Adding fostemsavir to reduce inflammation in people with well-controlled HIV

Reducing Systemic Inflammation in People on Antiretroviral Therapy

This trial will test whether adding fostemsavir to current HIV treatment lowers inflammation and heart disease risk for people with well-controlled HIV who have detectable sgp120.

Quick facts

• Phase: Phase 2
• Study type: Interventional
• Enrollment: 150 (estimated)
• Ages: 18 Years and up
• Sex: All
• Sponsor: Centre hospitalier de l'Université de Montréal (CHUM) (Academic / other)
• Drugs / interventions: radiation
• Locations: 1 site (Montreal, Quebec)
• Trial ID: NCT07030920 on ClinicalTrials.gov

What this trial studies

This is a randomized, open-label Phase 2b trial comparing the addition of fostemsavir (600 mg daily) to participants' existing antiretroviral therapy versus continuing standard care alone over 24 months. Eligible participants are people living with HIV who have undetectable plasma viral load, detectable soluble gp120 (sgp120), and at least one cardiovascular risk factor. Outcomes include imaging measures (such as perivascular fat attenuation index and uncalcified plaque volume), blood biomarkers of inflammation and immune activation, and clinical cardiovascular endpoints. The trial is led by Centre hospitalier de l'Université de Montréal (CR CHUM) with academic collaborators and will enroll participants at the Montreal site.

Who should consider this trial

Good fit: Ideal candidates are people living with HIV on antiretroviral therapy who have an undetectable viral load (<50 copies/ml), detectable plasma sgp120, are aged 40 or older (or have lived with HIV for 25+ years), and have at least one cardiovascular risk factor.

Not a fit: Patients without detectable sgp120, those with uncontrolled HIV viral load, or those without cardiovascular risk factors are less likely to benefit from this intervention.

Why it matters

Potential benefit: If successful, adding fostemsavir could reduce chronic inflammation and lower cardiovascular disease risk in people with well-controlled HIV who have detectable sgp120.

How similar studies have performed: Fostemsavir is an approved antiretroviral for treatment-experienced patients, but using it specifically to reduce inflammation and cardiovascular risk is a novel application with limited direct prior evidence.

Eligibility criteria

Inclusion Criteria:

* 40 years or older, or have lived with HIV for 25 years or more, any sex;
* Undetectable HIV viral load (defined as last viral load measurement less than 50 copies/ml within the last 6 months);
* Presence of at least one cardiovascular risk factor among the following: longstanding HIV infection (25 years or more), hypertension, diabetes, past or present smoking, dyslipidemia, family history of early onset CVD in a first-degree relative (defined as younger than 55 in males or younger than 65 in females (80)), known previous cardiovascular disease (defined as past myocardial infarction, coronary revascularization, stroke, or coronary artery atherosclerosis with \>= 50% stenosis demonstrated on coronary angiography or CCTA);
* Participants with past cardiovascular disease must be in a stable clinical condition as judged by the study clinicians;
* Past cardiovascular events are defined as having occurred at least 3 months before screening;
* 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;
* Concomitant treatment with strong cytochrome P450 (CYP3A) inducers, including but not limited to: carbamazepine, phenytoin (anticonvulsants), mitotane (antineoplastic), enzalutamide (androgen receptor inhibitor), rifampicin (antimycobacterial) and St John's wort (Hypericum perforatum, herbal supplement);
* Planning to become pregnant, pregnant, or breastfeeding (as requested per product monography (55)). Females of childbearing potential must have a negative pregnancy test at baseline visit, and follow contraception requirements throughout the treatment;
* Contraindication for CT scan use (estimated glomerular filtration rate \[eGFR\] less than 40ml/min using the Modification of Diet in Renal Diseases \[MDRD\] formula or iodine allergy);
* Elevated risk of prior ionizing radiation exposure outside clinical care exceeding 10 mSV over 3 years, per the investigator's judgement (eg. a participant with occupational ionizing radiation exposure, prior participation in clinical trials with multiple CT scans)
* Confirmed uncorrected QT value \>500ms or confirmed QTcF \>470 msec for women and \>450 msec for men;
* Acquired/ congenital long QT syndrome;
* Current or anticipated treatment with any of the following medications: amiodarone, disopyramide, dofetilide, ibutilide, procainamide, sotalol, and quinidine;
* Unstable liver disease (as defined by any of the following: presence of ascites, encephalopathy, coagulopathy (INR \> 2.0), hypoalbuminemia (\<30 mg/ml), untreated esophageal or gastric varices, or persistently elevated bilirubinemia (\>1.5x upper limit of normal \[ULN\]), known biliary abnormalities (except Gilbert's syndrome or asymptomatic gallstones or otherwise stable chronic liver disease per investigator assessment);
* ALT \>=5 times the ULN, OR ALT \>=3xULN and bilirubin \>=1.5xULN with \>35% direct bilirubin;
* History of liver cirrhosis with CHILD-PUGH classification C;
* Inability to provide informed consent;
* Life expectancy of less than 36 months;
* Inability to present to study visits;
* Participation in another interventional trial;
* Known Congestive heart failure with NYHA class 3 or 4.

Where this trial is running

Montreal, Quebec

• Cr Chum — Montreal, Quebec, Canada (Recruiting)

Study contacts

• Principal investigator: Madeleine Durand, MD MSc FRCPC — Cr Chum
• Study coordinator: Branka Vulesevic, TRIAL MANAGER

Conditions Human Immunodeficiency Virus; Cardiovascular Risk Factor; Fostemsavir; Rukobia; sgp120; Perivascular fat attenuation index; uncalcified plaque volume; Systemic inflammation