| E.1 Medical condition or disease under investigation |
| E.1.1 | Medical condition(s) being investigated |
| Myocardial Infarction (MI) |
|
| E.1.1.1 | Medical condition in easily understood language |
|
| E.1.1.2 | Therapeutic area | Diseases [C] - Cardiovascular Diseases [C14] |
| MedDRA Classification |
| E.1.2 Medical condition or disease under investigation |
| E.1.2 | Version | 20.0 |
| E.1.2 | Level | LLT |
| E.1.2 | Classification code | 10030272 |
| E.1.2 | Term | Old myocardial infarction |
| E.1.2 | System Organ Class | 100000004849 |
|
| E.1.3 | Condition being studied is a rare disease | No |
| E.2 Objective of the trial |
| E.2.1 | Main objective of the trial |
To evaluate the effect of MEDI6570 on non-calcified coronary
atherosclerotic plaques compared with placebo |
|
| E.2.2 | Secondary objectives of the trial |
- 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 |
|
| E.2.3 | Trial contains a sub-study | No |
| E.3 | Principal 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 < 125 pg/mL at
screening who can be randomized to a study intervention may be
capped. If this proportion is capped, a baseline NT-proBNP value of ≥
125 pg/mL will be required for inclusion in the study. During the study,
randomization to an intervention group may also be capped within other
specific participant subgroups.
In addition to the inclusion criteria specified above, study participants
may elect to take part in the Genomics Initiative; participants who chose
to do this must provide written informed consent before samples are
collected for the optional genetic research that supports the Genomics
Initiative. |
|
| E.4 | Principal 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 < 100000 platelets/μl.
9 Blood pressure (BP) values at screening Visit 1:
(a) Systolic BP < 90 mmHg or > 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 for inactive, non-replicating COVID-19
vaccines approved by Health Authorities or under emergency use
authorization.
12 Planned participation in an additional study of an intervention or
biologic before the end of the follow-up period.
13 Participants who are legally institutionalized.
14 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. |
|
| E.5 End points |
| E.5.1 | 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 |
|
| E.5.1.1 | Timepoint(s) of evaluation of this end point |
|
| E.5.2 | 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 |
|
| E.5.2.1 | Timepoint(s) of evaluation of this end point |
1. to 4. - Day 253
5. to 7. - During the intervention and follow up periods |
|
| E.6 and E.7 Scope of the trial |
| E.6 | Scope of the trial |
| E.6.1 | Diagnosis | No |
| E.6.2 | Prophylaxis | No |
| E.6.3 | Therapy | No |
| E.6.4 | Safety | Yes |
| E.6.5 | Efficacy | Yes |
| E.6.6 | Pharmacokinetic | Yes |
| E.6.7 | Pharmacodynamic | No |
| E.6.8 | Bioequivalence | No |
| E.6.9 | Dose response | No |
| E.6.10 | Pharmacogenetic | No |
| E.6.11 | Pharmacogenomic | No |
| E.6.12 | Pharmacoeconomic | No |
| E.6.13 | Others | Yes |
| E.6.13.1 | Other scope of the trial description |
| Immunogenicity, tolerability |
|
| E.7 | Trial type and phase |
| E.7.1 | Human pharmacology (Phase I) | No |
| E.7.1.1 | First administration to humans | No |
| E.7.1.2 | Bioequivalence study | No |
| E.7.1.3 | Other | No |
| E.7.1.3.1 | Other trial type description | |
| E.7.2 | Therapeutic exploratory (Phase II) | Yes |
| E.7.3 | Therapeutic confirmatory (Phase III) | No |
| E.7.4 | Therapeutic use (Phase IV) | No |
| E.8 Design of the trial |
| E.8.1 | Controlled | Yes |
| E.8.1.1 | Randomised | Yes |
| E.8.1.2 | Open | No |
| E.8.1.3 | Single blind | No |
| E.8.1.4 | Double blind | Yes |
| E.8.1.5 | Parallel group | Yes |
| E.8.1.6 | Cross over | No |
| E.8.1.7 | Other | No |
| E.8.2 | Comparator of controlled trial |
| E.8.2.1 | Other medicinal product(s) | No |
| E.8.2.2 | Placebo | Yes |
| E.8.2.3 | Other | No |
| E.8.2.4 | Number of treatment arms in the trial | 6 |
| E.8.3 |
The trial involves single site in the Member State concerned
| No |
| E.8.4 | The trial involves multiple sites in the Member State concerned | Yes |
| E.8.4.1 | Number of sites anticipated in Member State concerned | 6 |
| E.8.5 | The trial involves multiple Member States | Yes |
| E.8.5.1 | Number of sites anticipated in the EEA | 36 |
| E.8.6 Trial involving sites outside the EEA |
| E.8.6.1 | Trial being conducted both within and outside the EEA | Yes |
| E.8.6.2 | Trial being conducted completely outside of the EEA | No |
| E.8.6.3 | If E.8.6.1 or E.8.6.2 are Yes, specify the regions in which trial sites are planned |
| Canada |
| Japan |
| United States |
| Hungary |
| Italy |
| Netherlands |
| Poland |
| Spain |
| Czechia |
|
| E.8.7 | Trial has a data monitoring committee | Yes |
| E.8.8 |
Definition of the end of the trial and justification where it is not the last
visit of the last subject undergoing the trial
|
The end of the study is defined as the date of the last visit/assessment
(including telephone contact) of the last participant in the study
globally. |
|
| E.8.9 Initial estimate of the duration of the trial |
| E.8.9.1 | In the Member State concerned years | 2 |
| E.8.9.1 | In the Member State concerned months | 2 |
| E.8.9.1 | In the Member State concerned days | 0 |
| E.8.9.2 | In all countries concerned by the trial years | 2 |
| E.8.9.2 | In all countries concerned by the trial months | 5 |
| E.8.9.2 | In all countries concerned by the trial days | 0 |
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