Myocardial Infarction (MI) MedDRA version: 20.0 Level: LLT Classification code 10030272 Term: Old myocardial infarction System Organ Class: 100000004849
Conditions
Interventions
Product Code: MEDI6570
Pharmaceutical Form: Powder for solution for injection
INN or Proposed INN: Not assigned
CAS Number: 2418540-63-1
Current Sponsor code: MEDI6570
Other descriptive name: MEDI6570
Sponsors
AstraZeneca AB
Eligibility
Sex/Gender
All
Inclusion criteria
Inclusion criteria: 1 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. 2 Participant must be = 40 years of age at the time of signing the ICF. 3 Participant must: (a) 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. (b) have persistent inflammation, defined as hs-CRP = 1 mg/L, as measured centrally at screening Visit 1. 4 Participant must have body mass index within the range 18 to 40 kg/m2 inclusive. 5 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: (a) 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. (b) Documentation of irreversible surgical sterilization by hysterectomy, bilateral oophorectomy, or bilateral salpingectomy. Tubal ligation is not considered as irreversible surgical sterilization. 6 Participant must have an evaluable, pre-randomization CTA with quantifiable, non-calcified plaque, as confirmed by the core laboratory. Participants will be reassessed for study eligibility before study intervention is administered on Day 1 (Visit 3). Participants should be considered for a high-intensity statin based on existing guidelines for long-term management of patients after an MI. Participants should ideally be on a stable dose of lipid-lowering therapy throughout the treatment period of the study; therefore, efforts should be made to maximize statin intensity before randomization. The proportion of participants with an NT-proBNP value =65 years) yes F.1.3.1 Number of subjects for this age range 158
Exclusion criteria
Exclusion criteria: 1 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. 2 Percutaneous coronary intervention [PCI] planned after screening Visit 1. Eligible participants who have a PCI planned after screening Visit 1 may be rescreened after the PCI has been performed (Section 5.4). 3 History of or planned coronary artery bypass grafting. 4 Documented episode of post-MI pericarditis (eg, Dressler's Syndrome) in the past 3 months before enrollment. 5 Ongoing New York Heart Association Class IV (severe) HF. 6 Increased risk of bleeding (a) Patients with history or presence of any bleeding disorder. (b) Active bleeding or high risk for major bleeding (eg, gastrointestinal pathology, malignancy with high risk of bleeding, active peptic ulcer). (c) Need for chronic anticoagulation therapy (prophylactic doses of heparin are allowed). (d) Known severe liver disease (eg, ascites and/or clinical signs of coagulopathy). 7 History or presence of any of the following: (a) Ongoing infection or febrile illness that in the opinion of the investigator may be the cause of elevated hs-CRP on screening (Visit 1). (b) Ongoing atrial fibrillation or flutter. (c) Cancer within 5 years before randomization (Day 1; Visit 3), with the exception of non melanoma skin cancer. (d) Alcohol or substance abuse within 6 months before randomization (Day 1; Visit 3), as judged by the investigator. (e) 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. (f) Patients with active positive results on screening for serum hepatitis B surface antigen, hepatitis C antibody, or HIV. 8 Any clinically important abnormalities in clinical chemistry, hematology, coagulation parameters, as judged by the investigator, including but not limited to: (a) Aspartate transaminase (AST) > 2.0 × ULN. (b) Alanine transaminase (ALT) > 2.0 × ULN. (c) Total bilirubin (TBL) > 1.5 x ULN (unless due to Gilbert's syndrome). (d) Platelet count 180 mmHg. (b) Diastolic BP > 100 mmHg. (c) Participants who are excluded based on elevated BP may be rescreened following adequate treatment. The eligibility assessment is based on measurements taken starting from after 5 minutes of rest; if the result is outside these limits, additional BP measurements can be taken over the following 5 minutes, ie, up to a total of 10 minutes of rest (repeated a maximum of 3 times). If the result is outside these limits during this period, the participant is considered a screen fail. 10 Participants with any of the following contraindications to CTA: (a) 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. (b) Allergy to iodinated contrast. (c) History of contrast-induced nephropathy. (d) Contraindication to nitroglycerin. (e) Rapid heart rate that is uncontrolled by medical therapy. (f) Inability to hold breath for at least 6 seconds. 11 Receipt of any investigational device or therapy within 6 months or 5 half-lives before screening (whichever is longer). This criterion does NOT apply fo
Design outcomes
Primary
| Measure | Time frame |
|---|---|
| Main Objective: To evaluate the effect of MEDI6570 on non-calcified coronary atherosclerotic plaques compared with placebo;Secondary Objective: - To evaluate the effect of MEDI6570 on a surrogate biomarker of HF compared with placebo - To evaluate the effect of MEDI6570 on left ventricular systolic function compared with placebo - To evaluate the effect of MEDI6570 on left ventricular systolic function among participants with reduced ejection fraction (defined as < 50%) compared with placebo - To evaluate the effect of MEDI6570 on other measures of non-calcified coronary atherosclerotic plaque compared with placebo - To evaluate the effect of MEDI6570 on coronary inflammation compared with placebo - To evaluate the immunogenicity of MEDI6570 - To evaluate the PK of MEDI6570 - To assess the safety and tolerability of MEDI6570 compared with placebo;Primary end point(s): Change from baseline to Day 253 in non-calcified plaque volume in the most diseased coronary segment (NCPVMD), as measured by CTA imaging;Timepoint(s) of evaluation of this end point: Day 253 | — |
Secondary
| Measure | Time frame |
|---|---|
| Secondary end point(s): 1. Relative change from baseline to Day 253 in NT-proBN (N terminal prohormone brain natriuretic peptide) 2. Change from baseline to Day 253 in: • LVEF (Left ventricular ejection fraction) • GLS (Global longitudinal strain) as measured by echocardiography 3. Change from baseline to Day 253 in: • Global non-calcified plaque volume • Low attenuation plaque volume as measured by CTA imaging 4. Change from baseline to Day 253 in: • FAI (Fat attenuation index) as measured by CTA imaging 5. • ADA (Anti-drug antibody) incidence • Titer as measured in serum during the intervention and follow-up periods 6. MEDI6570 concentrations as measured in serum during the intervention and follow-up periods 7. During the intervention and follow up periods: • AEs • Clinically important changes in: Vital signs ECGs Safety laboratory assessments;Timepoint(s) of evaluation of this end point: 1. to 4. - Day 253 5. to 7. - During the intervention and follow up periods | — |
Countries
Canada, Czechia, Czech Republic, Hungary, Italy, Japan, Netherlands, Poland, Spain, United States
Contacts
Public ContactInformation Center
AstraZeneca
Outcome results
None listed