Clinical Trials Register

Summary
EudraCT Number:	2011-004580-79
Sponsor's Protocol Code Number:	A3921096
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:	2012-08-07
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

2011-004580-79

A.3

Full title of the trial

A MULTICENTRE, RANDOMIZED, DOUBLE-BLIND, PLACEBO-CONTROLLED, PARALLEL-GROUP STUDY OF ORAL CP-690,550 AS A MAINTENANCE THERAPY IN SUBJECTS WITH ULCERATIVE COLITIS

STUDIO MULTICENTRICO, RANDOMIZZATO, IN DOPPIO CIECO, CONTROLLATO CON PLACEBO, IN GRUPPI PARALLELI DI CP-690,550 ORALE COME TERAPIA DI MANTENIMENTO IN SOGGETTI CON COLITE ULCEROSA

A.3.1

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

maintenance therapy with CP-690,550 in subjects with ulcerative colitis

terapia di mantenimento con CP-690,550 orale in soggetti con colite ulcerosa

A.4.1

Sponsor's protocol code number

A3921096

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	PFIZER LIMITED
B.1.3.4	Country	United Kingdom
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	Pfizer Limited
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	Pfizer Limited, Ramsgate Road, Sandwick, Kent, UK
B.5.2	Functional name of contact point	ICON Clinical ResearchStart Up Team
B.5.3	Address:
B.5.3.1	Street Address	Concept House, 6 Stoneycroft Rise, Chandlers Ford
B.5.3.2	Town/ city	Eastleigh, Hampshire
B.5.3.3	Post code	SO53 3LD
B.5.3.4	Country	United Kingdom
B.5.4	Telephone number	+44 (0) 2380 688500
B.5.5	Fax number	+44 (0) 2081 005001
B.5.6	E-mail	kellie.macleod@iconplc.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	NA
D.3.2	Product code	CP-690,550-10
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.3.9.1	CAS number	540737-29-9
D.3.9.2	Current sponsor code	CP-690,550-10
D.3.9.3	Other descriptive name	tofacitinib
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	5
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	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	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	NA
D.3.2	Product code	CP-690,550-10
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.3.9.1	CAS number	540737-29-9
D.3.9.2	Current sponsor code	CP-690,550-10
D.3.9.3	Other descriptive name	tofacitinib
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	5
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	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	Tablet
D.8.4	Route of administration of the placebo	Oral 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 (UC)

colite ulcerosa (CU)

E.1.1.1

Medical condition in easily understood language

colite ulcerosa (CU)

ulcerative colitis (UC)

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.1.2 Medical condition or disease under investigation

E.1.2	Version	14.1
E.1.2	Level	SOC
E.1.2	Classification code	10017947
E.1.2	Term	Gastrointestinal disorders
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 demonstrate the efficacy of CP 690,550 as maintenance therapy in subjects with UC.

Dimostrare l'efficacia di CP-690,550 come terapia di mantenimento in soggetti affetti da colite ulcerosa.

E.2.2

Secondary objectives of the trial

- To evaluate the safety and tolerability of CP-690,550 as maintenance therapy in subjects with UC. - To evaluate the efficacy of CP-690,550 maintenance therapy in achieving mucosal healing in subjects with UC. - To evaluate the CP-690,550 pharmacokinetic exposure during maintenance therapy in subjects with UC. - To evaluate the effect of CP-690,550 as maintenance therapy on quality-of-life in subjects with UC.

- Valutare la sicurezza e la tollerabilità di CP-690,550 come terapia di mantenimento in soggetti affetti da colite ulcerosa.- Valutare l'efficacia della terapia di mantenimento con CP-690,550 nell'ottenimento della guarigione della mucosa in soggetti affetti da colite ulcerosa.- Valutare l'esposizione farmacocinetica di CP-690,550 durante la terapia di mantenimento in soggetti affetti da colite ulcerosa.- Valutare l'efficacia della terapia di mantenimento con CP-690,550 sulla qualità della vita in soggetti affetti da colite ulcerosa.

E.2.3

Trial contains a sub-study

E.3

Principal inclusion criteria

1.Subjects who met study entry criteria and completed 8-week induction treatment from Study A3921094 or A3921095. 2.Subjects who achieved clinical response in Study A3921094 or A3921095.- Clinical response is defined by a decrease from the induction study baseline (A3921094 or A3921095) Mayo score of at least 3 points and at least 30%, with an accompanying decrease in the rectal bleeding subscore of at least 1 point or an absolute rectal bleeding subscore of 0 or 1. For eligibility assessment, clinical response will be determined based on the central-read endoscopy performed at Week 8 of Study A3921094 or A3921095 and the central-read endoscopy performed at Week 0 of Study A3921094 or A3921095. 3.Women of childbearing potential must test negative for pregnancy prior to study enrollment.- Female subjects of childbearing potential must agree to use a highly effective method of contraception throughout the study and for at least 4 weeks after the last dose of assigned treatment. 4.Subjects who are willing and able to comply with scheduled visits,treatment plan, laboratory tests, and other study procedures. 5.Evidence of a personally signed and dated informed consent document(s) indicating that the subject (or a legally acceptable representative) has been informed of all pertinent aspects of the study.

1.Soggetti che hanno soddisfatto i criteri di arruolamento e hanno completato le 8 settimane di trattamento di induzione negli studi A3921094 e A3921095 2.Sogegtti che hanno ottenuto risposta clinica neglui studi A3921004 e A3921005.- La risposta clinica viene definita come riduzione di almeno 3 punti o del 30% del punteggio Mayo misurato al basale degli studi di induzione (A3921094 e A9321095), con concomitante riduzione del sanguinamento rettale di almeno 1 punto o con sottopunteggio assoluto di sanguinamento rettale di 0 o 1. Per valutare l'eliggibilità, la risposta clinica sarà determinata in base alla lettura centralizzata dell'endoscopia effettuata alla settimana 8 dello studio A3921094 o A3921095 e dell'endoscopia effettuata alla settimana 0 dello studio A3921094 o A3921095. 3.Donne potenzialmente fertili devono avere un test di gravidanza negativo prima dell'arruolamento nello studio. - Le donne potenzialmente fertili devono adottare un metodo di contraccezione efficace per tutta la durata dello studio e per almeno 4 settimane dopo l'ultima dose di trattamento assegnato. 4.Soggetti disposti e in grado di rispettare le visite programmate, il programma di terapia, gli esami di laboratorio e le altre procedure di studio. 5.Evidenza di rilascio di consenso informato personalmente firmato e datato indicante che il soggetto (o un suo rappresentate legale) è stato informato su tutti gli aspetti pertinenti dello studio.

E.4

Principal exclusion criteria

1.Subjects who had major protocol violation (as determined by the Sponsor) in Study A3921094 or A3921095. 2.Presence of indeterminate colitis, microscopic colitis, ischemic colitis, infectious colitis, or clinical findings suggestive of Crohn's disease. 3.Subjects who have had surgery for UC or in the opinion of the investigator, are likely to require surgery for UC during the study period. 4.Subjects who are expected to receive any of prohibited concomitant medications, including medications that are either moderate to potent CYP3A inducers or inhibitors, during the study period as specified in Appendix 2 of the protocol. 5.Subjects who are expected to receive live or attenuated virus vaccination during study period and for 6 weeks after last dose of study drug. 6.Women who are pregnant or lactating, or planning to become pregnant during the study period. 7.Baseline 12-lead ECG that demonstrates clinically relevant abnormalities which may affect subject safety or interpretation of study results (ie, baseline QTcF >450 ms, complete LBBB, acute or indeterminate age myocardial infarction, 2nd-3rd degree AV block, or serious bradyarrhythmias or tachyarrhythmias; see Appendix 4 of the protocol. 8.Subjects who, in the opinion of the investigator or Pfizer, will be uncooperative or unable to comply with study procedures. 9.Any other severe acute or chronic medical or psychiatric condition or laboratory abnormality that may increase the risk associated with study participation or investigational product administration or may interfere with the interpretation of study results and, in the judgment of the investigator, would make the subject inappropriate for entry into this study. 10.Subjects who are participating in or interested in participating in other investigational studies during study A3921096.

1.Soggetti con violazioni maggiori al protocollo (come determinato dallo Sponsor) durante la partecipazione allo studio A3921094 o A3921095. 2.Presenza di colite indeterminata, colite microscopica, colite ischemica, colite infettiva, o sintomi clinici suggestivi di morbo di Crohn. 3.Soggetti già sottoposti a intervento chirurgicoper CU o che, nell'opinione dello sperimentatore, potrebbero necessitare di chirurgia per CU durante il periodo di studio. 4.Soggetti che durante il periodo di studio si prevede possano assumere farmaci concomitanti vietati, incluso moderati o potenti induttori o inibitori di CYP3A, come specificato nell'Appendice 2 del protocollo. 5.Soggetti che si prevede possano ricevere vaccinazioni con virus vivi attenuati durante il periodo in studio e per 6 settimane dopo nl'ultima dose del farmaco in studio. 6.Donne incinte o in allattamento, o che prevedono di iniziare una gravidanza durante il periodo di studio 7.ECG basale a 12 derivazioni che dimostri anomali clinicamente rilevanti che possano compromettere la sicurezza del soggetto o influenzare l'interpretazione dei risultati dello studio (es, QTcF basale >450 ms, Blocco di branca sinistro completo, infarto del miocardio acuto o di periodo indefinito, blocco AV di grado 2-3, bradiaritmia o tacharitmia seria; si veda Appendice 4 del protocollo. 8.Soggetti che, nell'opinione dello sperimentatore o di Pfizer, non saranno collaborativi o rispettosi delle procedure dello studio. 9.Qualunque condizione medica o psichiatrica severa acuta o cronica o anomalia di laboratorio che possa aumentare il rischio associato con la partecipazione allo studio o la somministrazione del prodotto sperimentale o possa interferire con l'interpretazione dei risultati dello studio e, secondo il giudizio dello sperimentatore, renderebbe inappropriato l'arruolamento del soggetto nello studio. 10.Soggetti che stanno partecipando o hanno interesse a partecipare ad altri studi sperimentali durantelo studio A3921096.

E.5 End points

E.5.1

Primary end point(s)

The proportion of subjects in remission at Week 52. Remission is defined by a total Mayo score of 2 points or lower, with no individual subscore exceeding 1 point and a rectal bleeding subscore of 0.

Percentuale di soggetti in remissione alla settimana 52. Si definisce come remissione un punteggio Mayo totale di 2 punti o inferiore, con nessun sottopunteggio individuale eccedente 1 punto ed un sottopunteggio di sanguinamento rettale pari a 0.

E.5.1.1

Timepoint(s) of evaluation of this end point

Primary endpoint is the proportion of subjects in remission at Week 52.

Per endpoint primario si intende la proporzione di soggetti in remissione alla Settimana 52.

E.5.2

Secondary end point(s)

• The proportion of subjects with mucosal healing at Week 52. Mucosal healing is defined by a Mayo endoscopic subscore of 0 or 1. • The proportion of subjects in sustained steroid free remission among subjects in remission at baseline of Study A3921096. Sustained steroid-free remission is defined by being in remission and steroid-free at both Week 24 and Week 52. Steroid free remission is defined by being in remission (a total Mayo score of 2 points or lower, with no individual subscore exceeding 1 point and a rectal bleeding subscore of 0) in addition to not requiring any treatment with corticosteroid for at least 4 weeks prior to the visit. - Other secondary, exploratory, pharmacokinetic, biomarker, Health Outcome and safety endpoints are described within the protocol.

• Percentuale di soggetti con guarigione della mucosa alla settimana 52. Si definisce come guarigione della mucosa un sottopunteggio Mayo endoscopico di 0 o 1. • Percentuale dei soggetti in remissione sostenuta senza assunzione di steroidi tra soggetti in remissione al basale dello studio A3921096. Si definisce remissione sostenuta senza assunzione di steroidi la remissione senza uso di steroidi sia alla settimana 24 che alla settimana 52. Si definisce come remissione senza assunzione di steroidi la remissione (punteggio Mayo totale di 2 punti o inferiore, con nessun sottopunteggio individuale eccedente 1 punto ed un sottopunteggio di sanguinamento rettale pari a 0) senza necessità di nessun tipo di trattamento con corticosteroidi per almeno 4 settimane prima della visita. - Altri endpoint secondari, esploratori, di farmacocinetica, di biomarcatori, e di sicurezza come descritti all'interno del protocollo.

E.5.2.1

Timepoint(s) of evaluation of this end point

Secondary endpoints are measured at Weeks 24 and 52.

Gli endpoint secondari sono misurati alla Settimana 24 e alla 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

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

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

Quality of Life

Qualità della vita

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)

Yes

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

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

Brazil

Canada

Colombia

Croatia

India

Israel

Japan

Korea, Republic of

New Zealand

Russian Federation

South Africa

Taiwan

Ukraine

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:

534

F.1.3

Elderly (>=65 years)

Yes

F.1.3.1

Number of subjects for this age range:

120

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

225

F.4.2.2

In the whole clinical trial

654

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)

At the end of the double-blind treatment period, subject who complete the study will have an opportunity to enter the open-label study A3921139

Alla fine del periodo di trattamento in doppio cieco, i soggetti che completano lo studio avranno l'opportunità di partecipare allo studio in aperto A3921139

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

2013-01-18

Ethics Committee Opinion of the trial application

Favourable

Ethics Committee Opinion: Reason(s) for unfavourable opinion

Date of Ethics Committee Opinion

2012-05-29

P. End of Trial
P.	End of Trial Status	Completed
P.	Date of the global end of the trial	2016-05-27

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IMP with orphan designation in the indication
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