Clinical Trials Register

Summary
EudraCT Number:	2017-002954-35
Sponsor's Protocol Code Number:	EFC14828
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:	2021-05-25
Trial results	View 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

2017-002954-35

A.3

Full title of the trial

A Randomized, Double-blind, Placebo-controlled, Parallel-group, Multicenter Study to Evaluate the Effect of Efpeglenatide on Cardiovascular Outcomes in Type 2 Diabetes Patients at High Cardiovascular Risk

Studio randomizzato, in doppio cieco, controllato verso placebo, a gruppi paralleli, multicentrico per valutare l'effetto di efpeglenatide sugli esiti cardiovascolari in pazienti con diabete di tipo 2 ad alto rischio cardiovascolare

A.3.1

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

Effect of Efpeglenatide on Cardiovascular Outcomes

Effetto di Efpeglenatide sugli esiti cardiovascolari

A.3.2

Name or abbreviated title of the trial where available

Effect of Efpeglenatide on Cardiovascular Outcomes in High Cardiovascular Risk Type 2 Diabetes Patie

Effetto di Efpeglenatide sugli esiti cardiovascolari in pazienti con diabete di tipo 2 ad alto risch

A.4.1

Sponsor's protocol code number

EFC14828

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	SANOFI-AVENTIS RECHERCHE E DEVELOPPEMENT
B.1.3.4	Country	France
B.3.1 and B.3.2	Status of the sponsor	Commercial
B.4 Source(s) of Monetary or Material Support for the clinical trial:
B.4.1	Name of organisation providing support	RECHERCHE ET DEVELOPPEMNT
B.4.2	Country	France
B.5 Contact point designated by the sponsor for further information on the trial
B.5.1	Name of organisation	SANOFI S.p.A.
B.5.2	Functional name of contact point	CONTACT POINT
B.5.3	Address:
B.5.3.1	Street Address	VIALE BODIO, 37/B
B.5.3.2	Town/ city	MILANO
B.5.3.3	Post code	20158
B.5.3.4	Country	Italy
B.5.4	Telephone number	800226343
B.5.5	Fax number	0239394168
B.5.6	E-mail	informazioni.medicoscientifiche@sanofi.com

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	No
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	Efpeglenatide
D.3.2	Product code	SAR439977
D.3.4	Pharmaceutical form	Solution for injection
D.3.4.1	Specific paediatric formulation	No
D.3.7	Routes of administration for this IMP	Subcutaneous use
D.3.8 to D.3.10 IMP Identification Details (Active Substances)
D.3.8	INN - Proposed INN	efpeglenatide
D.3.9.1	CAS number	1296200-77-5
D.3.9.2	Current sponsor code	SAR439977
D.3.9.4	EV Substance Code	SUB31313
D.3.10	Strength
D.3.10.1	Concentration unit	mg milligram(s)
D.3.10.2	Concentration type	equal
D.3.10.3	Concentration number	2
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	Information not present in EudraCT
D.3.11.3.2	Gene therapy medical product	Information not present in EudraCT
D.3.11.3.3	Tissue Engineered Product	Information not present in EudraCT
D.3.11.3.4	Combination ATIMP (i.e. one involving a medical device)	Information not present in EudraCT
D.3.11.3.5	Committee on Advanced therapies (CAT) has issued a classification for this product	Information not present in EudraCT
D.3.11.4	Combination product that includes a device, but does not involve an Advanced Therapy	No
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	Yes
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.IMP: 2
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	No
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	Efpeglenatide
D.3.2	Product code	SAR439977
D.3.4	Pharmaceutical form	Solution for injection
D.3.4.1	Specific paediatric formulation	No
D.3.7	Routes of administration for this IMP	Subcutaneous use
D.3.8 to D.3.10 IMP Identification Details (Active Substances)
D.3.8	INN - Proposed INN	efpeglenatide
D.3.9.1	CAS number	1296200-77-5
D.3.9.2	Current sponsor code	SAR439977
D.3.9.4	EV Substance Code	SUB31313
D.3.10	Strength
D.3.10.1	Concentration unit	mg milligram(s)
D.3.10.2	Concentration type	equal
D.3.10.3	Concentration number	4
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	Information not present in EudraCT
D.3.11.3.2	Gene therapy medical product	Information not present in EudraCT
D.3.11.3.3	Tissue Engineered Product	Information not present in EudraCT
D.3.11.3.4	Combination ATIMP (i.e. one involving a medical device)	Information not present in EudraCT
D.3.11.3.5	Committee on Advanced therapies (CAT) has issued a classification for this product	Information not present in EudraCT
D.3.11.4	Combination product that includes a device, but does not involve an Advanced Therapy	No
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	Yes
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.IMP: 3
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	No
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	Efpeglenatide
D.3.2	Product code	SAR439977
D.3.4	Pharmaceutical form	Solution for injection
D.3.4.1	Specific paediatric formulation	No
D.3.7	Routes of administration for this IMP	Subcutaneous use
D.3.8 to D.3.10 IMP Identification Details (Active Substances)
D.3.8	INN - Proposed INN	efpeglenatide
D.3.9.1	CAS number	1296200-77-5
D.3.9.2	Current sponsor code	SAR439977
D.3.9.4	EV Substance Code	SUB31313
D.3.10	Strength
D.3.10.1	Concentration unit	mg milligram(s)
D.3.10.2	Concentration type	equal
D.3.10.3	Concentration number	6
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	Information not present in EudraCT
D.3.11.3.2	Gene therapy medical product	Information not present in EudraCT
D.3.11.3.3	Tissue Engineered Product	Information not present in EudraCT
D.3.11.3.4	Combination ATIMP (i.e. one involving a medical device)	Information not present in EudraCT
D.3.11.3.5	Committee on Advanced therapies (CAT) has issued a classification for this product	Information not present in EudraCT
D.3.11.4	Combination product that includes a device, but does not involve an Advanced Therapy	No
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	Yes
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
D.8 Placebo: 1
D.8.1	Is a Placebo used in this Trial?	Yes
D.8.3	Pharmaceutical form of the placebo	Solution for injection
D.8.4	Route of administration of the placebo	Subcutaneous use

E. General Information on the Trial

E.1 Medical condition or disease under investigation

E.1.1

Medical condition(s) being investigated

Type 2 diabetes mellitus

Diabete mellito di tipo 2

E.1.1.1

Medical condition in easily understood language

Type 2 diabetes mellitus

Diabete mellito di tipo 2

E.1.1.2

Therapeutic area

Diseases [C] - Nutritional and Metabolic Diseases [C18]

MedDRA Classification

E.1.2 Medical condition or disease under investigation

E.1.2	Version	21.1
E.1.2	Level	PT
E.1.2	Classification code	10067585
E.1.2	Term	Type 2 diabetes mellitus
E.1.2	System Organ Class	10027433 - Metabolism and nutrition disorders

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 demonstrate that, efpeglenatide doses 1 and 2 is noninferior to placebo on 3-point major adverse cardiac event (MACE) in Type 2 diabetes mellitus (T2DM) patients at high cardiovascular (CV) risk.

Dimostrare che efpeglenatide 4 e 6 mg (dosi 1 e 2) non ¿ inferiore al placebo sui MACE a 3 punti nei pazienti con T2DM a rischio CV elevato

E.2.2

Secondary objectives of the trial

-To demonstrate that efpeglenatide doses 1 and 2 is superior to placebo in T2DM patients with high CV risk on the following parameters:
-3-point MACE
-Expanded CV outcome.
-Composite outcome of new or worsening nephropathy.
-To assess the safety and tolerability of efpeglenatide doses 1 and 2, both added to standard of care in T2DM patients at high CV risk.

Dimostrare che efpeglenatide 4 e 6 mg ¿ superiore al placebo nei pazienti con T2DM a rischio CV elevato per i seguenti parametri:
- MACE a 3 punti
- outcome CV esteso
- outcome composito di insorgenza o peggioramento della nefropatia (dosi 1 e 2)
- Determinare la sicurezza e la tollerabilit¿ di efpeglenatide 4 e 6 mg una volta a settimana (QW), in entrambi i casi aggiunte alla terapia standard in pazienti con T2DM con rischio CV elevato

E.2.3

Trial contains a sub-study

E.3

Principal inclusion criteria

-Type 2 Diabetes Mellitus with glycosylated hemoglobin (HbA1c) > 7%.
-Age 18 years or older with established cardiovascular disease or age 50 years (male), 55 years (female) or older with eGFR =25 and <60 mL/min and at least one cardiovascular risk factor.
-Female patients must agree to follow contraceptive guidance.
-Signed written informed consent.

- Pazienti con T2DM e HbA1c >7%
- Pazienti di età =18 anni con patologia cardiovascolare conclamata o pazienti di sesso maschile di =50 anni di età o pazienti di sesso femminile di =55 anni di età con eGFR
=25ml/min e <60 ml/min, che presentano almeno un fattore di rischio cardiovascolare.
- Pazienti di sesso femminile che acconsentano all'utilizzo di metodi contraccettivi.
- Consenso informato scritto

E.4

Principal exclusion criteria

-Clinically relevant history of gastrointestinal disease associated with prolonged nausea and vomiting.
-History of chronic pancreatitis or acute idiopathic pancreatitis or diagnosis of any type of acute pancreatitis.
-Personal or family history of medullary thyroid cancer (MTC)
-Hypertension (with a systolic blood pressure >180 mmHg and/or diastolic blood pressure >100 mmHg).
-Hospitalization for hypertensive emergency within 3 months prior to randomization
-Planned coronary procedure or surgery after randomization.
-No documented ophthalmologic exam with fundoscopy within 6 months prior to screening
-Retinopathy or maculopathy with treatment, either recent (3 months prior to randomization) or planned during the study
-Treated with any glucagon-like peptide-1 (GLP-1) receptor agonist products (eg, exenatide, liraglutide, lixisenatide, albiglutide, dulaglutide, semaglutide) or in combination within 3 months prior to screening.
-Use of any DPP4 inhibitor within 3 months prior to screening
-Antihyperglycemic treatment has not been stable within 3 months prior to screening.

- Anamnesi clinicamente rilevante di malattia gastrointestinale associata a nausea e vomito prolungati
- Anamnesi di pancreatite cronica o pancreatite idiopatica acuta o diagnosi di qualunque tipo di pancreatite acuta.
- Anamnesi personale o familiare di tumore midollare della tiroide (MTC)
- Ipertensione (con BP sistolica >180 mmHg e/o DBP >100 mmHg)
- Ricovero per emergenze di natura ipertensiva nei 3 mesi precedenti la randomizzazione
- Previsione di procedure coronariche o chirurgia dopo la randomizzazione
- Nessun esame oftalmologico documentato con oftalmoscopia nei 6 mesi precedenti lo screening
- Retinopatia o maculopatia con un trattamento assunto di recente (nei 3 mesi precedenti la randomizzazione) o previsto durante lo studio
- Trattamento con un qualsiasi prodotto GLP-1 RA (ad es. exenatide, liraglutide, lixisenatide, albiglutide,
dulaglutide, semaglutide) o in combinazione nei 3 mesi precedenti lo screening
- Utilizzo di un qualsiasi inibitore del DPP4 nei 3 mesi precedenti lo screening
- Trattamento instabile del diabete nei 3 mesi precedenti lo screening

E.5 End points

E.5.1

Primary end point(s)

Time to first Major Adverse Cardiovascular Event (MACE): Time to the
first occurrence of any of the following clinical events: cardiovascular
death, non-fatal myocardial infarction (MI), non-fatal stroke

Tempo alla prima manifestazione di MACE (Major Adverse Cardiovascular Event): decesso per cause CV, infarto del miocardio (MI) non fatale;ictus non fatale

E.5.1.1

Timepoint(s) of evaluation of this end point

Baseline to approximately 36 months

Dal basale a circa 36 mesi

E.5.2

Secondary end point(s)

1) Time to first expanded cardiovascular outcome event: Time to the first
occurrence of any of the following clinical events, positively adjudicated
by the clinical endpoint committee (CEC): cardiovascular death, non-fatal
MI, non-fatal stroke, coronary revascularization, hospitalization for
unstable angina.
2) Time to first composite renal event: Time to the first occurrence of
any of the following clinical events: new onset or progression to macro
albuminuria (>300 mg/g) accompanied by a (UACR)urinary albumin-creatinina ratio value increase of =
30% from baseline, sustained =40% decrease in eGFR from baseline (for
=30 days), chronic dialysis (for =90 days), renal transplant, sustained
eGFR <15 mL/min/1.73 m2 (for =30 days).
3) Adverse Events (AEs): Number of patients with AEs

1) Tempo alla prima manifestazione di un outcome CV esteso tra i seguenti, aggiudicati
positivamente dal clinical endpoint committee (CEC): decesso per cause CV; infarto del miocardio (MI) non fatale; ictus non fatale; rivascolarizzazione coronarica; ricovero per angina instabile,
2) Tempo alla prima manifestazione di qualsiasi
evento clinico tra i seguenti:
¿ nuovo esordio o progressione di macro
albuminuria (> 300 mg/g) accompagnata da un
aumento =30% del valore del rapporto
albumina/creatinina (UACR) rispetto al basale;
¿ riduzione =40% costante della velocit¿ di
filtrazione glomerulare (eGFR) stimata rispetto
al basale (per =30 giorni);
¿ dialisi cronica (per =90 giorni);
¿ trapianto di reni;
¿ eGFR costante <15 ml/min/1,73 m2 (per =30
giorni).
3) Eventi avversi: numero di pazienti con Eventi Avversi

E.5.2.1

Timepoint(s) of evaluation of this end point

1) to 3) Baseline to approximately 36 months

Da 1) a 3)Dal basale a circa 36 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

Yes

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)

E.7.3

Therapeutic confirmatory (Phase III)

Yes

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

E.8.1.3

Single blind

E.8.1.4

Double blind

Yes

E.8.1.5

Parallel group

Yes

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)

E.8.2.2

Placebo

Yes

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

Yes

E.8.5.1

Number of sites anticipated in the EEA

123

E.8.6 Trial involving sites outside the EEA

E.8.6.1

Trial being conducted both within and outside the EEA

Yes

E.8.6.2

Trial being conducted completely outside of the EEA

Information not present in EudraCT

E.8.6.3

If E.8.6.1 or E.8.6.2 are Yes, specify the regions in which trial sites are planned

Brazil

Canada

Chile

India

Korea, Republic of

Mexico

Peru

Russian Federation

Serbia

South Africa

Turkey

Ukraine

United States

Bulgaria

Denmark

Estonia

Finland

Germany

Hungary

Italy

Latvia

Lithuania

Norway

Poland

Romania

Slovakia

Spain

Sweden

Argentina

E.8.7

Trial has a data monitoring committee

Yes

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

LVLS

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

E.8.9.2

In all countries concerned by the trial years

E.8.9.2

In all countries concerned by the trial months

E.8.9.2

In all countries concerned by the trial 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:

3000

F.1.3

Elderly (>=65 years)

Yes

F.1.3.1

Number of subjects for this age range:

2000

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

Yes

F.3.3.1

Women of childbearing potential not using contraception

F.3.3.2

Women of child-bearing potential using contraception

Yes

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

F.4.2

For a multinational trial

F.4.2.1

In the EEA

1800

F.4.2.2

In the whole clinical trial

5000

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)

None

Nessuno

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

2018-05-02

Ethics Committee Opinion of the trial application

Favourable

Ethics Committee Opinion: Reason(s) for unfavourable opinion

Date of Ethics Committee Opinion

2018-04-05

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

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