VH3810109 + Fostemsavir for HIV Infection

(ENTRANCE Trial)

Recruiting at 7 trial locations

Age: 18+

Sex: Any

Trial Phase: Phase 1

Sponsor: ViiV Healthcare

Must be taking: INSTI-based ART

Must not be taking: NNRTIs, FTR, Long-acting ARVs

Disqualifiers: Pregnancy, HIV-2, Cardiovascular disease, Hepatitis, others

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

Compensation: Varies

Number of Visits: Unknown

Duration: 12 weeks

100 Participants Needed

What You Need to Know Before You Apply

What is the purpose of this trial?

This trial aims to test a new treatment, VH3810109, to determine if it can reduce the HIV viral reservoir, which acts as a hidden stash of the virus in the body. It will compare individuals new to HIV treatment with those on a stable HIV treatment plan. One group will receive VH3810109 with their current medication, while another group will receive VH3810109 with an additional drug called fostemsavir, an antiretroviral medication. Suitable candidates for this trial are adults living with HIV who have either never been treated or are already stably treated with specific HIV medications. As a Phase 1 trial, the research focuses on understanding how the treatment works in people, offering participants the opportunity to be among the first to receive this new treatment.

Will I have to stop taking my current medications?

If you are in Population 2, you must continue your current HIV treatment. However, if you are taking any prohibited medications, you will need to stop them at least 7 days before joining the study. The protocol does not specify other medications, so it's best to discuss with the study team.

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

Research has shown that VH3810109 is safe. In earlier studies, people with HIV-1 generally tolerated VH3810109 well. It effectively targeted the virus with few side effects. Participants were comfortable with both IV (through a vein) and SC (under the skin) doses, and no serious side effects were directly attributed to the treatment.

When combined with fostemsavir (FTR), the safety profile remains strong. This combination aims to reduce HIV virus levels without causing major safety concerns. Overall, current evidence supports the safe use of VH3810109, both alone and with FTR, for people living with HIV. ^{1 2 3 4 5}

Why are researchers excited about this trial's treatments?

Researchers are excited about VH3810109 for HIV infection because it offers a potentially new way to enhance current treatment regimens. Unlike standard options that primarily focus on blocking the virus's ability to integrate into the host DNA, VH3810109 may work by targeting different pathways, potentially offering a complementary mechanism of action. This approach could enhance the effectiveness of existing integrase strand transfer inhibitor (INSTI)-based antiretroviral therapies (ART), especially when paired with fostemsavir. By exploring these unique combinations, there is hope for improved outcomes for individuals living with HIV.

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

Research shows that VH3810109, which participants in this trial may receive, has strong effects against HIV-1. Studies found that it was well tolerated and effectively lowered virus levels in the body. This drug attaches to the CD4 site on the virus, making it harder for the virus to infect new cells. Regarding fostemsavir, another treatment option in this trial, research has shown that it can significantly reduce the amount of virus in the blood when used with other HIV treatments. Together, VH3810109 and fostemsavir might help reduce the hidden virus in the body, making it a promising approach for controlling HIV. ^{1 2 3 4 6}

Are You a Good Fit for This Trial?

Adults aged 18-70 with HIV, either treatment-naïve or on stable ART regimens. Treatment-naïve participants must have a CD4+ count ≥300 cells/μL and viral load ≥2000 copies/mL; those on ART should be virologically suppressed with a CD4+ count ≥450 cells/μL. Exclusions include pregnancy, risk of cardiovascular disease, other significant health issues, or recent use of certain medications.

Inclusion Criteria

Population 2: CD4+ T cell count >=450 cells/μL at Screening

Population 1: Plasma HIV-1 RNA >=2000 copies/milliliter (c/mL) at Screening

Population 1: CD4+ T cell count >=300 cells/microliter (μL) at Screening

Exclusion Criteria

Participants who are at clinically significant risk of cardiovascular disease

Participant is pregnant, breastfeeding, or planning to become pregnant or breastfeed during the study

Participant is known to have acquired HIV via perinatal transmission

Timeline for a Trial Participant

Screening

Participants are screened for eligibility to participate in the trial

2-4 weeks

Treatment

Participants receive VH3810109 with or without Fostemsavir in combination with integrase inhibitor-based ART

12 weeks

Follow-up

Participants are monitored for safety and effectiveness after treatment

4 weeks

What Are the Treatments Tested in This Trial?

Interventions

• Fostemsavir (FTR)
• VH3810109

Trial Overview The trial is testing VH3810109 alone or combined with Fostemsavir to shrink the HIV viral reservoir in two groups: one new to treatment and another already taking standard antiretroviral therapy. The goal is to see if these drugs can further reduce the virus's presence and activity in the body.

How Is the Trial Designed?

Group I: Participants receiving SOC INSTI-based ART plus VH3810109 plus FTR Experimental Treatment 3 Interventions

Group II: Participants receiving SOC INSTI-based ART plus VH3810109 Experimental Treatment 2 Interventions

Group III: Participants receiving standard of care (SOC) integrase strand transfer inhibitor (INSTI)-based ART Active Control 1 Intervention

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

Citations

1. pubmed.ncbi.nlm.nih.gov pubmed.ncbi.nlm.nih.gov/40892985/

VH3810109 Efficacy, Safety, Pharmacokinetics, and ... Conclusions: N6LS was efficacious and generally safe, supporting further development of N6LS dosed IV or SC for the treatment of HIV-1 ( ...

2. academic.oup.com academic.oup.com/jid/advance-article/doi/10.1093/infdis/jiaf450/8246221

VH3810109 Efficacy, Safety, Pharmacokinetics, and Incidence ... In the BANNER study, VH3810109 (N6LS) demonstrated robust dose-dependent antiviral activity and was well tolerated in people with HIV-1, ...

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

VH3810109 Health Professional Drug Record | NIH VH3810109 has been studied for HIV prevention and is also being developed as a possible component to HIV treatment or cure.1,3,11. Half-life (T½). A Phase 1 ...

4. journals.asm.org journals.asm.org/doi/10.1128/aac.00258-25

VH3810109 (N6LS) broadly neutralizing antibody safety ... The CD4-binding site antibody VH3810109 (N6LS) demonstrated broad and potent neutralization activity in vitro and robust antiviral activity ...

5. 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 ...

6. clinicaltrials.gov clinicaltrials.gov/study/NCT07053384

NCT07053384 | A Study to Investigate the Use of ... This study investigates the use of VH3810109 with or without FTR to reduce the size and activity of the HIV viral reservoir in two sub-populations of people ...