A Study to Assess the Effect of AZD0780 on Low Density Lipoprotien Cholesterol in Patients with Clinical Atherosclerotic Cardiovascular Disease or are at Risk for a First Atherosclerotic Cardiovascular Disease Event
Scientific Title of Study
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 Elevated Low-Density Lipoprotein Cholesterol and Clinical Atherosclerotic Cardiovascular Disease or at Risk for a First Atherosclerotic Cardiovascular Disease Event (AZURE LDL)
Trial Acronym
AZURE LDL
Secondary IDs if Any
Secondary ID
Identifier
D7960C00012 Protocol Version number 1.0 dated 11 Apr 2025
Protocol Number
NCT07000123
ClinicalTrials.gov
Details of Principal Investigator or overall Trial Coordinator (multi-center study)
Name
Tapankumar M Shah
Designation
Senior Director – Site Management and Monitoring, Biopharmaceuticals R&D
Affiliation
AstraZeneca Pharma India Ltd
Address
Block N1, 12th Floor, Manyata Embassy Business Park, Rachenahalli, Outer Ring Road
Bangalore KARNATAKA 560045 India
Phone
9535104975
Fax
Email
tapankumar.shah@astrazeneca.com
Details of Contact Person Scientific Query
Name
Tapankumar M Shah
Designation
Senior Director – Site Management and Monitoring, Biopharmaceuticals R&D
Affiliation
AstraZeneca Pharma India Ltd
Address
Block N1, 12th Floor, Manyata Embassy Business Park, Rachenahalli, Outer Ring Road
KARNATAKA 560045 India
Phone
9535104975
Fax
Email
tapankumar.shah@astrazeneca.com
Details of Contact Person Public Query
Name
Tapankumar M Shah
Designation
Senior Director – Site Management and Monitoring, Biopharmaceuticals R&D
Affiliation
AstraZeneca Pharma India Ltd
Address
Block N1, 12th Floor, Manyata Embassy Business Park, Rachenahalli, Outer Ring Road
KARNATAKA 560045 India
Phone
9535104975
Fax
Email
tapankumar.shah@astrazeneca.com
Source of Monetary or Material Support
AstraZeneca AB
151 85 Södertälje, Sweden
Primary Sponsor
Name
AstraZeneca AB
Address
151 85 Södertälje, Sweden
Type of Sponsor
Pharmaceutical industry-Global
Details of Secondary Sponsor
Name
Address
AstraZeneca Pharma India Ltd
Block N1, 12th Floor, Manyata Embassy Business Park,
Rachenahalli, Outer Ring Road, Bangalore - 560045,
Karnataka, India
Countries of Recruitment
Argentina Australia Brazil Bulgaria Canada Chile Czech Republic Germany Hungary India Japan Malaysia Poland Republic of Korea Slovakia Spain Taiwan Turkey Ukraine United Kingdom United States of America Viet Nam
Sites of Study
No of Sites = 12
Name of Principal
Investigator
Name of Site
Site Address
Phone/Fax/Email
Dr Mohd Aziz Khan
Crescent Hospital & Heart Centre
Department of Cardiology, Crescent Hospital & Heart Centre, Behind Old Mount Carmel School, Near Lokmat Square, Dhantoli, PIN- 440012 Nagpur MAHARASHTRA
9823956551
khandraziz@gmail.com
Dr Gurpreet Singh Wander
Dayanand Medical College & Hospital, Unit - Hero DMC Heart Institute
Department of Cardiology, Dayanand Medical College & Hospital, Unit - Hero DMC Heart Institute, Tagore Nagar, Civil Lines, PIN- 141001 Ludhiana PUNJAB
9815545316
drgswander@yahoo.com
Dr Peeyush Jain
Fortis Escorts Heart Institute
Department of preventive
md Rehabilitative Cardiology, Fortis Escorts Heart Institute, Okhla Road, PIN 110025
New Delhi DELHI
9818701043
peeyush.jain@fortishealthcare.com
Dr Vimal Mehta
Govind Ballabh Pant Institute of Postgraduate Medical Education and Research
Department of Cardiology, Govind Ballabh Pant Institute of Postgraduate Medical Education and Research, First Floor, Academic Block, Department of Cardiology, Jawahar Lal Nehru Marg, PIN - 110002 New Delhi DELHI
9718599105
drvimalmehta@yahoo.co.in
Dr Srinivasu Yalaga
Govt. Siddhartha Medical College
Department of Cardiology, Govt. Siddhartha Medical College, Ring road, Gunadala, PIN- 520008 Krishna ANDHRA PRADESH
8328309714
dr.y.srinivasu@gmail.com
Dr Veerappa Annasaheb Kothiwale
KLES Dr Prabhakar Kore Hospital & Medical Research
Dept. of Cardiology, KLES Dr Prabhakar Kore Hospital & Medical Research Centre, Nehru Nagar, PIN-590010 Belgaum KARNATAKA
8312470400
nov10kothiwale@yahoo.co.in
Dr Jabir Abdullakutty
Lisie Hospital
Department of Cardiology, Lisie Hospital, P.B. No. 3053, Kochi - 682018 Ernakulam KERALA
9447011773
drjabi@yahoo.co.in
Dr Santosh Kumar Sinha
LPS Institute of Cardiology and Cardiac Surgery, G.S.V.M Medical College
Department of Cardiology, LPS Institute of Cardiology and Cardiac Surgery, G.S.V.M Medical College, G.T. Road, Swaroop Nagar, PIN- 208002 Kanpur Nagar UTTAR PRADESH
9670220088
fionasan@rediffmail.com
Dr Vijay Kumar Chopra
Max Super Speciality Hospital
Department of Cardiology, Max Super Speciality Hospital, Saket (East Block), (A unit of Devki Devi Foundation), 2, Press Enclave Road, Saket, PIN – 110017 New Delhi DELHI
9845695589
chopravk@gmail.com
Dr Nirav Chandulal Bhalani
Rhythm Heart Institute
Department of Cardiology, Rhythm Heart Institute, Near Siddharth Bungalows, Sama Savli Road, PIN- 390022 Vadodara GUJARAT
8128995863
drniravbhalani@hotmail.com
Dr Ajaykumar U Mahajan
Seth G.S Medical College & K.E.M Hospital
Department of Cardiology, Seth G.S Medical College & K.E.M Hospital, Dr. K.K Datey Department of Cardiology, Acharya Donde Marg, Patel, PIN- 400012 Mumbai MAHARASHTRA
99204326639
draumahajan@gmail.com
Dr Tanuj Bhatia
Shri Guru Ram Rai (SGRR) Institute of Medical & Health Sciences and Shri Mahant Indiresh Hospital
Department of Cardiology, Shri Guru Ram Rai (SGRR) Institute of Medical & Health Sciences and Shri Mahant Indiresh Hospital, Patel Nagar, Dehradun - 248001, Uttarakhand Dehradun UTTARANCHAL
Formulation: Tablet
Dose strength: 30mg
Route: Oral
Frequency: Once daily
Comparator Agent
Placebo
Formulation: Tablet
Dose strength: 30mg
Route: Oral
Frequency: Once daily
Inclusion Criteria
Age From
18.00 Year(s)
Age To
99.00 Year(s)
Gender
Both
Details
Age
1. greater than or equal to 18 years of age at the time of signing the ICF
Type of Participant and Disease Characteristics
2. History of clinical ASCVD or at risk for a first ASCVD event:
(a) Clinical ASCVD is defined as MI, stable or unstable angina, coronary or other arterial revascularisation, ischaemic stroke, or peripheral artery disease.
(b) 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 (greater than or equal to 50% stenosis in greater than or equal to 2 coronary artery territories or in greater than or equal to 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 other relevant national clinical ASCVD.
3. Fasting serum LDL-C by central laboratory at screening as follows: LDL-C greater than or equal to 55 mg/dL (greater than or equal to 1.4 mmol/L) in participants with clinical ASCVD or greater than or equal to 70 mg/dL (greater than or equal to 1.8 mmol/L) in participants without clinical ASCVD but at risk for a first ASCVD event
4. Participants should be receiving a maximally tolerated lipid-lowering regimen including a maximally tolerated dose of a statin.
(a) Participants must achieve a stable dose (greater than 28 days) of lipid-lowering therapies before screening.
(b) Participants who are judged by the treating physician not to tolerate high-intensity statins (according to guidelines, typically, atorvastatin greater than or equal to 40 mg once daily or rosuvastatin greater than or equal to 20 mg once daily) may be included if treated with a low- or moderate-intensity statin dose.
(c) Participants not receiving any statins must have documented intolerable side effects to at least 2 different statins, including one at the lowest standard dose or on a chronic medication that would prohibit the use of a statin (according to the prescribing information for the statin in question).
Sex and Contraceptive/Barrier Requirements
5.Male and/or female assigned at birth, inclusive of all gender identities.
6. WOCBP who are sexually active with a non-sterilised male partner must be on an established highly effective form of birth control from screening throughout the study and should continue with highly effective birth control for at least 10 days after last dose of IMP. A highly effective method of contraception is defined as one that can achieve a failure rate of less than 1% per year when used consistently and correctly. Such methods include:
- Systemic hormonal contraception associated with inhibition of ovulation (oral / transdermal / - injectable/implantable / intravaginal)
- Intrauterine device/intrauterine hormone-releasing system
- Bilateral tubal occlusion/vasectomised partner
Total sexual abstinence is an acceptable method provided it is the usual lifestyle of the participant (defined as refraining from heterosexual intercourse during the entire period of risk associated with the study treatments).
Periodic abstinence (calendar, ovulation, symptothermal, post-ovulation methods), withdrawal (coitus interruptus), spermicides only, and lactational amenorrhoea are not acceptable methods of contraception.
7. Female participants of non-childbearing potential are defined as females who are either permanently sterilised (hysterectomy, bilateral oophorectomy, or bilateral salpingectomy) or who are postmenopausal. Females will be considered postmenopausal if they have been amenorrhoeic for 12 months or more following cessation of exogenous hormonal treatment. A high FSH level in the postmenopausal range, which will depend on the normative data for the specific assay used, may also be used to confirm a postmenopausal state. At least 2 FSH levels (at least 4 weeks apart) should be within postmenopausal range. If hormonal replacement therapy is discontinued, the first of the 2 consecutive FSH levels should be done at least 6 weeks from stopping hormonal replacement therapy.
Informed Consent
8. Capable of giving signed informed consent as described in Appendix A, which includes compliance with the requirements and restrictions listed in the ICF and in this CSP
9. Participants must give informed consent before initiation of any study-related procedures and willing to comply with all required study procedures.
ExclusionCriteria
Details
Participants are excluded from the study if any of the following criteria apply:
Medical Conditions
1. Homozygous familial hypercholesterolaemia, known diagnosis of 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.
2. Uncontrolled severe hypertension: systolic BP greater than 160 mmHg or diastolic BP greater than 110 mmHg at screening or randomisation despite antihypertensive therapy (based on the mean of the 3 consecutive readings).
3. Severe concomitant non CV disease with risk of life expectancy less than 2 years Participants are excluded from the study if any of the following criteria apply:
Medical Conditions
1. Homozygous familial hypercholesterolaemia, known diagnosis of 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.
2. Uncontrolled severe hypertension: systolic BP greater than 160 mmHg or diastolic BP greater than 110 mmHg at screening or randomisation despite antihypertensive therapy (based on the mean of the 3 consecutive readings).
3. Severe concomitant non CV disease with risk of life expectancy less than 2 years
4. Malignancy (except non - melanoma skin cancers, cervical in situ carcinoma) within 5 years prior to screening
5. Any of the following laboratory values at screening Calculated eGFR less than 15 mL / min / 1.73 m2 (CKD EPI formula Delgado et al 2022, Inker et al 2021)
AST or ALT greater than 3 × ULN
TBL greater than 2 × ULN (except for patients with Gilberts syndrome, where TBL 3 × ULN is acceptable provided direct bilirubin less than 1.5 × ULN)
Fasting triglycerides greater than or equal to 400 mg / dL (greater than or equal to 4.52 mmol / L)
Creatine kinase greater than 5 × ULN
Urine albumin-to-creatinine ratio greater than or equal to 500 mg / g
6. For women only: currently pregnant (confirmed with positive pregnancy test at screening or randomisation) or breast - feeding or planning to become pregnant during the study
7. Acute ischaemic ASCVD event within 7 days prior to screening
8. QTcF greater than 470 msec at randomisation, or with family history of long QT syndrome
9. High-degree AV block II III or sinus node dysfunction with clinically significant sinus pause untreated with pacemaker
10. Heart failure with NYHA Class IV
11. Ventricular arrhythmia requiring treatment
12. Previously diagnosed hypertrophic obstructive cardiomyopathy or any infiltrative cardiomyopathy such as sarcoidosis or amyloidosis
13. Known history of alcohol and / or drug abuse within 5 years prior to screening
14. Recipient of any major organ transplant, eg, lung, liver, heart, bone marrow, renal
15. History of hypersensitivity to AZD0780 or drugs with a similar chemical structure
16. Uncontrolled type 2 diabetes mellitus defined as HbA1C greater than or equal to 9.5% at screening
17. Inadequately treated hypothyroidism defined as TSH greater than 1.5 ULN at screening or participants whose thyroid replacement therapy was initiated or modified within the last 3 months prior to screening
18. Any uncontrolled or serious disease, or any medical (eg, known major active infection [eg, hepatitis B and C] or major CV, haematological, renal, metabolic, gastrointestinal, respiratory, hepatic, or endocrine dysfunction) or surgical condition that, in the opinion of the Investigator, may either interfere with participation in the clinical study and / or put the participant at significant risk
Prior / Concomitant Therapy
19. Receiving, or has received within 14 days of screening, medication that contains a black box warning for significant QT prolongation
20. Use of mipomersen or lomitapide (cholesterol lowering medications) within 12 months prior to screening or planned use during the study
21. Use of gemfibrozil within 1 week prior to screening or planned use during the study
22. 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.
Prior / Concurrent Clinical Study Experience
23. Participation in another clinical study with an IMP administered or device used within 30 days or 5 half lives prior to the screening visit, whichever is longer
24. Planned use of other IMPs or devices during the study
Other Exclusions
25. Any condition that could interfere with the conduct of the study as judged by the Investigator, such as: Inability to communicate or to cooperate with the Investigator
Inability to understand, or unlikely to comply with, the CSP requirements, instructions, study related restrictions, and the nature, scope, and possible consequences of the study
26. Involvement in the planning and / or conduct of the study (applies to both AstraZeneca staff and staff at the study site)
27. Previous randomisation into the present study
Method of Generating Random Sequence
Stratified block randomization
Method of Concealment
Centralized
Blinding/Masking
Participant and Investigator Blinded
Primary Outcome
Outcome
TimePoints
To compare the effect of treatment with AZD0780 versus placebo on LDL-C at 12 weeks
To compare the effect of treatment with AZD0780 versus placebo on LDL-C at 12 weeks
Secondary Outcome
Outcome
TimePoints
To compare the effect of treatment with AZD0780 versus placebo on LDL-C at 12 weeks in patients on background statin therapy at baseline
Relative change in LDL-C from baseline to 12 weeks
To compare the effect of treatment with AZD0780 versus placebo on the probability of LDL-C less than 70 mg/dL at 12 weeks in patients with baseline LDL-C greater than or equal to 70 mg/dL
Indicator for LDL-C less than 70 mg/dL ( less than 1.8 mmol/L) at 12 weeks
To compare the effect of treatment with AZD0780 versus placebo on the probability of LDL-C less than 55 mg/dL at 12 weeks
Indicator for LDL-C less than 55 mg/dL ( less than 1.4 mmol/L) at 12 weeks
To compare the effect of treatment with AZD0780 versus placebo on LDL-C at 28 weeks
Relative change in LDL-C from baseline to 28 weeks
To compare the effect of treatment with AZD0780 versus placebo on LDL-C at 52 weeks
Relative change in LDL-C from baseline to 52 weeks
To compare the effect of treatment with AZD0780 versus placebo on Apo B at 12 weeks
Relative change in Apo B from baseline to 12 weeks
To compare the effect of treatment with AZD0780 versus placebo on non-HDL-C at 12 weeks
Relative change in non-HDL-C from baseline to 12 weeks
To compare the effect of treatment with AZD0780 versus placebo on total cholesterol at 12 weeks
Relative change in total cholesterol from baseline to 12 weeks
To compare the effect of treatment with AZD0780 versus placebo on Lp(a) at 12 weeks
Relative change in Lp(a) from baseline to 12 weeks
To compare the effect of treatment with AZD0780 versus placebo on Lp (a) at 12 weeks
Relative change in Lp (a) from baseline to 12 weeks
Target Sample Size
Total Sample Size="2800" Sample Size from India="100" Final Enrollment numbers achieved (Total)= "Applicable only for Completed/Terminated trials" Final Enrollment numbers achieved (India)="Applicable only for Completed/Terminated trials"
Phase of Trial
Phase 3
Date of First Enrollment (India)
15/12/2025
Date of Study Completion (India)
Applicable only for Completed/Terminated trials
Date of First Enrollment (Global)
28/05/2025
Date of Study Completion (Global)
Applicable only for Completed/Terminated trials
Estimated Duration of Trial
Years="2" Months="0" Days="0"
Recruitment Status of Trial (Global)
Open to Recruitment
Recruitment Status of Trial (India)
Not Yet Recruiting
Publication Details
N/A
Individual Participant Data (IPD) Sharing Statement
Will individual participant data (IPD) be shared publicly (including data dictionaries)?
Response - NO
Brief Summary
The study population comprises adults with
a fasting LDL C of greater than or equal
to 55 mg dL if history of clinical ASCVD or greater than or equal to 70 mg dL if at risk
for a first ASCVD event. Participants should be on maximally tolerated lipid lowering
therapy including maximally tolerated statin therapy.
Statins are the first-line therapy for
lowering of LDL-C recommended in dyslipidaemia guidelines (Grundy et al 2019, Mach et al 2020). Current
guidelines recommend lowering of LDL C to less than 70 mg dL in patients at risk for a
first ASCVD event and to less than 55 mg
dL (ESC EAS [Mach et al 2020]) or less than 70 mg dL (ACC AHA [Grundy et al 2019]) in patients at very high risk or with
existing ASCVD. Accordingly, the selected study population is participants who
despite maximally tolerated statin therapy have not achieved these LDL C
treatment goals.
Reduction of LDL C levels by statins leads to
significant reduction in CV events including coronary artery disease and other
CV deaths (Collins et al 2016). LDL C lowering is
therefore a clinically relevant outcome in this patient population.
Participants will
be randomised in a 1:1 ratio to either AZD0780 or placebo for a treatment
period of 52 weeks and a 10-day safety follow-up.