VH3810109 + Cabotegravir for HIV

(EMBRACE Trial)

Recruiting at 40 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

135 Participants Needed

Trial Summary

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.

What data supports the effectiveness of the drug Cabotegravir for HIV treatment?

Cabotegravir, when used in combination with rilpivirine, has been shown to maintain viral suppression in people with HIV, and its long-acting injectable form provides a convenient dosing option. Studies have demonstrated its safety and effectiveness in both treatment and prevention of HIV, making it a promising option for managing the infection. ^{1 2 3 4 5}

What makes the drug VH3810109 + Cabotegravir unique for HIV treatment?

VH3810109 + Cabotegravir is unique because it includes Cabotegravir, a long-acting injectable drug that can be administered less frequently than daily pills, offering a more convenient option for maintaining HIV treatment and prevention. ^{1 2 3 6 7}

What is the purpose of this trial?

This trial tests a new drug, VH3810109, given with an enzyme to help absorption, combined with cabotegravir shots in adults with controlled HIV who are already on treatment.

Eligibility Criteria

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

I am on a stable HIV medication regimen.

My weight is between 50kg and 115kg.

QTc Interval <450 milliseconds (msec)

Exclusion Criteria

Participants with gluteal implants/enhancements

I have an untreated syphilis infection.

I have previously received an HIV monoclonal antibody treatment.

Timeline

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

Treatment Details

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.

Participant Groups

Group I: 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 the VH3810109 Plus Cabotegravir arm at the next dosing visit or withdraw from the Investigational Product (IP) and enter the long-term follow up period.

Group II: Participants Receiving VH3810109 plus Cabotegravir Experimental Treatment 2 Interventions

Participants will receive VH3810109 intravenously (IV) and Cabotegravir intramuscularly (IM).

Group III: Participants Receiving Standard of Care (SOC) Antiretroviral Therapy (ART) Active Control 1 Intervention

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

Findings from Research

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 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 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]

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 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]

References

1. United States 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. [2023]

2. United States 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. [2020]

3. Netherlands pubmed.ncbi.nlm.nih.gov

Novel secondary mutations C56S and G149A confer resistance to HIV-1 integrase strand transfer inhibitors. [2020]

4. England pubmed.ncbi.nlm.nih.gov

Cabotegravir in the treatment and prevention of Human Immunodeficiency Virus-1. [2020]

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

Cabotegravir + Rilpivirine Long-Acting Injections for HIV Treatment in the US: Real World Data from the OPERA Cohort. [2023]

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

Cabotegravir (Apretude) for Pre-exposure Prophylaxis for HIV Type 1 Infection. [2023]

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

Are we ready for long-acting? A feasibility evaluation of long-acting cabotegravir-rilpivirine in clinical practice. [2022]