Clinical Trials Register

Summary
EudraCT Number:	2011-004812-40
Sponsor's Protocol Code Number:	D2211C00001
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:	2012-03-02
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

2011-004812-40

A.3

Full title of the trial

A phase IIa, randomised, double-blind, placebo-controlled, parallel-arm, multicenter study to evaluate the efficacy and safety of tralokinumab (CAT-354), a recombinant human monoclonal antibody directed against interleukin-13 (IL-13), as add-on therapy, on clinical response in patients with active, moderate-to-severe, ulcerative colitis

Studio di Fase IIa, randomizzato, in doppio cieco, controllato con placebo, a gruppi paralleli, multicentrico per valutare l'efficacia e la sicurezza di Tralokinumab (CAT- 354), un anticorpo monoclonale ricombinante umano diretto contro l'™Interleukina 13 (IL-13), come terapia aggiuntiva, sulla risposta clinica in pazienti con colite ulcerosa attiva, da moderata a grave.

A.3.1

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

Studio di Fase IIa, randomizzato, in doppio cieco, controllato con placebo, a gruppi paralleli, multicentrico per valutare l’efficacia e la sicurezza di Tralokinumab (CAT- 354), un anticorpo monoclonale ricombinante umano diretto contro l’Interleukina 13 (IL-13), come terapia aggiuntiva, sulla risposta clinica in pazienti con colite ulcerosa attiva, da moderata a grave.

A.4.1

Sponsor's protocol code number

D2211C00001

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	ASTRAZENECA
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	MedImmune Ltd
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	ASTRAZENECA
B.5.2	Functional name of contact point	ASTRAZENECA
B.5.3	Address:
B.5.3.1	Street Address	PALAZZO VOLTA VIA FRANCESCO SFORZA
B.5.3.2	Town/ city	BASIGLIO
B.5.3.3	Post code	20080
B.5.3.4	Country	Italy
B.5.4	Telephone number	029801 1
B.5.5	Fax number	029801 1
B.5.6	E-mail	FLORE.LATOUR@ASTRAZENECA.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	tralokinumab
D.3.2	Product code	CAT-354
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	tralokinumab
D.3.9.1	CAS number	1044515-88-9
D.3.9.2	Current sponsor code	CAT-354
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 milligram(s)
D.3.10.2	Concentration type	equal
D.3.10.3	Concentration number	150
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	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

Ulcerative Colitis

Colite ulcerosa

E.1.1.1

Medical condition in easily understood language

Ulcerative Colitis

Colite 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	14.1
E.1.2	Level	LLT
E.1.2	Classification code	10045282
E.1.2	Term	UC
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

The primary objective of the study is to assess the effect of tralokinumab compared with placebo in patients with active UC by assessment of clinical response, as defined by the Mayo score, at week 8.

L’obiettivo primario dello studio è valutare l’efficacia di trokalinumab 300 mg sottocute (SC) confrontato con placebo in pazienti con colite ulcerosa attiva (UC) sulla base della risposta clinica.

E.2.2

Secondary objectives of the trial

*To assess change in Mayo score from baseline to week 8. *To assess mucosal healing at week 8. *To assess change in partial Mayo score from baseline to week 4, 8, 12, 16, 20, and 24. *To assess the proportion of patients in clinical remission, as defined by the Mayo score, after 8 weeks. *To assess histology in biopsies from colonic mucosa at baseline and week 8. *To assess markers of disease activity and intestinal leakiness in serum and faeces at baseline, week 4, 8, 12, 16, 20, and 24. *To assess the pharmacokinetics and immunogenicity of tralokinumab. *To evaluate the safety and tolerability of tralokinumab by assessment of reported Adverse Events (AEs), safety laboratory values, electrocardiograms, vital signs, weight, and physical examination findings.

• Valutare il valore Mayo al basale alla settimana 8 • Valutare la guarigione della mucosa dal baseline alla settimana 8 • Valutare le variazioni del valore Mayo parziale dal basale alla settimana 4, 8, 12, 16, 20 e 24. • Valutare la quantità di pazienti in remissione clinica dopo 8 settimane • Valutare l’istologia (biopsia) al basale e alla settimana 8 • Valutare i marcatoridi infiammazione nel siero e nelle feci albasale, alle settimane 4, 8, 12, 16, 20 e 24. • Valutare la farmacocinetica e l’immunogenicità di tralokinumab.

E.2.3

Trial contains a sub-study

E.3

Principal inclusion criteria

1. Diagnosed ulcerative colitis at least 90 days prior randomisation. 2. Men or women age18 - 65 years. 3. Non-hospitalized patients with moderate-severe ulcerative colitis treated with stable background UC therapy (e.g. containing 5- aminosalisylates, and/or low dose of glucocorticosteroids, and/or purine analogue) prior to randomization 4. Females of childbearing potential who are sexually active with a nonsterilized male partner must use highly effective contraception from Day1. 5. Nonsterilized males or sterilized males who are ≤ 1 year postvasectomy who are sexually active with a female partner of childbearing potential must use a highly effective method of contraception

1. Diagnosi di colite ulcerosa confermata con endoscopia e biopsia almeno 90 giorni prima della randomizzazione.
2.Uomini o donne di età compresa tra i 18 e 65 anni.
3.Pazienti non ricoverati con colite ulcerosa da moderata a grave, con un punteggio ≥ 6 secondo Mayo ed un sotto-punteggio di endoscopia di almeno 2 (rispetto all’endoscopia basale), inclusi i pazienti con sottotipi di colite ulcerosa estesa o del lato sinistro.
4.Donne in età fertile che sono sessualmente attive con un partner maschile devono utilizzare un contraccettivo altamente efficace dall’arruolamento, e devono accettare di continuare ad utilizzare tali precauzioni dalla visita di arruolamento per tutto il corso dello studio fino alla visita finale.
5.Uomini non sterilizzati o che sono sterilizzati ≤ 1 anno dopo la vasectomia che sono sessualmente attivi con partner di sesso femminile in età fertile devono utilizzare metodi molto efficaci di contraccezione (vedi tabella 2)dalla visita di arruolamento per tutto il corso dello studio fino alla visita finale.

E.4

Principal exclusion criteria

1. Pregnant or breastfeeding women. 2. History of colostomy. 3. Current diagnosis of indeterminate colitis, Crohn's disease, ischemic colitis, fulminant colitis and/or toxic megacolon and patients with ulcerative colitis limited to the rectum (ulcerative proctitis). 4. Hepatitis B, C or HIV. 5. History of cancer.

1. Donne in gravidanza o allattamento
2. Storia di colostomia
3. Diagnosi attuale di colite cronica, morbo di Chron’s, colite ischemica, colite fulminante e/o megacolon tossico e pazienti con colite ulcerosa limitata al retto (proctite ulcerosa).
4.Epatite B, C o HIV.
5. Storia di cancro.

E.5 End points

E.5.1

Primary end point(s)

Clinical response (defined as a decrease in Mayo score from baseline of at least 3 points and at least 30% with an accompanying decrease in the sub score for rectal bleeding of at least 1 point or absolute sub score for rectal bleeding of 0 or 1).

La risposta clinica è definita come una diminuzione del valore Mayo dal basale di almeno 3 punti e almeno del 30% parallelamente a una diminuzione nel sub valore per il sanguinamento rettale di almeno un punto o un sub valore assoluto di 0 o 1 per il sanguinamento rettale.

E.5.1.1

Timepoint(s) of evaluation of this end point

At week 8.

Alla settimana 8

E.5.2

Secondary end point(s)

* Change in Mayo score (calculated as the sum of the four sub-scores: stool frequency rectal bleeding, endoscopy findings and the physician's overall assessment of the same in addition to abdominal discomfort and patient's general sense of well-being). * Mucosal healing (defined as an improvement of the endoscopy subscore (from the Mayo score) at week 8 from 3 or 2 to ≤1 point, or from 1 to 0 points). * Change in partial Mayo score (calculated as the sum of the scoring from the three sub-score areas: stool frequency, rectal bleeding and the physician's global assessment). * Clinical remission (defined as Mayo score of 2 or lower with no individual sub-score exceeding 1 point) * Histologic disease activity (assessment based on the modified Riley score). * Markers of disease activity (CRP, calprotectin) and intestinal leakiness (albumin). * Immunogenicity: incidence of anti-drug antibodies (ADA) to tralokinumab in serum. * Tralokinumab serum concentration. * Safety and tolerability of tralokinumab in terms of adverse events, safety laboratory values, electrocardiograms, vital signs, weight, and physical examination findings.

• Valore Mayo (calcolato come la somma di 4 sub-punteggi: frequenza di sanguinamento rettale, reperti endoscopici e loro valutazione da parte del medico, oltre a dolori addominali e stato generale di salute del paziente).
• Guarigione della mucosa definita come un aumento del sub valore dell’endoscopia (dal Mayo score) alla settimana 8 da 3 o 2 a 0 o 1 punti, o da 1 a 0 punti
• Cambiamenti del valore Mayo parziale (calcolato come la somma del punteggio totale derivante dall’osservazione di 3 aree di sub-punteggi: frequenza delle evacuazioni, sanguinamento rettale e loro valutazione da parte del medico).
• La remissione clinica è definita come valore Mayo di 2 o meno senza singoli sub valori che eccedono di 1punto.
• Attività istologica della malattia(valutazione fatta sul valore Riley modificato).
• Marcatori di attività patologica (CRP, calprotectina) e permeabilità intestinale (albumina).
• Immunogenicità: incidenza di anticorpi antifarmaco (ADA) verso tralokinumab nel siero.
• Concentrazioni seriche di tralokinumab.
• Sicurezza e tollerabilità del tralokinumab in termini di eventi avversi seri, variabili ematochimiche di sicurezza,elettrocardiogrammi, segni vitali, peso, ed esame fisico.

E.5.2.1

Timepoint(s) of evaluation of this end point

From baseline to week 8. * At week 8. * From baseline to week 4, 8, 12, 16, 20, and 24. * After 8 weeks. * At baseline and week 8. * At baseline, week 4, 8, 12, 16, 20, and 24. * Pre-dose sampling at baseline, week 8, 12, 16, and 24. * Pre-dose sampling at baseline, week 4, 8, 12, 16, 20, and 24. * From baseline to week 24.

• Dal basale alla settimana 8
• Alla settimana 8
• Dal basale alla settimana 4,8,12,16,20 e 24.
• Dopo 8 settimane
• Al basale ed alla settimana 8
• Al basale, alla settimana 4,8,12,16,20 e 24.
• Pre-dose di campionamento al basale, alla settimana 8,12,16 e 24.
• Pre-dose di campionamento al basale, alla settimana 4, 8,12,16,20 e 24.
• Dal basale alla settimana 24

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

Yes

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

Yes

E.6.13.1

Other scope of the trial description

Immunogencity

Immunogenicità

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

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

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

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

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:

106

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

F.4.2

For a multinational trial

F.4.2.1

In the EEA

110

F.4.2.2

In the whole clinical trial

110

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)

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

2011-11-14

Ethics Committee Opinion of the trial application

Favourable

Ethics Committee Opinion: Reason(s) for unfavourable opinion

Date of Ethics Committee Opinion

2011-12-12

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

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