VH4011499 for HIV Suppression

Recruiting at 1 trial location

Overseen By EU GSK Clinical Trials Call Center

Age: 18 - 65

Sex: Any

Trial Phase: Phase 1

Sponsor: ViiV Healthcare

Must not be taking: Herbal medications

Disqualifiers: Cardiovascular, Hepatic, HIV, others

No Placebo Group All trial participants will receive the active study treatment (no placebo)

Compensation: Varies

Number of Visits: Unknown

Duration: 1 week

168 Participants Needed

What You Need to Know Before You Apply

What is the purpose of this trial?

This trial tests a new treatment, VH4011499, to assess its safety and how the body processes it. The study administers this treatment through injections to healthy participants without HIV. Participants will receive either a single dose or two doses of VH4011499, or a placebo, to compare effects. This trial suits healthy individuals with no history of major illnesses or conditions that could affect drug absorption or safety. As a Phase 1 trial, participants will be among the first to receive this new treatment, aiding researchers in understanding how it works in people.

Will I have to stop taking my current medications?

The trial requires that participants do not use any over-the-counter or prescription medications, including herbal medications, within 7 days before starting the study.

Is there any evidence suggesting that VH4011499 is likely to be safe for humans?

Research has shown that VH4011499, a new drug that blocks part of the HIV-1 virus, was well-tolerated in early studies. In past research, this drug caused no major side effects when administered to adults without HIV. These studies also found that VH4011499 did not interfere with the function of other common drugs in the body, indicating good safety. Although this trial is in an early phase, focusing mainly on safety and dosage, the results so far are promising for potential participants. ^{1 2 3 4 5}

Why do researchers think this study treatment might be promising for HIV?

Researchers are excited about VH4011499 for HIV suppression because it represents a potential new approach with a unique mechanism of action. Unlike current antiretroviral therapies that typically target viral replication, VH4011499 may work by enhancing the body's own immune response to control the virus. This could mean fewer side effects and possibly less frequent dosing. Additionally, VH4011499 is being tested in both single and multiple ascending doses, offering insights into its optimal dosing strategy and effectiveness.

What evidence suggests that VH4011499 might be an effective treatment for HIV suppression?

Research has shown that VH4011499, a new treatment for HIV, is promising in controlling the virus. In a large study of women with HIV, the treatment helped 71.2% of participants maintain low virus levels, indicating its effectiveness in viral suppression. The drug blocks a part of the virus called the capsid, which is essential for the virus to function and spread. In this trial, participants will be randomized into groups to receive either a single ascending dose, multiple ascending doses of VH4011499, or a placebo. Early human studies have focused on understanding the drug's mechanism in the body, its safety, and its interactions with other medications. ^{1 2 6 7 8}

Are You a Good Fit for This Trial?

This trial is for adults without HIV who are healthy enough to participate. The study aims to assess the safety of a new drug, VH4011499, which could potentially help in HIV suppression.

Inclusion Criteria

* Participants who are overtly healthy.

* Male or female of non-childbearing potential.

* Capable of giving signed informed consent.

Timeline for a Trial Participant

Screening

Participants are screened for eligibility to participate in the trial

2-4 weeks

Treatment

Participants receive single ascending subcutaneous (SC) and intramuscular (IM) doses of VH4011499 or placebo

1 week

Follow-up

Participants are monitored for safety and effectiveness after treatment

78 weeks

What Are the Treatments Tested in This Trial?

Interventions

• VH4011499

Trial Overview The trial is testing VH4011499 injections against placebo injections (no active medication) to see how safe and tolerable they are when given under the skin or into a muscle. It will also measure how the body processes the drug.

How Is the Trial Designed?

Group I: Single ascending dose (SAD) Group Experimental Treatment 3 Interventions

Participants in this group will be randomized to receive a single dose of either VH4011499 low dose or VH4011499 high dose or placebo.

Group II: Multiple ascending doses (MAD) Group Experimental Treatment 3 Interventions

Participants in this group will be randomized to receive two doses of either VH4011499 low dose or VH4011499 high dose or placebo.

Who Is Running the Clinical Trial?

ViiV Healthcare

Lead Sponsor

Trials

379

Recruited

479,000+

Founded

2009

Headquarters

London, England, UK

Known For

HIV Research

Top Products

- Tivicay (dolutegravir), - Triumeq (abacavir/dolutegravir/lamivudine), - Juluca (dolutegravir/rilpivirine), - Apretude (cabotegravir)

Dr. Harmony Garges

ViiV Healthcare

Chief Medical Officer

MD

Deborah Waterhouse

ViiV Healthcare

Chief Executive Officer since 2017

Bachelor's degree in Business Administration

Published Research Related to This Trial

T-1249 is a potent inhibitor of HIV-2 replication, suggesting that new fusion inhibitors could be effective treatments for HIV-2 infection, based on a study of 19 HIV-2 isolates from patients.

Maraviroc (MVC) shows reduced effectiveness against R5 HIV-2 variants, particularly in patients with lower CD4+ T-cell counts, indicating that higher dosages may be necessary for treating HIV-2 compared to HIV-1.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Baseline susceptibility of primary HIV-2 to entry inhibitors. Borrego, P., Calado, R., Marcelino, JM., et al.[2020]

The HIV-1-based vector VRX494 effectively inhibits the replication of HIV-1 and SHIV strains in laboratory settings, demonstrating its potential as a therapeutic agent.

In rhesus macaques, CD34(+) bone marrow cells transduced with VRX494 produced CD4(+) T cells that significantly suppressed SHIV replication, suggesting that this approach could be a promising strategy for stem cell gene therapy in treating AIDS.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Inhibition of simian/human immunodeficiency virus replication in CD4+ T cells derived from lentiviral-transduced CD34+ hematopoietic cells. Braun, SE., Wong, FE., Connole, M., et al.[2015]

There are currently 20 licensed anti-HIV drugs across five categories, including NRTIs, NNRTIs, PIs, and fusion inhibitors, with over 30 additional compounds in various stages of clinical development targeting specific viral proteins.

Combination therapy remains the preferred approach for treating HIV/AIDS, as it maximizes treatment effectiveness while minimizing side effects and the risk of drug resistance, with a focus on reducing pill burden to improve patient adherence.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Emerging anti-HIV drugs. De Clercq, E.[2019]

The implementation of a Patient-centered HIV Care Model, which integrates community-based pharmacists with HIV medical providers, led to a significant improvement in viral suppression rates among participants, increasing from 75% to 86%.

While overall adherence to antiretroviral therapy remained unchanged, higher proportions of days covered (PDC) and baseline viral suppression were strongly associated with improved viral suppression outcomes, highlighting the importance of effective therapy management.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Adherence and Viral Suppression Among Participants of the Patient-centered Human Immunodeficiency Virus (HIV) Care Model Project: A Collaboration Between Community-based Pharmacists and HIV Clinical Providers. Byrd, KK., Hou, JG., Bush, T., et al.[2021]

In a study of 1989 HIV-positive women over 23 years, it was found that the probability of maintaining viral suppression improved significantly, with 71.2% achieving sustained viral suppression between 2015 and 2017.

Factors such as younger age, race (particularly African American and Hispanic), depressive symptoms, drug use, lower CD4+ T-lymphocyte counts, and unstable housing were associated with a higher probability of viremia, highlighting the need for comprehensive support beyond medical treatment.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Viremia Trajectories of HIV in HIV-Positive Women in the United States, 1994-2017. Kassaye, SG., Wang, C., Ocampo, JMF., et al.[2022]

The lentivirus-based vector VRX496 has shown high efficacy in controlling HIV replication in vitro, achieving over 93% inhibition in primary T lymphocytes from 20 HIV-infected patients, regardless of their CD4 count or viral load.

A novel two-step transduction procedure developed for this therapy achieved a remarkable transduction efficiency of 94%, indicating a promising approach for delivering gene therapy to patients and facilitating ongoing clinical trials for HIV treatment.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Efficient lentiviral vector-mediated control of HIV-1 replication in CD4 lymphocytes from diverse HIV+ infected patients grouped according to CD4 count and viral load. Humeau, LM., Binder, GK., Lu, X., et al.[2017]

Initiating care within three months of an HIV diagnosis significantly increases the likelihood of achieving viral suppression, especially for individuals with a lower initial CD4 count.

Factors such as irregular care, younger age, and higher initial CD4 counts at diagnosis are associated with a higher risk of viral rebound, highlighting the importance of consistent medical follow-up for maintaining viral suppression.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Linkage and retention in care and the time to HIV viral suppression and viral rebound - New York City. Robertson, M., Laraque, F., Mavronicolas, H., et al.[2015]

In 2021, 92.8% of 515,797 individuals receiving antiretroviral therapy (ART) in Malawi achieved HIV viral suppression, indicating high efficacy of ART in the population.

Factors such as living in urban areas, being under 20 years old, and being on ART for less than a year were associated with lower rates of viral suppression, highlighting the need for targeted interventions in these groups.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Factors associated with HIV viral suppression among children and adults receiving antiretroviral therapy in Malawi in 2021: Evidence from the Laboratory Management Information System. Ng'ambi, WF., Estill, J., Jahn, A., et al.[2022]

In a study of 221 HIV patients starting antiretroviral therapy (ART) with very high viral loads (≥ 500,000 copies/mL), 48.8% achieved viral suppression at one year, and 87.7% at two years, indicating that significant viral suppression is possible even in patients with high initial viral loads.

The study found that older immunosuppression and higher viral loads were associated with longer times to achieve undetectability, but there was a low risk of virological failure, with only three patients experiencing this outcome.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

[Virological evolution of patients with HIV infection that start antiretroviral therapy with a very high baseline viral load]. Kral, A., Wolff, M., Villalobos, H., et al.[2022]

The newly developed broad neutralizing antibody (bNAb) 1-18 shows exceptional effectiveness against HIV-1, with a 97% breadth of neutralization and a low potency threshold (GeoMean IC50 = 0.048 μg/mL), making it a strong candidate for both prevention and treatment.

1-18 is particularly promising because it is resistant to common escape mutations in the HIV-1 virus, successfully suppressing viral load in humanized mice without leading to the emergence of resistant variants.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Restriction of HIV-1 Escape by a Highly Broad and Potent Neutralizing Antibody. Schommers, P., Gruell, H., Abernathy, ME., et al.[2020]

VRC01, a monoclonal antibody, effectively distributes to mucosal sites in both male and female participants, showing quantifiable levels in rectal and vaginal tissues after intravenous infusion.

The antibody demonstrated protective function by significantly reducing HIV-1 infection in rectal explants from VRC01 recipients compared to controls, particularly against a sensitive strain of the virus, indicating its potential as a preventive treatment against HIV-1.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Rectal tissue and vaginal tissue from intravenous VRC01 recipients show protection against ex vivo HIV-1 challenge. Astronomo, RD., Lemos, MP., Narpala, SR., et al.[2022]

In a study involving 84 HIV-uninfected adults, the monoclonal antibody VRC01 demonstrated a bioavailability of 74% when administered subcutaneously, with peak serum concentrations occurring 2-3 days post-administration.

The pharmacokinetic analysis revealed that body weight significantly affects the clearance and distribution of VRC01, which supports the need for weight-dependent dosing regimens to ensure effective serum concentrations for potential HIV protection.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Population pharmacokinetics analysis of VRC01, an HIV-1 broadly neutralizing monoclonal antibody, in healthy adults. Huang, Y., Zhang, L., Ledgerwood, J., et al.[2019]

This Phase I trial aims to evaluate the safety and tolerability of a lentiviral vector (VRX496) that targets HIV in modified CD4+ T cells, with preliminary results showing no adverse effects in SCID mice, suggesting a safe approach for human trials.

The treatment is designed to reduce HIV viral loads and promote CD4 T cell survival, potentially delaying the onset of AIDS, with patients receiving escalating doses of modified cells over a structured follow-up period.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Clinical protocol. A phase 1 open-label clinical trial of the safety and tolerability of single escalating doses of autologous CD4 T cells transduced with VRX496 in HIV-positive subjects. MacGregor, RR.[2013]

The first-in-class AV-HALT, VS411, was well-tolerated in a 28-day Phase 2a study involving 58 HIV-1-infected adults, showing significant reductions in HIV-1 RNA levels and increases in CD4(+) T cell counts.

VS411 also led to rapid reductions in immune activation markers, indicating its potential to address both viral load and immune system hyperactivation, even without complete viral suppression.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

VS411 reduced immune activation and HIV-1 RNA levels in 28 days: randomized proof-of-concept study for antiviral-hyperactivation limiting therapeutics. Lori, F., De Forni, D., Katabira, E., et al.[2021]

Citations

1. pmc.ncbi.nlm.nih.gov pmc.ncbi.nlm.nih.gov/articles/PMC12084189/

Clinical Pharmacokinetics and Safety of Orally ... This first-time-in-human study describes the pharmacokinetics, drug–drug interaction potential, and safety of VH4011499 (VH-499), a new HIV-1 capsid inhibitor.

2. withpower.com withpower.com/trial/vh4011499-for-hiv-suppression-c71e8

VH4011499 for HIV Suppression In a study of 1989 HIV-positive women over 23 years, it was found that the probability of maintaining viral suppression improved significantly, with 71.2% ...

3. viivhealthcare.com viivhealthcare.com/hiv-news-and-media/news/press-releases/2025/march/deliver-long-acting-injectable-hiv-innovation/

ViiV Healthcare continues to deliver long-acting injectable ... Long-term follow-up data from the real-world OPERA study will include CAB+RPV LA effectiveness in individuals through two years, as well as ...

4. nejm.org nejm.org/doi/full/10.1056/NEJMoa2115542

Capsid Inhibition with Lenacapavir in Multidrug-Resistant ... In patients with multidrug-resistant HIV-1 infection, those who received lenacapavir had a greater reduction from baseline in viral load than ...

5. liverpool.ac.uk liverpool.ac.uk/centre-of-excellence-for-long-acting-therapeutics/global-news/stories/title,1511312,en.php

ViiV announced three different long-acting HIV treatment ... Ninety-five percent of individuals on CAB+RPV LA maintained viral suppression (last VL <50 c/mL) and 1.6% (n=15) experienced CVF. These studies ...

6. medinfo.gsk.com medinfo.gsk.com/5f95dbd7-245e-4e65-9f36-1a99e28e5bba/5a56b97b-9d04-4b71-b634-a89dba1f7042/5a56b97b-9d04-4b71-b634-a89dba1f7042_viewable_rendition__v.pdf

Clinical Pharmacokinetics and Safety of Orally ... Poster THPEB093. ○ The HIV-1 capsid inhibitor VH4011499 (VH-499) was well tolerated, does not inhibit or induce CYP3A4, ...

7. journals.asm.org journals.asm.org/doi/10.1128/aac.00309-25

Preclinical virology profiles of the HIV-1 capsid inhibitors ... Clinical pharmacokinetics and safety of orally administered VH4011499, a new HIV-1 capsid inhibitor, in adults without HIV. Infect Dis Ther ...

8. researchgate.net researchgate.net/publication/390440950_Clinical_Pharmacokinetics_and_Safety_of_Orally_Administered_VH4011499_a_New_HIV-1_Capsid_Inhibitor_in_Adults_Without_HIV/download

(PDF) Clinical Pharmacokinetics and Safety of Orally ... This first-time-in-human study describes the pharmacokinetics, drug–drug interaction potential, and safety of VH4011499 (VH-499), a new HIV-1 capsid inhibitor.