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

The safety and scientific validity of this study is the responsibility of the study sponsor and investigators. Listing a study does not mean it has been evaluated by the U.S. Federal Government. Know the risks and potential benefits of clinical studies and talk to your health care provider before participating. Read our disclaimer for details.
 
ClinicalTrials.gov Identifier: NCT04610892
Recruitment Status : Recruiting
First Posted : November 2, 2020
Last Update Posted : May 31, 2022
Sponsor:
Collaborator:
Thrombolysis in Myocardial Infarction (TIMI) Study Group
Information provided by (Responsible Party):
AstraZeneca

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

Condition or disease Intervention/treatment Phase
Coronary Heart Disease (CHD) Biological: MEDI6570 Biological: Placebo Phase 2

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.

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Study Type : Interventional  (Clinical Trial)
Estimated Enrollment : 400 participants
Allocation: Randomized
Intervention Model: Parallel Assignment
Masking: Quadruple (Participant, Care Provider, Investigator, Outcomes Assessor)
Primary Purpose: Treatment
Official Title: 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
Actual Study Start Date : November 4, 2020
Estimated Primary Completion Date : April 15, 2023
Estimated Study Completion Date : August 22, 2023

Resource links provided by the National Library of Medicine

MedlinePlus related topics: Heart Attack

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




Primary Outcome Measures :
  1. Non Calcified Plaque Volume [ Time Frame: 9 months ]
    Change in non-calcified plaque volume in the most diseased coronary segment (NCPVMD), as measured by CTA imaging compared to placebo.


Secondary Outcome Measures :
  1. NT proBNP [ Time Frame: 9 months ]
    Change in NT proBNP compared to placebo

  2. LVEF [ Time Frame: 9 months ]
    Change in LVEF as measured by echocardiography compared to placebo

  3. Global Longitudinal Strain (GLS) [ Time Frame: 9 months ]
    Change in GLS as measured by echocardiography compared to placebo

  4. Global non-calcified plaque volume [ Time Frame: 9 months ]
    Change in Global non-calcified plaque volume as measured by CTA imaging compared to placebo

  5. Low attenuation plaque volume [ Time Frame: 9 months ]
    Change in Low attenuation plaque volume as measured by CTA imaging compared to placebo

  6. Adverse Events as a measure of safety and tolerability of MEDI6570 [ Time Frame: 13.5 months ]
    Incidence of treatment-emergent adverse events (TEAEs) and treatment-emergent serious adverse events (TESAEs) compared to placebo

  7. Adverse events as a measure of safety and tolerability of MEDI6570 [ Time Frame: 13.5 months ]
    Adverse events (AEs) as evaluated by incidence of clinically important changes in vital signs, ECG, chemistry, or hematology values compared to placebo

  8. Incidence Rate of Immunogenicity [ Time Frame: 13.5 months ]
    Immunogenicity as measured by anti-drug antibodies (ADAs)

  9. Pharmacokinetics of MEDI6570 Cmax [ Time Frame: 13.5 months ]
    Non-compartmental analysis will be performed for MEDI6570 treated subjects

  10. Pharmacokinetics of MEDI6570 Terminal Half-life [ Time Frame: 13.5 months ]
    Non-compartmental analysis will be performed for MEDI6570 treated subjects

  11. LVEF [ Time Frame: 9 months ]
    Change in LVEF as measured by echocardiography among participants with reduced ejection fraction compared to placebo

  12. Global Longitudinal Strain (GLS) [ Time Frame: 9 months ]
    Change in GLS as measured by echocardiography among participants with reduced ejection fraction compared to placebo

  13. ADA titer [ Time Frame: 13.5 months ]
    Immunogenicity as measured by anti-drug antibodies (ADAs)



Information from the National Library of Medicine

Choosing to participate in a study is an important personal decision. Talk with your doctor and family members or friends about deciding to join a study. To learn more about this study, you or your doctor may contact the study research staff using the contacts provided below. For general information, Learn About Clinical Studies.


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Ages Eligible for Study:   21 Years and older   (Adult, Older Adult)
Sexes Eligible for Study:   All
Accepts Healthy Volunteers:   No
Criteria

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.

Information from the National Library of Medicine

To learn more about this study, you or your doctor may contact the study research staff using the contact information provided by the sponsor.

Please refer to this study by its ClinicalTrials.gov identifier (NCT number): NCT04610892


Contacts
Layout table for location contacts
Contact: AstraZeneca Clinical Study Information Center 1-877-240-9479 information.center@astrazeneca.com

Locations
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Sponsors and Collaborators
AstraZeneca
Thrombolysis in Myocardial Infarction (TIMI) Study Group
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Responsible Party: AstraZeneca
ClinicalTrials.gov Identifier: NCT04610892    
Other Study ID Numbers: D4920C00002
First Posted: November 2, 2020    Key Record Dates
Last Update Posted: May 31, 2022
Last Verified: May 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

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Studies a U.S. FDA-regulated Drug Product: Yes
Studies a U.S. FDA-regulated Device Product: No
Keywords provided by AstraZeneca:
Coronary Heart Disease
Atherosclerosis
Additional relevant MeSH terms:
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Myocardial Infarction
Heart Diseases
Coronary Disease
Coronary Artery Disease
Myocardial Ischemia
Infarction
Ischemia
Pathologic Processes
Necrosis
Cardiovascular Diseases
Vascular Diseases
Arteriosclerosis
Arterial Occlusive Diseases