Long-Acting VH4524184 for HIV

Recruiting at 1 trial location

Overseen By US GSK Clinical Trials Call Center

Age: 18 - 65

Sex: Any

Trial Phase: Phase 1

Sponsor: ViiV Healthcare

Must not be taking: Anticoagulants, Enzyme inducers, others

Disqualifiers: Liver disease, Cardiac disease, Cancer, others

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

Compensation: Varies

Number of Visits: Unknown

Duration: Up to 52 weeks

72 Participants Needed

Trial Summary

Will I have to stop taking my current medications?

The trial requires that participants stop using over-the-counter or prescription medications within 7 days (or 14 days if the drug is a potential enzyme inducer) before starting the study and for the duration of the study.

What data supports the effectiveness of the drug VH4524184 for HIV?

Long-acting antiretroviral drugs, like VH4524184, are promising for HIV treatment because they help with adherence (sticking to the treatment plan) and have shown effectiveness in other studies, such as the combination of long-acting fusion inhibitors like albuvirtide with other HIV drugs, which demonstrated strong results in reducing the virus in patients. ^{1 2 3 4 5}

What makes the drug VH4524184 unique for HIV treatment?

VH4524184 is a long-acting drug, which means it requires less frequent dosing compared to daily oral regimens, potentially improving adherence and making it easier for patients to stick to their treatment plan. ^{4 5 6 7 8}

What is the purpose of this trial?

The purpose of this study is to identify 1 or more doses of parenterally administered VH4524184 that are safe, well tolerated and yield a PK drug exposure profile necessary to deliver a long-acting antiretroviral therapy for the treatment of HIV-1 infection.

Eligibility Criteria

This trial is for individuals with HIV infection. It's a first-time study of VH4524184, which aims to find safe doses that can be given less often than current treatments. Specific eligibility details are not provided.

Inclusion Criteria

Participants must be able to understand and comply with protocol requirements and timetables, instructions, and protocol-stated restrictions

I tested negative for COVID-19 with a PCR test upon entering the study.

I am generally healthy according to recent medical exams and tests.

Exclusion Criteria

I have a history of liver disease or known liver problems.

Participation in the study resulting in loss of blood in excess of 500 mL over a 56-day period

Abnormal blood pressure as determined by the investigator

Timeline

Screening

Participants are screened for eligibility to participate in the trial

2-4 weeks

Treatment

Participants receive single or multiple doses of VH4524184 LAI formulations administered subcutaneously or intramuscularly

Up to 52 weeks

Follow-up

Participants are monitored for safety and effectiveness after treatment

4 weeks

Treatment Details

Interventions

• VH4524184

Trial Overview The trial tests various formulations and delivery methods (like injections into muscle or under the skin) of VH4524184, including placebos and an oral version, to see which works best as a long-acting antiretroviral therapy.

Participant Groups

Group I: Multiple doses Group Experimental Treatment 12 Interventions

VH4524184 LAI formulations administered SC or IM as single doses that achieve adequate PK exposure targets, may be evaluated for safety and tolerability as multiple doses.

Group II: Formulation C SC Group Experimental Treatment 4 Interventions

Participants receive a Formulation C starting dose of VH4524184 LAI subcutaneously. This intervention is optional and initiated only if Formulation B is poorly tolerated.

Group III: Formulation B SC Group Experimental Treatment 4 Interventions

Participants receive a Formulation B starting dose of VH4524184 LAI subcutaneously.

Group IV: Formulation B IM Group Experimental Treatment 3 Interventions

Participants receive a Formulation B starting dose of VH4524184 LAI intramuscularly (IM).

Group V: Formulation A SC Group Experimental Treatment 4 Interventions

Participants receive a Formulation A starting dose of VH4524184 LAI subcutaneously (SC).

Group VI: Formulation A IM Group Experimental Treatment 3 Interventions

Participants receive a Formulation A starting dose of VH4524184 LAI intramuscularly (IM).

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

GlaxoSmithKline

Industry Sponsor

Trials

4,834

Recruited

8,389,000+

Headquarters

London, UK

Known For

Vaccines & Medicines

Top Products

**Advair (salmeterol, fluticasone propionate)**, **Shingrix (shingles vaccine)**, **Augmentin (amoxicillin/clavulanate potassium)**, **Ventolin (salbutamol sulfate)

Dame Emma Walmsley

GlaxoSmithKline

Chief Executive Officer since 2017

MA in Classics and Modern Languages from Oxford University

Dr. Hal Barron

GlaxoSmithKline

Chief Medical Officer since 2018

MD from Harvard Medical School

Findings from Research

In a study of 428 HIV-1-infected patients with high pre-therapy viral loads, those starting treatment with a regimen containing a protease inhibitor plus an integrase inhibitor (PI+INI) or a non-nucleoside reverse transcriptase inhibitor (NNRTI) had a significantly higher probability of achieving virological success (VS) after 12 months compared to those on a protease inhibitor (PI)-based regimen.

The overall probability of immunological reconstitution (IR) was similar across treatment groups, but patients with AIDS had a lower chance of achieving IR compared to those without AIDS, highlighting the importance of early treatment initiation.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Viro-immunological response of drug-naive HIV-1-infected patients starting a first-line regimen with viraemia >500,000 copies/ml in clinical practice. Santoro, MM., Di Carlo, D., Armenia, D., et al.[2019]

Enfuvirtide, a fusion inhibitor, effectively reduces HIV plasma viral load by blocking the virus's ability to fuse with host cells, showing significant efficacy in Phase I and II clinical trials with minimal serious side effects.

In large randomized trials, enfuvirtide combined with optimized background therapy provided a significant virological advantage over optimized background therapy alone, indicating its potential as a valuable treatment option for patients with limited alternatives.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Enfuvirtide. Chen, RY., Kilby, JM., Saag, MS.[2019]

Enfuvirtide (ENF) combined with an optimized background (OB) antiretroviral regimen significantly delays virological failure and immunological failure in pretreated HIV-1 patients, with projected mean times of 1.0 years and 3.1 years respectively, compared to 0.5 years and 1.3 years for OB alone.

The cost-effectiveness analysis shows that while ENF+OB has higher lifetime medical costs (euro 126,487 vs. euro 84,416 for OB), it provides an additional 1.8 years of life expectancy, resulting in an incremental cost-effectiveness of euro 28,669 per quality-adjusted life year (QALY), which is comparable to other accepted therapies in Europe.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Cost-effectiveness of enfuvirtide for treatment-experienced patients with HIV in Italy. Hornberger, J., Green, J., Wintfeld, N., et al.[2018]

Long-acting formulations of antiretroviral drugs are being developed to improve adherence in HIV treatment and prevention, which is crucial for their effectiveness, especially since current regimens require daily dosing.

While these long-acting drugs show promise in clinical trials, challenges such as managing side effects, potential drug interactions, and the risk of drug resistance need to be addressed.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Long-Acting HIV Drugs for Treatment and Prevention. Gulick, RM., Flexner, C.[2019]

In a 7-week trial with 20 HIV-1-infected adults, albuvirtide (ABT) demonstrated a clear dose-efficacy relationship, with higher doses leading to greater reductions in HIV-1 RNA levels.

The combination of ABT with LPV/r resulted in 55.6% of patients achieving viral suppression below 50 copies/ml at the higher dose, indicating its potential as an effective treatment option for HIV.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Combination of long-acting HIV fusion inhibitor albuvirtide and LPV/r showed potent efficacy in HIV-1 patients. Zhang, H., Jin, R., Yao, C., et al.[2019]

ABX464, an investigational oral drug for HIV-1, was found to be safe and well-tolerated in a Phase IIa study involving 30 participants, with most adverse events being mild or moderate.

While ABX464 showed some potential in reducing HIV-1 DNA levels in blood cells, there was no significant difference in viral rebound time compared to placebo, indicating that further research is needed to confirm its efficacy.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Safety, tolerability and impact on viral reservoirs of the addition to antiretroviral therapy of ABX464, an investigational antiviral drug, in individuals living with HIV-1: a Phase IIa randomised controlled study. Rutsaert, S., Steens, JM., Gineste, P., et al.[2022]

MK-8591, an investigational drug for HIV treatment, shows promise for long-acting formulations that could improve adherence to treatment regimens, as it maintains effective drug levels for over 6 months after subcutaneous implantation in animal studies.

The drug's active form, MK-8591-TP, demonstrates prolonged intracellular persistence and significant viral load reduction, indicating its potential effectiveness for both treatment and pre-exposure prophylaxis (PrEP) against HIV.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Extended-Duration MK-8591-Eluting Implant as a Candidate for HIV Treatment and Prevention. Barrett, SE., Teller, RS., Forster, SP., et al.[2020]

Long-acting injectable agents, cabotegravir (CAB LA) and rilpivirine (RPV LA), show promise for HIV prevention by potentially improving adherence to dosing regimens due to their favorable pharmacokinetics.

Both CAB LA and RPV LA are currently undergoing phase 2a studies to assess their safety and tolerability, but injection site reactions may complicate their use, highlighting the need for careful evaluation before widespread implementation.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

The promise and pitfalls of long-acting injectable agents for HIV prevention. Landovitz, RJ., Kofron, R., McCauley, M.[2018]

References

1. England pubmed.ncbi.nlm.nih.gov

Viro-immunological response of drug-naive HIV-1-infected patients starting a first-line regimen with viraemia >500,000 copies/ml in clinical practice. [2019]

2. England pubmed.ncbi.nlm.nih.gov

Enfuvirtide. [2019]

3. England pubmed.ncbi.nlm.nih.gov

Cost-effectiveness of enfuvirtide for treatment-experienced patients with HIV in Italy. [2018]

4. United States pubmed.ncbi.nlm.nih.gov

Long-Acting HIV Drugs for Treatment and Prevention. [2019]

5. England pubmed.ncbi.nlm.nih.gov

Combination of long-acting HIV fusion inhibitor albuvirtide and LPV/r showed potent efficacy in HIV-1 patients. [2019]

6. England pubmed.ncbi.nlm.nih.gov

Safety, tolerability and impact on viral reservoirs of the addition to antiretroviral therapy of ABX464, an investigational antiviral drug, in individuals living with HIV-1: a Phase IIa randomised controlled study. [2022]

7. United States pubmed.ncbi.nlm.nih.gov

Extended-Duration MK-8591-Eluting Implant as a Candidate for HIV Treatment and Prevention. [2020]

8. United States pubmed.ncbi.nlm.nih.gov

The promise and pitfalls of long-acting injectable agents for HIV prevention. [2018]