NCT04610892已完成2 期
A Phase IIB, Randomized, Double Blinded, Placebo Controlled, Parallel Group Study to Evaluate the Efficacy and Safety of MEDI6570 in Participants With a Prior Myocardial Infarction and Persistent Inflammation
适应症
干预措施
相关药物
试验速览
- 阶段
- 2 期
- 状态
- 已完成
- 发起方
- AstraZeneca
- 入组人数
- 423
- 试验地点
- 1
- 主要终点
- Change From Baseline to Day 253 in Non-calcified Plaque Volume in the Most Diseased Coronary Segment (NCPVMD), as Measured by Computed Tomography Angiography (CTA) Imaging
研究概览
简要总结
A Phase IIB Parallel group Study to Evaluate the Efficacy and Safety of MEDI6570 in Participants with a Prior Myocardial Infarction.
详细描述
This Phase IIB, proof-of-concept, dose-range finding clinical study is being conducted to evaluate the anti-inflammatory potential of MEDI6570 and its effect on surrogates for atherosclerotic and heart failure (HF) events in patients with a history of myocardial infarction (MI). The results of the Phase IIB study will inform future clinical development options and precision medicine strategy for future clinical studies.
Participants will be randomized in a 2:2:1:1 ratio after protocol Amend 2, 360 evaluable participants (111 evaluable participants in each of the 2 MEDI6570 groups, plus 27 evaluable participants in the legacy low dose MEDI6570 group, plus 111 participants in pooled placebo) will complete the study.
研究设计
- 研究类型
- Interventional
- 分配方式
- Randomized
- 干预模型
- Parallel
- 主要目的
- Treatment
- 盲法
- Quadruple (Participant, Care Provider, Investigator, Outcomes Assessor)
入排标准
- 年龄范围
- 21 Years 至 —（Adult, Older Adult）
- 性别
- All
- 接受健康志愿者
- 否
入选标准
- •Participant must provide informed consent before any study specific activities are performed, must be able and willing to meet all requirements for randomization within 42 days after signing the full ICF, and must adhere to the schedules of activities.
- •Women must be ≥ 40 years of age at the time of signing the ICF. Men must be ≥ 21 years of age at the time of signing the ICF.
- •Participant must:
- •be 30 to 365 days after presumed type-1 (ie, due to plaque rupture or erosion) MI (either STEMI or NSTEMI) at the time of enrollment.
- •have persistent inflammation, defined as hs CRP ≥ 1 mg/L, as measured centrally at screening Visit
- •Participant must have body mass index within the range 18 to 40 kg/m2 inclusive.
- •For female participants, the participant must not be pregnant or lactating and must be of non-childbearing potential, confirmed at screening Visit 1 by one of the following:
- •Postmenopausal, defined as amenorrhea for ≥ 12 months following cessation of all exogenous hormonal treatments, and with luteinizing hormone and follicle stimulating hormone levels in the postmenopausal range.
- •Documentation of irreversible surgical sterilization by hysterectomy, bilateral oophorectomy, or bilateral salpingectomy. Tubal ligation is not considered as irreversible surgical sterilization.
- •Participant must have an evaluable, pre-randomization CTA with quantifiable, non calcified plaque.
排除标准
- •History of any clinically important disease or disorder which, in the opinion of the investigator, may either put the participant at risk because of participation in the study, or influence the results or the participant's ability to participate in the study.
- •Percutaneous coronary intervention or diagnostic angiogram planned after screening. Eligible participants who have a diagnostic angiogram performed in the absence of undergoing a new PCI may continue screening after the diagnostic angiogram has been performed or may be rescreened.
- •History of or planned coronary artery bypass grafting.
- •Documented episode of post-MI pericarditis in the 3 months before enrollment.
- •Ongoing New York Heart Association Class IV HF.
- •Increased risk of bleeding
- •Patients with history or presence of any bleeding disorder.
- •Signs of ongoing bleeding at screening (eg, identified macroscopic bleeding, low hemoglobin presumed to be caused by bleeding) or high risk for major bleeding in accordance with the Investigator's assessment.
- •Need for chronic therapeutic anticoagulation therapy anticipated to be required throughout the course of the study (short-term treatment with prophylactic doses of heparin/low molecular weight heparin are allowed).
- •Known severe liver disease.
- •History or presence of any of the following:
- •Ongoing infection or febrile illness that in the opinion of the investigator may be the cause of elevated hs-CRP on screening.
- •Ongoing atrial fibrillation or flutter.
- •Cancer within 5 years before randomization, with the exception of non melanoma skin cancer.
- •Alcohol or substance abuse within 6 months before randomization, as judged by the investigator.
- •Known history of hypersensitivity reactions to other biologics, to human IgG preparations, or to any component of MEDI6570, or ongoing severe allergy as judged by the investigator.
- •Patients with active positive results on screening for serum hepatitis B surface antigen, hepatitis C antibody, or HIV.
- •Any clinically important abnormalities in clinical chemistry, hematology, coagulation parameters, as judged by the investigator.
- •BP values at screening:
- •Systolic BP < 90 mmHg or > 180 mmHg.
- •Diastolic BP > 100 mmHg.
- •Participants who are excluded based on elevated BP may be rescreened following adequate treatment.
- •Participants with any of the following contraindications to CTA:
- •eGFR < 50 mL/min/1.73 m2 by the Chronic Kidney Disease Epidemiology Collaboration equation, or end stage renal disease treated with kidney transplant or renal replacement therapy.
- •Allergy to iodinated contrast.
- •History of contrast-induced nephropathy.
- •Contraindication to nitroglycerin.
- •Rapid heart rate that is uncontrolled by medical therapy.
- •Inability to hold breath for at least 6 seconds.
- •Receipt of any investigational device or therapy within 6 months or 5 half lives before screening (whichever is longer).
- •This criterion does NOT apply for inactive, non replicating COVID-19 vaccines approved by Health Authorities or under emergency use authorization.
- •Planned participation in an additional investigational study of an intervention or biologic before the end of the follow-up period. Participation in observational studies or studies without investigational drugs or devices is allowed.
- •Participants who are legally institutionalized.
- •An employee or close relative of an employee of the sponsor, the CRO, or the study site, regardless of the employee or close relative's role.
研究组 & 干预措施
MEDI6570 Low dose
Experimental
Monthly Subcutaneous administration.
干预措施: MEDI6570 (Biological)
MEDI6570 Medium dose
Experimental
Monthly Subcutaneous administration.
干预措施: MEDI6570 (Biological)
MEDI6570 High dose
Experimental
Monthly Subcutaneous administration.
干预措施: MEDI6570 (Biological)
Placebo Low dose
Placebo Comparator
Monthly Subcutaneous administration.
干预措施: Placebo (Biological)
Placebo Medium dose
Placebo Comparator
Monthly Subcutaneous administration
干预措施: Placebo (Biological)
Placebo High dose
Placebo Comparator
Monthly Subcutaneous administration
干预措施: Placebo (Biological)
结局指标
主要结局
Change From Baseline to Day 253 in Non-calcified Plaque Volume in the Most Diseased Coronary Segment (NCPVMD), as Measured by Computed Tomography Angiography (CTA) Imaging
时间窗: From baseline to Day 253
To evaluate the effect of MEDI6570 on non-calcified coronary atherosclerotic plaques compared with placebo. The primary endpoint of change in NCPVMD from baseline to Day 253 was assessed based on the CTA Analysis Populations.
次要结局
- Change From Baseline to Day 253 in N Terminal Prohormone Brain Natriuretic Peptide (NT-proBNP)(From baseline to Day 253)
- Change From Baseline to Day 253 in Left Ventricular Ejection Fraction (LVEF)(From baseline to Day 253)
- Left Ventricular Ejection Fraction (LVEF) Change From Baseline to Day 253 Among Subjects With Reduced Ejection Fraction (< 50%)(From baseline to Day 253)
- Change From Baseline to Day 253 in Global Longitudinal Strain (GLS)(From baseline to Day 253)
- Global Longitudinal Strain (GLS) Change From Baseline to Day 253 Among Subjects With Reduced Ejection Fraction (< 50%)(From baseline to Day 253)
- Change From Baseline to Day 253 in Global Non-calcified Plaque Volume (NCPV)(From baseline to Day 253)
- Change From Baseline to Day 253 in Low Attenuation Plaque Volume (LAPV)(From baseline to Day 253)
- Summary of ADA (Anti-drug Antibody) Responses During the Study(From baseline to Day 325/405. Day 325/405: for participants who completed the study under clinical study protocol (CSP) Amendment 1 & 2, the end of study visits were Day 405 and Day 325 respectively.)
- Anti-drug Antibody Titre Summary by Visit(From Baseline to Day 325/405. Day 325/405: for participants who completed the study under CSP Amendment 1 & 2, the end of study visits were Day 405 and Day 325 respectively.)
- Summary of Serum Concentrations (ug/mL) of MEDI6570(From baseline to Day 325/Day 405)
- Number of Participants With Adverse Events in Any Category(During study follow-up (from day 1 to day 325))
- Number of Participants With Most Common Adverse Events (Frequency > 5%)(During study follow-up (from day 1 to day 325))
- Vital Signs (Change in Systolic and Diastolic Blood Pressure From Baseline) Over Time(From baseline to Day 325/405. Day 325/405: for participants who completed the study under CSP Amendment 1 & 2, the end of study visits were Day 405 and Day 325 respectively.)
- Vital Signs (Change in Heart Rate From Baseline) Variables Over Time(From baseline to Day 325/405. Day 325/405: for participants who completed the study under CSP Amendment 1 & 2, the end of study visits were Day 405 and Day 325 respectively.)
- Vital Signs (Change of Weight From Baseline to Day 325/405 )(From baseline to Day 325/405. Day 325/405: for participants who completed the study under CSP Amendment 1 & 2, the end of study visits were Day 405 and Day 325 respectively)
研究者
研究点 (1)
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