A Study to Evaluate the Safety and Efficacy of MEDI6012 in Acute ST Elevation Myocardial Infarction (REAL-TIMI 63B)

A Randomized, Placebo-controlled Phase 2b Study to Evaluate the Safety and Efficacy of MEDI6012 in Acute ST Elevation Myocardial Infarction

This is a Phase 2b randomized, blinded, placebo controlled study to evaluate the efficacy, safety, PK/pharmacodynamic, and immunogenicity of repeat doses of MEDI6012 in adult participants presenting with acute STEMI (ST segment elevation myocardial infarction).

The study will enrol participants presenting with acute STEMI who are planned for primary percutaneous coronary intervention (pPCI). For all participants, an end of study CMR will be performed at 10-12 weeks (70-84 days following Dose 1). A subset of participants will also undergo an index and an end of study CTA.

Study Overview

• Status: Completed
• Conditions: ST Elevation Myocardial Infarction
• Intervention / Treatment: Other: Placebo; Biological: MEDI6012

• Study Type: Interventional
• Enrollment (Actual): 593
• Phase: Phase 2

Contacts and Locations

Study Locations

• Brazil
  • Belo Horizonte, Brazil, 30110-934
    • Research Site
  • Campinas, Brazil, 13060-080
    • Research Site
  • Porto Alegre, Brazil, 90610-000
    • Research Site
  • Porto Alegre, Brazil, 90620-001
    • Research Site
• Czechia
  • Brno, Czechia, 65691
    • Research Site
  • Hradec Kralove, Czechia, 500 05
    • Research Site
  • Liberec, Czechia, 46063
    • Research Site
  • Pardubice, Czechia, 53203
    • Research Site
  • Praha 10, Czechia, 10034
    • Research Site
  • Praha 2, Czechia, 12808
    • Research Site
  • Usti nad Labem, Czechia, 40113
    • Research Site
• Hungary
  • Budapest, Hungary, 1122
    • Research Site
  • Budapest, Hungary, 1134
    • Research Site
• Israel
  • Beer Sheva, Israel, 8410101
    • Research Site
  • Haifa, Israel, 3109601
    • Research Site
  • Jerusalem, Israel, 91120
    • Research Site
  • Jerusalem, Israel, 9103102
    • Research Site
  • Petah Tikva, Israel, 4941492
    • Research Site
  • Ramat Gan, Israel, 5265601
    • Research Site
  • Tel Aviv, Israel, 6423906
    • Research Site
• Netherlands
  • Alkmaar, Netherlands, 1815 JD
    • Research Site
  • Nijmegen, Netherlands, 6532 SZ
    • Research Site
  • Nijmegen, Netherlands, 6525 GA
    • Research Site
• Poland
  • Bydgoszcz, Poland, 85-094
    • Research Site
  • Lodz, Poland, 90-549
    • Research Site
  • Lodz, Poland, 91-347
    • Research Site
• Russian Federation
  • Kazan, Russian Federation, 420101
    • Research Site
  • Saint Petersburg, Russian Federation, 197044
    • Research Site
  • Saint Petersburg, Russian Federation, 197706
    • Research Site
• Slovakia
  • Banska Bystrica, Slovakia, 974 01
    • Research Site
  • Nitra, Slovakia, 949 01
    • Research Site
• Spain
  • Madrid, Spain, 28046
    • Research Site
  • Madrid, Spain, 28040
    • Research Site
  • Pontevedra, Spain, 36312
    • Research Site
• United Kingdom
  • Dundee, United Kingdom, DD1 9SY
    • Research Site
  • Leeds, United Kingdom, LS13EX
    • Research Site
  • Stevenage, United Kingdom, SG1 4AB
    • Research Site

Participation Criteria

Eligibility Criteria

• Ages Eligible for Study: 30 years to 80 years (Adult, Older Adult)
• Accepts Healthy Volunteers: No
• Genders Eligible for Study: All

Description

Inclusion Criteria:

• Acute STEMI (ST segment elevation myocardial infarction) diagnosed by ST elevation
• Planned for primary PCI (percutaneous coronary intervention)
• Men and women without child-bearing potential aged 30-80 years of age
• Capable and willing to provide informed consent.
• Capable of completing study visits

Exclusion Criteria:

• Fibrinolytic administration for index event
• Known prior MI or prior coronary artery bypass graft (CABG) surgery
• Known pre-existing cardiomyopathy
• History of anaphylaxis
• Suspected non-thrombotic etiology (ie, vasospasm, dissection, Takotsubo cardiomyopathy)

Study Plan

How is the study designed?

Design Details

• Primary Purpose: Treatment
• Allocation: Randomized
• Interventional Model: Parallel Assignment
• Masking: Triple

Number of Arms

4

Arms and Interventions

Participant Group / Arm	Intervention / Treatment
Placebo Comparator: Cohort A: Placebo; Participants will receive placebo matched to MEDI6012 on Day 1 prior to pPCI followed by a second inpatient dose on Day 3 by IV push.	Other: Placebo; Placebo; Other Names: Placebo matched to MEDI6012 will be administered on Day 1 and Day 3 by IV push in Cohorts A and B, and on Days 10, 17, 24, and 31 by IV push in Cohort B.
Experimental: Cohort A: MEDI6012; Participants will receive loading dose of MEDI6012 300 mg on Day 1 prior to pPCI followed by a second inpatient dose of MEDI6012 150 mg on Day 3 by IV push.	Biological: MEDI6012; MEDI6012; Other Names: MEDI6012 300 mg will be administered on Day 1 and MEDI6012 150 mg on Day 3 by IV push in Cohorts A and B. In Cohort B, MEDI6012 100 mg will be administered on Days 10, 17, 24, and 31 by IV push.
Placebo Comparator: Cohort B: Placebo; Participants will receive placebo matched to MEDI6012 on Day 1 prior to pPCI followed by a second inpatient dose on Day 3, and outpatient maintenance doses on Days 10, 17, 24, and 31 by IV push.	Other: Placebo; Placebo; Other Names: Placebo matched to MEDI6012 will be administered on Day 1 and Day 3 by IV push in Cohorts A and B, and on Days 10, 17, 24, and 31 by IV push in Cohort B.
Experimental: Cohort B: MEDI6012; Participants will receive loading dose of MEDI6012 300 mg on Day 1 prior to pPCI followed by a second inpatient dose of MEDI6012 150 mg on Day 3, and outpatient maintenance doses of MEDI6012 100 mg on Days 10, 17, 24, and 31 by IV push.	Biological: MEDI6012; MEDI6012; Other Names: MEDI6012 300 mg will be administered on Day 1 and MEDI6012 150 mg on Day 3 by IV push in Cohorts A and B. In Cohort B, MEDI6012 100 mg will be administered on Days 10, 17, 24, and 31 by IV push.

What is the study measuring?

Primary Outcome Measures

Outcome Measure	Measure Description	Time Frame
Global Infarct Size	Global infarct size expressed as a percentage of left ventricle (LV) mass measured on delayed-enhanced cardiovascular magnetic resonance (CMR) imaging in 10-12 weeks post myocardial infarction (MI) is reported.	70 to 84 days post Day 1 dose

Secondary Outcome Measures

Outcome Measure	Measure Description	Time Frame
Left Ventricular Ejection Fraction (LVEF)	The LVEF measured by cine magnetic resonance imaging (MRI) at 10-12 weeks post-MI is reported.	70 to 84 days post Day 1 dose
Change in Non-calcified Plaque Volume (NCPV) in the Coronary Arteries in Cohort B	Change in NCPV in the coronary arteries from index computed tomography angiography (CTA) to 10-12 weeks post-MI is reported. The index CTA was preferably to be performed between 48 to 72 hours post Dose 1 (could be done up to 5 days post Dose 1) but no earlier than 40 hours post Dose 1. Participants with creatinine clearance >= 60 mL/min (Cockcroft Gault equation) within 6 hours underwent an index coronary CTA no earlier than 40 hours following the first dose.	Day 1 dose (48 to 72 hours post Dose 1) through 70 to 84 days post Day 1 dose
Left Ventricular Mass by Late Gadolinium Enhancement (LGE)	The left ventricular mass by LGE is reported.	70 to 84 days post Day 1 dose
Left Ventricular Mass by Cine Magnetic Resonance Imaging (MRI)	The left ventricular mass by cine MRI is reported.	70 to 84 days post Day 1 dose
Left Ventricular End-diastolic and End-systolic Volume	Left ventricular end-diastolic and end-systolic volume is reported.	70 to 84 days post Day 1 dose
Left Ventricular End-diastolic and End-systolic Volume Index	Left ventricular end-diastolic and end-systolic volume index is reported.	70 to 84 days post Day 1 dose
Number of Participants With Treatment Emergent Adverse Events (TEAEs) and Treatment Emergent Serious Adverse Events (TESAEs)	An adverse event (AE) is any untoward medical occurrence in a participant who received study drug without regard to possibility of causal relationship. A serious adverse event (SAE) is an AE resulting in any of the following outcomes or deemed significant for any other reason: death; initial or prolonged inpatient hospitalization; life threatening experience (immediate risk of dying); persistent or significant disability/incapacity; congenital anomaly. The TEAEs are defined as events present at baseline that worsened in intensity after administration of study drug or events absent at baseline that emerged after administration of study drug.	Day 1 through Day 195 post Day 1 dose
Serum Concentration of MEDI6012 (Lecithin-cholesterol Acyltransferaes [LCAT] Mass)	Serum concentration of MEDI6012 is reported.	Pre- and post-dose on Days 1, 3, 17, and 31
Number of Participants With Positive Anti-Drug Antibodies (ADA) to MEDI6012	Number of participants with positive ADA titer to MEDI6012 are reported in 3 categories, ADA positive at any visit up to Day 70-84 follow-up visit, ADA positive with > 30% decrease in HDL-C from baseline (on the same date) at any visit up to D70-84 FU V, and ADA positive and > 30% decrease in HDL-C from baseline at Day 70-84 Follow-up Visit.	Predose on Day 1, Day 17, Day 31, 70 to 84 days, and on Day 195 post Day 1 dose

Collaborators and Investigators

• Sponsor: MedImmune LLC
• Collaborators: Thrombolysis in Myocardial Infarction (TIMI) Study Group

Publications and helpful links

General Publications

• Bonaca MP, Morrow DA, Bergmark BA, Berg DD, Lima JAC, Hoffmann U, Kato Y, Lu MT, Kuder J, Murphy SA, Spinar J, Oude Ophuis T, Kiss RG, Lopez-Sendon J, Averkov O, Wheatcroft SB, Kubica J, Carlos Nicolau J, Furtado RHM, Abuhatzira L, Hirshberg B, Omar SA, Vavere AL, Chang YT, George RT, Sabatine MS. Randomized, Placebo-Controlled Phase 2b Study to Evaluate the Safety and Efficacy of Recombinant Human Lecithin Cholesterol Acyltransferase in Acute ST-Segment-Elevation Myocardial Infarction: Results of REAL-TIMI 63B. Circulation. 2022 Sep 20;146(12):907-916. doi: 10.1161/CIRCULATIONAHA.122.059325. Epub 2022 Aug 30.

Helpful Links

• D5780C00007 CSP Redacted
• D5780C00007 SAP Redacted
• D5780C00007 CSR Synopsis Redacted

Study record dates

Study Major Dates

• Study Start (Actual): June 5, 2018
• Primary Completion (Actual): January 18, 2021
• Study Completion (Actual): January 18, 2021

Study Registration Dates

• First Submitted: June 8, 2018
• First Submitted That Met QC Criteria: July 5, 2018
• First Posted (Actual): July 6, 2018

Study Record Updates

• Last Update Posted (Actual): February 9, 2022
• Last Update Submitted That Met QC Criteria: January 13, 2022
• Last Verified: January 1, 2022

More Information

Terms related to this study

• Additional Relevant MeSH Terms: Ischemia; Pathologic Processes; Necrosis; Myocardial Ischemia; Heart Diseases; Cardiovascular Diseases; Vascular Diseases; Myocardial Infarction; Infarction; ST Elevation Myocardial Infarction
• Other Study ID Numbers: D5780C00007

Plan for Individual participant data (IPD)

• Plan to Share Individual Participant Data (IPD)?: Yes

IPD Plan Description

Qualified researchers can request access to anonymized individual patient-level data from AstraZeneca group of companies sponsored clinical trials via the request portal. All request will be evaluated as per the AZ disclosure commitment: https://astrazenecagrouptrials.pharmacm.com/ST/Submission/Disclosure.

Yes, indicates that AZ are accepting requests for IPD, but this does not mean all requests will be shared.

• IPD Sharing Time Frame: AstraZeneca will meet or exceed data availability as per the commitments made to the EFPIA Pharma Data Sharing Principles. For details of our timelines, please rerefer to our disclosure commitment at https://astrazenecagrouptrials.pharmacm.com/ST/Submission/Disclosure.
• IPD Sharing Access Criteria: When a request has been approved AstraZeneca will provide access to the de-identified individual patient-level data in an approved sponsored tool . Signed Data Sharing Agreement (non-negotiable contract for data accessors) must be in place before accessing requested information. Additionally, all users will need to accept the terms and conditions of the SAS MSE to gain access. For additional details, please review the Disclosure Statements at https://astrazenecagrouptrials.pharmacm.com/ST/Submission/Disclosure.
• IPD Sharing Supporting Information Type: Study Protocol; Statistical Analysis Plan (SAP)

Drug and device information, study documents

• Studies a U.S. FDA-regulated drug product: Yes
• Studies a U.S. FDA-regulated device product: No
• product manufactured in and exported from the U.S.: Yes