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

NCT07000136 | Active Not Recruiting Phase 3 DMC FDA Drug

• 2 other identifiers: D7960C000132025-520520-17
• Study Type: interventional
• Target: 473
• Locations: 24 countries
• Sites: 134

Brief Summary

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.

Conditions

Heterozygous Familial Hypercholesterolaemia

Keywords

Low-Density Lipoprotein Cholesterol

Outcome Measures

Primary Outcomes (1)

• Relative change in LDL-C from baseline to 12 weeks

  To compare the effect of treatment with AZD0780 versus placebo on LDL-C at 12 weeks

  Baseline - 12 weeks

Secondary Outcomes (9)

• Relative change in LDL-C from baseline to 12 weeks

  Baseline - 12 weeks

• Indicator for LDL-C < 70 mg/dL (< 1.8 mmol/L) at 12 weeks

  Baseline - 12 weeks

• Indicator for LDL-C < 55 mg/dL (< 1.4 mmol/L) at 12 weeks

  Baseline - 12 weeks

• Relative change in LDL-C from baseline to 28 weeks

  Baseline - 28 weeks

• Relative change in LDL-C from baseline to 52 weeks

  Baseline - 52 weeks

Study Arms (2)

AZD0780

EXPERIMENTAL

Participants will receive daily oral dose of AZD0780

Drug: AZD0780

Placebo

PLACEBO COMPARATOR

Participants will receive daily oral dose of placebo

Drug: Placebo

Interventions

AZD0780 DRUG

Participants will receive daily oral dose of AZD0780

AZD0780

Placebo DRUG

Participants will receive daily oral dose of placebo

Placebo

Eligibility Criteria

• Age: 18 Years+
• Sex: all
• Healthy Volunteers: No
• Age Groups: Adult (18-64), Older Adult (65+)

You may qualify if:

• ≥ 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.

You may not qualify if:

• 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.

Sponsors & Collaborators

• AstraZeneca: lead

Study Sites (134)

Research Site

Garden Grove, California, 92844, United States

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San Diego, California, 92111, United States

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Hialeah, Florida, 33012, United States

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Orlando, Florida, 32807, United States

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Peachtree Corners, Georgia, 30092, United States

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Chicago, Illinois, 60607, United States

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Hammond, Louisiana, 70403, United States

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Las Vegas, Nevada, 89119, United States

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New York, New York, 10029, United States

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Morganton, North Carolina, 28655, United States

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Cincinnati, Ohio, 45227, United States

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Lima, Ohio, 45801, United States

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Chattanooga, Tennessee, 37404, United States

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Houston, Texas, 77043, United States

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Humble, Texas, 77338, United States

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Kingwood, Texas, 77345, United States

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McAllen, Texas, 78503, United States

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Mesquite, Texas, 75149, United States

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Redmond, Washington, 98052, United States

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CABA, C1006ACC, Argentina

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Ciudad Autonoma de Bs As, C1023AAB, Argentina

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Ciudad de Buenos Aires, C1094AAD, Argentina

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Ciudad de Buenos Aires, C1425AGC, Argentina

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Mar del Plata, 7600, Argentina

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Rosario, 2000, Argentina

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Rosario, S2000PBJ, Argentina

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Melbourne, 3004, Australia

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Campinas, 13060-080, Brazil

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São Caetano do Sul, 09521-160, Brazil

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São Paulo, 04004-030, Brazil

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São Paulo, 04012-180, Brazil

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São Paulo, 05403-000, Brazil

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Plovdiv, 4002, Bulgaria

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Sofia, 1527, Bulgaria

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Sofia, 1618, Bulgaria

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Vancouver, British Columbia, V6Z2H2, Canada

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London, Ontario, N6A 5A5, Canada

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Chicoutimi, Quebec, G7H 7K9, Canada

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Montreal, Quebec, H2W 1R7, Canada

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Québec, Quebec, G1V 4W2, Canada

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Trois-Rivières, Quebec, G9A 4P3, Canada

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Santiago, 7770086, Chile

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Valdivia, 5090000, Chile

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Hradec Králové, 500 05, Czechia

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Prague, 140 00, Czechia

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Prague, 19800, Czechia

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Uherské Hradiště, 686 01, Czechia

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Aarhus N, 8200, Denmark

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Copenhagen, 2400, Denmark

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Esbjerg, 6700, Denmark

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Herlev, 2730, Denmark

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Herning, 7400, Denmark

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Hvidovre, DK-2650, Denmark

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Viborg, 8800, Denmark

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Helsinki, 00290, Finland

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Kuopio, 70210, Finland

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Tampere, 33520, Finland

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Turku, 20520, Finland

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Bron, 69677, France

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Dijon, 21079, France

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Marseille, 13005, France

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Paris, 75013, France

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Saint-Herblain, 44093, France

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Berlin, 10559, Germany

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Dresden, 1307, Germany

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Leipzig, 04103, Germany

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Budapest, 1036, Hungary

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Budapest, 1132, Hungary

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Debrecen, 4032, Hungary

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Nyíregyháza, 4400, Hungary

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Székesfehérvár, 8000, Hungary

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Chūōku, 103-0027, Japan

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Fukushima, 960-1295, Japan

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Hamamatsu, 432-8580, Japan

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Ichikawa-shi, 272-8516, Japan

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Kanazawa, 920-8530, Japan

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Kanazawa, 920-8641, Japan

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Kishiwada-shi, 596-8522, Japan

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Kita-gun, 761-0793, Japan

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Komatsu-shi, 923-8560, Japan

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Minatoku, 108-0014, Japan

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Minatoku, 108-0073, Japan

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Okayama, 700-0804, Japan

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Okayama, 702-8055, Japan

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Osaka, 543-8922, Japan

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Suita-shi, 564-8565, Japan

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Takatsuki-shi, 569-8686, Japan

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Tamanashi, 865-0016, Japan

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Urasoe-Shi, 901-2102, Japan

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Yokohama, 247-8581, Japan

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Amsterdam, 1105 AZ, Netherlands

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Roosendaal, 4708 AE, Netherlands

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Rotterdam, 3015 GD, Netherlands

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Utrecht, 3584 CX, Netherlands

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Christchurch, 8011, New Zealand

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Grafton, 1010, New Zealand

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Bodø, 8005, Norway

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Grålum, 1712, Norway

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Oslo, 0369, Norway

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Oslo, 0586, Norway

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Trondheim, 7030, Norway

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Bratislava, 83101, Slovakia

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Bratislava, 83106, Slovakia

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Košice, 04022, Slovakia

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Nitra, 949 11, Slovakia

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Žilina, 010 01, Slovakia

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Gyeonggi-do, 13620, South Korea

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Seoul, 03080, South Korea

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Seoul, 120-752, South Korea

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Seoul, 5278, South Korea

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A Coruña, 15006, Spain

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Barcelona, 08036, Spain

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Córdoba, 14004, Spain

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Reus, 43204, Spain

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Seville, 41013, Spain

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Gothenburg, 413 46, Sweden

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Linköping, 581 85, Sweden

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Lund, 22242, Sweden

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Stockholm, 117 27, Sweden

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Stockholm, 141 86, Sweden

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Uppsala, 75185, Sweden

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Kaohsiung City, 80756, Taiwan

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Taichung, 40705, Taiwan

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Taipei, 10002, Taiwan

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Taipei, 11217, Taiwan

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Adana, 01060, Turkey (Türkiye)

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Afyonkarahisar, 03030, Turkey (Türkiye)

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Ankara, 06530, Turkey (Türkiye)

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Izmir, 35100, Turkey (Türkiye)

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İzmit, 41380, Turkey (Türkiye)

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Hanoi, 100000, Vietnam

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Ho Chi Minh City, 700000, Vietnam

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Ho Chi Minh City, 70000, Vietnam

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Hồ Chí Minh, 9000, Vietnam

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Related Links

• 2025-520520-17-00-SUBSTANTIAL MODIFICATION

Study Design

• Study Type: interventional
• Phase: phase 3
• Allocation: RANDOMIZED
• Masking: TRIPLE
• Who Masked: PARTICIPANT, CARE PROVIDER, INVESTIGATOR
• Masking Details: Placebo controlled
• Purpose: TREATMENT
• Intervention Model: PARALLEL
• Sponsor Type: INDUSTRY
• Responsible Party: SPONSOR

Model Details: International, multi-centre, randomised, double-blind, placebo-controlled, parallel-group

Study Record Dates

• First Submitted: May 23, 2025
• First Posted: June 2, 2025
• Study Start: June 10, 2025
• Primary Completion (Estimated): January 4, 2027
• Study Completion (Estimated): January 4, 2027
• Last Updated: May 6, 2026

Record last verified: 2026-05

Data Sharing

• IPD Sharing: Will share
• Shared Documents: STUDY PROTOCOL, SAP
• Time Frame: AstraZeneca will meet or exceed data availability as per the commitments made to the EFPIA/PhRMA Data-Sharing Principles. For details of our timelines, please refer to our disclosure commitment at: https://astrazenecagrouptrials.pharmacm.com/ST/Submission/Disclosure
• Access Criteria: When a request has been approved AstraZeneca will provide access to the anonymized individual patient-level data via secure research environment Vivli.org. A Signed Data Usage Agreement (non-negotiable contract for data accessors) must be in place before accessing requested information.

Locations

FR (5); DE (3); BR (5); CA (6); NO (5); VN (4); CL (2); NZ (2); AR (7); TW (4); TU (5); BU (3); CZ (4); NL (4); KR (4); FI (4); SE (6); HU (5); SL (5); US (19); DK (7); ES (5); JP (19); AU (1)