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, Persistent Inflammation, and Elevated N terminal Prohormone Brain Natriuretic Peptide
- Conditions
- heart attackMyocardial Infarction1002859310003216
- Registration Number
- NL-OMON52059
- Lead Sponsor
- Astra Zeneca
- Brief Summary
Not available
- Detailed Description
Not available
Recruitment & Eligibility
- Status
- Completed
- Sex
- Not specified
- Target Recruitment
- 85
1 Participant must provide informed consent before any study specific
activities are performed (Appendix A 3), 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 (Appendix D 2).
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 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
Study & Design
- Study Type
- Interventional
- Study Design
- Not specified
- Primary Outcome Measures
Name Time Method
- Secondary Outcome Measures
Name Time Method