Capsid Inhibitors Safety Study for HIV Prevention

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

208 Participants Needed

Trial Summary

What is the purpose of this trial?

The primary purpose of the study is to investigate safety and tolerability following single and multiple ascending subcutaneous (SC) and intramuscular (IM) doses of capsid inhibitors in healthy participants. The study will also describe the pharmacokinetics following single and multiple ascending SC and IM doses of capsid inhibitors in healthy participants.

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.

What data supports the effectiveness of the drug VH4004280 for HIV prevention?

The research highlights the effectiveness of long-acting injectable cabotegravir (CAB-LA) for HIV prevention, which is similar to VH4004280 as both are used for HIV prevention. CAB-LA has shown high effectiveness and provides months of protection, suggesting that VH4004280 might also be effective in a similar way. ^{1 2 3 4 5}

Is the capsid inhibitor VH4004280 safe for humans?

There is no specific safety data available for VH4004280, but a similar capsid inhibitor, GS-CA1, showed high antiviral efficacy and was well-tolerated in a humanized mouse model, suggesting potential safety in humans. ^{5 6 7 8 9}

How does the capsid inhibitor drug for HIV prevention differ from other treatments?

This capsid inhibitor drug is unique because it is a long-acting treatment that can be administered less frequently, unlike daily pills. It works by targeting the HIV capsid protein, interfering with the virus's ability to replicate, and is effective against drug-resistant strains, offering a novel approach to HIV prevention and treatment. ^{7 10 11 12 13}

Eligibility Criteria

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.

Abnormal blood pressure

Timeline

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

Treatment Details

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.

Participant Groups

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

Findings from Research

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]

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]

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]

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]

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]

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]

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]

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]

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]

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]

References

1. United Arab Emirates pubmed.ncbi.nlm.nih.gov

Pre-Exposure Prophylaxis for HIV: Evidence and Perspectives. [2018]

2. Netherlands pubmed.ncbi.nlm.nih.gov

Pre-exposure prophylaxis--one more tool for HIV prevention. [2019]

3. Switzerland pubmed.ncbi.nlm.nih.gov

Securing accelerated access to long-acting injectable cabotegravir for HIV prevention in low- and middle-income countries. [2023]

4. United States 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. [2022]

5. New Zealand pubmed.ncbi.nlm.nih.gov

Pre-exposure prophylaxis for sexually-acquired HIV risk management: a review. [2020]

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

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

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

A highly potent long-acting small-molecule HIV-1 capsid inhibitor with efficacy in a humanized mouse model. [2022]

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

Acceptability of the Dapivirine Vaginal Ring in Postmenopausal US Women. [2022]

9. Netherlands pubmed.ncbi.nlm.nih.gov

HIV microbicides: where are we now? [2019]

10. England pubmed.ncbi.nlm.nih.gov

Long-acting capsid inhibitor protects macaques from repeat SHIV challenges. [2022]

11. England pubmed.ncbi.nlm.nih.gov

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

12. England pubmed.ncbi.nlm.nih.gov

Clinical targeting of HIV capsid protein with a long-acting small molecule. [2022]

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

A Lipopeptide HIV-1/2 Fusion Inhibitor with Highly Potent In Vitro, Ex Vivo, and In Vivo Antiviral Activity. [2018]