Fostemsavir for HIV Infection

Recruiting at 11 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?

In the SHIELD study, the study sponsor seeks to assess safety, PK and antiviral activity for children and adolescents with dual or triple class resistance. It will also assess the acceptability and swallowability of formulation among the pediatric population. The dose selection of FTR for children and adolescents ≥20kg utilized a population pharmacokinetic (POP PK) model-based approach to achieve similar adult TMR exposures following FTR 600mg BID administration with combination therapy that was demonstrated to be safe and effective in the FTR Phase 3 BRIGHTE study in HTE patients.

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 fostemsavir safe for humans?

Fostemsavir has been studied in clinical trials for people with HIV-1, and safety data from these trials suggest it is generally safe when used as part of a treatment plan for HIV-1 infection. ^{1 2 3 4 5}

How is the drug fostemsavir different from other HIV treatments?

Fostemsavir is unique because it is a first-in-class HIV-1 attachment inhibitor that works by binding to the virus's gp120 protein, preventing the virus from attaching to and entering human immune cells. This mechanism is different from other HIV treatments that typically target viral replication after the virus has entered the cell. ^{3 5 6 7 8}

What data supports the effectiveness of the drug Fostemsavir for HIV infection?

Fostemsavir is effective for people with HIV-1 who have tried many other treatments without success. It works by blocking the virus from attaching to immune cells, helping to control the infection and improve patients' health. ^{1 4 5 6 8}

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 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 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, 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]

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, 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, 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 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]

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]

Citations

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

Fostemsavir in Adults with Multidrug-Resistant HIV-1 Infection. [2020]

2. New Zealand 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. [2022]

3. United States 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. [2020]

4. England 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. [2022]

5. England pubmed.ncbi.nlm.nih.gov

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

6. England 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. [2018]

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

Fostemsavir: a first-in-class HIV-1 attachment inhibitor. [2023]

8. England pubmed.ncbi.nlm.nih.gov

Susceptibility of global HIV-1 clinical isolates to fostemsavir using the PhenoSense® Entry assay. [2021]