A Phase III Study to Assess the Effect of AZD0780 on LDL-C in Patients With HeFH

What this study involves

The registry does not currently label this study as recruiting. Ask about its status before planning a screening visit.

Study type

Interventional

Phase

Phase 3

Age range

18 years - Not specified

Sex eligible

All sexes

Healthy volunteers

Not accepted

Participants

473 Actual

These are starting points, not an eligibility decision. The research team must review the full requirements.

About the research

This is a study to evaluate the efficacy and safety of AZD0780 in adults with HeFH and elevated LDL-C, either with clinical ASCVD and LDL-C levels of 55 mg/dL or higher or without clinical ASCVD and LDL-C levels of 70 mg/dL or higher. 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.

Who may be able to participate?

The list below is the sponsor’s full registry wording. It can include conditions, prior treatment, test results and other requirements. A match in search does not mean you qualify.

Inclusion criteria:

•≥ 18 years of age at the time of signing the ICF.

• Diagnosis of HeFH by genetic confirmation or a definite clinical diagnosis, ie, a score \> x using the Dutch Lipid Network \[Nordestgaard et al 2013\] or equivalent as per internationally accepted diagnostic algorithms (AHA \[Gidding et al 2015\], US MEDPED \[Williams et al 1993\], Simon Broome \[Scientific Steering Committee on behalf of the Simon Broome Register Group 1991\], or Japanese Atherosclerosis Society Guidelines \[Okamura et al 2024\])
• Fasting serum by central laboratory at screening as follows: LDL-C ≥ 55 mg/dL (≥ 1.4 mmol/L) in participants with HeFH and clinical ASCVD or ≥ 70 mg/dL (≥ 1.8 mmol/L) in HeFH without clinical ASCVD. Clinical ASCVD is defined as MI, stable or unstable angina, coronary or other arterial revascularisation, ischaemic stroke, or peripheral artery disease.
• 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 - Oral combination therapy with ezetimibe and/or bempedoic acid is strongly recommended OR: (ii) A lower intensity statin regimen in combination with ezetimibe and/or bempedoic acid :

OR:

\- A maximally 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, 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 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
• 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.

Treatment, groups and participation

The registry may describe treatments and study duration without a complete visit calendar. Ask the study team for the exact schedule, procedures, risks, costs and alternatives. Keep your usual care plan unless your treating clinician tells you otherwise.

Assignment

Random assignment

Masking

Triple masked

What researchers are measuring

Outcome measures describe what is being studied. They are not proof that a treatment works.

Primary measures

Secondary measures

Research locations (133)

The overall study status and a local site’s status can differ. Confirm that location’s availability before traveling.

133 locations

Study team and timeline

Lead sponsor

AstraZeneca

Study start

Jun 10, 2025 Actual

Primary completion

Jan 4, 2027 Estimated

Study completion

Jan 4, 2027 Estimated

First posted

Jun 2, 2025 Actual

Last updated

Nov 9, 2026 Actual

Official study contacts

No central contact is listed. Check the locations and the official record.