseline value across all assessment timepoints during the monotherapy period. This is identified by subtracting the lowest post-dose visit value up to Day 10 (inclusive) from the baseline value. The baseline was defined as the most recent pre-dose assessment with a valid, non-missing value, including measurements from any unscheduled visits.	At Day 10

Secondary Outcome Measures

Outcome Measure	Measure Description	Time Frame
Monotherapy and Follow-up: Number of Participants With Any Adverse Event (AE)	An AE is any untoward medical occurrence in a clinical study participant, temporally associated with the use of a study intervention, whether or not considered related to the study intervention. An AE can be any unfavourable and unintended sign (including an abnormal laboratory finding), symptom, or disease (new or exacerbated) temporally associated with the use of a study intervention. Any AEs = occurrence of the symptom regardless of intensity grade.	Day 1 to Day 38
Monotherapy and Follow-up: Number of Participants With AEs by Severity	The severity was assessed using The Division of AIDS Table for Grading the Severity of Adult and Pediatric Adverse Events (DAIDS AE Grading Table) Version 2.1 where Grade 1 = mild, Grade 2 = moderate, Grade 3 = severe, Grade 4 = potentially life-threatening and Grade 5 = Death.	Day 1 to Day 38
Monotherapy: Number of Participants With AEs Leading to Study Treatment Discontinuation		Day 1 to Day 7
Monotherapy and Follow-up: Change From Baseline for Liver Panel Laboratory Parameters: Alanine Aminotransferase (ALT), Aspartate Aminotransferase (AST), Alkaline Phosphatase (ALP)	Blood samples were collected at the indicated timepoints.	At Baseline (Day 1), Day 2, Day 4, Day 7, Day 10, Day 17, Day 24, Day 31 and Day 38
Monotherapy and Follow-up: Change From Baseline for Liver Panel Laboratory Parameter: Bilirubin	Blood samples were collected at the indicated timepoints.	At Baseline (Day 1), Day 2, Day 4, Day 7, Day 10, Day 17, Day 24, Day 31 and Day 38
Monotherapy and Follow-up: Change From Baseline for Liver Panel Laboratory Parameter: Protein	Blood samples were collected at the indicated timepoints.	At Baseline (Day 1), Day 2, Day 4, Day 7, Day 10, Day 17, Day 24, Day 31 and Day 38
Monotherapy and Follow-up: Number of Participants With Maximum Toxicity Grade Increase Relative to Baseline in Liver Panel Laboratory Parameters: ALT, AST, ALP, Bilirubin	Liver panel parameters assessed were: ALT, AST, ALP, bilirubin. The parameters were graded according to DAIDS grading table Version 2.1 where grades were defined based on numeric criteria as follows Grade 0: participants with missing baseline values; Grade 1: Mild; Grade 2: moderate; Grade 3: severe or medically significant; Grade 4: life-threatening consequences. An increase is defined as an increase in grade relative to baseline grade.	From Baseline (Day 1) and up to Day 38
Monotherapy and Follow-up: Number of Participants With Maximum Toxicity Grade Increase Relative to Baseline in Liver Panel Laboratory Parameters: Protein	Participants are categorized based on changes in their liver panel laboratory parameters (protein) to 'Low,' 'Normal,' or 'High,' unless there is no change in their initial category. Participants whose lab values remain unchanged (e.g., 'High' to 'High') or whose values return to normal are recorded in the 'To Normal or No Change' category. Participants may be counted in both the 'To Low' and 'To High' categories if their values fluctuate between these states. As a result, the percentages may exceed 100% due to dual categorization. Participants with a missing baseline value are assumed to have a normal baseline value.	From Baseline (Day 1) and up to Day 38
Monotherapy: Maximum Observed Plasma Drug Concentration (Cmax) of VH4524184	Blood samples were collected at indicated time points for Pharmacokinetic (PK) analysis of VH4524184.	At Day 1 and Day 7
Monotherapy: Time to Maximum Observed Plasma Drug Concentration (Tmax) of VH4524184	Blood samples were collected at indicated time points for PK analysis of VH4524184.	At Day 1 and Day 7
Monotherapy: Plasma Concentration of VH4524184 at Day 10	Blood samples was collected at indicated time point for PK analysis of VH4524184.	At Day 10
Monotherapy: Correlation of VH4524184 Cmax With Maximum Plasma HIV-1 RNA Log 10 Change From Baseline Through Day 10	Plasma samples were collected for quantitative analysis of HIV-1 RNA. Baseline value was the latest pre-dose assessment with a non-missing value. Change from baseline is defined as post-dose visit value minus baseline value. Statistical analysis for relationship between PK parameter (Cmax) and PD measure (change from baseline in logarithm to base 10 (log10) values for maximum plasma HIV-1 RNA) were explored using an Emax non-linear mixed-effects model. The model parameters estimated were maximum response (Emax) which is defined as the maximum change (at infinite exposure) and EC50 which defines the PK parameter value that attains 50 percent (%) of the maximal effect	From Day 1 to Day 10
Monotherapy: Number of Participants With Treatment-emergent Genotypic Resistance	Plasma samples were collected to assess treatment emergent Genotypic Resistance.	At Baseline (Day 1) and Day 10
Monotherapy: Number of Participants With Treatment-emergent Phenotypic Resistance	Plasma samples were collected to assess treatment emergent Phenotypic Resistance.	At Baseline (Day 1) and Day 10
Monotherapy: Change From Baseline in Cluster of Differentiation 4 (CD4+) T-cell Counts at Day 10	Blood samples were collected for assessment of T-cells subsets (CD4+ T-cells count) by flow cytometry at Day 10 compared to Baseline.	At Day 10 compared to Baseline (Day 1)

Collaborators and Investigators

• Sponsor: ViiV Healthcare
• Collaborators: GlaxoSmithKline

Study record dates

Study Major Dates

• Study Start (Actual): February 7, 2024
• Primary Completion (Actual): June 12, 2024
• Study Completion (Actual): June 12, 2024

Study Registration Dates

• First Submitted: January 9, 2024
• First Submitted That Met QC Criteria: January 9, 2024
• First Posted (Actual): January 19, 2024

Study Record Updates

• Last Update Posted (Actual): June 29, 2025
• Last Update Submitted That Met QC Criteria: June 12, 2025
• Last Verified: June 1, 2025

More Information

Terms related to this study

• Keywords: Human immunodeficiency virus; Antiviral Agents; Virus Diseases; Proof of concept
• Additional Relevant MeSH Terms: Blood-Borne Infections; Urogenital Diseases; Genital Diseases; Immune System Diseases; Infections; RNA Virus Infections; Virus Diseases; Communicable Diseases; Sexually Transmitted Diseases, Viral; Sexually Transmitted Diseases; Lentivirus Infections; Retroviridae Infections; Immunologic Deficiency Syndromes; HIV Infections; Anti-Infective Agents; Antiviral Agents; Anti-Retroviral Agents
• Other Study ID Numbers: 218806; 2023-507173-18-00 (Other Identifier: EU CT Number)

Plan for Individual participant data (IPD)

• Plan to Share Individual Participant Data (IPD)?: YES
• IPD Plan Description: Study 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
• 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.: Yes