Fostemsavir for HIV Infection

Recruiting at 13 trial locations

Overseen By Alessandra Nardone

Age: < 18

Sex: Any

Trial Phase: Phase 1 & 2

Sponsor: PENTA Foundation

Must be taking: Antiretrovirals

Disqualifiers: Hepatitis B, HIV-2, liver disease, others

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

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

Compensation: Varies

Number of Visits: Unknown

Duration: 48 weeks

60 Participants Needed

What You Need to Know Before You Apply

What is the purpose of this trial?

This trial tests a new HIV treatment called Fostemsavir in children and teens whose HIV no longer responds well to other treatments. The goal is to assess the safety and effectiveness of Fostemsavir when combined with other HIV medications. The trial also examines whether children and teens can easily take the medication and if it helps reduce the virus in their bodies. Potential participants include children and teens with HIV who face drug resistance issues and struggle with their current treatment plan. As a Phase 1, Phase 2 trial, this research aims to understand how the treatment works in people and measure its effectiveness in an initial, smaller group.

Do I need to stop my current medications to join the trial?

The trial protocol does not specify if you must stop taking your current medications, but it mentions that certain medications are prohibited or restricted. You should discuss your current medications with the study team to see if they are allowed.

Is there any evidence suggesting that Fostemsavir is likely to be safe for humans?

Research has shown that fostemsavir is generally safe for people with HIV, including those with drug-resistant strains. Studies indicate that fostemsavir is well-tolerated over extended periods. For instance, in one study, participants took fostemsavir for nearly five years, and it remained safe for them. Most side effects were mild, such as headaches or nausea.

The FDA has approved fostemsavir for treating some adults with HIV, which increases confidence in its safety, even though this trial focuses on children and teens. In summary, early data suggest fostemsavir is a safe option for treating HIV in individuals who have not had success with other drugs. ^{1 2 3 4 5}

Why do researchers think this study treatment might be promising?

Fostemsavir is unique because it works by targeting the HIV-1 virus differently than most current treatments. While standard options often aim to inhibit enzymes like reverse transcriptase or protease, fostemsavir blocks the virus from attaching to and entering host cells, thanks to its action as an attachment inhibitor. Researchers are excited about fostemsavir because it is specifically designed for patients, including children and adolescents, who are resistant to multiple classes of antiretroviral drugs, offering hope to those who have limited treatment options.

What evidence suggests that Fostemsavir might be an effective treatment for HIV?

Research has shown that fostemsavir effectively treats HIV-1 infections resistant to many other drugs. In one study, a treatment plan using fostemsavir significantly lowered the viral load in 144 out of 272 patients, reducing the virus in their blood to very low levels. Another study found that fostemsavir brought life-changing results for patients with limited treatment options, greatly improving their immune system health. The BRIGHTE study reported a strong increase in CD4+ cell counts, crucial for a healthy immune system. These findings suggest fostemsavir can be a powerful treatment option for those with resistant forms of HIV. Participants in this trial will receive fostemsavir combined with optimized background therapy (OBT) to evaluate its effectiveness in HIV-1 infected children and adolescents who are failing their current combination antiretroviral therapy (cART) and have dual- or triple-class ARV resistance. ^{1 2 5 6 7}

Are You a Good Fit for This Trial?

This trial is for HIV-1 infected children and adolescents aged 6 to less than 18 years, weighing at least 20 kg, who are failing their current antiretroviral therapy with documented resistance to multiple drug classes. Participants must have a viral load ≥1000 c/mL and access to at least one fully active antiviral agent in two or more classes. Girls post-menarche must not be pregnant or breastfeeding and agree to use contraception.

Inclusion Criteria

I have HIV and my treatment history shows resistance to drugs from at least two different classes.

My current treatment is not working according to recent tests.

I am not pregnant, breastfeeding, and if sexually active, I agree to use effective birth control.

Exclusion Criteria

Platelets < 50,000 cells/mm3

Hemoglobin < 8.0 g/dL

I cannot take pills as required for the study.

Timeline for a Trial Participant

Screening

Participants are screened for eligibility to participate in the trial

2-4 weeks

Treatment

Participants receive Fostemsavir in combination with optimized background therapy (OBT) to assess safety, pharmacokinetics, and antiviral activity

48 weeks

Regular visits for monitoring and dose adjustments

Follow-up

Participants are monitored for safety and effectiveness after treatment

4 weeks

Long-term follow-up

Participants are monitored for long-term efficacy and safety, including changes in CD4+ T cell counts

up to 156 weeks

What Are the Treatments Tested in This Trial?

Interventions

• Fostemsavir

Trial Overview The SHIELD study tests the safety, pharmacokinetics (how the body processes the drug), and anti-HIV activity of Fostemsavir plus optimized background therapy in youths resistant to standard treatments. It also evaluates how well kids can take this new formulation based on adult studies showing effectiveness.

How Is the Trial Designed?

Group I: Fostemsavir Experimental Treatment 1 Intervention

Fostemsavir in combination with optimized background therapy (OBT) in HIV-1 infected children and adolescents who are failing their current combination antiretroviral therapy (cART) and have dual- or triple-class ARV resistance

Who Is Running the Clinical Trial?

PENTA Foundation

Lead Sponsor

Trials

35

Recruited

38,400+

ViiV Healthcare

Industry 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

PHPT Foundation

Collaborator

Trials

1

Recruited

60+

Hospital Universitario 12 de Octubre

Collaborator

Trials

87

Recruited

49,300+

Cromsource

Industry Sponsor

Trials

18

Recruited

3,200+

Published Research Related to This Trial

In a Phase 1 study with 14 healthy participants, co-administration of fostemsavir and maraviroc led to a 25% increase in maraviroc's plasma concentration over time, indicating a potential interaction, but without significant clinical implications.

The study concluded that fostemsavir and maraviroc can be safely co-administered without requiring dose adjustments, ensuring effective treatment for patients with multidrug-resistant HIV-1.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Evaluation of the pharmacokinetic drug-drug interaction between the antiretroviral agents fostemsavir and maraviroc: a single-sequence crossover study in healthy participants. Wire, MB., Magee, M., Ackerman, P., et al.[2022]

Fostemsavir, an attachment inhibitor for HIV-1, demonstrated a virological response rate of 61-82% in treatment-experienced patients after 48 weeks, comparable to 71% for the standard treatment (ritonavir-boosted atazanavir).

The treatment was generally well tolerated, with no adverse events leading to discontinuation, indicating its safety for patients with limited treatment options.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Safety and efficacy of the HIV-1 attachment inhibitor prodrug fostemsavir in antiretroviral-experienced subjects: week 48 analysis of AI438011, a Phase IIb, randomized controlled trial. Thompson, M., Lalezari, JP., Kaplan, R., et al.[2018]

Fostemsavir is the first FDA and EMA-approved attachment inhibitor for HIV-1, specifically designed for heavily-treatment-experienced individuals with multi-drug resistant HIV-1, highlighting its importance in expanding treatment options for this high-risk population.

The review discusses fostemsavir's mechanism of action, pharmacodynamics, pharmacokinetics, and its efficacy and safety, emphasizing its role in suppressing HIV-1 replication and improving the quality of life for patients who have failed previous antiretroviral therapies.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Efficacy and Safety Profile of Fostemsavir for the Treatment of People with Human Immunodeficiency Virus-1 (HIV-1): Current Evidence and Place in Therapy. Muccini, C., Canetti, D., Castagna, A., et al.[2022]

Fostemsavir, the first oral attachment inhibitor for HIV-1, has shown clinical efficacy in heavily treatment-experienced adults, making it a promising option for those with multidrug-resistant HIV-1 infections.

The drug is generally well-tolerated, with common side effects including nausea and headache, and it can be taken with acid suppressive agents, but caution is needed when coadministering with strong CYP3A inducers to avoid reduced effectiveness.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Fostemsavir: The first oral attachment inhibitor for treatment of HIV-1 infection. Chahine, EB.[2021]

Fostemsavir, a first-in-class HIV-1 attachment inhibitor, has been shown to be highly potent against most HIV-1 subtypes, with the majority of isolates exhibiting IC50 values below 10 nM, indicating strong efficacy in preventing HIV-1 infection.

The study analyzed 1337 HIV-1 isolates and found that temsavir's effectiveness is consistent across different tropisms (CCR5, CXCR4, and dual mixed-tropic), suggesting that its mechanism of action is broadly applicable regardless of the virus's entry pathway.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Susceptibility of global HIV-1 clinical isolates to fostemsavir using the PhenoSense® Entry assay. Gartland, M., Zhou, N., Stewart, E., et al.[2021]

In a phase 3 trial involving 371 patients with multidrug-resistant HIV-1, fostemsavir significantly reduced HIV-1 RNA levels compared to placebo, with a mean decrease of 0.79 log10 copies per milliliter versus 0.17 log10 copies (P<0.001) after 8 days.

At 48 weeks, 54% of patients in the randomized cohort achieved a virologic response (HIV-1 RNA <40 copies/mL), demonstrating sustained efficacy of fostemsavir, although 7% of patients discontinued due to adverse events.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Fostemsavir in Adults with Multidrug-Resistant HIV-1 Infection. Kozal, M., Aberg, J., Pialoux, G., et al.[2020]

Fostemsavir, an attachment inhibitor for HIV-1, was tested in a phase 2b trial with 251 treatment-experienced subjects, showing similar response rates to ritonavir-boosted atazanavir despite some subjects developing resistance to raltegravir.

While fostemsavir led to more frequent changes in viral susceptibility compared to atazanavir, some patients still achieved viral suppression below detectable levels, indicating potential efficacy even with emergent gp120 substitutions.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Viral Drug Resistance Through 48 Weeks, in a Phase 2b, Randomized, Controlled Trial of the HIV-1 Attachment Inhibitor Prodrug, Fostemsavir. Lataillade, M., Zhou, N., Joshi, SR., et al.[2020]

Fostemsavir is an FDA-approved HIV-1 attachment inhibitor that effectively prevents the virus from attaching to the CD4 receptor, making it a novel treatment option for patients with multidrug-resistant HIV-1.

Clinical trials show that fostemsavir is well tolerated and, when used with optimal background therapy, leads to virologic suppression in many heavily treatment-experienced individuals, highlighting its potential as a valuable addition to HIV treatment regimens.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Fostemsavir: a first-in-class HIV-1 attachment inhibitor. Grant, PM., Kozal, MJ.[2023]

Citations

1. pmc.ncbi.nlm.nih.gov pmc.ncbi.nlm.nih.gov/articles/PMC8183480/

Long-term efficacy and safety of fostemsavir among ... In the Randomized Cohort, treatment with fostemsavir plus OBT resulted in a virologic response (HIV-1 RNA <40 copies/ml by Snapshot analysis) in 144 out of 272 ...

2. nejm.org nejm.org/doi/full/10.1056/NEJMoa1902493

Fostemsavir in Adults with Multidrug-Resistant HIV-1 Infection A total of 371 patients were treated, including 272 in the randomized cohort and 99 in the nonrandomized cohort. At day 8, the mean decrease in ...

3. thelancet.com thelancet.com/journals/lanhiv/article/PIIS2352-3018(20)30240-X/fulltext

week 96 results of the phase 3 BRIGHTE study Fostemsavir-based regimens in the BRIGHTE study were life-changing for participants living with multidrug-resistant HIV-1, most of whom had AIDS. ... There is ...

4. academic.oup.com academic.oup.com/ofid/article/11/9/ofae469/7741535

Inflammatory Biomarker Reduction With Fostemsavir Over 96 ... In the phase 3 BRIGHTE study, heavily treatment-experienced adults with multidrug-resistant HIV-1 had robust improvements in immune parameters and markers.

5. sciencedirect.com sciencedirect.com/science/article/pii/S0149291822001461

Comparative Efficacy and Safety of Fostemsavir in Heavily ... Through 96 weeks, results from the BRIGHTE trial showed sustained improvement in CD4+ cell count (mean [SD] increase = 205 [191] cells/mm3 in the randomized ...

6. rukobiahcp.com rukobiahcp.com/

MDR HIV-1 Treatment Option | RUKOBIA (fostemsavir) | HCP ... Learn more about RUKOBIA (fostemsavir) for MDR HIV-1, including key efficacy and safety data, dosing and drug interactions, and how to identify the right ...

7. frontiersin.org frontiersin.org/journals/immunology/articles/10.3389/fimmu.2024.1394644/full

Long-term safety and impact of immune recovery in heavily ... Analysis of long-term data over a median follow-up of 258 weeks in BRIGHTE shows that fostemsavir was well tolerated with a safety profile that was consistent ...