Reducing Systemic Inflammation in People on Antiretroviral Therapy

NCT07030920 | Recruiting Phase 2 DMC

• 2 other identifiers: MP-02-2025-12725II2-195573
• Study Type: interventional
• Target: 150
• Locations: 1 country
• Sites: 1

Brief Summary

This randomized, open-label clinical trial will evaluate whether adding fostemsavir to current antiretroviral therapy can reduce the risk of cardiovascular disease in people with well-controlled HIV. Researchers will compare imaging, clinical and biomarker outcomes between participants who receive fostemsavir in addition to their existing treatment and those who continue with standard care alone.

Conditions

Human Immunodeficiency Virus (HIV); Cardiovascular Risk Factor

Keywords

Fostemsavir; Rukobia; sgp120; Perivascular fat attenuation index (P-FAI); uncalcified plaque volume; Systemic inflammation; Cardiovascular Risk Factor

Outcome Measures

Primary Outcomes (1)

• Change in total uncalcified plaque volume between baseline and month 24

  The change in total uncalcified plaque volume between baseline and month 24 will be measured by coronary compted tomography angiography and contrasted between fostemsavir and standard of care

  From baseline to end of treatment (+ 24 months)

Secondary Outcomes (5)

• Imaging outcome: Perivascular fat attenuation index at month 24, adjusted for baseline values

  From baseline to end of treatment (+ 24 months)

• Time to Major Adverse cardiovascular Event (MACE)

  From baseline to post-treatment visit (+ 27 months)

• Risk of severe and serious adverse events

  From baseline to post-treatment visit (+ 27 months)

• Grip strength at 24 months, adjusted for baseline

  From baseline to end of treatment (+ 24 months)

• Brief Cognitive Ability Measure (B-CAM) scores at month 24, adjusted for baseline

  From baseline to end of treatment (+ 24 months)

Other Outcomes (1)

• Biological biomarkers of inflammation and immune dysfunction

  From screening (up to T0 - 6 months) to post-treatment visit (T0 + 27 months)

Study Arms (2)

Rukobia 600 mg daily

EXPERIMENTAL

Drug: Fostemsavir

Standard of care (SOC)

NO INTERVENTION

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

Interventions

Fostemsavir DRUG

Addition of fostemsavir to the patient's current antiretroviral regimen: once daily oral administration (Rukobia 600 mg extended-release tablets) for 24 months

Rukobia 600 mg daily

Eligibility Criteria

• Age: 18 Years+
• Sex: all
• Healthy Volunteers: No
• Age Groups: Adult (18-64), Older Adult (65+)

You may qualify if:

• 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.

You may not qualify if:

• 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;

Sponsors & Collaborators

• Centre hospitalier de l'Université de Montréal (CHUM): lead
• McGill University Health Centre/Research Institute of the McGill University Health Centre: collaborator
• Clinique du Quartier Latin: collaborator
• BC Women's Hospital & Health Centre: collaborator

Study Sites (1)

CR CHUM

Montreal, Quebec, H2X 0A9, Canada

RECRUITING

Related Publications (4)

• Benlarbi M, Richard J, Bourassa C, Tolbert WD, Chartrand-Lefebvre C, Gendron-Lepage G, Sylla M, El-Far M, Messier-Peet M, Guertin C, Turcotte I, Fromentin R, Verly MM, Prevost J, Clark A, Mothes W, Kaufmann DE, Maldarelli F, Chomont N, Begin P, Tremblay C, Baril JG, Trottier B, Trottier S, Duerr R, Pazgier M, Durand M, Finzi A. Plasma Human Immunodeficiency Virus 1 Soluble Glycoprotein 120 Association With Correlates of Immune Dysfunction and Inflammation in Antiretroviral Therapy-Treated Individuals With Undetectable Viremia. J Infect Dis. 2024 Mar 14;229(3):763-774. doi: 10.1093/infdis/jiad503.

  PMID: 38035854 BACKGROUND

• Richard J, Prevost J, Bourassa C, Brassard N, Boutin M, Benlarbi M, Goyette G, Medjahed H, Gendron-Lepage G, Gaudette F, Chen HC, Tolbert WD, Smith AB 3rd, Pazgier M, Dube M, Clark A, Mothes W, Kaufmann DE, Finzi A. Temsavir blocks the immunomodulatory activities of HIV-1 soluble gp120. Cell Chem Biol. 2023 May 18;30(5):540-552.e6. doi: 10.1016/j.chembiol.2023.03.003. Epub 2023 Mar 22.

  PMID: 36958337 BACKGROUND

• Durand M, Sheehy O, Baril JG, Lelorier J, Tremblay CL. Association between HIV infection, antiretroviral therapy, and risk of acute myocardial infarction: a cohort and nested case-control study using Quebec's public health insurance database. J Acquir Immune Defic Syndr. 2011 Jul 1;57(3):245-53. doi: 10.1097/QAI.0b013e31821d33a5.

  PMID: 21499115 BACKGROUND

• Durand M, Chartrand-Lefebvre C, Baril JG, Trottier S, Trottier B, Harris M, Walmsley S, Conway B, Wong A, Routy JP, Kovacs C, MacPherson PA, Monteith KM, Mansour S, Thanassoulis G, Abrahamowicz M, Zhu Z, Tsoukas C, Ancuta P, Bernard N, Tremblay CL; investigators of the Canadian HIV and Aging Cohort Study. The Canadian HIV and aging cohort study - determinants of increased risk of cardio-vascular diseases in HIV-infected individuals: rationale and study protocol. BMC Infect Dis. 2017 Sep 11;17(1):611. doi: 10.1186/s12879-017-2692-2.

  PMID: 28893184 BACKGROUND

MeSH Terms

Conditions

Acquired Immunodeficiency Syndrome

Interventions

fostemsavir

Condition Hierarchy (Ancestors)

HIV Infections; Blood-Borne Infections; Communicable Diseases; Infections; Sexually Transmitted Diseases, Viral; Sexually Transmitted Diseases; Lentivirus Infections; Retroviridae Infections; RNA Virus Infections; Virus Diseases; Slow Virus Diseases; Genital Diseases; Urogenital Diseases; Immunologic Deficiency Syndromes; Immune System Diseases

Study Officials

• Madeleine Durand, MD MSc FRCPC

  CR CHUM

  PRINCIPAL INVESTIGATOR

Central Study Contacts

Branka Vulesevic, TRIAL MANAGER

CONTACT

15148908000; branka.vulesevic.chum@ssss.gouv.qc.ca

Madeleine Durand, STUDY SPONSOR

CONTACT

madeleine.durand@umontreal.ca

Study Design

• Study Type: interventional
• Phase: phase 2
• Allocation: RANDOMIZED
• Masking: SINGLE
• Who Masked: OUTCOMES ASSESSOR
• Masking Details: This trial will be conducted as an open-label study; however, assessors of the primary outcome (based on two CCTA scans) and of the biobank analyses will remain blinded to treatment allocation, as well as statisticians.
• Purpose: TREATMENT
• Intervention Model: PARALLEL
• Sponsor Type: OTHER
• Responsible Party: SPONSOR

Model Details: Randomization will be done in a 1:1 ratio, with allocation in parallel arms, stratified by sex and participant statin use at recruitment, through a computerized algorithm with permuted blocks of randomly varying size, to ensure allocation concealment.

Study Record Dates

• First Submitted: June 5, 2025
• First Posted: June 22, 2025
• Study Start: September 30, 2025
• Primary Completion (Estimated): October 1, 2028
• Study Completion (Estimated): January 1, 2029
• Last Updated: November 19, 2025

Record last verified: 2025-11

Data Sharing

• IPD Sharing: Will not share

Locations

CA (1)