A Study to Find Out How Safe and Effective AZD0780 Is for Adults with High 'Bad' Cholesterol from an Inherited Condition

Overview

Sponsor-declared trial summary

Key facts

Sponsor

AstraZeneca AB

Participant type

Patients

Age range

18-64 years, 65+ years

Gender

Male and Female

Therapeutic area

Diseases [C] - Cardiovascular Diseases [C14]

Trial duration

5 Sep 2025 → ongoing

Decision date (initial)

2025-08-21

Transition trial

No

Low-intervention

No

Rare-disease indication

No

Vulnerable population

Yes

Funding sources

AstraZeneca AB

Trial design

CTIS Part I — objectives, methods, condition coding

Main objective

Scope: Efficacy, Pharmacodynamic, Therapy, Safety, Pharmacokinetic

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

Secondary objectives 9

1. To compare the effect of treatment with AZD0780 versus placebo on LDL-C at 12 weeks in patients on background statin therapy at baseline
2. To compare the effect of treatment with AZD0780 versus placebo on the probability of LDL-C < 70 mg/dL at 12 weeks in patients with baseline LDL-C ≥ 70 mg/dL
3. To compare the effect of treatment with AZD0780 versus placebo on the probability of LDL C < 55 mg/dL at 12 weeks
4. To compare the effect of treatment with AZD0780 versus placebo on LDL-C at 28 weeks
5. To compare the effect of treatment with AZD0780 versus placebo on LDL-C at 52 weeks
6. To compare the effect of treatment with AZD0780 versus placebo on apolipoprotein (Apo) B at 12 weeks
7. To compare the effect of treatment with AZD0780 versus placebo on non-high-density lipoprotein cholesterol (HDL-C) at 12 weeks
8. To compare the effect of treatment with AZD0780 versus placebo on total cholesterol at 12 weeks
9. To compare the effect of treatment with AZD0780 versus placebo on lipoprotein(a) (Lp[a]) at 12 weeks

Conditions and MedDRA coding

Heterozygous familial hypercholesterolaemia

Regulatory references

Scientific advice from competent authorities

Food And Drug Administration, European Medicines Agency

Plan to share IPD

Yes

IPD plan description

Qualified researchers can request access to anonymized individual patient-level data from AstraZeneca group of companies sponsored clinical trials via the request portal Vivli.org. All requests will be evaluated as per the AZ disclosure commitment: https://astrazenecagrouptrials.pharmacm.com/ST/Submission/Disclosure. Yes, indicates that AZ are accepting requests for IPD, but this does not mean all requests will be shared. AstraZeneca will meet or exceed data availability as per the commitments made to the EFPIA PhRMA Data Sharing Principles. When a request has been approved AstraZeneca will provide access to the anonymized individual patient-level data via secure research environment https://vivli.org/. Signed Data Usage Agreement (non-negotiable contract for data accessors) must be in place before accessing requested information.

Eligibility criteria

Principal inclusion / exclusion criteria as submitted by sponsor

Inclusion criteria 4

1. ≥ 18 years of age at the time of signing the ICF.
2. 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])
3. 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.
4. 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 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 7

1. 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
2. Any of the following laboratory values at screening: - Calculated eGFR < 15 mL/min/1.73 m2 (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 ≥ 500mg/g
3. Uncontrolled type 2 diabetes mellitus defined as HbA1c ≥ 9.5% at screening
4. 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
5. Use of mipomersen or lomitapide (cholesterol-lowering medications) within 12 months prior to screening or planned use during the study
6. Use of gemfibrozil within 1 week prior to screening or planned use during the study
7. 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.

Endpoints

Primary and secondary outcome measures (English text)

Primary endpoints 1

1. Relative change in LDL-C from baseline to 12 weeks

Secondary endpoints 9

1. Relative change in LDL-C from baseline to 12 weeks (in patients on background statin therapy at baseline)
2. Indicator for LDL-C < 70 mg/dL (< 1.8 mmol/L) at 12 weeks
3. Indicator for LDL-C < 55 mg/dL (< 1.4 mmol/L) at 12 weeks
4. Relative change in LDL-C from baseline to 28 weeks
5. Relative change in LDL-C from baseline to 52 weeks
6. Relative change in Apo B from baseline to 12 weeks
7. Relative change in non-HDL-C from baseline to 12 weeks
8. Relative change in total cholesterol from baseline to 12 weeks
9. Relative change in Lp(a) from baseline to 12 weeks

Investigational products

Investigational medicinal products (IMPs), comparators, placebo, auxiliary

Test 1

Placebo 1

Sponsors and contacts

Sponsor organisations, regulatory contacts, third parties

AstraZeneca AB

Sponsor organisation

AstraZeneca AB

Address

-

City

Sodertalje

Postcode

151 85

Country

Sweden

Scientific contact point

Organisation

AstraZeneca AB

Contact name

AstraZeneca Clinical Study Information Center

Public contact point

Organisation

AstraZeneca AB

Contact name

AstraZeneca Clinical Study Information Center

Locations

12 EU/EEA countries · 72 investigational sites

By country

Investigational sites

Country notifications

Trial-start, recruitment-start, end and early-termination notifications submitted per Member State

Results and documents

Annex IV summary of results, Annex V layperson summary, and all documents registered in CTIS for this trial

Documents 59 files

Public protocol annexes, IB summaries, regulatory submissions and post-authorisation documents registered in CTIS.

Application history

10 submissions — initial application plus substantial / non-substantial modifications