Efficacy and Safety of MEDI6570 in Patients With a Histor... | NCT04610892

ID	Type	Description	Link
2020-000840-75	EudraCT Number

Name	Class
The TIMI Study Group	OTHER

Label	Type	Description	Intervention Names
MEDI6570 Low dose	Experimental	Monthly Subcutaneous administration.	Biological: MEDI6570
MEDI6570 Medium dose	Experimental	Monthly Subcutaneous administration.	Biological: MEDI6570
MEDI6570 High dose	Experimental	Monthly Subcutaneous administration.	Biological: MEDI6570
Placebo Low dose	Placebo Comparator	Monthly Subcutaneous administration.	Biological: Placebo
Placebo Medium dose	Placebo Comparator	Monthly Subcutaneous administration	Biological: Placebo
Placebo High dose	Placebo Comparator	Monthly Subcutaneous administration

Name	Type	Description	Arm Group Labels	Other Names
MEDI6570	Biological	MEDI6570	MEDI6570 High dose MEDI6570 Low dose MEDI6570 Medium dose

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

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)

Eligibility Module

Eligibility Criteria

Inclusion Criteria:

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.
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.
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.
Participant must have body mass index within the range 18 to 40 kg/m2 inclusive.
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.
Participant must have an evaluable, pre-randomization CTA with quantifiable, non calcified plaque.

Exclusion Criteria:

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.
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.
History of or planned coronary artery bypass grafting.
Documented episode of post-MI pericarditis in the 3 months before enrollment.
Ongoing New York Heart Association Class IV HF.
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.
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.
Any clinically important abnormalities in clinical chemistry, hematology, coagulation parameters, as judged by the investigator.
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.
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.
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.
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.
Participants who are legally institutionalized.
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.

Facility	Status	City	State	ZIP	Country	Contacts
Research Site		Mobile	Alabama	36608	United States
Research Site

Label	URL
redacted CSP	View source
redacted SAP	View source

IPD Sharing Statement Module

ID	Title	Description
FG000	MEDI6570 50 mg	Participants received MEDI6570 50 mg every 4 weeks for 32 weeks
FG001	MEDI6570 150 mg	Participants received MEDI6570 150 mg every 4 weeks for 32 weeks

Type	Includes Protocol	Includes SAP	Includes ICF	Document Label	Document Date	Document Uploaded Date	Document File Name
Prot	Yes	No	No	Study Protocol	Nov 10, 2021	Nov 8, 2024

Type

Title

Description

Population Description

Reporting Status

Anticipated Posting Date

Parameter Type

Dispersion Type

Unit of Measure

Calculate Percentage

Time Frame

Units Analyzed

Denominator Units Selected

Arm/Group Information

Denominators

Classes

Analyses

Primary

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.

Participants within the Intention To Treat (ITT) Population who had interpretable CTA scans at baseline and at Day 253. Participants were analyzed according to their randomized treatment group.

Subjects initially randomized to the 250 mg group switched dose to 400 mg following clinical study protocol (CSP) amendment 1 and were analysed according to the 400 mg group.

Posted

Least Squares Mean

Standard Error

mm^3

From baseline to Day 253

ID	Title	Description
OG000	MEDI6570 50 mg	Participants received MEDI6570 50 mg every 4 weeks for 32 weeks
OG001	MEDI6570 150 mg	Participants received MEDI6570 150 mg every 4 weeks for 32 weeks
OG002	MEDI6570 400 mg	Participants received MEDI6570 400 mg every 4 weeks for 32 weeks
OG003	MEDI6570 150 mg or 400 mg	Participants received MEDI6570 150 mg or 400 mg every 4 weeks for 32 weeks
OG004	Placebo	Participants received Placebo matched to MEDI6570 every 4 weeks for 32 weeks

Units	Counts
Participants	OG00035 OG001127 OG002118 OG003

Title

Denominators

Categories

Title	Measurements
	OG000-15.3220± 4.9219 OG001-4.5509± 3.1654 OG002-6.3658± 3.2559 OG003

Group IDs	Group Description	Statistical Method	Statistical Comment	P-Value	P-Value Comment	Parameter Type	Parameter Value	Dispersion Type	Dispersion Value	Confidence Interval Sides	Confidence Interval %	CI Lower Limit	CI Upper Limit	CI Lower Limit Comment	CI Upper Limit Comment	Estimate Comment	Tested Non-Inferiority	Non-Inferiority Type	Non-Inferiority Comment	Other Analysis Description
OG000 OG004		ANCOVA	The treatment as a fixed effects and the baseline value and the geographic region and statin therapy intensity at screening as covariates.	0.065	One-sided p-value	Least Square Mean difference	-8.3797				90	-17.4980	0.7387					Superiority
OG001 OG004

Secondary

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

Randomized subjects who received any study treatment will be included in the As-treated Population. Subjects will be analysed according to the actual treatment they received, regardless of their randomized treatment group. Subjects treated within 250 mg group that received at least one 400 mg dose during the study will be analysed according to the 400mg group.

Posted

Geometric Least Squares Mean

Geometric Coefficient of Variation

pg/mL

From baseline to Day 253

ID	Title	Description
OG000	MEDI6570 50 mg	Participants received MEDI6570 50 mg every 4 weeks for 32 weeks
OG001	MEDI6570 150 mg	Participants received MEDI6570 150 mg every 4 weeks for 32 weeks
OG002	MEDI6570 400 mg	Participants received MEDI6570 400 mg every 4 weeks for 32 weeks
OG003	MEDI6570 150 mg or 400 mg

Secondary

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

Subjects within the ITT population who have interpretable echocardiograms in the baseline and follow-up periods will be included in the Echocardiogram Analysis Population. Subjects will be analysed according to their randomized treatment group. subjects initially randomized to the 250 mg group switched dose to 400 mg following CSP amendment 1 and were analysed according to the 400 mg group

Posted

Least Squares Mean

Standard Error

Percentage of LVEF

From baseline to Day 253

ID	Title	Description
OG000	MEDI6570 50 mg	Participants received MEDI6570 50 mg every 4 weeks for 32 weeks
OG001	MEDI6570 150 mg	Participants received MEDI6570 150 mg every 4 weeks for 32 weeks
OG002	MEDI6570 400 mg	Participants received MEDI6570 400 mg every 4 weeks for 32 weeks
OG003	MEDI6570 150 mg or 400 mg

Secondary

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

Subjects within the ITT population who have interpretable echocardiograms in the baseline and follow-up periods will be included in the Echocardiogram Analysis Population. Subjects will be analysed according to their randomized treatment group. Subjects initially randomized to the 250 mg group switched dose to 400 mg following CSP amendment 1 and were analysed according to the 400 mg group.

Posted

Least Squares Mean

Standard Error

Percentage of LVEF

From baseline to Day 253

ID	Title	Description
OG000	MEDI6570 50 mg	Participants received MEDI6570 50 mg every 4 weeks for 32 weeks
OG001	MEDI6570 150 mg	Participants received MEDI6570 150 mg every 4 weeks for 32 weeks
OG002	MEDI6570 400 mg	Participants received MEDI6570 400 mg every 4 weeks for 32 weeks
OG003

Secondary

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

Subjects within the ITT population who have interpretable echocardiograms in the baseline and follow-up periods will be included in the Echocardiogram Analysis Population. Subjects will be analysed according to their randomized treatment group. Subjects initially randomized to the 250 mg group switched dose to 400 mg following CSP amendment 1 and were analysed according to the 400 mg group.

Posted

Least Squares Mean

Standard Error

Percentage of GLS

From baseline to Day 253

ID	Title	Description
OG000	MEDI6570 50 mg	Participants received MEDI6570 50 mg every 4 weeks for 32 weeks
OG001	MEDI6570 150 mg	Participants received MEDI6570 150 mg every 4 weeks for 32 weeks
OG002	MEDI6570 400 mg	Participants received MEDI6570 400 mg every 4 weeks for 32 weeks
OG003	MEDI6570 150 mg or 400 mg

Secondary

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

Subjects within the ITT population who have interpretable echocardiograms in the baseline and follow-up periods will be included in the Echocardiogram Analysis Population. Subjects will be analysed according to their randomized treatment group. Subjects initially randomized to the 250 mg group switched dose to 400 mg following CSP amendment 1 and were analysed according to the 400 mg group.

Posted

Least Squares Mean

Standard Error

Percentage of GLS

From baseline to Day 253

ID	Title	Description
OG000	MEDI6570 50 mg	Participants received MEDI6570 50 mg every 4 weeks for 32 weeks
OG001	MEDI6570 150 mg	Participants received MEDI6570 150 mg every 4 weeks for 32 weeks
OG002	MEDI6570 400 mg	Participants received MEDI6570 400 mg every 4 weeks for 32 weeks
OG003

Secondary

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

Participants within the ITT Population who had interpretable b CTA scans at baseline and at Day 253 or at Day 122 were included. (Note that separate analyses were conducted for Day 253 and Day 122). Participants were analyzed according to their randomized treatment group.

Subjects initially randomized to the 250 mg group switched dose to 400 mg following CSP amendment 1 and were analysed according to the 400 mg group.

Posted

Least Squares Mean

Standard Error

mm^3

From baseline to Day 253

ID	Title	Description
OG000	MEDI6570 50 mg	Participants received MEDI6570 50 mg every 4 weeks for 32 weeks
OG001	MEDI6570 150 mg	Participants received MEDI6570 150 mg every 4 weeks for 32 weeks
OG002	MEDI6570 400 mg	Participants received MEDI6570 400 mg every 4 weeks for 32 weeks
OG003	MEDI6570 150 mg or 400 mg

Secondary

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

Participants within the ITT Population who had interpretable CTA scans at baseline and at Day 253. Participants were analyzed according to their randomized treatment group.

Subjects initially randomized to the 250 mg group switched dose to 400 mg following CSP amendment 1 and were analysed according to the 400 mg group.

Posted

Least Squares Mean

Standard Error

mm3

From baseline to Day 253

ID	Title	Description
OG000	MEDI6570 50 mg	Participants received MEDI6570 50 mg every 4 weeks for 32 weeks
OG001	MEDI6570 150 mg	Participants received MEDI6570 150 mg every 4 weeks for 32 weeks
OG002	MEDI6570 400 mg	Participants received MEDI6570 400 mg every 4 weeks for 32 weeks
OG003	MEDI6570 150 mg or 400 mg	Participants received MEDI6570 150 mg or 400 mg every 4 weeks for 32 weeks

Secondary

Summary of ADA (Anti-drug Antibody) Responses During the Study

To evaluate the immunogenicity of MEDI6570

Subjects included in the As-treated Population who have ≥ 1 immunogenicity sample will be included in the Immunogenicity Population. Subjects will be analysed according to the actual treatment they received. Subjects initially randomized to the 250 mg group switched dose to 400 mg following CSP amendment 1 and were analysed according to the 400 mg group.

Posted

Count of Participants

Participants

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.

ID	Title	Description
OG000	MEDI6570 50 mg	Participants received MEDI6570 50 mg very 4 weeks for 32 weeks
OG001	MEDI6570 150 mg	Participants received MEDI6570 150 mg very 4 weeks for 32 weeks
OG002	MEDI6570 400 mg	Participants received MEDI6570 400 mg very 4 weeks for 32 weeks
OG003	MEDI6570 Total

Secondary

Anti-drug Antibody Titre Summary by Visit

To evaluate the immunogenicity of MEDI6570

Posted

Median

Full Range

Titer units

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.

ID	Title	Description
OG000	MEDI6570 50 mg	Participants received MEDI6570 50 mg every 4 weeks for 32 weeks
OG001	MEDI6570 150 mg	Participants received MEDI6570 150 mg every 4 weeks for 32 weeks
OG002	MEDI6570 400 mg	Participants received MEDI6570 400 mg every 4 weeks for 32 weeks
OG003	MEDI6570 Total

Secondary

Summary of Serum Concentrations (ug/mL) of MEDI6570

MEDI6570 concentrations as measured in serum during the intervention and follow-up periods

All subjects who received ≥ 1 dose of MEDI6570 and have ≥ 1 one post dose evaluable MEDI6570 serum concentration will be included in the PK population. Subjects will be analysed according to the actual treatment they received. The pk data was analysed only for 50 mg, 150mg and 400mg groups.

Posted

Geometric Mean

Geometric Coefficient of Variation

ug/mL

From baseline to Day 325/Day 405

ID	Title	Description
OG000	MEDI6570 50 mg	Participants received MEDI6570 50 mg every 4 weeks for 32 weeks
OG001	MEDI6570 150 mg	Participants received MEDI6570 150 mg every 4 weeks for 32 weeks
OG002	MEDI6570 400 mg	Participants received MEDI6570 400 mg every 4 weeks for 32 weeks

Units	Counts
Participants

Secondary

Number of Participants With Adverse Events in Any Category

To assess the safety and tolerability of MEDI6570 compared with placebo

Posted

Count of Participants

Participants

During study follow-up (from day 1 to day 325)

ID	Title	Description
OG000	MEDI6570 50 mg	Participants received MEDI6570 50 mg every 4 weeks for 32 weeks
OG001	MEDI6570 150 mg	Participants received MEDI6570 150 mg every 4 weeks for 32 weeks
OG002	MEDI6570 400 mg	Participants received MEDI6570 400 mg every 4 weeks for 32 weeks
OG003	MEDI6570 Total	Participants received MEDI6570 50 mg or 150 mg or 400 mg every 4 weeks for 32 weeks

Secondary

Number of Participants With Most Common Adverse Events (Frequency > 5%)

To assess the safety and tolerability of MEDI6570 compared with placebo

Posted

Count of Participants

Participants

During study follow-up (from day 1 to day 325)

ID	Title	Description
OG000	MEDI6570 50 mg	Participants received MEDI6570 50 mg every 4 weeks for 32 weeks
OG001	MEDI6570 150 mg	Participants received MEDI6570 150 mg every 4 weeks for 32 weeks
OG002	MEDI6570 400 mg	Participants received MEDI6570 400 mg every 4 weeks for 32 weeks
OG003	MEDI6570 Total	Participants received MEDI6570 50 mg or 150 mg or 400 mg every 4 weeks for 32 weeks

Secondary

Vital Signs (Change in Systolic and Diastolic Blood Pressure From Baseline) Over Time

To assess the safety and tolerability of MEDI6570 compared with placebo

Posted

Mean

Standard Deviation

mmHg

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.

ID	Title	Description
OG000	MEDI6570 50 mg	Participants received MEDI6570 50 mg every 4 weeks for 32 weeks
OG001	MEDI6570 150 mg	Participants received MEDI6570 150 mg every 4 weeks for 32 weeks
OG002	MEDI6570 400 mg	Participants received MEDI6570 400 mg every 4 weeks for 32 weeks
OG003	Placebo

Secondary

Vital Signs (Change in Heart Rate From Baseline) Variables Over Time

To assess the safety and tolerability of MEDI6570 compared with placebo

Posted

Mean

Standard Deviation

beats/min

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.

ID	Title	Description
OG000	MEDI6570 50 mg	Participants received MEDI6570 50 mg every 4 weeks for 32 weeks
OG001	MEDI6570 150 mg	Participants received MEDI6570 150 mg every 4 weeks for 32 weeks
OG002	MEDI6570 400 mg	Participants received MEDI6570 400 mg every 4 weeks for 32 weeks
OG003	Placebo

Secondary

Vital Signs (Change of Weight From Baseline to Day 325/405 )

To assess the safety and tolerability of MEDI6570 compared with placebo

Posted

Mean

Standard Deviation

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

ID	Title	Description
OG000	MEDI6570 50 mg	Participants received MEDI6570 50 mg every 4 weeks for 32 weeks
OG001	MEDI6570 150 mg	Participants received MEDI6570 150 mg every 4 weeks for 32 weeks
OG002	MEDI6570 400 mg	Participants received MEDI6570 400 mg every 4 weeks for 32 weeks
OG003	Placebo

Serious Adverse Events

Term	Organ System	Source Vocabulary	Assessment Type	Notes	Statistical Information
Coronary artery stenosis	Cardiac disorders	MedDRA 26.0	Systematic Assessment		EG0000 events0 affected39 at risk EG0010 events0 affected129 at risk EG0022 events1 affected126 at risk EG0030 events0 affected126 at risk
Retinal detachment	Eye disorders	MedDRA 26.0	Systematic Assessment		EG0000 events0 affected39 at risk EG0010 events0 affected129 at risk EG0021 events1 affected126 at risk EG003
Abdominal pain upper	Gastrointestinal disorders	MedDRA 26.0	Systematic Assessment		EG0000 events0 affected39 at risk EG0011 events1 affected129 at risk EG0020 events0 affected126 at risk EG003
Diarrhoea	Gastrointestinal disorders	MedDRA 26.0	Systematic Assessment		EG0000 events0 affected39 at risk EG0010 events0 affected129 at risk EG0020 events0 affected126 at risk EG003
Gastrointestinal polyp haemorrhage	Gastrointestinal disorders	MedDRA 26.0	Systematic Assessment		EG0000 events0 affected39 at risk EG0010 events0 affected129 at risk EG0020 events0 affected126 at risk EG003
Ileal perforation	Gastrointestinal disorders	MedDRA 26.0	Systematic Assessment		EG0000 events0 affected39 at risk EG0011 events1 affected129 at risk EG0020 events0 affected126 at risk EG003
Incarcerated umbilical hernia	Gastrointestinal disorders	MedDRA 26.0	Systematic Assessment		EG0001 events1 affected39 at risk EG0010 events0 affected129 at risk EG0020 events0 affected126 at risk EG003
Inguinal hernia	Gastrointestinal disorders	MedDRA 26.0	Systematic Assessment		EG0000 events0 affected39 at risk EG0010 events0 affected129 at risk EG0021 events1 affected126 at risk EG003
Omental necrosis	Gastrointestinal disorders	MedDRA 26.0	Systematic Assessment		EG0000 events0 affected39 at risk EG0011 events1 affected129 at risk EG0020 events0 affected126 at risk EG003
Acute myocardial infarction	Cardiac disorders	MedDRA 26.0	Systematic Assessment		EG0000 events0 affected39 at risk EG0012 events2 affected129 at risk EG0020 events0 affected126 at risk EG003
Pancreatitis	Gastrointestinal disorders	MedDRA 26.0	Systematic Assessment		EG0000 events0 affected39 at risk EG0010 events0 affected129 at risk EG0020 events0 affected126 at risk EG003
Rectal haemorrhage	Gastrointestinal disorders	MedDRA 26.0	Systematic Assessment		EG0000 events0 affected39 at risk EG0010 events0 affected129 at risk EG0021 events1 affected126 at risk EG003
Vomiting	Gastrointestinal disorders	MedDRA 26.0	Systematic Assessment		EG0000 events0 affected39 at risk EG0010 events0 affected129 at risk EG0021 events1 affected126 at risk EG003
Non-cardiac chest pain	General disorders	MedDRA 26.0	Systematic Assessment		EG0001 events1 affected39 at risk EG0010 events0 affected129 at risk EG0020 events0 affected126 at risk EG003
Bile duct stone	Hepatobiliary disorders	MedDRA 26.0	Systematic Assessment		EG0000 events0 affected39 at risk EG0010 events0 affected129 at risk EG0020 events0 affected126 at risk EG003
Cholecystitis acute	Hepatobiliary disorders	MedDRA 26.0	Systematic Assessment		EG0000 events0 affected39 at risk EG0010 events0 affected129 at risk EG0020 events0 affected126 at risk EG003
Anaphylactic reaction	Immune system disorders	MedDRA 26.0	Systematic Assessment		EG0000 events0 affected39 at risk EG0011 events1 affected129 at risk EG0020 events0 affected126 at risk EG003
Covid-19	Infections and infestations	MedDRA 26.0	Systematic Assessment	8 Subjects initially randomized to the 250 mg group switched dose to 400 mg following CSP amendment 1 and were analysed according to the 400 mg group.	EG0000 events0 affected39 at risk EG0010 events0 affected129 at risk EG0021 events1 affected126 at risk EG003
Gastroenteritis	Infections and infestations	MedDRA 26.0	Systematic Assessment		EG0001 events1 affected39 at risk EG0010 events0 affected129 at risk EG0020 events0 affected126 at risk EG003
Angina pectoris	Cardiac disorders	MedDRA 26.0	Systematic Assessment		EG0001 events1 affected39 at risk EG0012 events2 affected129 at risk EG0020 events0 affected126 at risk EG003
Peritonitis	Infections and infestations	MedDRA 26.0	Systematic Assessment		EG0000 events0 affected39 at risk EG0011 events1 affected129 at risk EG0020 events0 affected126 at risk EG003
Urinary tract infection bacterial	Infections and infestations	MedDRA 26.0	Systematic Assessment		EG0000 events0 affected39 at risk EG0010 events0 affected129 at risk EG0020 events0 affected126 at risk EG003
Urosepsis	Infections and infestations	MedDRA 26.0	Systematic Assessment		EG0001 events1 affected39 at risk EG0010 events0 affected129 at risk EG0020 events0 affected126 at risk EG003
Diabetes mellitus	Metabolism and nutrition disorders	MedDRA 26.0	Systematic Assessment		EG0000 events0 affected39 at risk EG0011 events1 affected129 at risk EG0020 events0 affected126 at risk EG003
Arthralgia	Musculoskeletal and connective tissue disorders	MedDRA 26.0	Systematic Assessment		EG0000 events0 affected39 at risk EG0010 events0 affected129 at risk EG0021 events1 affected126 at risk EG003
Lung adenocarcinoma	Neoplasms benign, malignant and unspecified (incl cysts and polyps)	MedDRA 26.0	Systematic Assessment		EG0000 events0 affected39 at risk EG0010 events0 affected129 at risk EG0020 events0 affected126 at risk EG003
Neuroendocrine tumour	Neoplasms benign, malignant and unspecified (incl cysts and polyps)	MedDRA 26.0	Systematic Assessment		EG0000 events0 affected39 at risk EG0011 events1 affected129 at risk EG0020 events0 affected126 at risk EG003
Prostate cancer	Neoplasms benign, malignant and unspecified (incl cysts and polyps)	MedDRA 26.0	Systematic Assessment		EG0000 events0 affected39 at risk EG0010 events0 affected129 at risk EG0020 events0 affected126 at risk EG003
Angina unstable	Cardiac disorders	MedDRA 26.0	Systematic Assessment		EG0000 events0 affected39 at risk EG0013 events3 affected129 at risk EG0022 events2 affected126 at risk EG003
Sciatica	Nervous system disorders	MedDRA 26.0	Systematic Assessment		EG0000 events0 affected39 at risk EG0010 events0 affected129 at risk EG0020 events0 affected126 at risk EG003
Transient ischaemic attack	Nervous system disorders	MedDRA 26.0	Systematic Assessment		EG0000 events0 affected39 at risk EG0011 events1 affected129 at risk EG0020 events0 affected126 at risk EG003
Stag horn calculus	Renal and urinary disorders	MedDRA 26.0	Systematic Assessment		EG0000 events0 affected39 at risk EG0010 events0 affected129 at risk EG0020 events0 affected126 at risk EG003
Epistaxis	Respiratory, thoracic and mediastinal disorders	MedDRA 26.0	Systematic Assessment	8 Subjects initially randomized to the 250 mg group switched dose to 400 mg following CSP amendment 1 and were analysed according to the 400 mg group.	EG0000 events0 affected39 at risk EG0012 events1 affected129 at risk EG0020 events0 affected126 at risk EG003
Haemoptysis	Respiratory, thoracic and mediastinal disorders	MedDRA 26.0	Systematic Assessment		EG0000 events0 affected39 at risk EG0010 events0 affected129 at risk EG0020 events0 affected126 at risk EG003
Psoriasis	Skin and subcutaneous tissue disorders	MedDRA 26.0	Systematic Assessment		EG0000 events0 affected39 at risk EG0011 events1 affected129 at risk EG0020 events0 affected126 at risk EG003
Aortic aneurysm	Vascular disorders	MedDRA 26.0	Systematic Assessment		EG0000 events0 affected39 at risk EG0010 events0 affected129 at risk EG0020 events0 affected126 at risk EG003
Atrial fibrillation	Cardiac disorders	MedDRA 26.0	Systematic Assessment		EG0000 events0 affected39 at risk EG0010 events0 affected129 at risk EG0021 events1 affected126 at risk EG003
Peripheral artery occlusion	Vascular disorders	MedDRA 26.0	Systematic Assessment		EG0000 events0 affected39 at risk EG0010 events0 affected129 at risk EG0020 events0 affected126 at risk EG003
Peripheral ischaemia	Vascular disorders	MedDRA 26.0	Systematic Assessment		EG0000 events0 affected39 at risk EG0010 events0 affected129 at risk EG0020 events0 affected126 at risk EG003
Cardiac arrest	Cardiac disorders	MedDRA 26.0	Systematic Assessment		EG0000 events0 affected39 at risk EG0011 events1 affected129 at risk EG0020 events0 affected126 at risk EG003
Cardiac failure	Cardiac disorders	MedDRA 26.0	Systematic Assessment		EG0000 events0 affected39 at risk EG0011 events1 affected129 at risk EG0020 events0 affected126 at risk EG003
Cardiogenic shock	Cardiac disorders	MedDRA 26.0	Systematic Assessment		EG0000 events0 affected39 at risk EG0010 events0 affected129 at risk EG0021 events1 affected126 at risk EG003
Coronary artery disease	Cardiac disorders	MedDRA 26.0	Systematic Assessment		EG0000 events0 affected39 at risk EG0010 events0 affected129 at risk EG0020 events0 affected126 at risk EG003

Other Adverse Events

Term	Organ System	Source Vocabulary	Assessment Type	Notes	Statistical Information
Diarrhoea	Gastrointestinal disorders	MedDRA 26.0	Systematic Assessment		EG0002 events2 affected39 at risk EG0015 events5 affected129 at risk EG0022 events2 affected126 at risk EG0033 events3 affected126 at risk
Nausea	Gastrointestinal disorders	MedDRA 26.0	Systematic Assessment		EG0002 events2 affected39 at risk EG0011 events1 affected129 at risk EG0021 events1 affected126 at risk EG003
Non-cardiac chest pain	General disorders	MedDRA 26.0	Systematic Assessment		EG0002 events2 affected39 at risk EG0015 events5 affected129 at risk EG0028 events6 affected126 at risk EG003
Pyrexia	General disorders	MedDRA 26.0	Systematic Assessment		EG0002 events2 affected39 at risk EG0011 events1 affected129 at risk EG0024 events3 affected126 at risk EG003
Covid-19	Infections and infestations	MedDRA 26.0	Systematic Assessment	8 Subjects initially randomized to the 250 mg group switched dose to 400 mg following CSP amendment 1 and were analysed according to the 400 mg group.	EG0002 events2 affected39 at risk EG0018 events8 affected129 at risk EG00217 events16 affected126 at risk EG003
Angina pectoris	Cardiac disorders	MedDRA 26.0	Systematic Assessment		EG0001 events1 affected39 at risk EG0017 events7 affected129 at risk EG0024 events3 affected126 at risk EG003
Influenza	Infections and infestations	MedDRA 26.0	Systematic Assessment		EG0002 events2 affected39 at risk EG0014 events4 affected129 at risk EG0022 events2 affected126 at risk EG003
Pain in extremity	Musculoskeletal and connective tissue disorders	MedDRA 26.0	Systematic Assessment		EG0002 events2 affected39 at risk EG0011 events1 affected129 at risk EG0021 events1 affected126 at risk EG003
Dyspnoea	Respiratory, thoracic and mediastinal disorders	MedDRA 26.0	Systematic Assessment		EG0002 events2 affected39 at risk EG0014 events3 affected129 at risk EG0025 events4 affected126 at risk EG003
Epistaxis	Respiratory, thoracic and mediastinal disorders	MedDRA 26.0	Systematic Assessment		EG0002 events2 affected39 at risk EG0011 events1 affected129 at risk EG0024 events2 affected126 at risk EG003
Hypertension	Vascular disorders	MedDRA 26.0	Systematic Assessment		EG0002 events2 affected39 at risk EG0015 events4 affected129 at risk EG0029 events9 affected126 at risk EG003
Hypotension	Vascular disorders	MedDRA 26.0	Systematic Assessment		EG0002 events2 affected39 at risk EG0011 events1 affected129 at risk EG0025 events4 affected126 at risk EG003

ID	Term
D003327	Coronary Disease
D050197	Atherosclerosis

ID	Term
D017202	Myocardial Ischemia
D006331	Heart Diseases
D002318	Cardiovascular Diseases
D014652	Vascular Diseases
D001161	Arteriosclerosis
D001157	Arterial Occlusive Diseases

ID	Title	Description
BG000	MEDI6570 50 mg	Participants received MEDI6570 50 mg every 4 weeks for 32 weeks
BG001	MEDI6570 150 mg	Participants received MEDI6570 150 mg every 4 weeks for 32 weeks
BG002	MEDI6570 400 mg	Participants received MEDI6570 400 mg every 4 weeks for 32 weeks
BG003	Placebo	Participants received Placebo matched to MEDI6570 every 4 weeks for 32 weeks
BG004	Total	Total of all reporting groups

ID	Title	Description	Deaths (Affected)	Deaths (At Risk)	Serious Events (Affected)	Serious Events (At Risk)	Other Events (Affected)	Other Events (At Risk)
EG000	MEDI6570 50 mg	Participants received MEDI6570 50 mg every 4 weeks for 32 weeks	0	39	4	39	15	39
EG001	MEDI6570 150 mg	Participants received MEDI6570 150 mg every 4 weeks for 32 weeks	1	129	17	129	33	129
EG002	MEDI6570 400 mg	Participants received MEDI6570 400 mg every 4 weeks for 32 weeks	1	126	10	126	37	126
EG003	Placebo	Participants received Placebo matched to MEDI6570 every 4 weeks for 32 weeks	0	126	13	126	23	126