This study has been transitioned to CTIS with ID 2024-515893-29-01 check the CTIS register for the current data. To study whether ziltivekimab therapy reduces arterial wall inflammation as assessed by imaging, and reduces the systemic inflammatory…
ID
Source
Brief title
Condition
- Coronary artery disorders
- Arteriosclerosis, stenosis, vascular insufficiency and necrosis
Synonym
Research involving
Sponsors and support
Intervention
Outcome measures
Primary outcome
The main outcome is the mean percentage change in coronary arteries target to
background ratio (TBRmax) and monocyte activation marker protein expression
between the treatment and placebo group, at the primary analysis time point of
20 weeks, compared to baseline.
Secondary outcome
Imaging:
• Difference in PCAT (CCTA derived) after ziltivekimab treatment.
• Correlation between changes in coronary 68Ga-DOTATATE uptake and anatomical
plaque changes on CCTA.
• Difference in 68Ga-DOTATATE SUVmax of bone marrow and spleen after treatment.
• Difference in 68Ga-DOTATATE TBRmax of ascending aorta after treatment.
Inflammation and proteomics:
• The impact of ziltivekimab on monocyte phenotype in transendothelial
migration (TEM) capacity and transcriptome profile.
• The mean percentage change in plasmatic proteins before and after
ziltivekimab treatment.
• The impact of ziltivekimab on inflammation in plasma cytokine and chemokine
levels.
Background summary
Inflammation is an important component in atherogenesis. The pro-inflammatory
cytokine interleukin-6 (IL-6) is a pivotal factor in plaque development and
rupture. Elevated IL-6 levels lead to more arterial wall inflammation and an
increased atherosclerotic cardiovascular disease (ASCVD) risk.
Ziltivekimab is a novel human monoclonal antibody targeting the IL-6 ligand and
is in development for ASCVD risk attenuation. Although the safety and efficacy
of ziltivekimab has been studied, the mechanistic effects on atherosclerotic
plaques and inflammatory pathways have not been investigated in humans to date.
In this study, we aim to unravel the effect of ziltivekimab on arterial wall
inflammation and systemic inflammatory tone. The insights will be vital for the
future selection of patients that will benefit from ziltivekimab and for the
further development of anti-inflammatory therapies for ASCVD.
Study objective
This study has been transitioned to CTIS with ID 2024-515893-29-01 check the CTIS register for the current data.
To study whether ziltivekimab therapy reduces arterial wall inflammation as
assessed by imaging, and reduces the systemic inflammatory tone as assessed by
circulating monocytes, inflammatory biomarkers and proteomics.
Study design
This study is designed as a randomized, double blind, placebo-controlled trial.
Intervention
Ziltivekimab 15 mg or placebo, subcutaneously delivered using a manual syringe,
once per every four weeks, for a total of 20 weeks (6 administrations).
Study burden and risks
Participants will be randomized to either ziltivekimab or placebo and will be
subjected to imaging scans and blood withdrawals. To date, ziltivekimab
administration has proven safe and well-tolerated. In theory, a modest increase
in infectious disease susceptibility may occur. The study will require a
maximum of eight study visits. The blood withdrawal will total 233 ml. The
radiation exposure from two 68Ga-DOTATATE PET/CT and two coronary CT
angiography (CCTA) scans is maximally estimated at 9.5 mSv. Awaiting the
ongoing cardiovascular outcome trial with ziltivekimab in secondary prevention
patients, the participating patients will likely not experience direct clinical
benefit by anti-inflammatory therapy, but they will contribute to the current
knowledge of a potential effective treatment option.
Meibergdreef 9
Amsterdam 1105 AZ
NL
Meibergdreef 9
Amsterdam 1105 AZ
NL
Listed location countries
Age
Inclusion criteria
- Aged 50 years and older.
- Multi-vessel coronary artery disease (defined as CAD-RADS >=2 and/or PAV/NCPV
stage >=2).
- Serum hsCRP level >=2 mg/L.
Exclusion criteria
- Coronary stents in situ.
- Chronic or recent (<1 month) (serious) infections and/or clinical signs of
acute (serious) infection.
- History of severe auto-immune diseases, or other (severe) (recurrent or
chronic) inflammatory disorders.
- Untreated latent tuberculosis, active hepatitis B (positive HBsAg and/or
positive anti-HBc with detectable HBV DNA) or C, human immunodeficiency virus
(HIV) not on stable antiretroviral regimen
Design
Recruitment
Medical products/devices used
Followed up by the following (possibly more current) registration
No registrations found.
Other (possibly less up-to-date) registrations in this register
No registrations found.
In other registers
| Register | ID |
|---|---|
| EU-CTR | CTIS2024-515893-29-01 |
| EudraCT | EUCTR2022-004078-53-NL |
| CCMO | NL83403.018.22 |