Clinical Trials Register

Summary
EudraCT Number:	2016-002707-25
Sponsor's Protocol Code Number:	SCILLA
National Competent Authority:	Italy - Italian Medicines Agency
Clinical Trial Type:	EEA CTA
Trial Status:	Completed
Date on which this record was first entered in the EudraCT database:	2021-01-13
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

2016-002707-25

A.3

Full title of the trial

Comparison between two therapeutic strategies for the maintenance of clinical and endoscopic remission in patients with ulcerative colitis treated by infliximab (SCILLA).

Confronto tra due strategie terapeutiche per il mantenimento della remissione clinica ed endoscopica in pazienti con rettocolite ulcerosa trattati con infliximab (SCILLA).

A.3.1

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

n.a.

A.3.2

Name or abbreviated title of the trial where available

n.a.

A.4.1

Sponsor's protocol code number

SCILLA

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	IRCCS ISTITUTO CLINICO HUMANITAS
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	AIFA - Italian Medicines Agency
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	IRCCS Istituto Clinico Humanitas
B.5.2	Functional name of contact point	n.a.
B.5.3	Address:
B.5.3.1	Street Address	Via Manzoni
B.5.3.2	Town/ city	Rozzano (MI)
B.5.3.3	Post code	20089
B.5.3.4	Country	Italy
B.5.4	Telephone number	0282247303
B.5.5	Fax number	0282241
B.5.6	E-mail	daniela.gilardi@humanitas.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	REMSIMA - 100 MG POLVERE PER CONCENTRATO PER SOLUZIONE PER INFUSIONE - USO ENDOVENOSO - FLANCONCINO (VETRO) - 1 FLACONCINO
D.2.1.1.2	Name of the Marketing Authorisation holder	CELLTRION HEALTHCARE HUNGARY KFT
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.3.4	Pharmaceutical form	Powder for solution for infusion
D.3.4.1	Specific paediatric formulation	No
D.3.7	Routes of administration for this IMP	Intravenous use
D.3.8 to D.3.10 IMP Identification Details (Active Substances)
D.3.8	INN - Proposed INN	INFLIXIMAB
D.3.9.2	Current sponsor code	n.a.
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	100
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	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	AZAFOR - 50 MG COMPRESSE RIVESTITE CON FILM 50 COMPRESSE IN BLISTER PVC/PVDC/AL
D.2.1.1.2	Name of the Marketing Authorisation holder	SOFAR 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.3.4	Pharmaceutical form	Tablet
D.3.4.1	Specific paediatric formulation	No
D.3.7	Routes of administration for this IMP	Oral use
D.3.8 to D.3.10 IMP Identification Details (Active Substances)
D.3.8	INN - Proposed INN	AZATIOPRINA
D.3.9.2	Current sponsor code	n.a.
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	50
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.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

patients with ulcerative colitis

pazienti con rettocolite ulcerosa

E.1.1.1

Medical condition in easily understood language

patients with ulcerative colitis

pazienti con rettocolite ulcerosa

E.1.1.2

Therapeutic area

Diseases [C] - Digestive System Diseases [C06]

MedDRA Classification

E.1.2 Medical condition or disease under investigation

E.1.2	Version	20.0
E.1.2	Level	LLT
E.1.2	Classification code	10045282
E.1.2	Term	UC
E.1.2	System Organ Class	100000004856

E.1.2 Medical condition or disease under investigation

E.1.2	Version	20.1
E.1.2	Level	LLT
E.1.2	Classification code	10045365
E.1.2	Term	Ulcerative colitis
E.1.2	System Organ Class	100000004856

E.1.3

Condition being studied is a rare disease

E.2 Objective of the trial

E.2.1

Main objective of the trial

Primary objective of the study is to evaluate whether the withdrawal of infliximab is associated with higher relapse rates compared to controls.

Obiettivo primario ¿ valutare se la sospensione di Infliximab ¿ associata a pi¿ alti tassi di recidiva.

E.2.2

Secondary objectives of the trial

Secondary objectives are:
¿ To investigate risk factors associated to a higher risk of relapse after infliximab withdrawal
¿ To investigate the mean time between infliximab withdrawal and clinical relapse.
¿ To assess the safety of the two therapeutic strategies.
¿ To evaluate the direct costs of the two different strategies

Obiettivi secondari sono:
¿ Indagare i fattori di rischio associati ad un pi¿ alto rischio di recidiva dopo la sospensione di infliximab.
¿ Studiare il tempo medio tra la sospensione di infliximab e la recidiva clinica.
¿ Valutare la sicurezza delle due strategie terapeutiche.
¿ Valutare i costi diretti delle due strategie terapeutiche.

E.2.3

Trial contains a sub-study

Yes

E.2.3.1

Full title, date and version of each sub-study and their related objectives

Other types of substudies
Specify title, date and version of each substudy with relative objectives: Trough levels and anti-drug antibodies substudy: patients will be asked to give their informed consent for an additional blood sampling at baselinescreening e and at week 52 for through levels and antidrug
antibodies evaluation. Additional samples will be collected if needed by medical needs. Sampling will also be repeated, for both groups, in case of loss of response to the assigned treatment. These samples will be stored at each center until the end of the study and then analysed at Humanitas Research Hospital, IBD Center, Rozzano, Milan, Italy.

Altre tipologie di sottostudi
specificare il titolo, la data e la versione di ogni sottostudio con i relativi obiettivi: ¿ stato introdotto un sottostudio sui livelli sierici e sull'analisi degli anticorpi antifarmaco:
come indicato dalle linee guida della European Crohn¿s and Colitis Organization del 216, ¿
ltamente consigliato dosare questi parametri nei pazienti con IBD (¿3 e ¿6.2).

E.3

Principal inclusion criteria

- Age 18 -65 years
- Written informed consent and willing to adhere to study procedures.
- Therapy with infliximab since at least 12 months, with one infusion every 8 weeks (, according to the summary of product characteristics)
- Sustained steroid-free remission in the last 6 months prior to inclusion, except for use of steroids as a preventive measure for infliximab infusion reaction, if required by local guidelines.
- Global Mayo score at baseline = 2
- All Mayo subscores = 1
- Absence of rectal bleeding
- Effective methods to avoid pregnancy during the study period

- Età 18-65 anni
- Consenso espresso in forma scritta
- Terapia con infliximab da almeno 12 mesi,
somministrato ogni 8 settimane (in accordo con il
Riassunto delle Caratteristiche del Prodotto)
- Remissione libera da steroidi sostenuta nei 6 mesi
che precedono l’inclusione; è consentito l’impiego
di steroidi iniettabili come pre-medicazione per
reazioni allergiche, secondo normale pratica
clinica.
- Mayo score totale al baseline = 2
- Tutti i Mayo subcsores = 1
- Assenza di sanguinamento rettale
- Adozione di metodi contraccettivi efficaci per evitar
gravidanze durante il periodo di studio

E.4

Principal exclusion criteria

- Disabling and persisting extraintestinal manifestation at baseline
- Patients unable to comply with study procedures
- Known intolerance or previous allergic reaction to
thiopurines
- Concomitant therapy with allopurinol
- Any disease not compatible with the use of infliximab or azathioprine, as per clinician’s judgement.
- Need for dose escalation of infliximab in the last 12
months prior to baseline.
- White blood cell count < 3000/mmc or absolute clinically relevant lymphopenia at baseline
- Active pregnancy or breastfeeding, willing for pregnancy during the study period.

- Manifestazioni extraintestinali di malattia
disabilitanti e persistenti al basale
- Pazienti non in grado di seguire le procedure di
studio
- Intolleranza nota o precedenti reazioni allergiche
alle tiopurine
- Terapia concomitante con allopurinolo
- Qualsiasi patologia non compatibile con l’impiego
di infliximab o azatioprina, secondo parere dello
sperimentatore
- Necessità di dose-escalation nei 12 mesi
antecedenti il basale
- Conta leucocitaria < 3000/mmc or linfopenia
clinicamente rilevante al basale
- Gravidanza o allattamento, desiderio di maternità
durante il periodo di studio.

E.5 End points

E.5.1

Primary end point(s)

The primary outcome will be the relapse rate by month 12 in the two study groups.

Endpoint primario sarà il tasso di ricaduta a 12 mesi nei due bracci.

E.5.1.1

Timepoint(s) of evaluation of this end point

12 months

12 mesi

E.5.2

Secondary end point(s)

Secondary outcomes will be:
- Mean time to relapse in the two groups
- Number of adverse events of the two study strategies
- Number of serious adverse events of the two study
strategies
- Impact of predetermined baseline risk factors (see below) for relapse
- Direct costs of the two treatment strategies; Sub-study endpoint
Predictive value of low TL and high ADA at baseline for relapse through week 52

Endpoint secondari saranno:
- tempo medio alla ricaduta nei due gruppi
- Numero degli eventi avversi nei due bracci
- Impatti di fattori di rischio predeterminati
- Costi diretti delle due strategie di trattamento; Endpoint sottostudio
Valore predittivo di bassa TL e elevata ADA al basale e alla settimana 52 per la ricaduta

E.5.2.1

Timepoint(s) of evaluation of this end point

12 months; baseline and week 52

12 mesi; basale e settimana 52

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

Yes

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

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

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

E.8.2.3

Other

Yes

E.8.2.3.1

Comparator description

entrambi i farmaci vengono somministrati come test

n.a.

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.8.5.1

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:

100

F.1.3

Elderly (>=65 years)

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

100

F.4.2

For a multinational trial

F.4.2.1

In the EEA

100

F.4.2.2

In the whole clinical trial

100

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)

n.a.

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

2017-03-31

Ethics Committee Opinion of the trial application

Favourable

Ethics Committee Opinion: Reason(s) for unfavourable opinion

Date of Ethics Committee Opinion

2017-01-17

P. End of Trial
P.	End of Trial Status	Completed

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