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

Primary Purpose

ST Elevation Myocardial Infarction

Status
Completed
Phase
Phase 2
Locations
International
Study Type
Interventional
Intervention
MEDI6012
Placebo
Sponsored by
MedImmune LLC
About
Eligibility
Locations
Arms
Outcomes
Full info

About this trial

This is an interventional treatment trial for ST Elevation Myocardial Infarction

Eligibility Criteria

30 Years - 80 Years (Adult, Older Adult)All SexesDoes not accept healthy volunteers

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)

Sites / Locations

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Arms of the Study

Arm 1

Arm 2

Arm 3

Arm 4

Arm Type

Placebo Comparator

Experimental

Placebo Comparator

Experimental

Arm Label

Cohort A: Placebo

Cohort A: MEDI6012

Cohort B: Placebo

Cohort B: MEDI6012

Arm Description

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.

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.

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.

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.

Outcomes

Primary Outcome Measures

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.

Secondary Outcome Measures

Left Ventricular Ejection Fraction (LVEF)
The LVEF measured by cine magnetic resonance imaging (MRI) at 10-12 weeks post-MI is reported.
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.
Left Ventricular Mass by Late Gadolinium Enhancement (LGE)
The left ventricular mass by LGE is reported.
Left Ventricular Mass by Cine Magnetic Resonance Imaging (MRI)
The left ventricular mass by cine MRI is reported.
Left Ventricular End-diastolic and End-systolic Volume
Left ventricular end-diastolic and end-systolic volume is reported.
Left Ventricular End-diastolic and End-systolic Volume Index
Left ventricular end-diastolic and end-systolic volume index is reported.
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.
Serum Concentration of MEDI6012 (Lecithin-cholesterol Acyltransferaes [LCAT] Mass)
Serum concentration of MEDI6012 is reported.
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.

Full Information

First Posted
June 8, 2018
Last Updated
January 13, 2022
Sponsor
MedImmune LLC
Collaborators
Thrombolysis in Myocardial Infarction (TIMI) Study Group
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1. Study Identification

Unique Protocol Identification Number
NCT03578809
Brief Title
A Study to Evaluate the Safety and Efficacy of MEDI6012 in Acute ST Elevation Myocardial Infarction
Acronym
REAL-TIMI 63B
Official Title
A Randomized, Placebo-controlled Phase 2b Study to Evaluate the Safety and Efficacy of MEDI6012 in Acute ST Elevation Myocardial Infarction
Study Type
Interventional

2. Study Status

Record Verification Date
January 2022
Overall Recruitment Status
Completed
Study Start Date
June 5, 2018 (Actual)
Primary Completion Date
January 18, 2021 (Actual)
Study Completion Date
January 18, 2021 (Actual)

3. Sponsor/Collaborators

Responsible Party, by Official Title
Sponsor
Name of the Sponsor
MedImmune LLC
Collaborators
Thrombolysis in Myocardial Infarction (TIMI) Study Group

4. Oversight

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
Data Monitoring Committee
Yes

5. 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.

6. Conditions and Keywords

Primary Disease or Condition Being Studied in the Trial, or the Focus of the Study
ST Elevation Myocardial Infarction

7. Study Design

Primary Purpose
Treatment
Study Phase
Phase 2
Interventional Study Model
Parallel Assignment
Masking
ParticipantCare ProviderOutcomes 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.
Allocation
Randomized
Enrollment
593 (Actual)

8. Arms, Groups, and Interventions

Arm Title
Cohort A: Placebo
Arm Type
Placebo Comparator
Arm Description
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.
Arm Title
Cohort A: MEDI6012
Arm Type
Experimental
Arm Description
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.
Arm Title
Cohort B: Placebo
Arm Type
Placebo Comparator
Arm Description
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.
Arm Title
Cohort B: MEDI6012
Arm Type
Experimental
Arm Description
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.
Intervention Type
Biological
Intervention Name(s)
MEDI6012
Other Intervention Name(s)
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.
Intervention Description
MEDI6012
Intervention Type
Other
Intervention Name(s)
Placebo
Other Intervention Name(s)
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.
Intervention Description
Placebo
Primary Outcome Measure Information:
Title
Global Infarct Size
Description
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.
Time Frame
70 to 84 days post Day 1 dose
Secondary Outcome Measure Information:
Title
Left Ventricular Ejection Fraction (LVEF)
Description
The LVEF measured by cine magnetic resonance imaging (MRI) at 10-12 weeks post-MI is reported.
Time Frame
70 to 84 days post Day 1 dose
Title
Change in Non-calcified Plaque Volume (NCPV) in the Coronary Arteries in Cohort B
Description
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.
Time Frame
Day 1 dose (48 to 72 hours post Dose 1) through 70 to 84 days post Day 1 dose
Title
Left Ventricular Mass by Late Gadolinium Enhancement (LGE)
Description
The left ventricular mass by LGE is reported.
Time Frame
70 to 84 days post Day 1 dose
Title
Left Ventricular Mass by Cine Magnetic Resonance Imaging (MRI)
Description
The left ventricular mass by cine MRI is reported.
Time Frame
70 to 84 days post Day 1 dose
Title
Left Ventricular End-diastolic and End-systolic Volume
Description
Left ventricular end-diastolic and end-systolic volume is reported.
Time Frame
70 to 84 days post Day 1 dose
Title
Left Ventricular End-diastolic and End-systolic Volume Index
Description
Left ventricular end-diastolic and end-systolic volume index is reported.
Time Frame
70 to 84 days post Day 1 dose
Title
Number of Participants With Treatment Emergent Adverse Events (TEAEs) and Treatment Emergent Serious Adverse Events (TESAEs)
Description
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.
Time Frame
Day 1 through Day 195 post Day 1 dose
Title
Serum Concentration of MEDI6012 (Lecithin-cholesterol Acyltransferaes [LCAT] Mass)
Description
Serum concentration of MEDI6012 is reported.
Time Frame
Pre- and post-dose on Days 1, 3, 17, and 31
Title
Number of Participants With Positive Anti-Drug Antibodies (ADA) to MEDI6012
Description
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.
Time Frame
Predose on Day 1, Day 17, Day 31, 70 to 84 days, and on Day 195 post Day 1 dose

10. Eligibility

Sex
All
Minimum Age & Unit of Time
30 Years
Maximum Age & Unit of Time
80 Years
Accepts Healthy Volunteers
No
Eligibility 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)
Facility Information:
Facility Name
Research Site
City
Belo Horizonte
ZIP/Postal Code
30110-934
Country
Brazil
Facility Name
Research Site
City
Campinas
ZIP/Postal Code
13060-080
Country
Brazil
Facility Name
Research Site
City
Porto Alegre
ZIP/Postal Code
90610-000
Country
Brazil
Facility Name
Research Site
City
Porto Alegre
ZIP/Postal Code
90620-001
Country
Brazil
Facility Name
Research Site
City
Brno
ZIP/Postal Code
65691
Country
Czechia
Facility Name
Research Site
City
Hradec Kralove
ZIP/Postal Code
500 05
Country
Czechia
Facility Name
Research Site
City
Liberec
ZIP/Postal Code
46063
Country
Czechia
Facility Name
Research Site
City
Pardubice
ZIP/Postal Code
53203
Country
Czechia
Facility Name
Research Site
City
Praha 10
ZIP/Postal Code
10034
Country
Czechia
Facility Name
Research Site
City
Praha 2
ZIP/Postal Code
12808
Country
Czechia
Facility Name
Research Site
City
Usti nad Labem
ZIP/Postal Code
40113
Country
Czechia
Facility Name
Research Site
City
Budapest
ZIP/Postal Code
1122
Country
Hungary
Facility Name
Research Site
City
Budapest
ZIP/Postal Code
1134
Country
Hungary
Facility Name
Research Site
City
Beer Sheva
ZIP/Postal Code
8410101
Country
Israel
Facility Name
Research Site
City
Haifa
ZIP/Postal Code
3109601
Country
Israel
Facility Name
Research Site
City
Jerusalem
ZIP/Postal Code
9103102
Country
Israel
Facility Name
Research Site
City
Jerusalem
ZIP/Postal Code
91120
Country
Israel
Facility Name
Research Site
City
Petah Tikva
ZIP/Postal Code
4941492
Country
Israel
Facility Name
Research Site
City
Ramat Gan
ZIP/Postal Code
5265601
Country
Israel
Facility Name
Research Site
City
Tel Aviv
ZIP/Postal Code
6423906
Country
Israel
Facility Name
Research Site
City
Alkmaar
ZIP/Postal Code
1815 JD
Country
Netherlands
Facility Name
Research Site
City
Nijmegen
ZIP/Postal Code
6525 GA
Country
Netherlands
Facility Name
Research Site
City
Nijmegen
ZIP/Postal Code
6532 SZ
Country
Netherlands
Facility Name
Research Site
City
Bydgoszcz
ZIP/Postal Code
85-094
Country
Poland
Facility Name
Research Site
City
Lodz
ZIP/Postal Code
90-549
Country
Poland
Facility Name
Research Site
City
Lodz
ZIP/Postal Code
91-347
Country
Poland
Facility Name
Research Site
City
Kazan
ZIP/Postal Code
420101
Country
Russian Federation
Facility Name
Research Site
City
Saint Petersburg
ZIP/Postal Code
197044
Country
Russian Federation
Facility Name
Research Site
City
Saint Petersburg
ZIP/Postal Code
197706
Country
Russian Federation
Facility Name
Research Site
City
Banska Bystrica
ZIP/Postal Code
974 01
Country
Slovakia
Facility Name
Research Site
City
Nitra
ZIP/Postal Code
949 01
Country
Slovakia
Facility Name
Research Site
City
Madrid
ZIP/Postal Code
28040
Country
Spain
Facility Name
Research Site
City
Madrid
ZIP/Postal Code
28046
Country
Spain
Facility Name
Research Site
City
Pontevedra
ZIP/Postal Code
36312
Country
Spain
Facility Name
Research Site
City
Dundee
ZIP/Postal Code
DD1 9SY
Country
United Kingdom
Facility Name
Research Site
City
Leeds
ZIP/Postal Code
LS13EX
Country
United Kingdom
Facility Name
Research Site
City
Stevenage
ZIP/Postal Code
SG1 4AB
Country
United Kingdom

12. IPD Sharing Statement

Plan to Share IPD
Yes
IPD Sharing 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 URL
https://astrazenecagroup-dt.pharmacm.com/DT/Home
Citations:
PubMed Identifier
36039762
Citation
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.
Results Reference
derived
Links:
URL
https://filehosting-v2.pharmacm.com/api/Attachment/Download?tenantId=80217111&parentIdentifier=D5780C00007&attachmentIdentifier=f9c1bc23-394a-4215-977e-3838819a18ee&fileName=d5780c00007-csp-amendment-6_redacted_Final_Redacted.pdf&versionIdentifier=
Description
D5780C00007 CSP Redacted
URL
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Description
D5780C00007 SAP Redacted
URL
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Description
D5780C00007 CSR Synopsis Redacted

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A Study to Evaluate the Safety and Efficacy of MEDI6012 in Acute ST Elevation Myocardial Infarction

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