Ignite Creation Date:
2025-12-25 @ 4:07 AM
Ignite Modification Date:
2025-12-26 @ 3:04 AM
Study NCT ID:
NCT07030920
Status:
RECRUITING
Last Update Posted:
2025-11-19
First Post:
2025-06-05
Is NOT Gene Therapy:
False
Has Adverse Events:
False
Brief Title:
Reducing Systemic Inflammation in People on Antiretroviral Therapy
Sponsor:
Centre hospitalier de l'Université de Montréal (CHUM)
Organization:
Study Overview
Official Title:
Reducing Systemic Inflammation in People on Antiretroviral Therapy
Status:
RECRUITING
Status Verified Date:
2025-11
Last Known Status:
None
Delayed Posting:
No
If Stopped, Why?:
Not Stopped
Has Expanded Access:
False
If Expanded Access, NCT#:
N/A
Has Expanded Access, NCT# Status:
N/A
Acronym:
RESTART
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.
Detailed Description:
A randomized, controlled trial of fostemsavir versus standard of care to curb comorbidity in people with well-controlled HIV. (Phase IIb study)
Background and hypothesis: People living with HIV, even when treated with antiretrovirals, develop early onset comorbidities such as cardiovascular disease, cognitive decline and frailty. In a subset of those, this could be due to residual viral particles driving chronic inflammation. Soluble glycoprotein 120 (sgp120) is detectable in close to a third of people living with HIV with undetectable HIV plasma viral loads. It is associated to increased inflammation and immune dysfunction.
People living with HIV with undetectable viral load but detectable soluble HIV gp120 (sgp120) are exposed to chronic inflammation, sustained immune dysfunction, and increased risk of comorbidity. The investigators hypothesize that the addition of fostemsavir, which has been shown to prevents the binding of sgp120 to the human CD4 receptor, to reduce cytokine burst and antibody-dependant cellular citotoxicity, decreased inflammation and immune dysfunction, leading to improved health.
Study population: People living with HIV on antiretroviral therapy, with undetectable viral load and detectable plasmatic sgp120.
Study intervention: The intervention will be either the addition of fostemsavir (Rukobia 600 mg daily) for 24 months to the patient's current ART regimen, or standard of care, which includes the continuation of the ARV regimen and other medications prescribed by their physicians.
Randomization: This is a randomized, open label study with blind outcome adjudication. 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.
Treatment groups:
Arm 1 (active):
* Once daily oral administration (600 mg extended-release tablet) for 24 months Arm 2 (Standard of care)
* Participants will continue to follow their current ART regimen, as well as other medications prescribed by their treating physician throughout the trial
Study procedures: At baseline, participants will undergo a CCTA, grip strenght, a B-CAM (online cognitive testing) and contribute blood to the study biobank. Participants will be randomized during the baseline visit, and those randomized to fostemsavir will start taking study treatment. Visits will be done at month 1, 6, 12, 18, 24 and 27. The duration of treatment will be 24 months. At month 24, the CCTA, grip strenght and cognition measures will be repeated. Participants will contribute to the biobank at each study visit.
Study outcomes:
Primary Outcome: Change in total uncalcified plaque volume between baseline and month 24, contrasted between fostemsavir and standard of care.
Imaging Secondary Outcome: Perivascular fat attenuation index at month 24, adjusted for baseline values.
Clinical Secondary Outcome: Clinical events - time to major adverse cardiovascular event, B-CAM (cognition testing) and grip strength at month 24 (adjusted for baseline values).
Biomarker Secondary Outcomes: Biomarkers identified in biobanking samples (virology, immunology, inflammation).
Safety Secondary Outcomes: Risk of adverse events and incidence of treatment discontinuation due to side effects.
A biomarker interim analysis will be performed when 50% of the planned samples size will have completed 1 year of follow-up. Pre-specified biomarker outcomes will be measured using the study-associated biobank.
The intervention will be either the addition of fostemsavir (Rukobia 600 mg daily) to the patient's current ART regimen, or the participant receiving the standard of care.
Statistical considerations:
The planned sample size is 150 (approxiimately 75 per arrm. ) Statistical analysis will be conducted by CITADEL (CRCHUM) after the closing of the study database, according to the statistical analysis plan, which will be registered before the analysis is conducted. All analyses will be done by intention-to-treat; patients will be analyzed in the group they were randomized to. Biobank analyses planned after 50% of participants completed the 12 months biobanking will be done by CITADEL after this part of the data collection is closed.
Background and hypothesis: People living with HIV, even when treated with antiretrovirals, develop early onset comorbidities such as cardiovascular disease, cognitive decline and frailty. In a subset of those, this could be due to residual viral particles driving chronic inflammation. Soluble glycoprotein 120 (sgp120) is detectable in close to a third of people living with HIV with undetectable HIV plasma viral loads. It is associated to increased inflammation and immune dysfunction.
People living with HIV with undetectable viral load but detectable soluble HIV gp120 (sgp120) are exposed to chronic inflammation, sustained immune dysfunction, and increased risk of comorbidity. The investigators hypothesize that the addition of fostemsavir, which has been shown to prevents the binding of sgp120 to the human CD4 receptor, to reduce cytokine burst and antibody-dependant cellular citotoxicity, decreased inflammation and immune dysfunction, leading to improved health.
Study population: People living with HIV on antiretroviral therapy, with undetectable viral load and detectable plasmatic sgp120.
Study intervention: The intervention will be either the addition of fostemsavir (Rukobia 600 mg daily) for 24 months to the patient's current ART regimen, or standard of care, which includes the continuation of the ARV regimen and other medications prescribed by their physicians.
Randomization: This is a randomized, open label study with blind outcome adjudication. 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.
Treatment groups:
Arm 1 (active):
* Once daily oral administration (600 mg extended-release tablet) for 24 months Arm 2 (Standard of care)
* Participants will continue to follow their current ART regimen, as well as other medications prescribed by their treating physician throughout the trial
Study procedures: At baseline, participants will undergo a CCTA, grip strenght, a B-CAM (online cognitive testing) and contribute blood to the study biobank. Participants will be randomized during the baseline visit, and those randomized to fostemsavir will start taking study treatment. Visits will be done at month 1, 6, 12, 18, 24 and 27. The duration of treatment will be 24 months. At month 24, the CCTA, grip strenght and cognition measures will be repeated. Participants will contribute to the biobank at each study visit.
Study outcomes:
Primary Outcome: Change in total uncalcified plaque volume between baseline and month 24, contrasted between fostemsavir and standard of care.
Imaging Secondary Outcome: Perivascular fat attenuation index at month 24, adjusted for baseline values.
Clinical Secondary Outcome: Clinical events - time to major adverse cardiovascular event, B-CAM (cognition testing) and grip strength at month 24 (adjusted for baseline values).
Biomarker Secondary Outcomes: Biomarkers identified in biobanking samples (virology, immunology, inflammation).
Safety Secondary Outcomes: Risk of adverse events and incidence of treatment discontinuation due to side effects.
A biomarker interim analysis will be performed when 50% of the planned samples size will have completed 1 year of follow-up. Pre-specified biomarker outcomes will be measured using the study-associated biobank.
The intervention will be either the addition of fostemsavir (Rukobia 600 mg daily) to the patient's current ART regimen, or the participant receiving the standard of care.
Statistical considerations:
The planned sample size is 150 (approxiimately 75 per arrm. ) Statistical analysis will be conducted by CITADEL (CRCHUM) after the closing of the study database, according to the statistical analysis plan, which will be registered before the analysis is conducted. All analyses will be done by intention-to-treat; patients will be analyzed in the group they were randomized to. Biobank analyses planned after 50% of participants completed the 12 months biobanking will be done by CITADEL after this part of the data collection is closed.
Study Oversight
Has Oversight DMC:
True
Is a FDA Regulated Drug?:
False
Is a FDA Regulated Device?:
False
Is an Unapproved Device?:
None
Is a PPSD?:
None
Is a US Export?:
None
Is an FDA AA801 Violation?:
Secondary ID Infos
| Secondary ID | Type | Domain | Link | View |
|---|---|---|---|---|
| II2-195573 | OTHER_GRANT | Canadian Institutes of Heallth Research | View |