Specifying the Anti-inflammatory Effects of Ziltivekimab (SPIDER)

Academisch Medisch Centrum - Universiteit van Amsterdam (AMC-UvA)

Status and phase: Not yet enrolling; Phase 3

Conditions: Inflammation; Atherosclerosis

Treatments: Drug: Placebo; Drug: Ziltivekimab

Study type: Interventional

Funder types: Other

Identifiers

NCT06263244

NL83403.018.22

Details and patient eligibility

About

The goal of this randomized, double blind, placebo controlled trial is 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.

Full description

Considering that ziltivekimab is currently undergoing a phase 3 CVOT trial, it is of great importance to elucidate its mechanistic effects. The objective of this study is to research whether ziltivekimab therapy for 20 weeks reduces arterial wall inflammation, as assessed by state-of-the-art imaging modalities, and reduces systemic inflammatory tone, as assessed by in depth phenotyping of circulating monocytes, inflammatory biomarkers and proteomics. The imaging modalities used in this study are 68Ga-DOTATATE PET/CT and CCTA. This study is designed as a single center, randomized, double-blinded, placebo-controlled intervention study in 40 atherosclerotic patients of 50 years and older with hsCRP levels of 2 mg/L and above.

Enrollment: 40 estimated patients

Sex: All

Ages: 50 to 85 years old

Volunteers: No Healthy Volunteers

Inclusion criteria

• Aged 50 years and older.
• Multi-vessel coronary artery disease (defined as CAD-RADS ≥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.
• Use of preventive systemic antibiotics (antibiotics used to treat latent tuberculosis are exempted).
• Stable lipid lowering treatment for less than 4 weeks, including statins, ezetimibe and PCSK9 inhibition.
• 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
• Uncontrolled diabetes (HbA1c >90 mmol/mol).
• Renal insufficiency, defined as eGFR <45 ml/min/1.73 m2.
• Platelet count <120,000 and >450,000 /mm3.
• Elevated liver enzymes (>3 ULN of liver transaminases), acute liver failure or known (severe) liver disease.
• Premenopausal women not using birth-control.
• History of gastrointestinal perforation, active diverticulitis (within 5 years) or active inflammatory bowel disease (within 12 months).
• Uncontrolled hypertension (systolic >180 mmHg; diastolic >110 mmHg).
• Diagnosis of (active) malignancy in last 5 years.
• Standard contra-indications to 68Ga-DOTATATE PET, and CT based on physician's experience and current practices.
• Inability or unwillingness to comply with the protocol requirements, or deemed by investigator to be unfit for the study.

Trial design

Primary purpose: Prevention

Allocation: Randomized

Interventional model: Parallel Assignment

Masking: Quadruple Blind

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40 participants in 2 patient groups, including a placebo group

Ziltivekimab

Experimental group

Description:

15 mg ziltivekimab subcutaneously once per month for 5 months

Treatment:

Drug: Ziltivekimab

Placebo

Placebo Comparator group

Description:

Placebo, subcutaneously, once per month for 5 months

Treatment:

Drug: Placebo