VH3810109 + Cabotegravir for HIV

(EMBRACE Trial)

Not currently recruiting at 43 trial locations

Age: 18+

Sex: Any

Trial Phase: Phase 2

Sponsor: ViiV Healthcare

Must be taking: Antiretrovirals

Must not be taking: Anticonvulsants, Antimycobacterials, Glucocorticoids, St John's wort

Disqualifiers: Pregnancy, Skin disorders, Cirrhosis, others

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

Prior Safety Data This treatment has passed at least one previous human trial

Breakthrough Therapy This drug has been fast-tracked for approval by the FDA given its high promise

Compensation: Varies

Number of Visits: Unknown

Duration: 12 weeks

What You Need to Know Before You Apply

What is the purpose of this trial?

This trial tests a new combination of treatments for individuals with HIV who have been on antiretroviral therapy and are managing their condition well. The focus is on the effectiveness and safety of the new treatment combination of VH3810109 (an experimental treatment) and cabotegravir, administered as an infusion and injection, respectively. Participants who have maintained a stable HIV treatment for at least six months and have consistently low viral levels might be suitable candidates. As a Phase 2 trial, the research measures the treatment's effectiveness in an initial, smaller group of participants.

Will I have to stop taking my current medications?

The trial does not specify if you need to stop your current medications, but it does exclude those currently using cabotegravir or fostemsavir. You should discuss your specific medications with the trial team to see if any adjustments are needed.

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

Research has shown that the combination of VH3810109 and cabotegravir has generally been well-tolerated in earlier studies. Specifically, using VH3810109 (also known as N6LS) with cabotegravir has successfully kept the virus under control in people with HIV, suggesting it is safe for long-term use. Some side effects occurred, but they were usually mild and manageable.

The FDA has already approved cabotegravir for other uses, providing extra reassurance about its safety. Studies on cabotegravir have shown it is safe for people with HIV, with common side effects being mild reactions at the injection site.

However, the study involving VH3810109 plus rHuPH20 (a substance that helps drugs spread under the skin) was stopped. Early results suggested possible safety concerns or that the combination wasn't effective.

Overall, while the combination of VH3810109 and cabotegravir looks promising, any new treatment can have risks. Prospective trial participants should consult their healthcare provider to understand what it means for them personally. ^{1 2 3 4 5}

Why are researchers excited about this trial's treatments?

Researchers are excited about VH3810109 combined with Cabotegravir for HIV because it offers a fresh approach to treatment, unlike traditional antiretroviral therapies. VH3810109 is a novel agent administered intravenously, and when paired with Cabotegravir given intramuscularly, it may improve adherence and reduce the frequency of dosing compared to daily oral medications. Additionally, VH3810109's unique formulation could potentially enhance the effectiveness of HIV management by targeting the virus differently than current standard treatments. This innovative delivery method and potential for less frequent dosing make it a promising option for those living with HIV.

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

Studies have shown that cabotegravir, when combined with VH3810109, can effectively manage HIV. This trial will administer different formulations of VH3810109 with cabotegravir to identify the most effective regimen. Research indicates that cabotegravir is generally well-tolerated, leading to fewer discontinuations due to side effects compared to other HIV medications. This suggests it is safer and easier for long-term use. VH3810109 is being tested in various forms to determine the most effective one. The goal of combining it with cabotegravir is to extend the duration people remain free from the virus between doses. However, one part of the study using VH3810109 with an enzyme called rHuPH20 was stopped, indicating mixed early results. ^{1 3 6 7 8}

Are You a Good Fit for This Trial?

Adults living with HIV who have been virologically suppressed on antiretroviral therapy (ART) are eligible for this trial. They must have had stable ART regimens, a CD4+ T-cell count ≥350 cells/mm^3, and weigh between 50-115 kg. Participants cannot be using cabotegravir or fostemsavir currently, nor can they have certain health conditions like cirrhosis or untreated syphilis.

Inclusion Criteria

QTc Interval <450 milliseconds (msec)

I am on a stable HIV medication regimen.

My weight is between 50kg and 115kg.

Exclusion Criteria

Participants with gluteal implants/enhancements

I have an untreated syphilis infection.

I have previously received an HIV monoclonal antibody treatment.

Timeline for a Trial Participant

Screening

Participants are screened for eligibility to participate in the trial

2-4 weeks

Treatment

Participants receive VH3810109 intravenously and Cabotegravir intramuscularly, or VH3810109 plus rHuPH20 via subcutaneous infusion and Cabotegravir intramuscularly

12 weeks

Follow-up

Participants are monitored for safety and effectiveness after treatment

24 weeks

Long-term follow-up

Participants from the discontinued arm transition to long-term follow-up

Long-term

What Are the Treatments Tested in This Trial?

Interventions

• Cabotegravir
• VH3810109

Trial Overview The trial is testing the effectiveness of VH3810109 in combination with Cabotegravir against standard HIV treatments. VH3810109 will be administered either intravenously or subcutaneously along with recombinant hyaluronidase (rHuPH20), while Cabotegravir will be given as an intramuscular injection.

How Is the Trial Designed?

Group I: Part 3B: Participants receiving VH3810109 Formulation 2 plus Cabotegravir Experimental Treatment 2 Interventions

Participants will receive VH3810109 formulation 2 intravenously (IV) and Cabotegravir intramuscularly (IM) at Day 1, Month 1, Month 2 and then Q2M.

Group II: Part 3A: Participants continuing VH3810109 Formulation 2 plus Cabotegravir Q2M Experimental Treatment 2 Interventions

Participants will continue to receive VH3810109 formulation 2 intravenously (IV) and Cabotegravir intramuscularly (IM) every 2 months (Q2M).

Group III: Part 2B: Participants Receiving VH3810109 Formulation 2 plus Cabotegravir Experimental Treatment 2 Interventions

Participants will receive VH3810109 formulation 2 intravenously (IV) and Cabotegravir intramuscularly (IM) at Day 1, Month 1, Month 2 and then Q2M. Participants from this arm will either transition to Part 3A or discontinue from the study and enter the LTFU period.

Group IV: Part 2A: Participants Receiving VH3810109 Formulation 2 plus Cabotegravir Q2M Experimental Treatment 2 Interventions

Participants will receive VH3810109 formulation 2 intravenously (IV) and Cabotegravir intramuscularly (IM) every 2 months (Q2M). Participants from this arm will either transition to Part 3A or discontinue from the study and enter the LTFU period.

Group V: Part 1B: Participants Receiving VH3810109 plus rHuPH20 plus Cabotegravir Experimental Treatment 3 Interventions

Participants will receive VH3810109 plus rHuPH20 via subcutaneous (SC) infusion and Cabotegravir IM. This arm was discontinued following preliminary results. Participants from this arm will either transition to Part 1A at the next dosing visit or withdraw from the Investigational Product (IP) and enter the LTFU.

Group VI: Part 1A: Participants Receiving VH3810109 Formulation 1 plus Cabotegravir Experimental Treatment 2 Interventions

Participants will receive VH3810109 formulation 1 intravenously (IV) and Cabotegravir intramuscularly (IM) every month (QM). Participants from this arm will either transition to Part 2A or discontinue from the study and enter the LTFU period.

Group VII: Part 1C: Participants Receiving SOC ART Active Control 1 Intervention

Participants in this arm will either transition to Part 2B or Part 2C or discontinue from the study.

Group VIII: Part 2C: Participants continuing SOC ART Active Control 1 Intervention

Participants in this arm will either transition to Part 3B or discontinue from the study.

Cabotegravir is already approved in European Union, United States, Canada, Japan for the following indications:

Approved in European Union as Vocabria for:

• HIV-1 infection

Approved in United States as Vocabria for:

• HIV-1 infection

Approved in Canada as Vocabria for:

• HIV-1 infection

Approved in Japan as Vocabria for:

• HIV-1 infection

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

Cabotegravir (Apretude) is an effective extended-release injectable medication used as pre-exposure prophylaxis (PrEP) to significantly reduce the risk of acquiring HIV-1 in HIV-negative individuals at risk.

It is approved for use in adults and adolescents who weigh at least 35 kg (77 lb), highlighting its targeted application for those most vulnerable to sexually transmitted HIV-1.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Cabotegravir (Apretude) for Pre-exposure Prophylaxis for HIV Type 1 Infection. El-Haddad, A., Erlich, D.[2023]

In the LATTE trial involving 243 antiretroviral-naive HIV-1-infected adults, cabotegravir combined with rilpivirine maintained viral suppression effectively, with 82% of patients achieving fewer than 50 copies of HIV-1 RNA at week 48, compared to 71% in the efavirenz group.

Cabotegravir was well tolerated, with fewer treatment-related adverse events leading to withdrawal (3%) compared to efavirenz (15%), suggesting a favorable safety profile for cabotegravir in long-term use.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Cabotegravir plus rilpivirine, once a day, after induction with cabotegravir plus nucleoside reverse transcriptase inhibitors in antiretroviral-naive adults with HIV-1 infection (LATTE): a randomised, phase 2b, dose-ranging trial. Margolis, DA., Brinson, CC., Smith, GHR., et al.[2020]

Cabotegravir (CAB) is an effective treatment for HIV-1 infection, showing efficacy both as part of combination therapy and as a long-acting injectable formulation administered every 4 to 8 weeks.

CAB is also being explored as a pre-exposure prophylaxis (PrEP) for high-risk individuals, with ongoing studies comparing its effectiveness to standard PrEP regimens, indicating its potential to reduce new infections.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Cabotegravir in the treatment and prevention of Human Immunodeficiency Virus-1. McPherson, TD., Sobieszczyk, ME., Markowitz, M.[2020]

In a study of 1,752 HIV-positive patients, 31.2% were found ineligible for the injectable treatment of cabotegravir and rilpivirine due to factors like detectable viral load and history of virological failures.

The proportion of ineligible patients increased to 47.3% when considering those with complete resistance test data, highlighting significant barriers to the feasibility of this treatment strategy.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Are we ready for long-acting? A feasibility evaluation of long-acting cabotegravir-rilpivirine in clinical practice. Borghetti, A., Farinacci, D., Ciccullo, A., et al.[2022]

Cabotegravir long-acting injectable (CAB LA) was found to be well tolerated among participants, with a high completion rate of injections (80% in Cohort 1 and 92% in Cohort 2), despite common injection site reactions (ISRs) that were mostly mild to moderate.

The study demonstrated that CAB LA 600 mg administered every 8 weeks successfully maintained drug levels above effective thresholds in 95% of participants, supporting its potential for HIV prevention and treatment.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Safety, tolerability, and pharmacokinetics of long-acting injectable cabotegravir in low-risk HIV-uninfected individuals: HPTN 077, a phase 2a randomized controlled trial. Landovitz, RJ., Li, S., Grinsztejn, B., et al.[2023]

In a study of 321 adults with HIV receiving the CAB + RPV LA injectable regimen, 90% of continuation injections were administered on time, indicating strong adherence to the injection schedule.

Among those who started with a viral load < 50 copies/mL, 95% remained undetectable and 99% were suppressed at their last measurement, demonstrating the high efficacy of CAB + RPV LA in maintaining virologic control in routine clinical care.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Cabotegravir + Rilpivirine Long-Acting Injections for HIV Treatment in the US: Real World Data from the OPERA Cohort. Sension, MG., Brunet, L., Hsu, RK., et al.[2023]

Citations

1. clinicaltrials.gov clinicaltrials.gov/study/NCT05996471

NCT05996471 | A Study to Investigate the Virologic ... The study aims at evaluating the efficacy of VH3810109, dosed in accordance with the dosing schedule as either intravenous (IV) infusion or subcutaneous ...

2. centerwatch.com centerwatch.com/clinical-trials/listings/NCT05996471/a-study-to-investigate-the-virologic-efficacy-and-safety-of-vh3810109-cabotegravir-compared-to-standard-of-care-soc-in-male-and-female-adults-living-with-human-immunodeficiency-virus-hiv

A Study to Investigate the Virologic Efficacy and Safety of ... The study aims at evaluating the efficacy of VH3810109, dosed in accordance with the dosing schedule as either intravenous (IV) infusion or subcutaneous (SC) ...

3. withpower.com withpower.com/trial/phase-2-hiv-infections-7-2023-c0343

VH3810109 + Cabotegravir for HIV (EMBRACE Trial) Cabotegravir was well tolerated, with fewer treatment-related adverse events leading to withdrawal (3%) compared to efavirenz (15%), suggesting a favorable ...

4. trial.medpath.com trial.medpath.com/clinical-trial/9affb11c430d4e4d/nct05996471-efficacy-safety-vh3810109-hiv

A Study to Investigate the Virologic Efficacy and Safety of ... The study aims at evaluating the efficacy of VH3810109, dosed in accordance with the dosing schedule as either intravenous (IV) infusion or subcutaneous ...

5. viivhealthcare.com viivhealthcare.com/hiv-news-and-media/news/press-releases/2024/february/next-generation-of-ultra-long-acting/

ViiV Healthcare to present data for its next generation of ... ViiV Healthcare will share findings from a phase I study evaluating different formulations of cabotegravir and their potential for dosing every four months.

6. viivhealthcare.com viivhealthcare.com/hiv-news-and-media/news/press-releases/2025/march/investigational-broadly-neutralising-antibody/

N6LS - successfully maintains viral suppression in long ... The study found that N6LS (VH3810109 or VH109), given every four months in combination with monthly cabotegravir long-acting (CAB LA), successfully kept viral ...

7. us.gsk.com us.gsk.com/en-us/media/press-releases/viiv-healthcare-to-present-data-for-its-next-generation-of-ultra-long-acting-treatments-for-hiv/

ViiV Healthcare to present data for its next generation of ... VH3810109 (N6LS) in Antiretroviral Therapy–Naive Adults With HIV-1: Phase IIa BANNER Efficacy Data. Presented at 31st Conference on ...

8. clinicalinfo.hiv.gov clinicalinfo.hiv.gov/en/drugs/vh3810109/health-professional

VH3810109 Health Professional Drug Record | NIH Investigational HIV drug information about VH3810109 for health professionals: pharmacology, clinical trials, adverse events, and more.