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Clinical Trial Details — Status: Completed

Administrative data

NCT number NCT04610892
Other study ID # D4920C00002
Secondary ID 2020-000840-75
Status Completed
Phase Phase 2
First received
Last updated
Start date November 4, 2020
Est. completion date November 8, 2023

Study information

Verified date November 2023
Source AstraZeneca
Contact n/a
Is FDA regulated No
Health authority
Study type Interventional

Clinical Trial Summary

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


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.


Recruitment information / eligibility

Status Completed
Enrollment 423
Est. completion date November 8, 2023
Est. primary completion date November 8, 2023
Accepts healthy volunteers No
Gender All
Age group 21 Years and older
Eligibility 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 Design


Intervention

Biological:
MEDI6570
MEDI6570
Placebo
Buffer

Locations

Country Name City State
Australia Research Site Adelaide
Australia Research Site Bedford Park
Australia Research Site Clayton
Australia Research Site Murdoch
Australia Research Site Perth
Canada Research Site Montreal Quebec
Canada Research Site Ottawa Ontario
Canada Research Site Toronto Ontario
Czechia Research Site Brno
Czechia Research Site Hradec Králové
Czechia Research Site Liberec
Czechia Research Site Pardubice
Czechia Research Site Plzen - Bory
Czechia Research Site Praha 5
Hungary Research Site Budapest
Hungary Research Site Budapest
Hungary Research Site Budapest
Hungary Research Site Debrecen
Hungary Research Site Székesfehérvár
Italy Research Site Cona
Italy Research Site Milan
Italy Research Site Parma
Italy Research Site Rozzano
Japan Research Site Himeji-shi
Japan Research Site Kasuga-shi
Japan Research Site Kasugai-shi
Japan Research Site Kitakyushu-shi
Japan Research Site Kumamoto-shi
Japan Research Site Kyoto-shi
Japan Research Site Matsudo-Shi
Japan Research Site Minami-ku
Japan Research Site Miyazaki-shi
Japan Research Site Morioka-shi
Japan Research Site Osaka-shi
Japan Research Site Sendai-shi
Netherlands Research Site Alkmaar
Netherlands Research Site Deventer
Netherlands Research Site Heerlen
Netherlands Research Site Nijmegen
Netherlands Research Site Nijmegen
Netherlands Research Site Tilburg
Netherlands Research Site Utrecht
Netherlands Research Site Venlo
Netherlands Research Site Zwolle
Poland Research Site Bialystok
Poland Research Site Bydgoszcz
Poland Research Site Katowice
Poland Research Site Krakow
Poland Research Site Kraków
Poland Research Site Kraków
Poland Research Site Opole
Poland Research Site Wroclaw
Spain Research Site Barcelona
Spain Research Site El Palmar
Spain Research Site Hospitalet de Llobregat(Barcel
Spain Research Site Madrid
Spain Research Site Madrid
Spain Research Site Pontevedra
Spain Research Site Santiago de Compostela
Spain Research Site Sevilla
United Kingdom Research Site Aylesbury
United Kingdom Research Site Exeter
United Kingdom Research Site Middlesborough
United Kingdom Research Site Newcastle upon Tyne
United Kingdom Research Site Wythenshawe
United States Research Site Beverly Hills California
United States Research Site Buffalo New York
United States Research Site Canton Ohio
United States Research Site Columbia Missouri
United States Research Site Covina California
United States Research Site Decatur Georgia
United States Research Site Madison Wisconsin
United States Research Site Midland Michigan
United States Research Site Mobile Alabama
United States Research Site Muncie Indiana
United States Research Site New Brunswick New Jersey
United States Research Site Northridge California
United States Research Site Northridge California
United States Research Site Ponte Vedra Florida
United States Research Site Rapid City South Dakota
United States Research Site Richmond Indiana
United States Research Site Torrance California
United States Research Site West Des Moines Iowa
United States Research Site Winchester Virginia

Sponsors (2)

Lead Sponsor Collaborator
AstraZeneca Thrombolysis in Myocardial Infarction (TIMI) Study Group

Countries where clinical trial is conducted

United States,  Australia,  Canada,  Czechia,  Hungary,  Italy,  Japan,  Netherlands,  Poland,  Spain,  United Kingdom, 

Outcome

Type Measure Description Time frame Safety issue
Primary Non Calcified Plaque Volume Change in non-calcified plaque volume in the most diseased coronary segment (NCPVMD), as measured by CTA imaging compared to placebo. 9 months
Secondary NT proBNP Change in NT proBNP compared to placebo 9 months
Secondary LVEF Change in LVEF as measured by echocardiography compared to placebo 9 months
Secondary Global Longitudinal Strain (GLS) Change in GLS as measured by echocardiography compared to placebo 9 months
Secondary Global non-calcified plaque volume Change in Global non-calcified plaque volume as measured by CTA imaging compared to placebo 9 months
Secondary Low attenuation plaque volume Change in Low attenuation plaque volume as measured by CTA imaging compared to placebo 9 months
Secondary Adverse Events as a measure of safety and tolerability of MEDI6570 Incidence of treatment-emergent adverse events (TEAEs) and treatment-emergent serious adverse events (TESAEs) compared to placebo 13.5 months
Secondary Adverse events as a measure of safety and tolerability of MEDI6570 Adverse events (AEs) as evaluated by incidence of clinically important changes in vital signs, ECG, chemistry, or hematology values compared to placebo 13.5 months
Secondary Incidence Rate of Immunogenicity Immunogenicity as measured by anti-drug antibodies (ADAs) 13.5 months
Secondary Pharmacokinetics of MEDI6570 Cmax Non-compartmental analysis will be performed for MEDI6570 treated subjects 13.5 months
Secondary Pharmacokinetics of MEDI6570 Terminal Half-life Non-compartmental analysis will be performed for MEDI6570 treated subjects 13.5 months
Secondary LVEF Change in LVEF as measured by echocardiography among participants with reduced ejection fraction compared to placebo 9 months
Secondary Global Longitudinal Strain (GLS) Change in GLS as measured by echocardiography among participants with reduced ejection fraction compared to placebo 9 months
Secondary ADA titer Immunogenicity as measured by anti-drug antibodies (ADAs) 13.5 months
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