A Study to Investigate the Use of VH3810109 With or Without Fostemsavir (FTR) to Reduce the Size and Activity of the Viral Reservoir in People Living With HIV (ENTRANCE)

An Exploratory Phase 1b, Multicenter, Randomized, Open-Label Study to Investigate the Impact of the Administration of Intravenous VH3810109 With or Without Oral Fostemsavir in Combination With Integrase Inhibitor-Based Antiretroviral Therapy on the Viral Reservoir in Adults Living With HIV-1

This study investigates the use of VH3810109 with or without FTR to reduce the size and activity of the HIV viral reservoir in two sub-populations of people living with HIV: treatment-naïve adults (Population 1) and treatment-experienced adults currently taking a standard of care (SOC) integrase strand transfer inhibitor (INSTI)-based antiretroviral therapy (ART) regimen (Population 2).

Study Overview

• Status: Active, not recruiting
• Conditions: HIV Infections
• Intervention / Treatment: Biological: VH3810109; Drug: SOC INSTI-based ART; Drug: Fostemsavir (FTR)

• Study Type: Interventional
• Enrollment (Actual): 107
• Phase: Phase 1

Contacts and Locations

Study Locations

• Belgium
  • Brussels, Belgium, 1000
    • GSK Investigational Site
  • Ghent, Belgium, 9000
    • GSK Investigational Site
• Denmark
  • Aarhus, Denmark, 8200
    • GSK Investigational Site
  • Hvidovre, Denmark, 2650
    • GSK Investigational Site
• Netherlands
  • Rotterdam, Netherlands, 3015 GD
    • GSK Investigational Site
• Spain
  • Barcelona, Spain, 08036
    • GSK Investigational Site
  • Barcelona, Spain, 08035
    • GSK Investigational Site
  • Barcelona, Spain, 08003
    • GSK Investigational Site
  • Barcelona, Spain, 8907
    • GSK Investigational Site
  • Barcelona, Spain, 08026
    • GSK Investigational Site
  • Barcelona, Spain, 08916
    • GSK Investigational Site
  • Córdoba, Spain, 14004
    • GSK Investigational Site
  • La Laguna Santa Cruz, Spain, 38320
    • GSK Investigational Site
  • Madrid, Spain, 28041
    • GSK Investigational Site
  • Madrid, Spain, 28040
    • GSK Investigational Site
  • Madrid, Spain, 28046
    • GSK Investigational Site
  • Madrid, Spain, 28034
    • GSK Investigational Site
  • Madrid, Spain, 28031
    • GSK Investigational Site
  • Madrid, Spain, 28020
    • GSK Investigational Site
  • Madrid, Spain, 28224
    • GSK Investigational Site
  • Palma de Mallorca, Spain, 07120
    • GSK Investigational Site
  • Palma de Mallorca, Spain, 7198
    • GSK Investigational Site
  • Seville, Spain, 41013
    • GSK Investigational Site
  • Valencia, Spain, 46026
    • GSK Investigational Site
  • Valencia, Spain, 46014
    • GSK Investigational Site
• United Kingdom
  • London, United Kingdom, SE1 7EH
    • GSK Investigational Site
  • London, United Kingdom, NW3 2QG
    • GSK Investigational Site
  • London, United Kingdom, W2 1NY
    • GSK Investigational Site
• United States
  • California
    • Bakersfield, California, United States, 93301
      • GSK Investigational Site
    • San Diego, California, United States, 92103
      • GSK Investigational Site
  • Florida
    • Ft. Pierce, Florida, United States, 34982
      • GSK Investigational Site
    • Orlando, Florida, United States, 32803
      • GSK Investigational Site
  • Illinois
    • Chicago, Illinois, United States, 60611
      • GSK Investigational Site
  • Missouri
    • Kansas City, Missouri, United States, 64111
      • GSK Investigational Site
    • St Louis, Missouri, United States, 63110
      • GSK Investigational Site
  • New York
    • New York, New York, United States, 10032
      • GSK Investigational Site
  • Ohio
    • Cincinnati, Ohio, United States, 45267
      • GSK Investigational Site
  • Pennsylvania
    • Philadelphia, Pennsylvania, United States, 19104
      • GSK Investigational Site
    • Pittsburgh, Pennsylvania, United States, 15213
      • GSK Investigational Site
  • Texas
    • Dallas, Texas, United States, 75246
      • GSK Investigational Site
    • Dallas, Texas, United States, 75208
      • GSK Investigational Site

Participation Criteria

Eligibility Criteria

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

Description

Inclusion Criteria:

• Age between 18 years and 70 years old at the time of obtaining informed consent.
• Persons of any sex or gender are eligible. Note: Participants of childbearing potential (POCBP) are eligible to participate if not pregnant, not lactating, and agreeing to adhere to study requirements for use of contraception and pregnancy avoidance.
• Participant has a documented diagnosis of HIV-1 infection Note: Participants in Population 1 must have a documented positive HIV antibody result available for Screening.

Population 1 only:

• Plasma HIV-1 RNA >=2000 copies/milliliter (c/mL) at Screening.
• CD4+ T cell count >=300 cells/microliter (μL) at Screening.
• Antiretroviral treatment naïve, defined as no exposure to ART after a diagnosis of HIV-1 infection, prior to enrollment.

Population 2 only:

• Participant is stably virologically suppressed (plasma HIV-1 RNA <50 c/mL).
• Documented evidence of uninterrupted treatment with oral non-boosted INSTI-based ART for at least 6 months prior to Screening, as well as uninterrupted treatment with ART (any guideline-recommended oral regimen) for at least 24 months prior to Screening.
• CD4+ T cell count >=450 cells/μL at Screening.
• Body weight >=50 kg to <=115 kg.
• Participant is capable of giving written informed consent, which includes adherence to the requirements and restrictions listed in the consent form and in the protocol.

Exclusion Criteria:

CONCURRENT MEDICAL CONDITIONS & MEDICAL HISTORY

• Participant is pregnant, breastfeeding, or planning to become pregnant or breastfeed during the study.
• Participant has documented diagnosis of HIV-2 infection.
• Participant is known to have acquired HIV via perinatal transmission.
• Any evidence of a current or known past Center for Disease Control and Prevention (CDC) Stage 3 disease.
• Any ongoing malignancy or history of systemic cancers, such as Kaposi's sarcoma and lymphoma, or other virus-associated malignancies.
• Ongoing or clinically relevant pancreatitis.
• Current HIV-related kidney disease.
• History of or active HIV-associated dementia or progressive multifocal leukoencephalopathy.

CARDIAC & CARDIOVASCULAR CONDITIONS

• Participants who are at clinically significant risk of cardiovascular disease.

• Ongoing or any lifetime history of clinically significant cardiovascular or cardiac disease.
• Confirmed QTcF value outside normal range at Screening or Day 1.

HEPATIC CONDITIONS

• History of clinically relevant hepatitis in the 6 months prior to Screening.

• Participants with severe hepatic impairment.
• Advanced MAFLD and advanced non-alcoholic steatohepatitis, if evidence for substantial fibrosis (fibrosis score ≥F2) or evidence of cirrhosis.
• Unstable liver disease.
• History of liver cirrhosis with or without hepatitis viral co-infection.

NEUROPSYCHIATRIC CONDITIONS

• Participants who pose a significant suicide risk.

LABORATORY DIAGNOSTIC ASSESSMENTS

• Participants who are experiencing (Population 1) or are known to have initiated ART during (Population 2) acute HIV infection.
• Any verified Grade 4 laboratory abnormality at Screening, excluding asymptomatic elevations of lipids or CPK.
• Alanine transferase (ALT) >=3 times the upper limit of normal (ULN) at Screening.
• Estimated glomerular filtration rate (eGFR) of <60 mL/min/1.73 m^2.
• Hemoglobin >=Grade 2 at Screening.
• Platelets >=Grade 2 at Screening.
• Absolute Neutrophil Count (ANC) ≥Grade 2 at Screening.
• Any acute abnormality at Screening, which, in the opinion of the investigator, would preclude the participant's inclusion in an interventional clinical study.

Population 2 only • Two or more plasma HIV-1 RNA results >=50 c/mL in the 18 months prior to Screening.

INFECTIOUS DISEASES

• Active hepatitis B virus (HBV) co-infection.
• Active hepatitis C virus (HCV) co-infection.
• Participant has untreated syphilis before enrolment.
• Known current untreated or incompletely treated active Mycobacterium TB infection.

ANTIRETROVIRAL RESISTANCE

• Known major resistance-associated mutations to second-generation INSTIs or to antiretroviral (ARV) agents from 2 or more drug classes.

PRIOR AND CONCOMITANT MEDICATIONS

• Prior use of any of the following agents:

  o long-acting ARVs (any dose in the past 24 months or within 5 half-lives [whichever is longer])

  o FTR (any lifetime use)

  • HIV-1 immunotherapeutic vaccines or prophylactic vaccines (any lifetime use)
  • HIV-1 monoclonal antibody therapy (any lifetime use).
• Prior receipt of any approved or experimental non-HIV vaccination within 2 weeks prior to study enrolment.
• History of systemic corticosteroids, immunosuppressive anti-cancer, interleukins, systemic interferons, or systemic chemotherapy, within 6 months prior to Screening.
• Participant has received 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 enrolment.

• Treatment with any of the following agents within 30 days of enrolment:

  o radiation therapy

  o cytotoxic chemotherapeutic agents

  • anti-tuberculosis therapy
  • immunomodulators that alter immune responses such as chronic systemic corticosteroids, interleukins, or interferons.
• Participant is receiving any protocol-defined prohibited medication and is unwilling or unable to switch to an alternate medication. Prohibited medications must be stopped within 7 days (or 14 days if the drug is a potential CYP3A4 enzyme inducer) or 5 half-lives (whichever is longer), prior to enrolment.

Population 1 only • Known use of PrEP or PEP within <30 days (for oral agents) or <52 weeks (for LA parenteral agents) of HIV-1 diagnosis. Participants with a documented seronegative result >=30 days after the last dose of oral PrEP or PEP (or >=52 weeks after the last dose of LA PrEP) are not excluded.

Population 2 only

• Current use of NNRTI-containing ART.

OTHER EXCLUSIONS

• History or presence of allergy or intolerance to the study drugs or their components or drugs of their class, or a history of drug or other allergy that contraindicates study participation.
• Any condition which may interfere with the absorption, distribution, metabolism or excretion of the study drugs or render the participant unable to receive study drugs.
• Any pre-existing physical or mental condition (including substance use disorder) which, 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.
• Participant is currently participating in, or anticipates being selected for, any other interventional study.

Study Plan

How is the study designed?

Design Details

• Primary Purpose: Treatment
• Allocation: Randomized
• Interventional Model: Parallel Assignment
• Masking: None (Open Label)

Number of Arms

3

Arms and Interventions

Participant Group / Arm	Intervention / Treatment
Active Comparator: Participants receiving standard of care (SOC) integrase strand transfer inhibitor (INSTI)-based ART	Drug: SOC INSTI-based ART; A SOC INSTI-based ART regimen will be administered.
Experimental: Participants receiving SOC INSTI-based ART plus VH3810109	Biological: VH3810109; VH3810109 will be administered.; Drug: SOC INSTI-based ART; A SOC INSTI-based ART regimen will be administered.
Experimental: Participants receiving SOC INSTI-based ART plus VH3810109 plus FTR	Biological: VH3810109; VH3810109 will be administered.; Drug: SOC INSTI-based ART; A SOC INSTI-based ART regimen will be administered.; Drug: Fostemsavir (FTR); Fostemsavir will be administered.; Other Names: RUKOBIA

What is the study measuring?

Primary Outcome Measures

Outcome Measure	Time Frame
Change from baseline in cell-associated HIV-1 RNA transcripts per million cluster of differentiation 4 (CD4+) T cells	From Baseline (Day 1) to Month 12

Secondary Outcome Measures

Outcome Measure	Time Frame
Change from baseline in total, intact, and defective proviral HIV-1 DNA per million CD4+ T cells	From Baseline (Day 1) to Month 12
Absolute change in cell-associated HIV-1 RNA/proviral DNA ratios in CD4+ T cells	From Baseline (Day 1) to Month 12
Absolute values for p24+ CD4+ T cell count	From Baseline (Day 1) to Month 12
Change from baseline in number of p24+ CD4+ T cells	From Baseline (Day 1) to Month 12
Absolute values for HIV-1-specific CD8+ T cell count	From Baseline (Day 1) to Month 12
Change from baseline in HIV-1-specific CD8+ T cell count	From Baseline (Day 1) to Month 12
Number of participants with Grade 3 and Grade 4 adverse events (AEs)	From Baseline (Day 1) to Month 12
Number of participants with serious adverse events (SAEs), deaths and AEs leading to discontinuation of study intervention	From Baseline (Day 1) to Month 12

Collaborators and Investigators

• Sponsor: ViiV Healthcare

Study record dates

Study Major Dates

• Study Start (Actual): July 10, 2025
• Primary Completion (Estimated): January 22, 2027
• Study Completion (Estimated): September 6, 2028

Study Registration Dates

• First Submitted: June 26, 2025
• First Submitted That Met QC Criteria: June 26, 2025
• First Posted (Actual): July 8, 2025

Study Record Updates

• Last Update Posted (Actual): March 24, 2026
• Last Update Submitted That Met QC Criteria: March 23, 2026
• Last Verified: March 1, 2026

More Information

Terms related to this study

• Keywords: Human Immunodeficiency Virus (HIV); HIV reservoir; VH3810109; N6LS; Broadly neutralizing antibody (bNAb); Fostemsavir (FTR); RUKOBIA; INSTI-based ART; Adults living with HIV
• 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; Slow Virus Diseases; HIV Infections; Acquired Immunodeficiency Syndrome; Anti-Infective Agents; Molecular Mechanisms of Pharmacological Action; Antiviral Agents; Anti-HIV Agents; Anti-Retroviral Agents; HIV Fusion Inhibitors; Viral Fusion Protein Inhibitors; fostemsavir
• Other Study ID Numbers: 221794; 2025-520629-19-00 (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 asset(s) with development terminated 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