AZD0780 plus rosuvastatin to lower LDL cholesterol in adults with dyslipidaemia

A Phase II, Randomised, Double-Blind, Placebo-Controlled, Parallel Group Study to Assess the Effect of AZD0780 in Combination With Rosuvastatin on Low Density Lipoprotein Cholesterol in Participants With Dyslipidaemia (LAZURE)

This will test whether adding AZD0780 to rosuvastatin lowers LDL cholesterol in adults in Russia who have dyslipidaemia and are at risk for or have atherosclerotic cardiovascular disease.

Quick facts

• Phase: PHASE2
• Study type: Interventional
• Enrollment: 76 (estimated)
• Ages: 18 Years and up
• Sex: All
• Sponsor: AstraZeneca (industry)
• Drugs / interventions: evolocumab, alirocumab
• Locations: 9 sites (Aramil and 8 other locations)
• Trial ID: NCT07218900 on ClinicalTrials.gov

What this trial studies

This is a randomized, double-blind, placebo-controlled Phase II study in which adults with dyslipidaemia will receive a 28-day rosuvastatin run-in and then be randomized 1:1 to once-daily AZD0780 or matching placebo added to rosuvastatin for 12 weeks, with a 10-day safety follow-up. The primary focus is change in LDL-C measured by a central laboratory, with additional monitoring for safety and tolerability. Approximately 76 participants will be enrolled across about 11 centers in Russia. The trial uses standard blinded methods to compare the investigational small molecule AZD0780 against placebo when given on top of moderate-intensity statin therapy or no prior statin.

Who should consider this trial

Good fit: Adults aged 18 or older with LDL-C above the study thresholds and either established ASCVD or defined risk factors who can take rosuvastatin and attend visits at participating Russian sites are the intended participants.

Not a fit: People without elevated LDL-C by the study criteria, those who cannot take rosuvastatin or meet exclusion criteria (such as certain medical conditions or pregnancy), or those unable to attend the Russian study sites are unlikely to benefit from participation.

Why it matters

Potential benefit: If effective, AZD0780 could further lower LDL cholesterol when added to statin therapy and potentially reduce future cardiovascular risk.

How similar studies have performed: Other add-on LDL-lowering therapies such as ezetimibe or PCSK9 inhibitors have lowered LDL-C in prior trials, but AZD0780 is an investigational small molecule and this Phase II trial is an early test of its effect.

Eligibility criteria

Inclusion Criteria:

* ≥ 18 years of age at the time of signing the ICF
* History of clinical Atherosclerotic cardiovascular disease (ASCVD) or at risk for a first ASCVD event:

  1. Clinical ASCVD is defined as MI, stable or unstable angina, coronary or other arterial revascularisation, ischaemic 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 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 meet 1 of the following before screening:

  1. On a stable dose of Lipid-lowering therapy (LLTs) including moderate statins.
  2. On a stable dose of LLTs without any statins (either have been previously treated or be statins treatment naïve).
  3. Not received treatment with any LLTs (either have been previously treated or be LLTs treatment naïve).

Exclusion Criteria:

* Homozygous familial hypercholesterolaemia, known diagnosis of heterozygous familial hypercholesterolaemia (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:

  1. Calculated eGFR \< 15 mL/min/1.73 m2
  2. AST or ALT \> 3 × ULN
  3. TBL \> 2 × ULN (except for patients with Gilberts syndrome, where TBL 3 × ULN is acceptable provided direct bilirubin \< 1.5 × ULN)
  4. Fasting triglycerides ≥ 400 mg/dL (≥ 4.52 mmol/L)
  5. Creatine kinase \> 5 × ULN
  6. 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.

Where this trial is running

Aramil and 8 other locations

• Research Site — Aramil, Russia (RECRUITING)
• Research Site — Ivanovo, Russia (RECRUITING)
• Research Site — Moscow, Russia (RECRUITING)
• Research Site — Moscow, Russia (RECRUITING)
• Research Site — Moscow, Russia (RECRUITING)
• Research Site — Moscow, Russia (RECRUITING)
• Research Site — Perm, Russia (RECRUITING)
• Research Site — Saint Petersburg, Russia (RECRUITING)
• Research Site — Saratov, Russia (SUSPENDED)

Study contacts

• Study coordinator: AstraZeneca Clinical Study Information Center

Conditions: Dyslipidaemia, AZD0780, Low-Density Lipoprotein Cholesterol