Clinical Trials Register

Summary
EudraCT Number:	2011-005251-13
Sponsor's Protocol Code Number:	20110166
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:	2012-08-27
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

Expand All Collapse All

A. Protocol Information

A.1

Member State Concerned

Italy - Italian Medicines Agency

A.2

EudraCT number

2011-005251-13

A.3

Full title of the trial

A Randomized, Double blind, Multiple Dose Placebo Controlled Study to Evaluate the Safety, Tolerability, and Efficacy of AMG 181 in Subjects with Moderate to Severe Ulcerative Colitis

Studio randomizzato, in doppio cieco, a dosi multiple, controllato verso placebo per valutare la sicurezza, la tollerabilità e l’efficacia di AMG 181 in soggetti con colite ulcerosa da moderata a severa

A.3.1

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

A study to find out more about the effect of AMG 181 in people with moderate to severe ulcerative colitis

Uno studio per approfondire gli effetti di AMG 181 in persone con colite ulcerosa da moderata a grave

A.4.1

Sponsor's protocol code number

20110166

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	AMGEN INC.
B.1.3.4	Country	United States
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	Amgen Inc
B.4.2	Country	United States
B.5 Contact point designated by the sponsor for further information on the trial
B.5.1	Name of organisation	Amgen Domp� SpA
B.5.2	Functional name of contact point	Dipartimento Regolatorio
B.5.3	Address:
B.5.3.1	Street Address	Via E. Tazzoli
B.5.3.2	Town/ city	Milano
B.5.3.3	Post code	20125
B.5.3.4	Country	Italy
B.5.4	Telephone number	02624112367
B.5.5	Fax number	02624112302
B.5.6	E-mail	gbotta@amgen.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	AMG181
D.3.2	Product code	AMG181
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.3.9.2	Current sponsor code	AMG181
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	70
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	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
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

Moderate to severe Ulcerative Colitis

Colite ulcerosa da moderata a severa

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	10045365
E.1.2	Term	Ulcerative colitis
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

To evaluate the effect of AMG 181 on induction of remission in subjects with moderate to severe UC at week 8 as assessed by a total Mayo Score ≤ 2 points, with no individual subscore > 1 point

Valutare l’effetto di AMG 181 nell’indurre la remissione in soggetti con CU da moderata a severa alla settimana 8 definita da un Mayo score totale ≤ 2 punti, senza alcun subscore individuale >1 punto.

E.2.2

Secondary objectives of the trial

Key Secondary Objectives: - To evaluate the effects of AMG 181 on induction of response at week 8 as assessed by the total Mayo Score - To evaluate the effects of AMG 181 on mucosal healing at week 8 as assessed by rectosigmoidoscopy Other Secondary objective: - To evaluate the effects of AMG 181 on sustained remission at both week 8 and week 24 as assessed by the total Mayo Score

Principali obiettivi secondari:  Valutare gli effetti di AMG 181 nell’indurre la risposta alla settimana 8 definita dal punteggio Mayo score totale  Valutare gli effetti di AMG 181 sulla guarigione della mucosa alla settimana 8 valutata con la rettosigmoidoscopia Altri obiettivi secondari:  Valutare gli effetti di AMG 181 sul mantenimento della remissione sia alla settimana 8 che alla settimana 24 definita dal punteggio Mayo score totale

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

PHARMACOGENETIC:
Vers:Pr20110166
Date:2012/03/05
Title:Pharmacogenetic Substudy
Objectives:A subgroup of subjects who provide
additional informed consent will participate in the pharmacogenetic
substudy. Participation in this substudy is optional. Subjects can only
participate in the pharmacogenetic substudy if they have also provided
consent for the biomarker substudy. No additional blood samples will be collected.

PHARMACOKINETIC/PHARMACODYNAMIC:
Vers:Pr20110166
Date:2012/03/05
Title:PK Substudy
Objectives:Participation in the PK substudy is optional. Subjects will
visit the clinic for additional pharmacokinetic samples

OTHER SUBSTUDIES:
- Biomarker Development Blood and Stool Samples Substudy (prot 20110166-05March2012)- Immunophenotyping and Absolute Counting (IPAC) PD Assay
Substudy (prot 20110166-05March2012)

FARMACOGENETICA:
Vers:Pr20110166
Data:2012/03/05
Titolo:Sottostudio di farmacogenetica
Obiettivi:Un sottogruppo di soggetti che forniscono
un ulteriore consenso informato parteciperà al sottostudio farmacogenetica. La partecipazione a questo sottostudio è facoltativa. I soggetti possono solo
partecipare al sottostudio di farmacogenetica se hanno anche fornito il
consenso per il sottostudio sui biomarker. Non ci saranno altri campioni di sangue da raccogliere

FARMACOCINETICA/FARMACODINAMICA:
Vers:Pr20110166
Data:2012/03/05
Titolo:Sottostudio di Farmacocinetica
Obiettivi:La partecipazione al sottostudio PK è facoltativo. I soggetti dovranno
recarsi al centro per la raccolta di ulteriori campioni per la farmacocinetica

ALTRI SOTTOSTUDI:
- Sottostudio di Sviluppo dei Biomarker su campioni di sangue e feci (Prot. 20110166-05Mar2012) - immunofenotipizzazione e conteggio assoluto (IPAC) dosaggio PD
Sottostudio (Prot. 20110166-05Mar201

E.3

Principal inclusion criteria

■ Age 18 to 65 at screening (inclusive) ■ Diagnosis of UC established ≥ 3 months before baseline by clinical and endoscopic evidence and corroborated by a histopathology report ■ Moderate to severe active UC as defined by a total Mayo score of 6 to 12 with a centrally read rectosigmoidoscopy score ≥ 2 prior to baseline ■ Demonstrated an inadequate response to, loss of response to, or intolerance to Immunomodulators or anti-TNF agents ■ Subjects can be receiving the following treatments: • Azathioprine or 6 mercaptopurine if treatment initiated at least 12 weeks prior to baseline and if stable dosage for ≥ 8 weeks prior to baseline • Methotrexate up to 25 mg/week if stable dosage for ≥ 8 weeks prior to baseline • 5 aminosalicylates and/or oral prednisone or equivalent up to 20 mg/day, if stable dosage for ≥ 2 weeks prior to baseline ■ Neurological exam free of clinically significant, unexplained signs or symptoms in the opinion of the investigator at screening ■ Subject has no known history of active tuberculosis ■ Subject has a negative test for tuberculosis during screening ■ Subject has provided informed consent For full list of inclusion criteria, please refer to section 4.1 of the protocol

■ età tra 18 e 65 allo screening (comprese) ■ diagnosi di CU stabilita ≥ 3 mesi prima del basale tramite evidenza clinica ed endoscopica e corroborata da un rapporto di istopatologia ■ CU attiva da moderata a grave come definito da un punteggio Mayo totale tra 6 e 12 con un punteggio di rectosigmoidosopia ≥ 2 con lettura centralizzata prima del basale ■ Dimostrata risposta inadeguata, una perdita di risposta, o intolleranza agli immunomodulatori o agli agenti anti-TNF ■ I soggetti possono ricevere i seguenti trattamenti: • Azatioprina o 6 mercaptopurina se il trattamento è iniziato almeno 12 settimane prima del basale e se il dosaggio è stabile per ≥ 8 settimane prima del basale • Methotrexate fino a 25 mg / settimana, se il dosaggio è stabile per ≥ 8 settimane prima del basale • 5 aminosalicilati e / o prednisone orale o equivalente fino a 20 mg / die, se il dosaggio è stabile per ≥ 2 settimane prima del basale ■ esame neurologico allo screening esente da segni inspiegabili o sintomi clinicamente significativi secondo il parere del ricercatore ■Il soggetto non ha una storia conosciuta di tubercolosi attiva ■Il soggetto ha un test negativo per la tubercolosi durante lo screening ■Il soggetto ha fornito il consenso informato Per l'elenco completo dei criteri di inclusione, si rimanda alla sezione 4.1 del protocollo

E.4

Principal exclusion criteria

Disease specific: ■ Disease limited to the rectum (ie, within 10 cm of the anal verge) ■ Toxic megacolon ■ Crohn's Disease ■ History of subtotal colectomy with ileorectostomy or colectomy with ileoanal pouch, Koch pouch, or ileostomy for UC ■ Stool positive for C. Difficile toxin at screening Excluded Medications: ■ Immunosuppressive therapy with either cyclosporine A, tacrolimus, or mycophenolate mofetil, within 1 month prior to baseline ■ Prior exposure to anti TNF agents, within 2 months, or 5 times the respective elimination half life (whichever is longer) prior to baseline ■ Any prior exposure to vedolizumab, rituximab, efalizumab, natalizumab ■ Use of topical (rectal) aminosalicylic acid (eg, mesalamine) or topical (rectal) steroids within 2 weeks prior to baseline ■ Use of intravenous or intramuscolar corticosteroids within 2 weeks prior to screening and during screening Laboratory Abnormalities: ■ Abnormal laboratory results at screening: •Liver tests: either aspartate aminotransferase (AST), alanine transaminase (ALT) or alkaline phosphatase (ALP) > 2.0 Upper Limit of Normal (ULN) OR total bilirubin (TBL) > 1.5 ULN (except for subjects with Gilbert Syndrome) • White blood cell count < 3,000 cells/mm³(< 3 x 10^9/L in SI units) •Hemoglobin < 10 g/dL General: ■ Female subject is not willing to use two highly effective methods of birth control during treatment and for ≥ 7 months after the last dose of investigational product (except if ≥ 2 years postmenopausal or surgically sterile)Highly effective methods of birth control include not having intercourse or using birth control methods that work at least at 99% of the time when used correctly and include hormonal birth control methods (pills, shots, implants or patches), intrauterine device, sexual activity with a male partner who had a vasectomy, condom or occlusive cap (diaphragm or cervical/vault caps) used with spermicide ■ Subject is pregnant or breast feeding, or might become pregnant within 7 months after the last dose of investigational product For full list of exclusion criteria, please refer to section 4.2 of the protocol

Patologia specifici: ■ Malattia limitata al retto (cioè, entro 10 cm dal margine anale) ■ megacolon tossico ■Malattia di Crohn ■ Storia di colectomia subtotale con ileorectostomyia o colectomia con sacca ileoanale, sacchetto di Koch, o ileostomia per CU ■ Test positivo allo screening per la tossina del C. difficile Farmaci esclusi: ■ Terapia immunosoppressiva o con ciclosporina A, tacrolimus o Micofenolato Mofetile, entro 1 mese prima del basale ■ Precedente esposizione ad agenti anti-TNF, entro 2 mesi, o 5 volte la rispettiva emivita di eliminazione (a seconda di quale è più lunga) prima del basale ■ Esposizione precedente a vedolizumab, rituximab, efalizumab, natalizumab ■ Uso topico (rettale) di Acido aminosalicilico (ad esempio, mesalazina) o topico (rettale) di steroidi entro 2 settimane prima del basale ■ Uso di corticosteroidi per via endovenosa o intramuscolare entro 2 settimane prima dello screening e durante lo screening Anomalie di laboratorio: ■ Risultati di laboratorio anormali allo screening: • test epatici: o aspartato aminotransferasi (AST), alanina transaminasi (ALT) o della fosfatasi alcalina (ALP)> 2.0 ULN o la bilirubina totale (TBL) > 1,5 ULN (tranne per i soggetti con sindrome di Gilbert) • numero di globuli bianchi <3.000 cellule / mm ³ (<3 x 10 ^ 9 / L in unità SI) • emoglobina <10 g / dL Generale: ■ soggetti femminili non disposti a utilizzare due metodi altamente efficaci per il controllo delle nascite durante il trattamento e per ≥ 7 mesi dopo l'ultima dose di prodotto in studio (tranne se ≥ 2 anni dopo la menopausa o se chirurgicamente sterile)Metodi molto efficaci per il controllo delle nascite comprendono non avere rapporti sessuali o utilizzare metodi di controllo delle nascite che funzionino almeno al 99% del tempo quando usati correttamente e si include anche i metodi anticoncezionali ormonali (pillole, iniezioni, impianti o cerotti), dispositivo intrauterino, attività sessuale con un partner maschile che abbia avuto una vasectomia, uso di preservativo o contraccettivi di barriera (diaframma o coppette cervicali) utilizzate con spermicida ■ soggetti in gravidanza o allattamento, o potrebbe rimanere incinta entro 7 mesi dopo l'ultima dose di prodotto in sperimentazione Per l'elenco completo dei criteri di esclusione, si prega di fare riferimento alla sezione 4.2 della protocollo

E.5 End points

E.5.1

Primary end point(s)

Remission at week 8 defined by a total Mayo Score ≤ 2 points, with no individual subscore > 1 point

Remissione alla settimana 8 definita da un Mayo score totale ≤ 2 punti, senza alcun subscore individuale >1 punto

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)

Key Secondary Endpoints - Response at week 8 as defined by a decrease from baseline in the total Mayo Score of ≥ 3 points and ≥ 30%, with an accompanying decrease in the subscore for rectal bleeding of ≥ 1 point or an absolute subscore for rectal bleeding of 0 or 1 - Mucosal healing at week 8 as defined by an absolute subscore for rectosigmoidoscopy of 0 or 1 Other Secondary Endpoints: - Sustained remission at both week 8 and week 24

Principali endopoint secondari:  Risposta alla settimana 8 definita da una riduzione dal basale del Mayo score ≥ 3 punti e ≥ 30%, accompagnata da una riduzione del subscore del sanguinamento rettale ≥ 1 punto o un subscore assoluto del sanguinamento rettale uguale a 0 o 1.  Guarigione della mucosa alla settimana 8 definita da un subscore assoluto della rettosigmoidoscopia pari a 0 o 1. Altri endpoint secondari:  Mantenimento della remissione sia alla settimana 8 che alla settimana 24

E.5.2.1

Timepoint(s) of evaluation of this end point

key secondary endpoints: at week 8 Other secondary endpoint (i.e. sustained remission): week 8 and week 24

Principali endopoint secondari: Alla settimana 8 Principali endopoint secondari: Settimana 8 e 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

Yes

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

Yes

E.6.10

Pharmacogenetic

Yes

E.6.11

Pharmacogenomic

E.6.12

Pharmacoeconomic

E.6.13

Others

Yes

E.6.13.1

Other scope of the trial description

Tolerability

Tollerabilità

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

Yes

E.8.1.7.1

Other trial design description

Periodo placebo-controllato seguito da un periodo in paerto - Prot. sez. 3.1

placebo-controlled period followed by open label period -see Prot Sect 3.1l

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

Yes

E.8.6.2

Trial being conducted completely outside of the EEA

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

Australia

Canada

Switzerland

United States

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

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:

305

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

210

F.4.2.2

In the whole clinical trial

315

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)

Plans for treatment of care after the subject has ended participation
are not different from the expected normal treatment for this condition

Come da trattamento previsto dalla pratica clinica per la patologia oggetto della speriementazione.

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

2012-09-16

Ethics Committee Opinion of the trial application

Favourable

Ethics Committee Opinion: Reason(s) for unfavourable opinion

Date of Ethics Committee Opinion

2012-07-25

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