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

• ClinicalTrials.gov Identifier: NCT03578809
• Recruitment Status: Completed
• First Posted: July 6, 2018
• Results First Posted: February 9, 2022
• Last Update Posted: February 9, 2022
• Sponsor: MedImmune LLC
• Collaborator: Thrombolysis in Myocardial Infarction (TIMI) Study Group
• Information provided by (Responsible Party): MedImmune LLC

Study Description

Brief Summary:

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.

Condition or disease	Intervention/treatment	Phase
ST Elevation Myocardial Infarction	Biological: MEDI6012; Other: Placebo	Phase 2

Study Design

• Study Type: Interventional (Clinical Trial)
• Actual Enrollment: 593 participants
• Allocation: Randomized
• Intervention Model: Parallel Assignment
• Masking: Triple (Participant, Care Provider, Outcomes Assessor)
• Masking Description: In this study, the participant and sponsor staff will be blinded. Sites will be trained to keep the investigator blinded. However, due to the acute nature of the study, members of the research team and, possibly, the investigator may be unblinded.
• Primary Purpose: Treatment
• Official Title: A Randomized, Placebo-controlled Phase 2b Study to Evaluate the Safety and Efficacy of MEDI6012 in Acute ST Elevation Myocardial Infarction
• Actual Study Start Date: June 5, 2018
• Actual Primary Completion Date: January 18, 2021
• Actual Study Completion Date: January 18, 2021

Arms and Interventions

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 Name: 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 Name: 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 Name: 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 Name: 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.

Outcome Measures

Primary Outcome Measures :

1. Global Infarct Size [ Time Frame: 70 to 84 days post Day 1 dose ]
   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.

Secondary Outcome Measures :

1. Left Ventricular Ejection Fraction (LVEF) [ Time Frame: 70 to 84 days post Day 1 dose ]
   The LVEF measured by cine magnetic resonance imaging (MRI) at 10-12 weeks post-MI is reported.
2. Change in Non-calcified Plaque Volume (NCPV) in the Coronary Arteries in Cohort B [ Time Frame: Day 1 dose (48 to 72 hours post Dose 1) through 70 to 84 days post Day 1 dose ]
   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.
3. Left Ventricular Mass by Late Gadolinium Enhancement (LGE) [ Time Frame: 70 to 84 days post Day 1 dose ]
   The left ventricular mass by LGE is reported.
4. Left Ventricular Mass by Cine Magnetic Resonance Imaging (MRI) [ Time Frame: 70 to 84 days post Day 1 dose ]
   The left ventricular mass by cine MRI is reported.
5. Left Ventricular End-diastolic and End-systolic Volume [ Time Frame: 70 to 84 days post Day 1 dose ]
   Left ventricular end-diastolic and end-systolic volume is reported.
6. Left Ventricular End-diastolic and End-systolic Volume Index [ Time Frame: 70 to 84 days post Day 1 dose ]
   Left ventricular end-diastolic and end-systolic volume index is reported.
7. Number of Participants With Treatment Emergent Adverse Events (TEAEs) and Treatment Emergent Serious Adverse Events (TESAEs) [ Time Frame: Day 1 through Day 195 post Day 1 dose ]
   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.
8. Serum Concentration of MEDI6012 (Lecithin-cholesterol Acyltransferaes [LCAT] Mass) [ Time Frame: Pre- and post-dose on Days 1, 3, 17, and 31 ]
   Serum concentration of MEDI6012 is reported.
9. Number of Participants With Positive Anti-Drug Antibodies (ADA) to MEDI6012 [ Time Frame: Predose on Day 1, Day 17, Day 31, 70 to 84 days, and on Day 195 post Day 1 dose ]
   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.

Eligibility Criteria

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

Criteria

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)

Contacts and Locations

Locations

Brazil

Research Site

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

Czechia

Research Site

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

Hungary

Research Site

Budapest, Hungary, 1122

Research Site

Budapest, Hungary, 1134

Israel

Research Site

Beer Sheva, Israel, 8410101

Research Site

Haifa, Israel, 3109601

Research Site

Jerusalem, Israel, 9103102

Research Site

Jerusalem, Israel, 91120

Research Site

Petah Tikva, Israel, 4941492

Research Site

Ramat Gan, Israel, 5265601

Research Site

Tel Aviv, Israel, 6423906

Netherlands

Research Site

Alkmaar, Netherlands, 1815 JD

Research Site

Nijmegen, Netherlands, 6525 GA

Research Site

Nijmegen, Netherlands, 6532 SZ

Poland

Research Site

Bydgoszcz, Poland, 85-094

Research Site

Lodz, Poland, 90-549

Research Site

Lodz, Poland, 91-347

Russian Federation

Research Site

Kazan, Russian Federation, 420101

Research Site

Saint Petersburg, Russian Federation, 197044

Research Site

Saint Petersburg, Russian Federation, 197706

Slovakia

Research Site

Banska Bystrica, Slovakia, 974 01

Research Site

Nitra, Slovakia, 949 01

Spain

Research Site

Madrid, Spain, 28040

Research Site

Madrid, Spain, 28046

Research Site

Pontevedra, Spain, 36312

United Kingdom

Research Site

Dundee, United Kingdom, DD1 9SY

Research Site

Leeds, United Kingdom, LS13EX

Research Site

Stevenage, United Kingdom, SG1 4AB

Sponsors and Collaborators

MedImmune LLC

Thrombolysis in Myocardial Infarction (TIMI) Study Group

  Study Documents (Full-Text)

Documents provided by MedImmune LLC:

Study Protocol  [PDF] May 4, 2020

Statistical Analysis Plan  [PDF] December 4, 2020

More Information

Additional Information:

D5780C00007 CSP Redacted 

D5780C00007 SAP Redacted 

D5780C00007 CSR Synopsis Redacted 

• Responsible Party: MedImmune LLC
• ClinicalTrials.gov Identifier: NCT03578809
• Other Study ID Numbers: D5780C00007
• First Posted: July 6, 2018
• Results First Posted: February 9, 2022
• Last Update Posted: February 9, 2022
• Last Verified: January 2022

Individual Participant Data (IPD) Sharing Statement:

• Plan to Share IPD: Yes

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.

• Supporting Materials: Study Protocol; Statistical Analysis Plan (SAP)
• 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.
• 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.
• URL: https://astrazenecagroup-dt.pharmacm.com/DT/Home

• 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

Additional relevant MeSH terms:

Myocardial Infarction; ST Elevation Myocardial Infarction; Infarction; Ischemia; Pathologic Processes; Necrosis; Myocardial Ischemia; Heart Diseases; Cardiovascular Diseases; Vascular Diseases