Clinical Trials Register

Summary
EudraCT Number:	2018-001065-17
Sponsor's Protocol Code Number:	EXO_01
National Competent Authority:	Italy - Italian Medicines Agency
Clinical Trial Type:	EEA CTA
Trial Status:	Prematurely Ended
Date on which this record was first entered in the EudraCT database:	2020-05-04
Trial results

Index
A. PROTOCOL INFORMATION
B. SPONSOR INFORMATION
C. APPLICANT IDENTIFICATION
D. IMP IDENTIFICATION
D.8 INFORMATION ON PLACEBO
E. GENERAL INFORMATION ON THE TRIAL
F. POPULATION OF TRIAL SUBJECTS
G. INVESTIGATOR NETWORKS TO BE INVOLVED IN THE TRIAL
N. REVIEW BY THE COMPETENT AUTHORITY OR ETHICS COMMITTEE IN THE COUNTRY CONCERNED
P. END OF TRIAL

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A. Protocol Information

A.1

Member State Concerned

Italy - Italian Medicines Agency

A.2

EudraCT number

2018-001065-17

A.3

Full title of the trial

Early treatment with evOlocumab in patients with sT-elevation
myocardial Infarction undergoing primary pCi

Trattamento precoce con evOlocumab in pazienti con infarto miocardico acuto con sopraslivellamento del tratto ST sottoposti a PCI primaria

A.3.1

Title of the trial for lay people, in easily understood, i.e. non-technical, language

Early treatment with evOlocumab in patients with sT-elevation
myocardial Infarction undergoing primary pCi

Trattamento precoce con evOlocumab in pazienti con infarto miocardico acuto con sopraslivellamento del tratto ST sottoposti a PCI primaria

A.3.2

Name or abbreviated title of the trial where available

ExOTIC Study

A.4.1

Sponsor's protocol code number

EXO_01

A.7

Trial is part of a Paediatric Investigation Plan

A.8

EMA Decision number of Paediatric Investigation Plan

B. Sponsor Information
B.Sponsor: 1
B.1.1	Name of Sponsor	Fondazione IRCCS Policlinico San Matteo
B.1.3.4	Country	Italy
B.3.1 and B.3.2	Status of the sponsor	Non-Commercial
B.4 Source(s) of Monetary or Material Support for the clinical trial:
B.4.1	Name of organisation providing support	AMGEN Srl
B.4.2	Country	Italy
B.5 Contact point designated by the sponsor for further information on the trial
B.5.1	Name of organisation	Fondazione IRCCS Policlinico San Matteo
B.5.2	Functional name of contact point	U.O.C. Cardiologia
B.5.3	Address:
B.5.3.1	Street Address	P.le Golgi 19
B.5.3.2	Town/ city	Pavia
B.5.3.3	Post code	27100
B.5.3.4	Country	Italy
B.5.4	Telephone number	+390382503158
B.5.5	Fax number	+390382503159
B.5.6	E-mail	segreteria.cardiologia@smatteo.pv.it

D. IMP Identification
D.IMP: 1
D.1.2 and D.1.3	IMP Role	Test
D.2	Status of the IMP to be used in the clinical trial
D.2.1	IMP to be used in the trial has a marketing authorisation	Yes
D.2.1.1.1	Trade name	REPATHA - 140 MG- SOLUZIONE INIETTABILE- USO SOTTOCUTANEO- SIRINGA PRERIEMPITA (VETRO) (SURECLICK) 1 ML- 1 PENNA PRERIEMPITA
D.2.1.1.2	Name of the Marketing Authorisation holder	AMGEN EUROPE B.V.
D.2.1.2	Country which granted the Marketing Authorisation	European Union
D.2.5	The IMP has been designated in this indication as an orphan drug in the Community	No
D.2.5.1	Orphan drug designation number
D.3 Description of the IMP
D.3.1	Product name	Evolocumab
D.3.2	Product code	AMG 145
D.3.4	Pharmaceutical form	Injection
D.3.4.1	Specific paediatric formulation	No
D.3.7	Routes of administration for this IMP	Subcutaneous use
D.3.11 The IMP contains an:
D.3.11.1	Active substance of chemical origin	No
D.3.11.2	Active substance of biological/ biotechnological origin (other than Advanced Therapy IMP (ATIMP)	Yes
	The IMP is a:
D.3.11.3	Advanced Therapy IMP (ATIMP)	No
D.3.11.3.1	Somatic cell therapy medicinal product	No
D.3.11.3.2	Gene therapy medical product	No
D.3.11.3.3	Tissue Engineered Product	No
D.3.11.3.4	Combination ATIMP (i.e. one involving a medical device)	No
D.3.11.3.5	Committee on Advanced therapies (CAT) has issued a classification for this product	No
D.3.11.4	Combination product that includes a device, but does not involve an Advanced Therapy	Yes
D.3.11.5	Radiopharmaceutical medicinal product	No
D.3.11.6	Immunological medicinal product (such as vaccine, allergen, immune serum)	No
D.3.11.7	Plasma derived medicinal product	No
D.3.11.8	Extractive medicinal product	No
D.3.11.9	Recombinant medicinal product	No
D.3.11.10	Medicinal product containing genetically modified organisms	No
D.3.11.11	Herbal medicinal product	No
D.3.11.12	Homeopathic medicinal product	No
D.3.11.13	Another type of medicinal product	No

D.8 Information on Placebo

E. General Information on the Trial

E.1 Medical condition or disease under investigation

E.1.1

Medical condition(s) being investigated

Acute myocardial infarction with persistent ST segment elevation (STEMI)

Infarto miocardico acuto con persistente sopraslivellamento del tratto ST (STEMI)

E.1.1.1

Medical condition in easily understood language

Myocardial infarction

Infarto miocardico

E.1.1.2

Therapeutic area

Diseases [C] - Cardiovascular Diseases [C14]

MedDRA Classification

E.1.3

Condition being studied is a rare disease

E.2 Objective of the trial

E.2.1

Main objective of the trial

To assess whether early evolocumab administration reduces infarct size in patients with STEMI undergoing primary PCI

Determinare se la somministrazione precoce di evolocumab riduce ’area infartuale nei pazienti con STEMI candidati a angioplastica primaria (pPCI)

E.2.2

Secondary objectives of the trial

To assess whether early evolocumab administration is associated with:
• a significant decrease in inflammatory cytokine response
• a significant absolute and percentage changes in choletesrol LDL
levels
Exploratory evaluation of MACE at 12 months
Safety of early evolocumab administration
Quality of life

Determinare se la somministrazione precoce di evolocumb si associa a:
• Una significativa riduzione delle citochine infiammatorie
• Una significativa riduzione dei livelli di colesterolo LDL (cLDL)
Valutazione esplorativa dei MACE a 12 mesi
Sicurezza della somministrazione precoce di evolucomab
Valutazione della qualità di vita

E.2.3

Trial contains a sub-study

E.3

Principal inclusion criteria

Age ≥ 18 years old;
Chest pain or equivalent lasting > 20 minutes;
ST elevation myocardial infarction scheduled for primary PCI;
Signed written informed consent

Età > 18 anni
Dolore toracico o equivalente di durata > 20 minutes;
Infarto miocardico con sopraslivellamento del tratto ST candidato ad angioplastica primaria;
• Firma del consenso informato

E.4

Principal exclusion criteria

• Previous myocardial infarction
• Previous percutaneous or surgical myocardial revascularization
• Ongoing treatment with any statin or ezetimibe
• History of congestive heart failure
• Cardiogenic shock at presentation (killip IV)
• Known Pregnancy
• Women of Childbearing Age
• Known major active infection or major hematologic, renal, hepatic, or endocrine
dysfunction
• Malignancy (except non-melanoma skin cancer, cervical in situ carcinoma, breast ductal carcinoma in situ, stage 1 prostate
carcinoma)
within the last 10 years
• Patients with hypersensitivity to the active substance (evolocumab) or to any of its excipients
• Inability to attend the scheduled clinical evaluation and laboratory tests
• Inability to undergo the pharmacological treatment or other procedures of the study
• Currently enrolled in another investigational drug study, or < 30 days/<5 half-life since ending another investigational drug study(s).

• Pregresso infarto miocardico
• Pregressa rivascolarizzazione miocardica percutanea o chirurgica
• Trattamento con statine e/o ezetimibe
• Storia di scompenso cardiaco
• Shock cardiogeno alla presentazione (killip IV)
• Gravidanza nota
• Donne in età fertile
• Note infezioni maggiori, malattie ematologiche, epatiche, renali o disfunzioni ormonali
• Neoplasie nei 10 anni precedenti (ad eccezione di tumori cutanei non-melanoma,carcinoma in situ della cerivice, carcinoma duttale mammario in situ, carcinoma prostatico in stadio 1)
• Ipersensibilità al principio arrivo o ad uno qualsiasi degli eccipienti
• Incapacità di attenersi alle visite programmate, al programma di trattamento, ai test di laboratorio ed altre procedure dello studio
• Partecipazione ad uno studio clinico in cui è stato somministrato un farmaco sperimentale entro 30 giorni o 5 emivite del farmaco in studio

E.5 End points

E.5.1

Primary end point(s)

Myocardial salvage index (MSI) at 6 months evaluated with cardiac magnetic resonance (CMR)

Myocardial salvage index (MSI) a 6 mesi valutato con risonanza magnetica cardiaca (CMR)

E.5.1.1

Timepoint(s) of evaluation of this end point

6 months

6 mesi

E.5.2

Secondary end point(s)

• Area at risk at baseline CMR
• Microvascular Obstruction (MVO) at baseline CMR
• Absolute changes of hs-CRP, IL-1, IL-6, IL-10, and TNFalfa at 6 months follow up
• Absolute and percentage changes in c-LDL levels at 6 months follow-up
• Composite of cardiovascular death, MI or stroke at 12 months
• Single: cardiovascular death, all cause mortality, MI, stroke, stent thrombosis at 12 months
• Euroqol 5-dimension questionnaire at 12 months

• Area infartuata a rischio alla CMR basale
• Microvascular Obstruction (MVO) alla CMR basale
• Riduzione in termini assoluti dei livelli plasmatici di hs-CRP, IL-1, IL-6, IL-10,
and TNFalfa a 6 mesi
• Variazione in termini assoluti e percentuali dei livelli plasmatici di cLDL a 6 mesi
• Composito morte cardiovascolare, infarto miocardico o stroke a 12 mesi
• Singoli: morte cardiovascolare, infarto miocardico, stroke a 12 mesi
• Questionario Euroqol 5-dimension a 12 mesi

E.5.2.1

Timepoint(s) of evaluation of this end point

Basal, 6 months, 12 months

Basale, 6 mesi, 12 mesi

E.6 and E.7 Scope of the trial

E.6

Scope of the trial

E.6.1

Diagnosis

E.6.2

Prophylaxis

E.6.3

Therapy

E.6.4

Safety

Yes

E.6.5

Efficacy

Yes

E.6.6

Pharmacokinetic

E.6.7

Pharmacodynamic

E.6.8

Bioequivalence

E.6.9

Dose response

E.6.10

Pharmacogenetic

E.6.11

Pharmacogenomic

E.6.12

Pharmacoeconomic

E.6.13

Others

E.7

Trial type and phase

E.7.1

Human pharmacology (Phase I)

E.7.1.1

First administration to humans

E.7.1.2

Bioequivalence study

E.7.1.3

Other

E.7.1.3.1

Other trial type description

E.7.2

Therapeutic exploratory (Phase II)

Yes

E.7.3

Therapeutic confirmatory (Phase III)

E.7.4

Therapeutic use (Phase IV)

E.8 Design of the trial

E.8.1

Controlled

Yes

E.8.1.1

Randomised

Yes

E.8.1.2

Open

Yes

E.8.1.3

Single blind

E.8.1.4

Double blind

E.8.1.5

Parallel group

E.8.1.6

Cross over

E.8.1.7

Other

E.8.2

Comparator of controlled trial

E.8.2.1

Other medicinal product(s)

Yes

E.8.2.2

Placebo

E.8.2.3

Other

E.8.2.4

Number of treatment arms in the trial

E.8.3

The trial involves single site in the Member State concerned

E.8.4

The trial involves multiple sites in the Member State concerned

Yes

E.8.4.1

Number of sites anticipated in Member State concerned

E.8.5

The trial involves multiple Member States

E.8.6 Trial involving sites outside the EEA

E.8.6.1

Trial being conducted both within and outside the EEA

E.8.6.2

Trial being conducted completely outside of the EEA

E.8.7

Trial has a data monitoring committee

E.8.8

Definition of the end of the trial and justification where it is not the last visit of the last subject undergoing the trial

E.8.9 Initial estimate of the duration of the trial

E.8.9.1

In the Member State concerned years

E.8.9.1

In the Member State concerned months

E.8.9.1

In the Member State concerned days

F. Population of Trial Subjects

F.1 Age Range

F.1.1

Trial has subjects under 18

F.1.1.1

In Utero

F.1.1.2

Preterm newborn infants (up to gestational age < 37 weeks)

F.1.1.3

Newborns (0-27 days)

F.1.1.4

Infants and toddlers (28 days-23 months)

F.1.1.5

Children (2-11years)

F.1.1.6

Adolescents (12-17 years)

F.1.2

Adults (18-64 years)

Yes

F.1.2.1

Number of subjects for this age range:

118

F.1.3

Elderly (>=65 years)

Yes

F.1.3.1

Number of subjects for this age range:

F.2 Gender

F.2.1

Female

Yes

F.2.2

Male

Yes

F.3 Group of trial subjects

F.3.1

Healthy volunteers

F.3.2

Patients

Yes

F.3.3

Specific vulnerable populations

F.3.3.1

Women of childbearing potential not using contraception

F.3.3.2

Women of child-bearing potential using contraception

F.3.3.3

Pregnant women

F.3.3.4

Nursing women

F.3.3.5

Emergency situation

F.3.3.6

Subjects incapable of giving consent personally

F.3.3.7

Others

F.4 Planned number of subjects to be included

F.4.1

In the member state

154

F.5

Plans for treatment or care after the subject has ended the participation in the trial (if it is different from the expected normal treatment of that condition)

Patients will return to the drug therapy prescribed according to clinical practice

I pazienti ritorneranno alla terapia farmacologica prescritta secondo pratica clinica

G. Investigator Networks to be involved in the Trial

N. Review by the Competent Authority or Ethics Committee in the country concerned

Competent Authority Decision

Authorised

Date of Competent Authority Decision

Ethics Committee Opinion of the trial application

Favourable

Ethics Committee Opinion: Reason(s) for unfavourable opinion

Date of Ethics Committee Opinion

2019-08-12

P. End of Trial
P.	End of Trial Status	Prematurely Ended

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