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

Coronary Heart Disease (CHD) Clinical Trial

— GOLDILOX  

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

Clinical Trial Details — Status: Completed

Administrative data

• NCT number: NCT04610892
• Other study ID #: D4920C00002
• Secondary ID: 2020-000840-75
• Status: Completed
• Phase: Phase 2
• 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
• 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.

Related Conditions & MeSH terms

• Coronary Artery Disease
• Coronary Disease
• Coronary Heart Disease (CHD)
• Heart Diseases
• Infarction
• Myocardial Infarction
• Myocardial Ischemia

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