Clinical Trials Register

Summary
EudraCT Number:	2011-002640-27
Sponsor's Protocol Code Number:	GED-301-01-11
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:	2012-02-09
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

2011-002640-27

A.3

Full title of the trial

A phase II multicenter, randomized, double-blind, controlled vs placebo, dose-finding study on the efficacy and safety of GED-0301, in patients with active Crohn‟s disease (Ileo-Colitis)

Studio multicentrico di fase II, randomizzato, in doppio cieco, per la determinazione della dose efficace, controllato vs placebo sull'efficacia, la sicurezza di GED-0301, in pazienti con Morbo di Crohn in fase attiva (Ileo-Colite)

A.3.1

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

A phase II multicenter, randomized, double-blind, controlled vs placebo, dose-finding study on the efficacy and safety of GED-0301, in patients with active Crohn’s disease (Ileo-Colitis)

Studio multicentrico di fase II, randomizzato, in doppio cieco, per la determinazione della dose efficace, controllato vs placebo sull’efficacia, la sicurezza di GED-0301, in pazienti con Morbo di Crohn in fase attiva (Ileo-Colite)

A.3.2

Name or abbreviated title of the trial where available

I.G.O.N. 1 STUDY

A.4.1

Sponsor's protocol code number

GED-301-01-11

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	GIULIANI
B.1.3.4	Country	Italy
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	GIULIANI S.P.A.
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	GIULIANI S.P.A.
B.5.2	Functional name of contact point	PHARMA DIVISION
B.5.3	Address:
B.5.3.1	Street Address	VIA PALAGI 2
B.5.3.2	Town/ city	MILANO
B.5.3.3	Post code	20129
B.5.3.4	Country	Italy
B.5.4	Telephone number	+39020541
B.5.6	E-mail	sbellinvia@giulianipharma.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	GED-0301
D.3.2	Product code	NA
D.3.4	Pharmaceutical form	Modified-release capsule, hard
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	NA
D.3.9.1	CAS number	NA
D.3.9.2	Current sponsor code	NA
D.3.9.3	Other descriptive name	NA
D.3.9.4	EV Substance Code	NA
D.3.10	Strength
D.3.10.1	Concentration unit	mg/g milligram(s)/gram
D.3.10.2	Concentration type	up to
D.3.10.3	Concentration number	160
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	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	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	Yes
D.3.11.13.1	Other medicinal product type	OLIGONUCLEOTIDE ANTISENSO

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

ACTIVE CROHN'S DISEASE

MORBO DI CROHN IN FASE ATTIVA

E.1.1.1

Medical condition in easily understood language

ACTIVE CROHN'S DISEASE

MORBO DI CROHN IN FASE ATTIVA

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	14.1
E.1.2	Level	LLT
E.1.2	Classification code	10021315
E.1.2	Term	Ileitis terminal
E.1.2	System Organ Class	10017947 - Gastrointestinal 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

a. Efficacy: the primary efficacy endpoint will be the percentage of patients in remission defined as CDAI < 150 at day 15 (after 14 days of study drug treatment) wich is maintained at Week 4. b. Evaluation of safety of GED-0301, 14-day oral administration.

a) Efficacia: l’obiettivo primario di efficacia dovra' essere la percentuale di pazienti in remissione definita come CDAI < 150 al giorno 15 (dopo 14 giorni di trattamento con il prodotto in studio) che e' mantenuta alla Settimana 4. b) Valutazione della sicurezza di GED-0301, dopo 14 giorni di somministrazione orale.

E.2.2

Secondary objectives of the trial

%of pts in remission at week 2,4 and at week 12 - %of patients attaining 70-point clinical response (defined as a decrease from baseline in CDAI score of 70 points or more) at week 4 and at week 12. -%of patients attaining 100-point clinical response (defined as a decrease from baseline in CDAI score of 100 points or more) at week 4 and at week 12. - Time to Symptoms Disappearance (SD) : for each symptom, time to disappearance is defined as the interval of time in days between the date of symptom disappearance, evaluated on the basis of the data recorded in the patient’s diary, and the date of randomisation . - %of steroid-dependent patients achieving steroid therapy discontinuation at week 12 - Change in the endoscopic index of severity for Crohn’s Disease (SES-CD).This analysis will be done in the patients who accept to perform ileocolonoscopy before treatment and at week 4

- %di pz in remissione alla sett 2,4 e alla sett12 - %di pz che raggiungano 70-pt di risposta clinica,(definita come un decremento rispetto al basale nel punteggio CDAI di 70pt o piu') alla sett 4 e alla sett12 - %di pz che raggiungano 100-pt di risposta clinica,(decremento rispetto al basale nel punteggio CDAI di 100 pt o piu') alla sett4 e alla sett12. - Tempo di scomparsa dei sintomi(SD):per ciascun sintomo definito come l’intervallo di tempo in giorni fra la data della scomparsa del sintomo, valutata sulla base dei dati registrati nel diario del paziente,e la data di randomizzazione. - %di pz steroido dipendenti che raggiungono una discontinuita' nella terapia con steroidi alla sett12 - Variazione nell’indice SES-CD Quest`analisi verra' eseguita su pazienti che accettano di sottoporsi a ileocolonscopia prima del trattamento e alla settimana 4

E.2.3

Trial contains a sub-study

E.3

Principal inclusion criteria

1. Written informed consent, personally signed and dated by the patient prior any study-related procedures is carried out. 2. Male and female outpatients aging 18-75 years old. 3. Female patients not of childbearing potential (women in menopause defined as surgically sterile or one year postmenopausal); female patients of childbearing potential upon negative pregnancy testing at screening and using effective method of birth control during the study. 4. Patients with Crohn’s disease in the active phase at screening visit (the activity is defined using the Crohn’s disease Activity Index (CDAI) according to the European guidelines). 5. Crohn’s disease limited to terminal ileum and/or right colon,.that has been documented by instrumental information on localization and extension according to inclusion criteria 9. . 6. Patients with a CDAI score of >220 and ≤400 for at least one week prior to enrollment. 7. No treatment with biologics (e.g.:infliximab, adalimumab, or natalizumab), in the 90 days prior the enrolment. 8. Patients with steroid resistance or steroid dependence, defined according to the ECCO consensus document 9. Absence of Strictures with pre-stenotic dilatation documented by ultrasonography or Rx or NMR, performed within 1 year prior to the enrollment 10. Ability to understand and comply with study procedures and restrictions.

1) Consenso informato scritto, firmato e datato personalmente dal paziente prima dell’esecuzione di qualsiasi procedura dello studio deve essere raccolto. 2) Pazienti di sesso maschile o femminile tra i 18 e i 75 anni di eta'. 3) Pazienti di sesso femminile potenzialmente non fertili (donne in menopausa definite come intervento chirurgico di sterilita' o in post-menopausa da un anno); pazienti di sesso femminile potenzialmente fertili con test di gravidanza negativo alla visita di screening e che facciano uso di un valido metodo contraccettivo durante lo studio. 4) Pazienti con diagnosi di morbo di Crohn in fase attiva alla visita di screening (l’attivita' e' definita utilizzando l’Indice di Attivita' del Morbo di Crohn (CDAI) in accordo alle linee guida Europee). 5) Malattia di Crohn limitata al segmento ileo terminale e/o al colon destro, che sia stata documentata da informazioni strumentali sulla localizzazione ed estensione in accordo al criterio di inclusione n. 9. 6) Pazienti con punteggio CDAI >220 e ≤400 per almeno una settimana prima dell’arruolamento. 7) Nessun trattamento con biologici (es. infliximab, adalimumab o natalizumab) nei 90 giorni precedenti l’arruolamento. 8) Pazienti con resistenza agli steroidi o steroido dipendenza, definita in accordo all’ECCO consensus document. 9) Assenza di stenosi con dilatazione pre-stenotica documentata da ecografia o RX o RMN, eseguita entro 1 anno prima dell’arruolamento. 10) Capacita' di comprendere e di attenersi alle procedure e restrizioni dello studio.

E.4

Principal exclusion criteria

Pregnant or breast-feeding women. 2. Patients with Ulcerative Colitis. 3. Patients with Crohn’s disease involving the stomach and/or the proximal small intestine, or patients with lesions confined to the transverse or left colon as assessed by standard clinical criteria. 4. Patients treated with biologics(e.g.:infliximab, adalimumab, or natalizumab), in the 90 days prior the enrolment. 5. Patients in treatment with a standard dose of immunomodulators (e.g.: azathioprine, mercaptopurine, methotrexate) maintained stably for less than 6 months (patients treated with a stable dose for at least 6 months are eligible).The standard doses, according to ECCO consensus document, are 2-2.5 mg/kg/day for azathioprine and 1-1.5 mg/kg/day for mercaptopurine. 6. Oral and/or systemic antibiotic treatment within 3 weeks before screening 7. Presence of local complications (e.g. abscesses, strictures and fistulae), dysplasia and malignancies. 8. A history of colon surgery performed within the past 12 months prior to first dose or an ileal resection more than 70 cm in the past. 9. Strictures with pre-stenotic dilatation. 10. Presence of stoma or ileo-recto-anastomosis. 11. Screening laboratory values within the following parameters:  APTT > 1.5 ULN  plateletcount ≤100,000 /mm3  serum creatinine >1.5 ULN  total bilirubin >1.5 ULN (excluding Gilbert Syndrome)  AST and ALT >1.5 ULN. 12. QTc interval >450 msec for males and >470 msec for females. 13. Current or relevant previous history of serious, severe or unstable (acute or progressive) physical or psychiatric illness, including infections, malignancy, medical disorder that may require treatment (e.g. renal or hepatic impairment) or that make the subject unlikely to fully complete the study, or any condition that presents undue risk from the study medication or procedures. 14. History of alcohol or other drug abuse within the last year. 15. Patients potentially presenting poor reliability (e.g. bad mental conditions). 16. Known hypersensitivity to oligonucleotides or any ingredient in the study products. 17. Patients who used another investigational agent or who took part in a clinical trial within the last 6 months prior first dose.

1) Donne in gravidanza o in corso di allattamento. 2) Pazienti con Colite Ulcerosa 3) Pazienti con malattia di Crohn che coinvolge lo stomaco e/o la parte prossimale dell’intestino tenue o pazienti con lesioni confinate alla porzione trasversa o sinistra del colon come dimostrato dai criteri clinici standard. 4) Pazienti trattati con biologici (es.: infliximab, adalimumab o natalizumab), nei 90 giorni prima dell’arruolamento. 5) Pazienti in trattamento con una dose standard di immunomodulatori (es: azathioprine, mercaptopurine, methotrexate) mantenuta stabile da meno di 6 mesi (i pazienti trattati con una dose stabile da almeno 6 mesi sono eleggibili). Le dosi standard, in accordo all’ECCO Consensus document, sono 2-2.5 mg/kg/giorno per azathioprine e 1-1.5 mg/kg/giorno per mercaptopurine. 6) Pazienti trattati con antibiotici sistemici e/o orali nelle 3 settimane prima dello screening. 7) Presenza di complicazioni locali (es. ascessi, stenosi e fistole), displasia e tumori maligni. 8) Storia di interventi chirurgici intestinali, effettuati entro gli ultimi 12 mesi prima della prima dose o una resezione ileale superiore a 70 cm nel passato. 9) Stenosi con dilatazione pre-stenotica. 10) Presenza di stoma o ileo-retto-anastomosi. 11) Valori dei parametri di laboratorio allo screening con i seguenti valori:  APTT > 1.5 ULN  Conta delle piastrine ≤100,000 /mm3  Creatinina serica >1.5 ULN  Bilirubina totale >1.5 ULN (esclusa la Sindrome di Gilbert)  AST e ALT >1.5 ULN 12) Intervallo QTc >450 msec per i maschi e >470 msec per le femmine. 13) Concomitante o rilevante pregressa patologia, fisica o psichiatrica, grave o instabile (acuta o progressiva) incluse le infezioni, i tumori maligni, i disturbi che possono richiedere trattamento (come per esempio patologie renali o epatiche) o compromettere il completamento dello studio da parte del paziente o qualsiasi altra condizione considerata rischiosa in seguito all’assunzione del farmaco sperimentale o alle procedure dello studio. GED-301-01-11 Sinossi ITA vers. 3 del 15.11.2011 - Protocollo version 2.0 del 15.11.2011 (including Amendment 1) Pagina 5 di 9 14) Storia di alcolismo o abuso di alter sostanze nell’ultimo anno. 15) Pazienti potenzialmente poco affidabili (es. condizioni mentali precarie). 16) Nota ipersensibilita' agli oligonucleotidi o a qualsiasi altro componente del prodotto in studio. 17) Pazienti che hanno assunto un altro prodotto sperimentale o che hanno preso parte ad uno studio clinico nei 6 mesi precedenti alla prima dose.

E.5 End points

E.5.1

Primary end point(s)

E.5.1.1

Timepoint(s) of evaluation of this end point

14 days and 28 days

14 giorni e 28 giorni

E.5.2

Secondary end point(s)

E.5.2.1

Timepoint(s) of evaluation of this end point

14 days, week4 and week12

14 giorni, settimana 4 e settimana 12

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

Yes

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

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

Yes

E.8.2.3.1

Comparator description

- Stesso farmaco ad altro dosaggio

- same IMP used at different dosage

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

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

F. Population of Trial Subjects

F.1 Age Range

F.1.1

Trial has subjects under 18

F.1.1

Number of subjects for this age range:

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:

140

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

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

160

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)

Investigator's decision

Secondo il giudizio dello Sperimentatore Specialista

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

2011-07-14

Ethics Committee Opinion of the trial application

Favourable

Ethics Committee Opinion: Reason(s) for unfavourable opinion

Date of Ethics Committee Opinion

2011-06-14

P. End of Trial
P.	End of Trial Status	Completed
P.	Date of the global end of the trial	2013-09-30

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