Inclisiran for Primary hypercholesterolaemia (heterozygous familial and non-familial) | Mixed dyslipidaemia associated with atherosclerotic cardiovascular disease

Inclusion criteria

• {"criterion_text":"- Male or female ≥ 18 years of age at signing of informed consent"}
• {"criterion_text":"- Subject agrees to the Maximum dose Statin therapy (Rosuvastatin min. 20 mg or Atorvastatin min. 40 mg) Fasting LDL-C local lab value at the Screening Visit ≥ 1.8 mmol/L proved atherosclerotic coronary disease (at least 1 of the below): 1)"}
• {"criterion_text":"- proved atherosclerotic coronary disease (at least 1 of the below): 1) non-obstructive coronary plaques on CT scan in the last 6 months without revascularization, at least in 4 four regions (1-69% stenosis is 2 regions and 25-69% stenosis in 2 other regions); 2)proved acute coronary syndrome in one year with multi-vessel disease (at least 50% stenosis on another artery; post-PCI patient with at least 2 coronary XML File Identifier: ZRG11sdk8OXqmN4mxy3KFqZT0uQ=Page 11/22 arteries involved"}
• {"criterion_text":"- Written informed consent must be obtained before any assessment is performed."}

Exclusion criteria

• {"criterion_text":"- Pregnant or nursing (lactating) women. Women of child-bearing potential, defined as all women physiologically capable of becoming pregnant, unless they are using highly effective methods of contraception"}
• {"criterion_text":"- Ongoing malignancy at the time of the first study visit"}
• {"criterion_text":"- Renal insufficiency (eGFR <30 mL/min/1.73m2) as measured by the Modification of Diet in Renal Disease (MDRD) formula at the Screening Visit."}
• {"criterion_text":"- Active liver disease defined as any known current infectious, neoplastic, or metabolic pathology of the liver at the Screening Visit. Participants who enter must have AST and ALT ≤3x ULN"}
• {"criterion_text":"- Use of other investigational drugs within 5 half-lives of the first study visit (Screening Visit), within 30 days (e.g., small molecules), or until the expected pharmacodynamic effect has returned to baseline (e.g., biologics), whichever is longer; or if required by local regulations. COVID-19 vaccines granted Emergency Use Authorization are not considered investigational drugs for the purpose of this study."}
• {"criterion_text":"- Heart failure (New York Heart Association (NYHA) class IV) at the Screening Visit."}
• {"criterion_text":"- current PCSK-9 inhibitor treatment"}

Primary endpoints

• {"endpoint_text":"- absolute and percent change in LDL-level from first to last visit (mmol/L)","definition_or_measurement_approach":"Change in LDL cholesterol (mmol/L) measured from baseline (first visit) to the last visit; reported as absolute and percent change."}
• {"endpoint_text":"- absolute and percent LDL-change from visit to visit","definition_or_measurement_approach":"Absolute and percent change in LDL cholesterol measured between consecutive study visits."}

Secondary endpoints

• {"endpoint_text":"- change (from first to last visit) in percent of patients reaching LDL target (LDL<1.4 mmol/L)","definition_or_measurement_approach":"Proportion of patients achieving LDL <1.4 mmol/L at last visit compared with first visit; reported as percent change in patients reaching target."}
• {"endpoint_text":"- change in coronary CT paramteres (total plaque volumen; „low-attenuation\" plaque volumen; Agatston score; plaque composition; pericoronarial and pericardial fat tissue)","definition_or_measurement_approach":"Change in coronary CT measures including total plaque volume, low-attenuation plaque volume, Agatston score, plaque composition, and pericoronary/pericardial fat tissue between baseline and follow-up."}
• {"endpoint_text":"- Ultrasound (femoral/carotid) endpoints: change in (from first to last visit): Total plaque area (mm2) Intima:media thickness plaque composition","definition_or_measurement_approach":"Change from baseline to last visit in ultrasound-assessed total plaque area (mm2), intima-media thickness, and plaque composition in femoral/carotid arteries."}
• {"endpoint_text":"- change in BMI","definition_or_measurement_approach":"Change in body mass index from first to last visit."}
• {"endpoint_text":"- Change in lifestyle, diet and health behaviour","definition_or_measurement_approach":"Assessment of changes in lifestyle, dietary habits and health behavior from baseline to last visit (methodology as per study questionnaires/supporting material)."}

Hungary

Earliest CTIS Part Ii Submission Date

15-10-2024

Latest Decision Or Authorization Date

22-10-2024

Processing Time Days

7

Number Of Sites

1

Number Of Participants

200

Primary sponsor

Full Name

Semmelweis University

Organisation Type

Educational Institution

Country Of Registered Address

Hungary

Third parties

• {"country":"","full_name":"Novartis Hungary Ltd","duties_or_roles":"Monetary support","organisation_type":""}