ACTIVE_NOT_RECRUITING

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

Conditions

Heterozygous Familial Hypercholesterolaemia Low-Density Lipoprotein Cholesterol

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Study Overview

This clinical trial focuses on testing the efficacy of different digital interventions to promote re-engagement in cancer-related long-term follow-up care for adolescent and young adult (AYA) survivors of childhood cancer.

Description

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.

Official Title

A Phase III, Randomised, Double-Blind, Placebo-Controlled, Parallel-Group Study to Assess the Effect of AZD0780 on Low-Density Lipoprotein Cholesterol in Patients With Heterozygous Familial Hypercholesterolaemia

Quick Facts

Study Start:2025-06-10

Study Completion:2027-01-04

Study Type:Not specified

Phase:Not Applicable

Enrollment:Not specified

Status:ACTIVE_NOT_RECRUITING

Study ID

NCT07000136

Participation Criteria

Researchers look for people who fit a certain description, called eligibility criteria. Some examples of these criteria are a person's general health condition or prior treatments.

Ages Eligible for Study:18 Years

Sexes Eligible for Study:ALL

Accepts Healthy Volunteers:No

Standard Ages:ADULT, OLDER_ADULT

Inclusion Criteria	Exclusion Criteria
* 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).	* 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.

Inclusion Criteria

Exclusion Criteria

* 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).

* 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.

Contacts and Locations

Study Locations (Sites)

Research Site

Garden Grove, California, 92844

United States

Research Site

San Diego, California, 92111

United States

Research Site

Hialeah, Florida, 33012

United States

Research Site

Orlando, Florida, 32807

United States

Research Site

Peachtree Corners, Georgia, 30092

United States

Research Site

Chicago, Illinois, 60607

United States

Research Site

Hammond, Louisiana, 70403

United States

Research Site

Las Vegas, Nevada, 89119

United States

Research Site

New York, New York, 10029

United States

Research Site

Morganton, North Carolina, 28655

United States

Research Site

Cincinnati, Ohio, 45227

United States

Research Site

Lima, Ohio, 45805

United States

Research Site

Chattanooga, Tennessee, 37404

United States

Research Site

Houston, Texas, 77043

United States

Research Site

Humble, Texas, 77338

United States

Research Site

Kingwood, Texas, 77345

United States

Research Site

McAllen, Texas, 78503

United States

Research Site

Mesquite, Texas, 75149

United States

Research Site

Redmond, Washington, 98052

United States

Collaborators and Investigators

Sponsor: AstraZeneca

Study Record Dates

These dates track the progress of study record and summary results submissions to ClinicalTrials.gov. Study records and reported results are reviewed by the National Library of Medicine (NLM) to make sure they meet specific quality control standards before being posted on the public website.

Study Registration Dates

Study Start Date2025-06-10

Study Completion Date2027-01-04

Study Record Updates

Study Start Date2025-06-10

Study Completion Date2027-01-04

Terms related to this study

Keywords Provided by Researchers

Low-Density Lipoprotein Cholesterol

Additional Relevant MeSH Terms

Heterozygous Familial Hypercholesterolaemia