Evaluation of Laroprovstat (AZD0780) on LDL-C Levels in Patients with Hyperlipidemia and Atherosclerotic Cardiovascular Disease: A Randomized, Double-Blind, Placebo-Controlled Study
- Trial ID
- 2025-520521-21-00
- Protocol
- D7960C00012
- Sponsor
- AstraZeneca AB
Trial statistics
Diseases & Conditions
Objectives
The primary objective of this study is to evaluate the effect of **AZD0780** compared to placebo on low-density lipoprotein cholesterol (LDL-C) levels at 12 weeks in patients with **hyperlipidemia** and **atherosclerotic cardiovascular disease** or those at risk for a first atherosclerotic cardiovascular disease event. This is clinically relevant as reducing LDL-C is a critical factor in managing cardiovascular risk and preventing cardiovascular events.
Secondary objectives include:
- Comparing the effect of AZD0780 versus placebo on LDL-C levels at 28 and 52 weeks.
- Assessing the probability of achieving LDL-C levels below 70 mg/dL and 55 mg/dL at 12 weeks in patients with baseline LDL-C ≥ 70 mg/dL.
- Evaluating the impact on apolipoprotein B, non-high-density lipoprotein cholesterol, total cholesterol, and lipoprotein(a) at 12 weeks.
Participants
The clinical trial involves a total of **2020 participants** diagnosed with **hyperlipidemia** and **atherosclerotic cardiovascular disease**. The study population includes both male and female subjects, aged **18 years and older**, who are either at risk for or have a history of clinical atherosclerotic cardiovascular disease (ASCVD). Participants are required to have a fasting serum LDL-C level of at least 55 mg/dL if they have clinical ASCVD, or at least 70 mg/dL if they are at risk for a first ASCVD event. All participants should be on a maximally tolerated lipid-lowering regimen, including a stable dose of statins, unless they have documented intolerance to statins. The trial population was selected based on these criteria, ensuring that individuals are receiving appropriate lipid-lowering therapies. The study includes a vulnerable population, and lifestyle factors such as diet and physical activity are considered in the context of managing hyperlipidemia and cardiovascular risk. The selection process ensures a representative sample of individuals who meet the inclusion criteria, providing a comprehensive assessment of the treatment's effect on LDL-C levels over a 12-week period.
Plans and Procedures
The clinical trial is a **Phase III**, randomized, double-blind, placebo-controlled, parallel-group study designed to evaluate the efficacy of AZD0780 in reducing low-density lipoprotein cholesterol (LDL-C) levels in patients with **hyperlipidemia** and **atherosclerotic cardiovascular disease** or those at risk for a first atherosclerotic cardiovascular disease event. The trial will involve the administration of AZD0780, a synthetic molecule in the form of a film-coated tablet, and a matching placebo, both administered orally. The primary objective is to compare the effect of AZD0780 versus placebo on LDL-C levels at 12 weeks, with secondary endpoints including changes in LDL-C at 28 and 52 weeks, as well as other lipid parameters.
The trial is expected to commence recruitment on May 30, 2025, and conclude by March 26, 2027. Participants will be involved in the study for a maximum of 52 weeks. The study will begin with a screening visit to confirm eligibility based on criteria such as age (≥ 18 years), history of clinical atherosclerotic cardiovascular disease, or risk factors for a first event, and specific LDL-C levels. Participants must be on a stable, maximally tolerated lipid-lowering regimen prior to screening. Following randomization, participants will attend regular follow-up visits to monitor safety, adherence, and efficacy outcomes. The end-of-study visit will occur at the conclusion of the treatment period, where final assessments will be conducted.
Participants may be withdrawn from the study early if they experience significant adverse events, fail to adhere to the study protocol, or if the investigator deems it necessary for their safety. The trial will adhere to rigorous ethical standards and regulatory requirements to ensure the integrity of the data and the safety of the participants.
Treatment
The clinical trial involves the administration of **AZD0780**, an experimental medication formulated as a **film-coated tablet**. The active substance in AZD0780 is **laroprovstat**, a synthetic chemical compound. The medication is intended for **oral use**. The trial does not specify a maximum daily dose or total dose amount, but the treatment period is set for up to 52 weeks. AZD0780 is developed by AstraZeneca AB and is not a paediatric formulation. The primary objective of the trial is to assess the effect of AZD0780 on low-density lipoprotein cholesterol (LDL-C) levels in patients with elevated LDL-C and clinical atherosclerotic cardiovascular disease or those at risk for a first atherosclerotic cardiovascular disease event.
The study also includes a **placebo** group, which will receive a placebo treatment designed to match the AZD0780 in appearance but without the active substance. The placebo is used to maintain the double-blind nature of the trial, ensuring that neither the participants nor the investigators know which treatment is being administered. This approach helps to objectively evaluate the efficacy of AZD0780 by comparing it against the placebo group. The placebo is not specified in terms of pharmaceutical form or route of administration, but it is implied to be administered in a manner consistent with the experimental treatment to ensure blinding.
Efficacy
The efficacy of the investigational product AZD0780 will be assessed in a Phase III, randomized, double-blind, placebo-controlled, parallel-group study. The primary endpoint for evaluating efficacy is the relative change in low-density lipoprotein cholesterol (**LDL-C**) from baseline to 12 weeks. Secondary endpoints include the relative change in LDL-C from baseline to 12 weeks in patients on background statin therapy, indicators for achieving LDL-C levels below 70 mg/dL and 55 mg/dL at 12 weeks, and the relative change in LDL-C at 28 and 52 weeks. Additional secondary endpoints involve the relative change in apolipoprotein B (Apo B), non-high-density lipoprotein cholesterol (non-HDL-C), total cholesterol, and lipoprotein(a) [Lp(a)] from baseline to 12 weeks.
Efficacy parameters will be measured and collected at specified timepoints, including baseline, week 12, week 28, and week 52. The assessments will be conducted using validated laboratory tests to ensure accuracy and reliability. The primary and secondary endpoints will be analyzed to determine the effect of AZD0780 compared to placebo in patients with elevated LDL-C and clinical atherosclerotic cardiovascular disease or those at risk for a first atherosclerotic cardiovascular disease event. The study aims to provide comprehensive data on the efficacy of AZD0780 in lowering LDL-C and other related lipid parameters over the course of the treatment period.
Inclusion and Exclusion Criteria
Inclusion Criteria
- ≥ 18 years of age at the time of signing the ICF
- History of clinical ASCVD or at risk for a first ASCVD event: (a) Clinical ASCVD is defined as MI, stable or unstable angina, coronary or other arterial revascularisation, ischaemic stroke, or peripheral artery disease. (b) 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.
- 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
- 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
- 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.
- 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
- Uncontrolled type 2 diabetes mellitus defined as HbA1c ≥ 9.5% at screening
- 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 of mipomersen or lomitapide (cholesterol-lowering medications) within 12 months prior to screening or planned use during the study
- Use of gemfibrozil within 1 week prior to screening or planned use during the study
- 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.
Trial Status by Country
| Country | Status | Start of Recruitment | Planned Patients |
|---|---|---|---|
 Bulgaria | Not Recruiting | 30 May 2025 | 80 |
 Czechia | Not Recruiting | 30 May 2025 | 90 |
 Germany | Not Recruiting | 30 May 2025 | 215 |
 Hungary | Not Recruiting | 30 May 2025 | 145 |
 Poland | Not Recruiting | 30 May 2025 | 120 |
 Slovakia | Not Recruiting | 30 May 2025 | 80 |
 Spain | Not Recruiting | 30 May 2025 | 50 |
Sites & Investigators
Investigational Products
Details about the medicinal products being studied in this clinical trial.
| Product Name | Role in Trial | Formulation | Administration | Max Daily Dose | Treatment Duration | EU MP Number |
|---|---|---|---|---|---|---|
AZD0780 | Test | FILM-COATED TABLET | ORAL USE | 0 | 52 | PRD10648575 |
AZD0780 Placebo | Placebo | N/A | — | — | — | N/A |