To evaluate the effect of MEDI6012 on infarct size compared with placebo.
ID
Source
Brief title
Condition
- Myocardial disorders
Synonym
Research involving
Sponsors and support
Intervention
Outcome measures
Primary outcome
Infarct size as a percentage of LV mass measured on delayed-enhanced (CV
magnetic resonance [CMR]) imaging 10-12 weeks post-MI compared to placebo.
Secondary outcome
* EF measured by cine magnetic resonance imaging (MRI) at 10-12 weeks post-MI
compared to placebo.
* Change in NCPV in the coronary arteries from index computed tomography
angiography (CTA) to 10-12 weeks post-MI compared with placebo.
* Myocardial mass and LV volumes at end-systole and end-diastole.
* Incidence of treatment-emergent adverse events (TEAEs) and treatment-emergent
serious adverse events (SAEs).
* Lecithin-cholesterol acyltransferase (LCAT) mass and anti-drug antibodies
(ADAs).
Background summary
Acute STEMI is a major contributor to the development of heart failure (HF) and
death in
patients with CHD. The risk of HF and death is related to the size of the MI
and the impact it
has on heart function. Furthermore, the extent of coronary plaque burden is
directly related to
the risk of death and MI. The only therapy shown to reduce infarct size in
humans with acute
STEMI is primary percutaneous coronary intervention (PCI). In addition, statins
and
proprotein convertase subtilisin kexin 9 inhibitors have demonstrated a
reduction in the
progression of coronary atheroma and reductions in major adverse CV events.
MEDI6012,
with its ability to increase functional HDL-C and apoA1, has the potential to
be the first
therapeutic that can mitigate ischemia-reperfusion injury associated with
primary PCI, confer
cardioprotection by decreasing infarct size and improving LV function, and
induce regression
of coronary atheroma.
Study objective
To evaluate the effect of MEDI6012 on infarct size compared with placebo.
Study design
This is a Phase 2b randomized, blinded (subject/MedImmune blinded, investigator
unblinded), placebocontrolled study to evaluate the efficacy, safety,
PK/pharmacodynamic, and immunogenicity of repeat doses of MEDI6012 in adult
subjects presenting with acute STEMI. At least 414 subjects are planned to be
randomized across approximately 40 study sites in approximately 10 countries,
to evaluate a 2-dose regimen and a 6-dose regimen of MEDI6012. The study will
enrol subjects presenting with acute STEMI within 6 hours of symptom onset who
are planned for primary percutaneous coronary intervention (pPCI). Following
initial screening, subjects will be randomized in a 1:1 ratio to a 2-dose or
6-dose regimen and then randomized within that dose regimen to a 2:1 ratio to
receive MEDI6012 or placebo. For both the 2-dose and the 6-dose regimens, the
first two doses of investigational product will be administered in the
inpatient setting on study Days 1 and 3. Subjects randomized to the 2-dose
regimen will receive standard of care treatment post pPCI. Subjects randomized
to the 6-dose regimen will receive standard of care treatment post pPCI and
additional administration of investigational product on Days 10, 17, 24, and
31. For all subjects, an end of study CMR will be performed at 10-12 weeks
(70-84 days following Dose 1). Subjects randomized to the 6-dose regimen will
also undergo an index (Days 3-5) and an end of study CTA (70-84 days following
Dose 1). If a subject*s Day 70-84 immunogenicity sample is confirmed as ADA
positive and there is a > 30% decrease in HDL-C or a neutralizing antibody
(nAb) is present, the subject will return for additional assessments
Intervention
Cohort A: 2-Dose Regimen
300 mg of MEDI6012 or placebo on Day 1 (loading dose) prior to pPCI followed by
a second inpatient dose
of 150 mg or placebo on Day 3 by intravenous (IV) push.
Cohort B: 6-Dose Regimen
300 mg of MEDI6012 or placebo on Day 1 (loading dose) prior to pPCI followed by
a second inpatient dose
of 150 mg or placebo on Day 3 and outpatient maintenance doses of 100 mg or
placebo on Days 10, 17, 24,
and 31 by IV push.
Study burden and risks
Risks: possible side effects of the study drug and the study procedures.
Burden: Blood draws, physical examination, vital signs measurement, study
visits
MedImmune Way 1
Gaithersburg, Maryland 20878
US
MedImmune Way 1
Gaithersburg, Maryland 20878
US
Listed location countries
Age
Inclusion criteria
1. Men and women without child-bearing potential aged 30-80 years of age who
are capable and willing to provide informed consent.
2. Acute STEMI diagnosed by ST elevation (* 0.1 mV) in 2 contiguous leads
3. Planned for primary PCI
4. Ischemic symptoms for * 6 hours
5. Capable of completing study visit
Exclusion criteria
1. Pre-randomization cardiogenic shock or cardiopulmonary resuscitation
2. Fibrinolytic administration for index event
3. Known prior MI or prior coronary artery bypass grafting
4. Known pre-existing cardiomyopathy
5. History of anaphylaxis
6. Suspected non-thrombotic etiology (ie, vasospasm, dissection, Takotsubo
cardiomyopathy)
7. Other condition or severe illness that the investigator feels would limit
the prognosis of the patient (eg, malignancy with life-expectancy < 3 months)
or would make the patient otherwise unsuitable for enrollment (eg, pose a
hazard or undue burden to the patient [known chronic renal or hepatic
impairment, recent (< 30 days), cerebrovascular accident or transient ischemic
attack] unable to complete study visits)
8. Known contraindication to MR imaging (eg, metallic implant, claustrophobia,
implantable cardioverter-defibrillator (ICD), pacemaker, known CrCl < 30 mL/min
(Cockcroft Gault equation)
9. Pregnant women and/or breastfeeding women.
10. Current or previous participation within the last 30 days in a study using
an investigational therapy or device.
Design
Recruitment
Medical products/devices used
Followed up by the following (possibly more current) registration
No registrations found.
Other (possibly less up-to-date) registrations in this register
No registrations found.
In other registers
| Register | ID |
|---|---|
| EudraCT | EUCTR2017-004521-32-NL |
| CCMO | NL65065.091.18 |