Efficacy and Safety of MEDI6570 in Patients With a History of Myocardial Infarction (GOLDILOX)

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 and Persistent Inflammation

A Phase IIB Parallel group Study to Evaluate the Efficacy and Safety of MEDI6570 in Participants with a Prior Myocardial Infarction.

Study Overview

• Status: Completed
• Conditions: Coronary Heart Disease (CHD)
• Intervention / Treatment: Biological: MEDI6570; Biological: Placebo

Detailed Description

This Phase IIB, proof-of-concept, dose-range finding clinical study is being conducted to evaluate the anti-inflammatory potential of MEDI6570 and its effect on surrogates for atherosclerotic and heart failure (HF) events in patients with a history of myocardial infarction (MI). The results of the Phase IIB study will inform future clinical development options and precision medicine strategy for future clinical studies.

Participants will be randomized in a 2:2:1:1 ratio after protocol Amend 2, 360 evaluable participants (111 evaluable participants in each of the 2 MEDI6570 groups, plus 27 evaluable participants in the legacy low dose MEDI6570 group, plus 111 participants in pooled placebo) will complete the study.

• Study Type: Interventional
• Enrollment (Actual): 423
• Phase: Phase 2

Contacts and Locations

Study Locations

• Australia
  • Adelaide, Australia, 5000
    • Research Site
  • Bedford Park, Australia, 5042
    • Research Site
  • Clayton, Australia, 3168
    • Research Site
  • Murdoch, Australia, WA6150
    • Research Site
  • Perth, Australia, WA 6000
    • Research Site
• Canada
  • Ontario
    • Ottawa, Ontario, Canada, K1Y 4W7
      • Research Site
    • Toronto, Ontario, Canada, M5G 2C4
      • Research Site
  • Quebec
    • Montreal, Quebec, Canada, H1T 1C8
      • Research Site
• Czechia
  • Brno, Czechia, 656 91
    • Research Site
  • Hradec Králové, Czechia, 500-05
    • Research Site
  • Liberec, Czechia, 46002
    • Research Site
  • Pardubice, Czechia, 532 03
    • Research Site
  • Plzen - Bory, Czechia, 305 99
    • Research Site
  • Praha 5, Czechia, 150 06
    • Research Site
• Hungary
  • Budapest, Hungary, 1134
    • Research Site
  • Budapest, Hungary, 1133
    • Research Site
  • Budapest, Hungary, H-1122
    • Research Site
  • Debrecen, Hungary, 4032
    • Research Site
  • Székesfehérvár, Hungary, 8000
    • Research Site
• Italy
  • Cona, Italy, 44124
    • Research Site
  • Milan, Italy, 20138
    • Research Site
  • Parma, Italy, 43126
    • Research Site
  • Rozzano, Italy, 20089
    • Research Site
• Japan
  • Himeji-shi, Japan, 670-0981
    • Research Site
  • Kasuga-shi, Japan, 816-0864
    • Research Site
  • Kasugai-shi, Japan, 487-0016
    • Research Site
  • Kitakyushu-shi, Japan, 802-8555
    • Research Site
  • Kumamoto-shi, Japan, 860-0008
    • Research Site
  • Kyoto-shi, Japan, 606-8507
    • Research Site
  • Matsudo-Shi, Japan, 271-0077
    • Research Site
  • Minami-ku, Japan, 861-4193
    • Research Site
  • Miyazaki-shi, Japan, 880-0834
    • Research Site
  • Morioka-shi, Japan, 020-0066
    • Research Site
  • Osaka-shi, Japan, 558-8558
    • Research Site
  • Sendai-shi, Japan, 980-0873
    • Research Site
• Netherlands
  • Alkmaar, Netherlands, 1814 HB
    • Research Site
  • Deventer, Netherlands, 7416 SE
    • Research Site
  • Heerlen, Netherlands, 6419 PC
    • Research Site
  • Nijmegen, Netherlands, 6532 SZ
    • Research Site
  • Nijmegen, Netherlands, 6525 GA
    • Research Site
  • Tilburg, Netherlands, 5042AD
    • Research Site
  • Utrecht, Netherlands, 3508 AB
    • Research Site
  • Venlo, Netherlands, 5912 BL
    • Research Site
  • Zwolle, Netherlands, 8025 AB
    • Research Site
• Poland
  • Bialystok, Poland, 15-276
    • Research Site
  • Bydgoszcz, Poland, 85-095
    • Research Site
  • Katowice, Poland, 40-635
    • Research Site
  • Krakow, Poland, 31-202
    • Research Site
  • Kraków, Poland, 30-688
    • Research Site
  • Kraków, Poland, 30-082
    • Research Site
  • Opole, Poland, 45-401
    • Research Site
  • Wroclaw, Poland, 50-556
    • Research Site
• Spain
  • Barcelona, Spain, 08003
    • Research Site
  • El Palmar, Spain, 30120
    • Research Site
  • Hospitalet de Llobregat(Barcel, Spain, 08907
    • Research Site
  • Madrid, Spain, 28046
    • Research Site
  • Madrid, Spain, 28040
    • Research Site
  • Pontevedra, Spain, 36312
    • Research Site
  • Santiago de Compostela, Spain, 15706
    • Research Site
  • Sevilla, Spain, 41009
    • Research Site
• United Kingdom
  • Aylesbury, United Kingdom, HP21 8AL
    • Research Site
  • Exeter, United Kingdom, EX2 5DW
    • Research Site
  • Middlesborough, United Kingdom, TS4 3BW
    • Research Site
  • Newcastle upon Tyne, United Kingdom, NE7 7DN
    • Research Site
  • Wythenshawe, United Kingdom, M23 9LT
    • Research Site
• United States
  • Alabama
    • Mobile, Alabama, United States, 36608
      • Research Site
  • California
    • Beverly Hills, California, United States, 90211
      • Research Site
    • Covina, California, United States, 91723
      • Research Site
    • Northridge, California, United States, 91324
      • Research Site
    • Northridge, California, United States, 91325
      • Research Site
    • Torrance, California, United States, 90502
      • Research Site
  • Florida
    • Ponte Vedra, Florida, United States, 32081
      • Research Site
  • Georgia
    • Decatur, Georgia, United States, 30033
      • Research Site
  • Indiana
    • Muncie, Indiana, United States, 47303
      • Research Site
    • Richmond, Indiana, United States, 47374
      • Research Site
  • Iowa
    • West Des Moines, Iowa, United States, 50266
      • Research Site
  • Michigan
    • Midland, Michigan, United States, 48640
      • Research Site
  • Missouri
    • Columbia, Missouri, United States, 65212
      • Research Site
  • New Jersey
    • New Brunswick, New Jersey, United States, 08901
      • Research Site
  • New York
    • Buffalo, New York, United States, 14221
      • Research Site
  • Ohio
    • Canton, Ohio, United States, 44710
      • Research Site
  • South Dakota
    • Rapid City, South Dakota, United States, 57701
      • Research Site
  • Virginia
    • Winchester, Virginia, United States, 22601
      • Research Site
  • Wisconsin
    • Madison, Wisconsin, United States, 53792
      • Research Site

Participation Criteria

Eligibility Criteria

• Ages Eligible for Study: 21 years and older (Adult, Older Adult)
• Accepts Healthy Volunteers: No

Description

Inclusion Criteria:

1. Participant must provide informed consent before any study specific activities are performed, 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. Women must be ≥ 40 years of age at the time of signing the ICF. Men must be ≥ 21 years of age at the time of signing the ICF.

3. Participant must:

   1. 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.
   2. 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:

   1. 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.
   2. 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.

Exclusion Criteria:

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 or diagnostic angiogram planned after screening. Eligible participants who have a diagnostic angiogram performed in the absence of undergoing a new PCI may continue screening after the diagnostic angiogram has been performed or may be rescreened.
3. History of or planned coronary artery bypass grafting.
4. Documented episode of post-MI pericarditis in the 3 months before enrollment.
5. Ongoing New York Heart Association Class IV HF.

6. Increased risk of bleeding

   1. Patients with history or presence of any bleeding disorder.
   2. Signs of ongoing bleeding at screening (eg, identified macroscopic bleeding, low hemoglobin presumed to be caused by bleeding) or high risk for major bleeding in accordance with the Investigator's assessment.
   3. Need for chronic therapeutic anticoagulation therapy anticipated to be required throughout the course of the study (short-term treatment with prophylactic doses of heparin/low molecular weight heparin are allowed).
   4. Known severe liver disease.

7. History or presence of any of the following:

   1. Ongoing infection or febrile illness that in the opinion of the investigator may be the cause of elevated hs-CRP on screening.
   2. Ongoing atrial fibrillation or flutter.
   3. Cancer within 5 years before randomization, with the exception of non melanoma skin cancer.
   4. Alcohol or substance abuse within 6 months before randomization, as judged by the investigator.
   5. 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.
   6. 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.

9. BP values at screening:

   1. Systolic BP < 90 mmHg or > 180 mmHg.
   2. Diastolic BP > 100 mmHg.
   3. Participants who are excluded based on elevated BP may be rescreened following adequate treatment.

10. Participants with any of the following contraindications to CTA:

    1. 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.
    2. Allergy to iodinated contrast.
    3. History of contrast-induced nephropathy.
    4. Contraindication to nitroglycerin.
    5. Rapid heart rate that is uncontrolled by medical therapy.
    6. Inability to hold breath for at least 6 seconds.

11. Receipt of any investigational device or therapy within 6 months or 5 half lives before screening (whichever is longer).

    This criterion does NOT apply for inactive, non replicating COVID-19 vaccines approved by Health Authorities or under emergency use authorization.

12. Planned participation in an additional investigational study of an intervention or biologic before the end of the follow-up period. Participation in observational studies or studies without investigational drugs or devices is allowed.
13. Participants who are legally institutionalized.
14. An employee or close relative of an employee of the sponsor, the CRO, or the study site, regardless of the employee or close relative's role.

Study Plan

How is the study designed?

Design Details

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

Number of Arms

6

Arms and Interventions

Participant Group / Arm	Intervention / Treatment
Experimental: MEDI6570 Low dose; Monthly Subcutaneous administration.	Biological: MEDI6570; MEDI6570
Experimental: MEDI6570 Medium dose; Monthly Subcutaneous administration.	Biological: MEDI6570; MEDI6570
Experimental: MEDI6570 High dose; Monthly Subcutaneous administration.	Biological: MEDI6570; MEDI6570
Placebo Comparator: Placebo Low dose; Monthly Subcutaneous administration.	Biological: Placebo; Buffer
Placebo Comparator: Placebo Medium dose; Monthly Subcutaneous administration	Biological: Placebo; Buffer
Placebo Comparator: Placebo High dose; Monthly Subcutaneous administration	Biological: Placebo; Buffer

What is the study measuring?

Primary Outcome Measures

Outcome Measure	Measure Description	Time Frame
Change From Baseline to Day 253 in Non-calcified Plaque Volume in the Most Diseased Coronary Segment (NCPVMD), as Measured by Computed Tomography Angiography (CTA) Imaging	To evaluate the effect of MEDI6570 on non-calcified coronary atherosclerotic plaques compared with placebo. The primary endpoint of change in NCPVMD from baseline to Day 253 was assessed based on the CTA Analysis Populations.	From baseline to Day 253

Secondary Outcome Measures

Outcome Measure	Measure Description	Time Frame
Change From Baseline to Day 253 in N Terminal Prohormone Brain Natriuretic Peptide (NT-proBNP)	To evaluate the effect of MEDI6570 on a surrogate biomarker of Heart Failure (HF) compared with placebo	From baseline to Day 253
Change From Baseline to Day 253 in Left Ventricular Ejection Fraction (LVEF)	To evaluate the effect of MEDI6570 on left ventricular systolic function compared with placebo	From baseline to Day 253
Left Ventricular Ejection Fraction (LVEF) Change From Baseline to Day 253 Among Subjects With Reduced Ejection Fraction (< 50%)	To evaluate the effect of MEDI6570 on left ventricular systolic function among participants with reduced ejection fraction (defined as <50%) compared with placebo	From baseline to Day 253
Change From Baseline to Day 253 in Global Longitudinal Strain (GLS)	To evaluate the effect of MEDI6570 on left ventricular systolic function compared with placebo	From baseline to Day 253
Global Longitudinal Strain (GLS) Change From Baseline to Day 253 Among Subjects With Reduced Ejection Fraction (< 50%)	To evaluate the effect of MEDI6570 on left ventricular systolic function among participants with reduced ejection fraction (defined as <50%) compared with placebo	From baseline to Day 253
Change From Baseline to Day 253 in Global Non-calcified Plaque Volume (NCPV)	To evaluate the effect of MEDI6570 on other measures of non-calcified coronary atherosclerotic plaque compared with placebo	From baseline to Day 253
Change From Baseline to Day 253 in Low Attenuation Plaque Volume (LAPV)	To evaluate the effect of MEDI6570 on other measures of non-calcified coronary atherosclerotic plaque compared with placebo	From baseline to Day 253
Summary of ADA (Anti-drug Antibody) Responses During the Study	To evaluate the immunogenicity of MEDI6570	From baseline to Day 325/405. Day 325/405: for participants who completed the study under clinical study protocol (CSP) Amendment 1 & 2, the end of study visits were Day 405 and Day 325 respectively.
Anti-drug Antibody Titre Summary by Visit	To evaluate the immunogenicity of MEDI6570	From Baseline to Day 325/405. Day 325/405: for participants who completed the study under CSP Amendment 1 & 2, the end of study visits were Day 405 and Day 325 respectively.
Summary of Serum Concentrations (ug/mL) of MEDI6570	MEDI6570 concentrations as measured in serum during the intervention and follow-up periods	From baseline to Day 325/Day 405
Number of Participants With Adverse Events in Any Category	To assess the safety and tolerability of MEDI6570 compared with placebo	During study follow-up (from day 1 to day 325)
Number of Participants With Most Common Adverse Events (Frequency > 5%)	To assess the safety and tolerability of MEDI6570 compared with placebo	During study follow-up (from day 1 to day 325)
Vital Signs (Change in Systolic and Diastolic Blood Pressure From Baseline) Over Time	To assess the safety and tolerability of MEDI6570 compared with placebo	From baseline to Day 325/405. Day 325/405: for participants who completed the study under CSP Amendment 1 & 2, the end of study visits were Day 405 and Day 325 respectively.
Vital Signs (Change in Heart Rate From Baseline) Variables Over Time	To assess the safety and tolerability of MEDI6570 compared with placebo	From baseline to Day 325/405. Day 325/405: for participants who completed the study under CSP Amendment 1 & 2, the end of study visits were Day 405 and Day 325 respectively.
Vital Signs (Change of Weight From Baseline to Day 325/405 )	To assess the safety and tolerability of MEDI6570 compared with placebo	From baseline to Day 325/405. Day 325/405: for participants who completed the study under CSP Amendment 1 & 2, the end of study visits were Day 405 and Day 325 respectively

Collaborators and Investigators

• Sponsor: AstraZeneca
• Collaborators: The TIMI Study Group

Publications and helpful links

Helpful Links

• redacted CSP
• redacted SAP
• redacted CSR

Study record dates

Study Major Dates

• Study Start (Actual): November 4, 2020
• Primary Completion (Actual): November 8, 2023
• Study Completion (Actual): November 8, 2023

Study Registration Dates

• First Submitted: July 28, 2020
• First Submitted That Met QC Criteria: October 26, 2020
• First Posted (Actual): November 2, 2020

Study Record Updates

• Last Update Posted (Actual): March 25, 2025
• Last Update Submitted That Met QC Criteria: January 31, 2025
• Last Verified: January 1, 2025

More Information

Terms related to this study

• Keywords: Atherosclerosis; Coronary Heart Disease
• Additional Relevant MeSH Terms: Vascular Diseases; Cardiovascular Diseases; Pathologic Processes; Necrosis; Arteriosclerosis; Arterial Occlusive Diseases; Ischemia; Heart Diseases; Coronary Artery Disease; Myocardial Ischemia; Coronary Disease; Myocardial Infarction; Infarction
• Other Study ID Numbers: D4920C00002; 2020-000840-75 (EudraCT Number)

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; 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