LAROPROVSTAT for Hyperlipidemia | Atherosclerotic cardiovascular disease

Inclusion criteria

• {"criterion_text":"- ≥ 18 years of age at the time of signing the ICF"}
• {"criterion_text":"- History of clinical ASCVD or at risk for a first ASCVD event: (a)\tClinical ASCVD is defined as MI, stable or unstable angina, coronary or other arterial revascularisation, ischaemic stroke, or peripheral artery disease. (b)\tA participant is considered at risk for a first ASCVD event if the participant has one or more of the following conditions: atherosclerotic vascular disease (≥ 50% stenosis in ≥ 2 coronary artery territories or in ≥ 2 vascular beds [coronary, carotid, lower extremity], diagnosed by any imaging modality), diabetes mellitus, hypertension, cigarette smoking, chronic kidney disease (moderate to severe stage), or obesity. Investigators can also use the ACC/AHA or ESC or other relevant national clinical guidelines for risk assessment to identify participants with at least moderate risk for ASCVD."}
• {"criterion_text":"- Fasting serum LDL-C by central laboratory at screening as follows: LDL-C ≥ 55 mg/dL (≥ 1.4 mmol/L) in participants with clinical ASCVD; or ≥ 70 mg/dL (≥ 1.8 mmol/L) in participants without clinical ASCVD but at risk for a first ASCVD event"}
• {"criterion_text":"- Participants should receive a background lipid lowering regimen anticipated to achieve at least a ~50% reduction in LDL-C. Except in cases of intolerance, the regimen should include a high-intensity statin therapy or lower intensity statin therapy in combination with an oral agent with proven outcome benefit (eg, ezetimibe and/or bempedoic acid). Thus, the background lipid-lowering therapy must consist of one of the following: − A high-intensity LDL lowering regimen (i) A high intensity statin regimen, as defined by country specific guidelines OR: (ii) A lower intensity statin regimen in combination with ezetimibe and/or bempedoic acid OR: − A maximum tolerated statin regimen - Oral combination therapy with ezetimibe and/or bempedoic acid is strongly recommended. Participants must achieve a stable background lipid-lowering therapy > 28 days before screening."}

Exclusion criteria

• {"criterion_text":"- Homozygous familial hypercholesterolaemia, known diagnosis of HeFH, LDL apheresis or plasma apheresis within 12 months prior to screening, or any other underlying known disease or condition that may interfere with interpretation of the clinical study results as judged by the Investigator."}
• {"criterion_text":"- Any of the following laboratory values at screening: Calculated eGFR < 15 mL/min/1.73 m^2 (CKD-EPI formula; Delgado et al 2022, Inker et al 2021) AST or ALT > 3 × ULN TBL > 2 × ULN (except for patients with Gilberts syndrome, where TBL 3 × ULN is acceptable provided direct bilirubin < 1.5 × ULN) Fasting triglycerides ≥ 400 mg/dL (≥ 4.52 mmol/L) Creatine Kinase > 5X ULN Urine albumin to creatinine ratio ≥ 500 mg/g"}
• {"criterion_text":"- Uncontrolled type 2 diabetes mellitus defined as HbA1c ≥ 9.5% at screening"}
• {"criterion_text":"- Inadequately treated hypothyroidism defined as TSH > 1.5 ULN at screening or participants whose thyroid replacement therapy was initiated or modified within the last 3 months prior to screening"}
• {"criterion_text":"- Use of mipomersen or lomitapide (cholesterol-lowering medications) within 12 months prior to screening or planned use during the study"}
• {"criterion_text":"- Use of gemfibrozil within 1 week prior to screening or planned use during the study"}
• {"criterion_text":"- Use of PCSK-9 inhibitors: evolocumab/alirocumab within 12 weeks of the screening visit or planned use during the study or inclisiran within 18 months of the screening visit or planned use during the study. Any other approved PCSK-9 inhibitor use within 5 half lives prior to the screening visit or planned use during the study."}

Primary endpoints

• {"endpoint_text":"- Relative change in LDL-C from baseline to 12 weeks","definition_or_measurement_approach":"Relative change in LDL-C from baseline to 12 weeks; measurement method not specified in the endpoint section (screening LDL-C is performed by central laboratory as stated in eligibility criteria)."}

Secondary endpoints

• {"endpoint_text":"- Relative change in LDL-C from baseline to 12 weeks (in patients on background statin therapy at baseline)","definition_or_measurement_approach":"Relative change in LDL-C from baseline to 12 weeks in the subgroup on background statin therapy; measurement method not specified."}
• {"endpoint_text":"- Indicator for LDL-C < 70 mg/dL (< 1.8 mmol/L) at 12 weeks","definition_or_measurement_approach":"Binary indicator of LDL-C < 70 mg/dL at 12 weeks; measurement method not specified."}
• {"endpoint_text":"- Indicator for LDL-C < 55 mg/dL (< 1.4 mmol/L) at 12 weeks","definition_or_measurement_approach":"Binary indicator of LDL-C < 55 mg/dL at 12 weeks; measurement method not specified."}
• {"endpoint_text":"- Relative change in LDL-C from baseline to 28 weeks","definition_or_measurement_approach":"Relative change in LDL-C from baseline to 28 weeks; measurement method not specified."}
• {"endpoint_text":"- Relative change in LDL-C from baseline to 52 weeks","definition_or_measurement_approach":"Relative change in LDL-C from baseline to 52 weeks; measurement method not specified."}
• {"endpoint_text":"- Relative change in Apo B from baseline to 12 weeks","definition_or_measurement_approach":"Relative change in apolipoprotein B (Apo B) from baseline to 12 weeks; measurement method not specified."}
• {"endpoint_text":"- Relative change in non-HDL-C from baseline to 12 weeks","definition_or_measurement_approach":"Relative change in non-HDL-C from baseline to 12 weeks; measurement method not specified."}
• {"endpoint_text":"- Relative change in total cholesterol from baseline to 12 weeks","definition_or_measurement_approach":"Relative change in total cholesterol from baseline to 12 weeks; measurement method not specified."}
• {"endpoint_text":"- Relative change in Lp(a) from baseline to 12 weeks","definition_or_measurement_approach":"Relative change in lipoprotein(a) from baseline to 12 weeks; measurement method not specified."}

Methods

• Site-based recruitment through participating hospitals, clinics and research centres (country-specific site lists provided in Part II).
• Printed materials: pamphlets / leaflets / flyers for site distribution (documents titled 'Pamphlet', 'Leaflet', 'Flyer').
• Digital / social media advertising: Instagram posts and Reels (documents titled 'Text Instagram Post', 'Reels').
• Website adverts / study pages (documents titled 'Website_Gyncentrum Sp zoo').
• Prescreening / online prescreening tools and recruitment text used by site networks (documents titled 'Prescreening Tool Questions', 'Velocity Sites_Recruitment Text').

Bulgaria

Earliest CTIS Part Ii Submission Date

07-08-2025

Latest Decision Or Authorization Date

14-01-2026

Processing Time Days

160

Number Of Sites

11

Number Of Participants

80

Hungary

Earliest CTIS Part Ii Submission Date

08-08-2025

Latest Decision Or Authorization Date

15-01-2026

Processing Time Days

160

Number Of Sites

29

Number Of Participants

145

Slovakia

Earliest CTIS Part Ii Submission Date

07-08-2025

Latest Decision Or Authorization Date

09-12-2025

Processing Time Days

124

Number Of Participants

80

Poland

Earliest CTIS Part Ii Submission Date

06-08-2025

Latest Decision Or Authorization Date

14-12-2025

Processing Time Days

130

Number Of Participants

120

Spain

Earliest CTIS Part Ii Submission Date

18-07-2025

Latest Decision Or Authorization Date

24-04-2026

Processing Time Days

280

Number Of Sites

10

Number Of Participants

50

Germany

Earliest CTIS Part Ii Submission Date

07-08-2025

Latest Decision Or Authorization Date

20-03-2026

Processing Time Days

225

Number Of Participants

215

Czechia

Earliest CTIS Part Ii Submission Date

05-08-2025

Latest Decision Or Authorization Date

02-04-2026

Processing Time Days

300

Number Of Participants

90

Primary sponsor

Full Name

AstraZeneca AB

Organisation Type

Pharmaceutical company

Country Of Registered Address

Sweden