Capsid Inhibitors Safety Study for HIV Prevention

Not currently 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: Herbal medications

Disqualifiers: Cardiovascular, Hepatic, HIV, others

Compensation: Varies

Number of Visits: Unknown

Duration: 1 week

What You Need to Know Before You Apply

What is the purpose of this trial?

This trial examines the safety and tolerability of a new treatment called VH4004280, a capsid inhibitor, for preventing HIV. Researchers will test different doses administered by injection under the skin or into a muscle to observe how the body reacts and absorbs the drug. Healthy individuals who have tested negative for COVID-19 may be suitable candidates for this study. As a Phase 1 trial, participants will be among the first to receive this new treatment, aiding researchers in understanding its effects in people.

Will I have to stop taking my current medications?

The trial requires participants to not have used over-the-counter or prescription medications, including herbal medications, before joining. This means you would need to stop taking your current medications to participate.

Is there any evidence suggesting that this trial's treatments are likely to be safe?

A previous study, VH4004280, found a new treatment for HIV-1 to be safe for participants. It caused no major side effects and did not interfere with CYP3A4, a common liver enzyme. This suggests it likely won't affect how other medications are processed, indicating a positive safety profile.

Research also examined VH4011499, another HIV-1 treatment. Like VH4004280, it was safe for participants, with no major side effects reported, and it did not affect the CYP3A4 enzyme. Current evidence suggests both treatments appear safe for humans. ^{1 2 3 4 5}

Why are researchers excited about this trial's treatments?

Researchers are excited about VH4004280 and VH4011499 because these treatments offer a fresh approach to HIV prevention. Unlike current antiretroviral therapies that focus on inhibiting viral replication, these new treatments are capsid inhibitors. They target the protein shell of the virus, which could prevent the virus from infecting new cells in a different way. This novel mechanism of action, alongside their administration methods—subcutaneous and intramuscular injections—could lead to more effective prevention options with possibly fewer side effects.

What evidence suggests that this trial's treatments could be effective for HIV prevention?

Studies have shown that VH4004280, a treatment in this trial, effectively blocks key steps in the HIV-1 virus's life cycle, potentially stopping the virus from multiplying in the body. Lab tests indicate that VH4004280 has strong activity against HIV-1. Similarly, VH4011499, another treatment option in this trial, showed promising early results in fighting HIV by reducing the virus's ability to reproduce. Researchers are further investigating both treatments in this trial to confirm their potential in preventing HIV. ^{1 4 6 7 8}

Are You a Good Fit for This Trial?

Healthy adults who can consent, are not at risk of pregnancy, and test negative for SARS-CoV-2. Excluded are those with significant health issues, abnormal blood tests, recent drug trials participation, certain cancer histories or high-risk behaviors for HIV.

Inclusion Criteria

Participants who are overtly healthy

I cannot become pregnant or get someone pregnant.

Participants who test negative for Severe Acute Respiratory Syndrome Coronavirus 2 (SARS-CoV-2) on a single approved molecular polymerase chain reaction (PCR) or point of care test on the day of admission (Day -1)

Exclusion Criteria

History of sensitivity to study interventions, drug allergy, or other contraindicating allergies

I have no major health issues that could affect how a drug works in my body.

I haven't had cancer, except for certain skin cancers, in the last 5 years.

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 capsid inhibitors

1 week

Follow-up

Participants are monitored for safety and effectiveness after treatment

52 weeks

What Are the Treatments Tested in This Trial?

Interventions

• VH4004280

Trial Overview The trial is testing the safety and how the body processes two new capsid inhibitors (VH4011499 & VH4004280) given by injection compared to a placebo in healthy people. It involves single doses administered either under the skin or into a muscle.

How Is the Trial Designed?

Group I: Part 2 SAD: Participants Receiving VH4011499 Experimental Treatment 1 Intervention

VH4011499 injections are administered SC, SC+ rHuPH20, or IM.

Group II: Part 2 Multiple Ascending Dose (MAD): Participants Receiving VH4011499 Experimental Treatment 1 Intervention

VH4011499 injections are administered IM.

Group III: Part 1 Single Ascending Dose (SAD): Participants Receiving VH4004280 Experimental Treatment 1 Intervention

VH4004280 injections are administered subcutaneously (SC), SC+ rHuPH20, or intramuscularly (IM).

Group IV: Part 1: Participants Receiving Placebo Placebo Group 1 Intervention

Placebo injection is administered.

Group V: Part 2: Participants Receiving Placebo Placebo Group 1 Intervention

Placebo injection is administered.

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

A single subcutaneous dose of GS-CA1, an HIV capsid inhibitor, provided 97% protection against repeated SHIV challenges in rhesus macaques for 24 weeks, demonstrating its potential as a long-acting pre-exposure prophylaxis (PrEP) against HIV.

The study found a direct correlation between GS-CA1 plasma concentration and protection levels, with concentrations above a certain threshold offering complete protection, suggesting a promising new approach for HIV prevention in humans.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Long-acting capsid inhibitor protects macaques from repeat SHIV challenges. Vidal, SJ., Bekerman, E., Hansen, D., et al.[2022]

GS-6207 is a novel long-acting antiretroviral agent that targets the HIV capsid protein, showing potent antiviral activity at very low concentrations against all tested HIV-1 subtypes.

In phase-1 clinical trials, a single subcutaneous dose of GS-6207 significantly reduced plasma viral load by an average of 2.2 log10 after 9 days, with sustained antiviral effects lasting over 6 months, indicating its potential for improved adherence and treatment outcomes in HIV patients.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Clinical targeting of HIV capsid protein with a long-acting small molecule. Link, JO., Rhee, MS., Tse, WC., et al.[2022]

GS-CA1 is a new small-molecule HIV capsid inhibitor that shows exceptional potency against various strains of HIV, including those resistant to current antiretroviral therapies, making it a promising option for treatment.

In studies with humanized mice, GS-CA1 demonstrated high antiviral efficacy as a long-acting injectable treatment, outperforming existing long-acting options like rilpivirine, which could help improve adherence and reduce the stigma associated with daily pill regimens.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

A highly potent long-acting small-molecule HIV-1 capsid inhibitor with efficacy in a humanized mouse model. Yant, SR., Mulato, A., Hansen, D., et al.[2022]

Lenacapavir is the first FDA-approved capsid inhibitor for treating multidrug-resistant HIV-1, specifically for heavily treatment-experienced adults whose current therapies are failing due to resistance or safety issues.

In a phase 3 clinical trial, lenacapavir significantly reduced viral load compared to placebo, and it is administered as a long-acting injection every 6 months, although 63% of participants experienced injection site reactions.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Lenacapavir: A first-in-class capsid inhibitor for the treatment of highly treatment-resistant HIV. Prather, C., Lee, A., Yen, C.[2023]

HIV pre-exposure prophylaxis (PrEP) using daily tenofovir/emtricitabine has been proven effective in reducing the risk of HIV infection and is recommended by health organizations for high-risk populations, following successful clinical trials.

Despite its effectiveness, the uptake of PrEP has been slow due to various barriers, highlighting the need for additional strategies to promote its use, support adherence, and prevent risky behaviors among users.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Pre-exposure prophylaxis for sexually-acquired HIV risk management: a review. Wilton, J., Senn, H., Sharma, M., et al.[2020]

In a phase II trial with 96 postmenopausal women, the dapivirine vaginal ring demonstrated high acceptability, with 75% of participants reporting perfect adherence and 72% finding it very easy to use.

Participants' concerns about the ring significantly decreased over the study period, indicating it is a promising and non-burdensome HIV prevention method that may be preferred over condoms for some couples.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Acceptability of the Dapivirine Vaginal Ring in Postmenopausal US Women. Shapley-Quinn, MK., Laborde, N., Luecke, E., et al.[2022]

Antiretroviral treatment as Pre-exposure Prophylaxis (PrEP) has been shown to be both effective and safe in reducing the risk of HIV acquisition when taken daily or intermittently, based on evidence from animal studies and human clinical trials.

Concerns about the development of HIV-resistant strains due to PrEP use have not been supported by research, and ongoing demonstration projects indicate high interest and satisfactory adherence to PrEP among individuals at high risk.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Pre-Exposure Prophylaxis for HIV: Evidence and Perspectives. Nikolopoulos, GK., Christaki, E., Paraskevis, D., et al.[2018]

Despite advancements in HIV treatment allowing patients to live longer, HIV prevention efforts, particularly through pre-exposure prophylaxis (PrEP), have not significantly reduced new diagnoses in the U.S.

Studies like CAPRISA 004 and iPrEx show promise for PrEP in high-risk individuals, but challenges remain regarding safety, adherence, and the potential for drug resistance, indicating that PrEP should be part of a comprehensive prevention strategy.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Pre-exposure prophylaxis--one more tool for HIV prevention. Person, AK., Hicks, CB.[2019]

Long-acting injectable cabotegravir (CAB-LA) has been shown to be highly effective in preventing HIV, offering months of protection compared to daily oral PrEP, and has the potential to reduce costs, making it a promising option for HIV prevention.

The Clinton Health Access Initiative (CHAI) has developed a comprehensive roadmap to ensure equitable introduction of CAB-LA, focusing on coordination among stakeholders, community engagement, and incentivizing generic product development to maximize its impact in low- and middle-income countries.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Securing accelerated access to long-acting injectable cabotegravir for HIV prevention in low- and middle-income countries. Jenkins, SY., Resar, D., Panos, Z., et al.[2023]

Effective HIV prevention today requires a combination of behavioral, biomedical, and structural strategies, including consistent condom use, reducing the number of sexual and needle-sharing partners, male circumcision, and antiretroviral treatment.

Despite the identification of 144 effective behavioral prevention programs, scaling these initiatives outside the United States has been limited, highlighting the need for integrating behavioral strategies with biomedical innovations to enhance overall effectiveness in HIV prevention.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

The past, present, and future of HIV prevention: integrating behavioral, biomedical, and structural intervention strategies for the next generation of HIV prevention. Rotheram-Borus, MJ., Swendeman, D., Chovnick, G.[2022]

The novel lipopeptide inhibitor LP-19 demonstrated strong antiviral activity against HIV-1, HIV-2, and simian immunodeficiency virus (SIV), effectively inhibiting viral entry and infection in vitro and showing significant efficacy in rhesus macaques.

LP-19 not only exhibited a longer half-life and increased anti-HIV activity compared to existing treatments like enfuvirtide (T-20), but it also reduced viral loads to undetectable levels in SHIV-infected monkeys, indicating its potential as a new therapeutic option for HIV treatment.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

A Lipopeptide HIV-1/2 Fusion Inhibitor with Highly Potent In Vitro, Ex Vivo, and In Vivo Antiviral Activity. Chong, H., Xue, J., Xiong, S., et al.[2018]

Antiretroviral pre-exposure prophylaxis (PrEP) using oral emtricitabine-tenofovir disoproxil fumarate has been proven effective and safe in preventing HIV infection, leading to regulatory approval in nearly 70 countries.

Ongoing development of next-generation PrEP formulations aims to simplify access and increase user choice, which could enhance coverage and further reduce HIV infection rates at the population level.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

PrEP for HIV Prevention: Evidence, Global Scale-up, and Emerging Options. Celum, C., Baeten, J.[2020]

HIV infections are primarily transmitted through sexual contact, and current prevention methods include behavioral interventions and pre-exposure prophylaxis (PrEP) using topical microbicides or oral antiretroviral drugs.

While initial trials like CAPRISA 004 and iPreX showed promise for using tenofovir-based gels and oral TRUVADA® to prevent HIV transmission, recent trials such as FEMPreP and VOICE indicate that further research is needed to enhance the effectiveness and safety of these prevention strategies.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

HIV microbicides: where are we now? Quiñones-Mateu, ME., Vanham, G.[2019]

Citations

1. pmc.ncbi.nlm.nih.gov pmc.ncbi.nlm.nih.gov/articles/PMC12151970/

Clinical Pharmacokinetics and Safety of a New HIV-1 ... VH4004280 (VH-280), a new HIV-1 capsid inhibitor, inhibits both early and late steps of the HIV-1 life cycle and has demonstrated potent in ...

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

Preclinical virology profiles of the HIV-1 capsid inhibitors ... EC50, half-maximal effective concentration; SD, standard deviation; VH-280, VH4004280; and VH-499, VH4011499. Data were rounded to two ...

3. viivexchange.com viivexchange.com/content/dam/cf-viiv/viivexchange/medical/pdf/aids-2024-wang-vh-280-vh-499-virology-wepea027-final-updated-disc.pdf

Pre-Clinical Profiles of HIV-1 Capsid Inhibitors VH4004280 ... • Data on the pharmacokinetics and safety of orally administered VH-280 and VH-499 in participants without HIV are presented in Poster ...

4. clinicaltrials.gov clinicaltrials.gov/study/NCT05163522

Study Details | NCT05163522 | First-Time-in-Human (FTIH) ... This FTIH study aims to evaluate the safety, tolerability and PK of the novel investigational Human immunodeficiency virus (HIV)-1 capsid inhibitor ...

5. 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 ...

6. viivexchange.com viivexchange.com/content/dam/cf-viiv/viivexchange/medical/pdf/aids-2024-griesel-vh-280-oral-ftih-thpeb093-final-disc.pdf

aids-2024-griesel-vh-280-oral-ftih- ... Poster WEPEB105. ○ The HIV-1 capsid inhibitor VH4004280 (VH-280) was well tolerated, does not inhibit or induce CYP3A4, ...

7. pubmed.ncbi.nlm.nih.gov pubmed.ncbi.nlm.nih.gov/40287607/

Clinical Pharmacokinetics and Safety of a New HIV-1 ... The pharmacokinetics, drug-drug interaction potential, and safety of a new HIV-1 capsid inhibitor, VH4004280 (VH-280), are described in this first-time-in- ...

8. medinfo.gsk.com medinfo.gsk.com/5f95dbd7-245e-4e65-9f36-1a99e28e5bba/6f002977-bd52-465c-b6cb-a96150deaed9/6f002977-bd52-465c-b6cb-a96150deaed9_viewable_rendition__v.pdf

Pre-Clinical Profiles of HIV-1 Capsid Inhibitors VH4004280 ... • Data on the pharmacokinetics and safety of orally administered VH-280 and VH-499 in participants without HIV are presented in Poster ...