CTRI/2025/08/093484尚未招募3 期
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)
试验速览
- 阶段
- 3 期
- 状态
- 尚未招募
- 入组人数
- 2,800
- 试验地点
- 12
- 主要终点
- To compare the effect of treatment with AZD0780 versus placebo on LDL-C at 12 weeks
研究概览
简要总结
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.
研究设计
- 研究类型
- Interventional
- 分配方式
- Randomized
- 盲法
- Participant and Investigator Blinded
入排标准
- 年龄范围
- 18.00 Year(s) 至 99.00 Year(s)（—）
- 性别
- All
入选标准
- •greater than or equal to 18 years of age at the time of signing the ICF Type of Participant and Disease Characteristics
- •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.
- •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
- •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.
- •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.
- •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
- •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
- •Participants must give informed consent before initiation of any study-related procedures and willing to comply with all required study procedures.
排除标准
- •Participants are excluded from the study if any of the following criteria apply: Medical Conditions
- •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.
- •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).
- •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
- •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.
- •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).
- •Severe concomitant non CV disease with risk of life expectancy less than 2 years
- •Malignancy (except non.
- •melanoma skin cancers, cervical in situ carcinoma) within 5 years prior to screening
- •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
- •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
- •Acute ischaemic ASCVD event within 7 days prior to screening
- •QTcF greater than 470 msec at randomisation, or with family history of long QT syndrome
- •High-degree AV block II III or sinus node dysfunction with clinically significant sinus pause untreated with pacemaker
- •Heart failure with NYHA Class IV
- •Ventricular arrhythmia requiring treatment
- •Previously diagnosed hypertrophic obstructive cardiomyopathy or any infiltrative cardiomyopathy such as sarcoidosis or amyloidosis
- •Known history of alcohol and / or drug abuse within 5 years prior to screening
- •Recipient of any major organ transplant, eg, lung, liver, heart, bone marrow, renal
- •History of hypersensitivity to AZD0780 or drugs with a similar chemical structure
- •Uncontrolled type 2 diabetes mellitus defined as HbA1C greater than or equal to 9.5% at screening
- •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
- •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
- •Receiving, or has received within 14 days of screening, medication that contains a black box warning for significant QT prolongation
- •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. Prior / Concurrent Clinical Study Experience
- •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
- •Planned use of other IMPs or devices during the study Other Exclusions
- •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
- •Involvement in the planning and / or conduct of the study (applies to both AstraZeneca staff and staff at the study site)
- •Previous randomisation into the present study.
结局指标
主要结局
To compare the effect of treatment with AZD0780 versus placebo on LDL-C at 12 weeks
时间窗: To compare the effect of treatment with AZD0780 versus placebo on LDL-C at 12 weeks
次要结局
- 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)
研究者
Tapankumar M Shah
AstraZeneca Pharma India Ltd
研究点 (12)
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