Study for Adults With Clinical ASCVD or at Risk for a First ASCVD Event

Do you suffer from Clinical Atherosclerotic Cardiovascular Disease (ACVD)?

This is a study to evaluate the efficacy and safety of AZD0780 in adults with clinical ASCVD or who are at risk for a first ASCVD event and who have elevated LDL-C. AZD0780 is a small molecule that reduces the amount of LDL-C in the blood. Placebo will be used for comparison, and neither the participants nor the Investigators will know who is receiving the AZD0780 medication and who is receiving the placebo until the end of study.

The total length of the study for an individual participant will be up to approximately 56 weeks, including a screening period of up to 14 days, treatment with AZD0780 or placebo for 52 weeks, and a safety follow-up period of 10 days.

Would you like to take part? Would you like a friend or family member to take part?

As a volunteer in a research study, you will receive personal study-related medical care from the study doctor and regular follow up on your ASCVD to monitor the effectiveness of the care you will receive. The results of this research will be used to find out if the experimental medication being studied will be of benefit to others with ASCVD or not. Study volunteers are an important part of moving medical care forward.

You may qualify to participate in this study if you:

• Are ≥ 18 years of age at the time of signing the ICF
• Have history of clinical ASCVD or are at risk for a first ASCVD event:
  1. Clinical ASCVD is defined as MI, stable or unstable angina, coronary or other arterial revascularization, ischemic stroke, or peripheral artery disease.
  2. A 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.
• Have 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
• Are receiving a maximally tolerated lipid lowering regimen including a maximally tolerated dose of a statin.
  1. Participants must achieve a stable dose (> 28 days) of lipid lowering therapies before screening.
  2. Participants who are judged by the treating physician not to tolerate high intensity statins (according to guidelines, typically, atorvastatin ≥ 40 mg once daily or rosuvastatin ≥ 20 mg once daily) may be included if treated with a low- or moderate intensity statin dose.
  3. Participants not receiving any statins must have documented intolerable side effects to at least 2 different statins, including one at the lowest standard dose or on a chronic medication that would prohibit the use of a statin (according to the prescribing information for the statin in question)

You may not qualify to participate in this study if you:

• Have homozygous familial hypercholesterolemia, 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.
• Have any of the following laboratory values at screening:
  • Calculated eGFR < 15 mL/min/1.73 m2
  • 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 > 5 × ULN
  • Urine albumin-to-creatinine ratio ≥ 500 mg/g
• Have uncontrolled type 2 diabetes mellitus defined as HbA1C ≥ 9.5% at screening
• Have 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
• Use mipomersen or lomitapide (cholesterol-lowering medications) within 12 months prior to screening or planned use during the study.
• Use gemfibrozil within 1 week prior to screening or planned use during the study.
• Use 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

There are other eligibility requirements that the study doctor will review. Only the study doctor can finally determine whether you are eligible to participate in the study or not.

Participants who qualify for this study will receive a study-related health examination at no cost, as well as possible compensation for time and travel.