Fostemsavir for HIV/AIDS

(RESTART Trial)

Overseen By Madeleine Durand, STUDY SPONSOR

Age: 18+

Sex: Any

Trial Phase: Phase 2

Sponsor: Centre hospitalier de l'Université de Montréal (CHUM)

Must be taking: Antiretrovirals

Must not be taking: Anticonvulsants, Antineoplastic, Androgen inhibitors, others

Disqualifiers: Pregnancy, Liver disease, QT syndrome, 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: 2

Duration: 24 months

150 Participants Needed

What You Need to Know Before You Apply

What is the purpose of this trial?

This trial tests whether adding fostemsavir to current HIV treatments can reduce heart disease risk in individuals with well-managed HIV. Participants will be divided into two groups: one will continue their usual HIV treatment, while the other will add fostemsavir to their regimen. This study targets individuals with HIV who have not had a detectable viral load recently and possess at least one heart disease risk factor, such as high blood pressure, diabetes, or a history of smoking. As a Phase 2 trial, this research focuses on measuring the treatment's effectiveness in an initial, smaller group of people.

Will I have to stop taking my current medications?

The trial does not specify if you need to stop taking your current medications, but you cannot participate if you are taking certain drugs like strong CYP3A inducers or specific heart medications. It's best to 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 easy for people to take. In studies, individuals who used fostemsavir for about five years managed their HIV effectively. The medication is safe for most people, typically not causing serious side effects. Another study, which followed patients for about 258 weeks, also found it well-tolerated. While any medication can have side effects, fostemsavir has proven to be relatively safe for many over time. ^{1 2 3 4 5}

Why do researchers think this study treatment might be promising for HIV?

Fostemsavir is unique because it targets the HIV virus differently than most current treatments. While standard antiretroviral therapies (ART) typically block the virus from replicating, Fostemsavir binds to the virus itself, preventing it from entering human cells in the first place. This new mechanism of action could be a game-changer for patients who have developed resistance to existing treatments. Researchers are excited about Fostemsavir as it offers a promising option for those who have limited choices due to drug resistance.

What evidence suggests that fostemsavir might be an effective treatment for reducing cardiovascular disease risk in people with well-controlled HIV?

Research has shown that fostemsavir, administered as Rukobia 600 mg daily in this trial, can effectively lower HIV levels in the body. In one study, 59% of participants had very low HIV levels (less than 40 copies per milliliter) after 96 weeks of treatment. Another study found that the drug continued to work well for about five years. Fostemsavir prevents the virus from attaching to cells, helping to stop its spread. This makes it a promising option for people with HIV who have limited treatment choices. ^{1 2 3 4 6}

Who Is on the Research Team?

Madeleine Durand, MD MSc FRCPC

Principal Investigator

CR CHUM

Are You a Good Fit for This Trial?

This trial is for people over 40 with well-controlled HIV and a history of cardiovascular issues or risk factors like hypertension, diabetes, smoking, dyslipidemia, or family history of early CVD. They must have an undetectable viral load and not be pregnant, breastfeeding, or planning pregnancy. Those with severe heart failure, liver disease, long QT syndrome or taking certain drugs can't join.

Inclusion Criteria

Undetectable HIV viral load (defined as last viral load measurement less than 50 copies/ml within the last 6 months)

Participants with past cardiovascular disease must be in a stable clinical condition as judged by the study clinicians

Evidence of detectable plasmatic sgp120 levels at any point in the past year, using the assay described priorly and performed at CRCHUM in Dr Andrés Finzi's laboratory

Exclusion Criteria

Known allergy to study drug

I am unable to understand or sign the consent form.

Participation in another interventional trial

Timeline for a Trial Participant

Screening

Participants are screened for eligibility to participate in the trial

up to 6 months

Treatment

Participants receive either fostemsavir in addition to their current ART regimen or continue with standard care for 24 months

24 months

Visits at month 1, 6, 12, 18, 24, and 27

Follow-up

Participants are monitored for safety and effectiveness after treatment

3 months

1 visit (in-person) at month 27

What Are the Treatments Tested in This Trial?

Interventions

• Fostemsavir

Trial Overview The study tests if adding Fostemsavir to existing antiretroviral therapy reduces cardiovascular disease risk in HIV-positive individuals. It compares the health outcomes between those receiving Fostemsavir and those on standard care by using imaging techniques and biomarker analysis.

How Is the Trial Designed?

Group I: Rukobia 600 mg daily Experimental Treatment 1 Intervention

Group II: Standard of care (SOC) Active Control 1 Intervention

Participants will continue to follow their current ART regimen, as well as other medications prescribed by their treating physician throughout the trial

Who Is Running the Clinical Trial?

Centre hospitalier de l'Université de Montréal (CHUM)

Lead Sponsor

Trials

389

Recruited

143,000+

BC Women's Hospital & Health Centre

Collaborator

Trials

15

Recruited

1,010,000+

McGill University Health Centre/Research Institute of the McGill University Health Centre

Collaborator

Trials

476

Recruited

170,000+

Clinique du Quartier Latin

Collaborator

Trials

1

Recruited

40+

Citations

1. viivhealthcare.com viivhealthcare.com/en-us/media-center/news/press-releases/2022/july/viiv-healthcare-presents-positive-five-year-data-at-aids/

ViiV Healthcare presents positive five-year data at AIDS ... People living with multidrug-resistant HIV-1 treated for approximately five years with fostemsavir-based regimens experienced durable virologic responses.

2. 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 ...

3. rukobiahcp.com rukobiahcp.com/clinical-trial-and-efficacy/

Clinical Trial & Efficacy | RUKOBIA (fostemsavir) Virologic outcomes (HIV-1 RNA <40 copies/mL) by subgroup (randomized cohort, ITT–E population, Snapshot algorithm) at Week 96: Male, 59% (118/200); female ...

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

week 96 results of the phase 3 BRIGHTE study This report provides long-term data (through 96 weeks) on the safety and efficacy of fostemsavir, a first-in-class attachment inhibitor, in heavily treatment- ...

5. rukobia.com rukobia.com/about-rukobia/rukobia-study/

RUKOBIA Study | RUKOBIA (fostemsavir) Official Website RUKOBIA, with other medications, helped reduce the HIV viral load for people with no or limited options left* · 89% had a viral load of >1000 copies/mL · 75% had ...

6. 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 ...