Clinical Trials Register

Summary
EudraCT Number:	2015-004459-38
Sponsor's Protocol Code Number:	TREACE_2015
National Competent Authority:	Italy - Italian Medicines Agency
Clinical Trial Type:	EEA CTA
Trial Status:	Ongoing
Date on which this record was first entered in the EudraCT database:	2021-01-28
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

Expand All Collapse All

A. Protocol Information

A.1

Member State Concerned

Italy - Italian Medicines Agency

A.2

EudraCT number

2015-004459-38

A.3

Full title of the trial

EXPLORATIVE STUDY TO IDENTIFY A SPECIFIC TRANSCRIPTOMIC PROFILE FOR PREDICTING THE MAJOR ADVERSE EFFECTS ASSOCIATED WITH CERTICAN (EVEROLIMUS) IN RENAL TRANSPLANT RECIPIENTS: A PHARMACOGENOMIC APPROACH

STUDIO SPERIMENTALE ESPLORATIVO VOLTO AD IDENTIFICARE L¿ESISTENZA DI UNO SPECIFICO PROFILO TRASCRITTOMICO PREDITTIVO PER I MAGGIORI EVENTI AVVERSI ASSOCIATI ALL¿UTILIZZO
DI CERTICAN (EVEROLIMUS) IN PAZIENTI PORTATORI DI TRAPIANTO RENALE: UN APPROCCIO FARMACOGENOMICO

A.3.1

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

PHARMACOGENOMIC STUDY AIMED TO IDENTIFY A GENETIC PROFILE ABLE TO EARLY IDENTIFY RENAL TRANSPLANT RECIPIENTS AT HIGH RISK TO DEVELOP THE MAJOR ADVERSE EFFECTS ASSOCIATED WITH CERTICAN (EVEROLIMUS)

STUDIO DI FARMACOGENOMICA CHE SI PREFIGGE DI INDIVIDUARE UN PROFILO GENETICO IN GRADO DI INDIVIDUARE PAZIENTI APPENA SOTTOPOSTI A TRAPIANTO RENALE AD ALTO RISCHIO DI SVILUPPARE I PIU' COMUNI EFFETTI AVVERSI CORRELATI ALL'USO DI CERTICAN (EVEROLIMUS)

A.3.2

Name or abbreviated title of the trial where available

TREACE_2015

A.4.1

Sponsor's protocol code number

TREACE_2015

A.5.4

Other Identifiers

Name:

TREACE_2015

Number:

TREACE_2015

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	AZIENDA OSPEDALIERA UNIVERSITARIA INTEGRATA VERONA
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	Novartis
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	Unit¿ Supporto alla Ricerca e Biostatistica Azienda Ospedaliera Universitaria Integrata Verona
B.5.2	Functional name of contact point	Unit¿ Supporto alla Ricerca e Biost
B.5.3	Address:
B.5.3.1	Street Address	P.le Stefani, 1 (B.go Trento, presso Ospedale Geriatrico, 1¿ Piano lato Adige)
B.5.3.2	Town/ city	Verona
B.5.3.3	Post code	37126
B.5.3.4	Country	Italy
B.5.4	Telephone number	045-8127051
B.5.5	Fax number	045-8122814
B.5.6	E-mail	supporto.noprofit@ospedaleuniverona.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	CERTICAN - 60 COMPRESSE IN BLISTER ALU/PA/ALU/PVC DA 0.25 MG
D.2.1.1.2	Name of the Marketing Authorisation holder	NOVARTIS FARMA S.P.A.
D.2.1.2	Country which granted the Marketing Authorisation	Italy
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	certican 60CPR 0,25MG
D.3.2	Product code	036373025
D.3.4	Pharmaceutical form	Tablet
D.3.4.1	Specific paediatric formulation	No
D.3.7	Routes of administration for this IMP	Buccal use
D.3.8 to D.3.10 IMP Identification Details (Active Substances)
D.3.8	INN - Proposed INN	EVEROLIMUS
D.3.9.2	Current sponsor code	036373025
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	3
D.3.11 The IMP contains an:
D.3.11.1	Active substance of chemical origin	Yes
D.3.11.2	Active substance of biological/ biotechnological origin (other than Advanced Therapy IMP (ATIMP)	No
	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	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.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	Yes
D.2.1.1.1	Trade name	CERTICAN - 60 COMPRESSE IN BLISTER ALU/PA/ALU/PVC DA 0.75 MG
D.2.1.1.2	Name of the Marketing Authorisation holder	NOVARTIS FARMA S.P.A.
D.2.1.2	Country which granted the Marketing Authorisation	Italy
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	Certican 0,75 mg
D.3.2	Product code	Certican 0,75 mg compresse
D.3.4	Pharmaceutical form	Tablet
D.3.4.1	Specific paediatric formulation	No
D.3.7	Routes of administration for this IMP	Buccal use
D.3.8 to D.3.10 IMP Identification Details (Active Substances)
D.3.8	INN - Proposed INN	EVEROLIMUS
D.3.9.2	Current sponsor code	everolimus
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	3
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)	No
	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	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

kidney transplant

trapianto renale

E.1.1.1

Medical condition in easily understood language

kidney transplant

trapianto renale

E.1.1.2

Therapeutic area

Body processes [G] - Biological Phenomena [G16]

MedDRA Classification

E.1.2 Medical condition or disease under investigation

E.1.2	Version	21.0
E.1.2	Level	PT
E.1.2	Classification code	10038533
E.1.2	Term	Renal transplant
E.1.2	System Organ Class	10042613 - Surgical and medical procedures

E.1.2 Medical condition or disease under investigation

E.1.2	Version	21.0
E.1.2	Level	PT
E.1.2	Classification code	10038533
E.1.2	Term	Renal transplant
E.1.2	System Organ Class	10042613 - Surgical and medical procedures

E.1.3

Condition being studied is a rare disease

E.2 Objective of the trial

E.2.1

Main objective of the trial

1. To evaluate the differences in transcriptomic profile of peripheral blood mononuclear cells (PBMC) during the treatment of Everolimus in renal transplant recipients. We will perform transcriptomic analysis at the time of transplantation and after 3, 6, and 9 months post-transplant. The choice of this time period depends on the incidence of adverse effects caused by high dosage of maintenance immunosuppressive drugs.

1. Osservare le variazioni del profilo trascrittomico di linfomonociti del sangue periferico (LMP) durante la
terapia con EVR dopo trapianto renale. In particolare saranno registrate le differenze dopo 3, 6 e 9 mesi di
trattamento post-trapianto. La scelta di limitare l¿analisi transcrittomica a 9 mesi ¿ legata alla maggior incidenza
degli eventi avversi entro questo periodo motivata da pi¿ elevate dosi dei farmaci immunosoppressivi di
mantenimento.

E.2.2

Secondary objectives of the trial

2. To study the relationship between gene expression and clinical data collected at any time point
3. To assess a specific correlation between gene expression and adverse effects (proteinuria, lymphedema, pulmonary toxicity) in order to obtain a transcriptomic biomarker able to early identify renal transplant recipients at high risk to develop adverse effects associated with Everolimus. This biomarker could be used by clinicians in order to personalize immunosuppressive therapy and reduce clinical complications
4. To study the biological pathway including the genes selected by transcriptomic analysis. The transcriptomic analysis will be performed on entire genome and for the subsequent analysis we will select only the genes strongly associated with adverse effects.

2. Correlare il profilo trascrittomico con le variabili cliniche ad ogni singolo time point;
3. Esplorare la possibile associazione specifica tra la variazione del profilo trascrittomico e la comparsa di
eventi avversi (proteinuria, linfedema e tossicit¿ polmonare) al fine di individuare un biomarker trascrittomico
predittivo utile per l¿identificazione precoce di pazienti con trapianto renale ad alto rischio di sviluppare eventi
avversi associate all¿uso di EVR. L¿uso routinario di questo strumento permetterebbe ai clinici di personalizzare
la terapia immunosoppressiva e evitare importanti complicanze cliniche.
4. Studiare il ruolo, le funzioni biologiche e le pathway funzionali di alcuni dei geni selezionati e identificati
tramite l¿analisi microarray. L¿analisi trascrittomica verr¿ fatta sull¿intero genoma e i geni di interesse per le
successive analisi saranno selezionati tra quelli che sono maggiormente correlati agli eventi avversi registrati

E.2.3

Trial contains a sub-study

E.3

Principal inclusion criteria

• Informed consent
• Age > 18
• First kidney transplant
• patients treated with everolimus in combination with CNI (Ciclosporin or Tacrolimus) and corticosteroids

-Consenso informato scritto
-età > 18 anni
-Primo trapianto renale
-Trattamento cronico con Everolimus in combinazione con CNI (Ciclosporina o Tacrolimus) e corticosteroidi

E.4

Principal exclusion criteria

• Transplant of other organs associated with renal transplant
• Active neoplasia (but not skin cancer non melanoma)
• Acute and chronic hepatitis (hepatitis B, C)
• Positive pregnancy test at the time of enrolment
• Women in reproductive age without contraceptive method or breastfeeding women
• HIV infection
• hyperlipidemia/ Clotting problems
• interstitial lung disease/ No infectious pneumonia

• Trapianto di altro organo solido in associazione al trapianto di rene
• Neoplasia maligna in fase attiva (escluso tumore della cute tipo non-melanoma)
• Severa epatopatia acuta e cronica (Epatite virus B correlata, virus C correlata, tossica, immunoallergica)
• Donne con positività al test di gravidanza al momento dell’arruolamento
• Donne in età fertile senza una contraccezione efficace o donne in periodo di allattamento
• Infezione nota da HIV
• Iperlipidemia/complicanze nella coagulazione,
• Malattia polmonare interstiziale/polmonite non infettiva

E.5 End points

E.5.1

Primary end point(s)

To analyze the differences in transcriptome profiles from T0 to T3

Valutare le variazioni del livello di espressione del profilo trascrittomico nel periodo tra T0 e T3.

E.5.1.1

Timepoint(s) of evaluation of this end point

(1 year)

1 anno

E.5.2

Secondary end point(s)

2. To study the relationship between gene expression and clinical data collected at any time point (2 years);
3. To evaluate differences in gene expression among patients with adverse effects (proteinuria, lymphedema, pulmonary toxicity) and patients with no adverse effects during 24 months (2 years);
4. To study biological pathways containing the genes selected in point 1, 2 and 3 (2 years).

2. Individuare una associazione tra il livello di espressione di alcuni geni e le variabili cliniche registrate ad ogni
time point;
3. Individuare, ad ogni singolo time point, eventuali differenze nel livello di espressione di alcuni geni tra i
pazienti che sviluppano nei 24 mesi eventi avversi (proteinuria, linfedema e tossicit¿ polmonare) versus quelli
che non li sviluppano;
4. Studiare le pathway biologiche in cui sono coinvolti i geni selezionati nei punto 1, 2 e 3.

E.5.2.1

Timepoint(s) of evaluation of this end point

(2 years).

(2 anni).

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

E.6.6

Pharmacokinetic

E.6.7

Pharmacodynamic

E.6.8

Bioequivalence

E.6.9

Dose response

E.6.10

Pharmacogenetic

Yes

E.6.11

Pharmacogenomic

Yes

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)

E.7.4

Therapeutic use (Phase IV)

Yes

E.8 Design of the trial

E.8.1

Controlled

E.8.1.1

Randomised

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)

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

Yes

E.8.4

The trial involves multiple sites in the Member State concerned

E.8.4.1

Number of sites anticipated in Member State concerned

E.8.5

The trial involves multiple Member States

E.8.5.1

Number of sites anticipated in the EEA

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

Information not present in EudraCT

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

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:

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

F.4.2

For a multinational trial

F.4.2.1

In the EEA

F.4.2.2

In the whole clinical trial

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 be treated according to our clinical protocols. Immunosuppressive treatment will be withdraw or changed only in presence of severe adverse effects/toxicities or whether incompatible with clinical conditions (e.g., severe infection diseases, neoplasm).

I pazienti verranno trattati secondo protocolli. La terapia immunosoppressiva verr¿ variata solo in presenza di eventi avversi gravi (infezioni severe in aumento, ..)

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

2016-01-28

Ethics Committee Opinion of the trial application

Favourable

Ethics Committee Opinion: Reason(s) for unfavourable opinion

Date of Ethics Committee Opinion

2016-02-24

P. End of Trial
P.	End of Trial Status	Ongoing

Select Country:	Select Age Range:
Select Trial Status:	Select Trial Phase:
Select Gender:
Select Date Range: to
Select Rare Disease:
IMP with orphan designation in the indication
Orphan Designation Number:
Results Status:
Clear advanced search filters

Austria
Belgium
Bulgaria
Croatia
Cyprus
Czechia
Denmark
Estonia
Finland
France
Germany
Greece
Hungary
Iceland
Ireland
Italy
Latvia
Liechtenstein
Lithuania
Luxembourg
Malta
Netherlands
Norway
Poland
Portugal
Romania
Slovakia
Slovenia
Spain
Sweden
United Kingdom
Outside EU/EEA

Clinical trials