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

NCT06214052 | Completed Phase 2 Results FDA Drug

• 2 other identifiers: 2188062023-507173-18-00
• Study Type: interventional
• Target: 22
• Locations: 5 countries
• Sites: 17

Brief Summary

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.

Conditions

HIV Infections

Keywords

Human immunodeficiency virus; Proof of concept; Antiviral Agents; Virus Diseases

Outcome Measures

Primary Outcomes (1)

• 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 Outcomes (15)

• Monotherapy and Follow-up: Number of Participants With Any Adverse Event (AE)

  Day 1 to Day 38

• Monotherapy and Follow-up: Number of Participants With AEs by Severity

  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)

  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

  At Baseline (Day 1), Day 2, Day 4, Day 7, Day 10, Day 17, Day 24, Day 31 and Day 38

Study Arms (4)

VH4524184 Dose 1

EXPERIMENTAL

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; Drug: Antiretroviral therapy

VH4524184 Dose 2

EXPERIMENTAL

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; Drug: Antiretroviral therapy

VH4524184 Dose 3

EXPERIMENTAL

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; Drug: Antiretroviral therapy

Placebo

PLACEBO COMPARATOR

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: Matching Placebo; Drug: Antiretroviral therapy

Interventions

VH4524184 DRUG

VH4524184 was administered as tablets orally at Day 1.

VH4524184 Dose 1; VH4524184 Dose 2; VH4524184 Dose 3

Matching Placebo DRUG

VH4524184 Matching Placebo was administered as tablets orally at Day 1.

Placebo

Antiretroviral therapy DRUG

Antiretroviral therapy was administered as available and as per investigator's recommendation.

Placebo; VH4524184 Dose 1; VH4524184 Dose 2; VH4524184 Dose 3

Eligibility Criteria

• Age: 18 Years - 65 Years
• Sex: all
• Healthy Volunteers: No
• Age Groups: Adult (18-64), Older Adult (65+)

You may qualify if:

• 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.
• 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.

You may not qualify if:

• 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

Sponsors & Collaborators

• ViiV Healthcare: lead
• GlaxoSmithKline: collaborator

Study Sites (17)

GSK Investigational Site

Bakersfield, California, 93301, United States

Location

GSK Investigational Site

Los Angeles, California, 90027, United States

Location

GSK Investigational Site

West Hollywood, California, 90046, United States

Location

GSK Investigational Site

DeLand, Florida, 32720, United States

Location

GSK Investigational Site

Orlando, Florida, 32803, United States

Location

GSK Investigational Site

Buenos Aires, C1202, Argentina

Location

GSK Investigational Site

Buenos Aires, C1425AGC, Argentina

Location

GSK Investigational Site

Ciudad Autonoma de Bueno, C1405CKC, Argentina

Location

GSK Investigational Site

Montreal, Quebec, H4A 3J1, Canada

Location

GSK Investigational Site

Québec, Quebec, G1V 4G2, Canada

Location

GSK Investigational Site

Milan, 20162, Italy

Location

GSK Investigational Site

Barcelona, 08003, Spain

Location

GSK Investigational Site

Barcelona, 08026, Spain

Location

GSK Investigational Site

Elche Alicante, 03203, Spain

Location

GSK Investigational Site

Madrid, 28020, Spain

Location

GSK Investigational Site

Murcia, 30003, Spain

Location

GSK Investigational Site

Valencia, 46026, Spain

Location

MeSH Terms

Conditions

HIV Infections; Acquired Immunodeficiency Syndrome; Virus Diseases

Interventions

Antiretroviral Therapy, Highly Active

Condition Hierarchy (Ancestors)

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

Intervention Hierarchy (Ancestors)

Drug Therapy, Combination; Drug Therapy; Therapeutics

Results Point of Contact

• Title: GSK Response Center
• Organization: GlaxoSmithKline

GSKClinicalSupportHD@gsk.com

866-435-7343

Publication Agreements

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

Study Design

• Study Type: interventional
• Phase: phase 2
• Allocation: RANDOMIZED
• Masking: DOUBLE
• Who Masked: PARTICIPANT, INVESTIGATOR
• Masking Details: Data will be collected in a double-blind manner during the monotherapy phase.
• Purpose: TREATMENT
• Intervention Model: PARALLEL
• Sponsor Type: INDUSTRY
• Responsible Party: SPONSOR

Study Record Dates

• First Submitted: January 9, 2024
• First Posted: January 19, 2024
• Study Start: February 7, 2024
• Primary Completion: June 12, 2024
• Study Completion: June 12, 2024
• Last Updated: June 29, 2025
• Results First Posted: June 29, 2025

Record last verified: 2025-06

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

CA (2); AR (3); US (5); IT (1); ES (6)