Clinical Trials Register

Summary
EudraCT Number:	2015-000609-38
Sponsor's Protocol Code Number:	D5170C00002
National Competent Authority:	Italy - Italian Medicines Agency
Clinical Trial Type:	EEA CTA
Trial Status:	Prematurely Ended
Date on which this record was first entered in the EudraCT database:	2018-02-21
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

2015-000609-38

A.3

Full title of the trial

A Phase 2B Double-Blind, Multi-Dose, Placebo-Controlled Study to Evaluate the Efficacy and Safety of MEDI2070 in Subjects with Moderate to Severe
Crohn's Disease Who Have Failed or Are Intolerant to Anti-Tumor Necrosis Factor-Alpha-Therapy

Studio di Fase 2b, in doppio cieco, a dosi multiple, controllato con placebo per valutare l’efficacia e la sicurezza di MEDI2070 in soggetti affetti da morbo di Crohn da moderato a grave con risposta inadeguata o intolleranza alla terapia anti-fattore di necrosi tumorale alfa

A.3.1

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

A Phase 2B study of multiple doses to evaluate the safety and treatment benefits of MEDI2070 in subjects with Crohn's Disease who have failed or are Intolerant to Anti Tumor Necrosis Factor-Alpha Therapy

Studio di Fase 2b a dosi multiple per valutare la sicurezza e i benefici del trattamento con MEDI2070 in in soggetti affetti da morbo di Crohn con risposta inadeguata o intolleranza alla terapia anti-fattore di necrosi tumorale alfa

A.3.2

Name or abbreviated title of the trial where available

A.4.1

Sponsor's protocol code number

D5170C00002

A.5.4

Other Identifiers

Name:

Number:

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	MEDIMMUNE, LLC
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	MedImmune, LLC, a wholly owned subsidiary of
B.4.2	Country	United Kingdom
B.5 Contact point designated by the sponsor for further information on the trial
B.5.1	Name of organisation	MedImmune
B.5.2	Functional name of contact point	MedImmune Contact
B.5.3	Address:
B.5.3.1	Street Address	Milstein Building, Granta Park
B.5.3.2	Town/ city	Cambridge
B.5.3.3	Post code	CB21 6GH
B.5.3.4	Country	United Kingdom
B.5.4	Telephone number	0013013982273
B.5.5	Fax number	0013013982273
B.5.6	E-mail	clinicaltrialtransparency@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	MEDI2070
D.3.2	Product code	MEDI2070
D.3.4	Pharmaceutical form	Solution for infusion
D.3.4.1	Specific paediatric formulation	No
D.3.7	Routes of administration for this IMP
D.3.8 to D.3.10 IMP Identification Details (Active Substances)
D.3.9.1	CAS number	1610353-18-8
D.3.9.2	Current sponsor code	MEDI2070
D.3.9.3	Other descriptive name	anticorpo monoclonale anti-IL-23
D.3.10	Strength
D.3.10.1	Concentration unit	mg/ml milligram(s)/millilitre
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	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	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

E. General Information on the Trial

E.1 Medical condition or disease under investigation

E.1.1

Medical condition(s) being investigated

Crohn's Disease

Morbo di Crohn

E.1.1.1

Medical condition in easily understood language

Crohn's Disease

Morbo di Crohn

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	PT
E.1.2	Classification code	10011401
E.1.2	Term	Crohn's disease
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 this study is to evaluate the efficacy of MEDI2070 versus placebo to induce clinical remission based on the CDAI score at Week 8 in subjects with moderate to severe CD who have failed or are intolerant to anti-TNFα therapy.

L'obiettivo primario di questo studio è valutare l’efficacia di MEDI2070 rispetto al placebo nell’indurre la remissione clinica in base al punteggio CDAI alla Settimana 8 in soggetti affetti da CD da moderato a grave con risposta inadeguata o intolleranza alla terapia anti-TNFα.

E.2.2

Secondary objectives of the trial

To evaluate the efficacy of MEDI2070 to induce remission based on theSES-CD
To evaluate the efficacy of MEDI2070 to induce response based on the SES-CD
To evaluate the efficacy of MEDI2070 to induce remission based on the PRO2
To evaluate the efficacy of MEDI2070 to induce response based on the PRO2
To assess the safety and tolerability of MEDI2070
To evaluate the PK and IM of MEDI2070
To characterize MEDI2070's dose-exposure & exposure-response relationships
To evaluate the efficacy of MEDI2070 to induce clinical response based on the CDAI
To evaluate the efficacy of MEDI2070 to induce clinical remission based on the CDAI
To evaluate the efficacy of MEDI2070 on modified sustained remission, based on the SES-CD
To evaluate the efficacy of MEDI2070 on modified sustained remission based on the PRO2
To evaluate the efficacy of MEDI2070 on modified sustained remission based on the CDAI
To assess the relationship of biomarker 1 & biomarker 2 to CDAI remission

Valutare l’efficacia di MEDI2070 rispetto al placebo nell’indurre:
- la remissione alla Sett 16 in base al punteggio SES-CD;
- una risposta alla Sett 16 in base al punteggio SES-CD.
- la remissione alla Sett 8 in base al punteggio a 2 voci degli esiti riferiti dai pazienti (PRO2).
- una risposta alla Sett 8 in base al punteggio PRO2.
- una risposta clinica alla Sett 8 in base al punteggio CDAI.
- la remissione alla Sett 16 in base al punteggio PRO2.
- una risposta alla Sett 16 in base al punteggio PRO2
- la remissione clinica alla Sett 16 in base al punteggio CDAI
-una risposta clinica alla Sett 16 in base al punteggio CDA
- Dimostrare la sicurezza e tollerabilità della terapia con MEDI2070
- Caratterizzare la PK e l’immunogenicità di MEDI2070.
- Caratterizzare le relazioni dose-risposta ed esposizione-risposta
- Valutare i liv sierici di IL-22 e LCN2 per determinarne l’importanza nel predire l’efficacia di MEDI2070 in relazione all’induzione di risposta e remissione alla Sett 16

E.2.3

Trial contains a sub-study

E.3

Principal inclusion criteria

-Diagnosis of ileal, ileo-colonic, or colonic CD for > 3 months prior to screening
- Men or women age 18 - 80 years at the time of screening
- Moderate to severely active CD, as defined by CDAI AND endoscopic demonstration of inflammation
- Stable dose of medications for Crohn's disease therapy
- Prior treatment failure or intolerance with at least one anti-TNFα agent
-Effective contraception from screening, and for 26 weeks after the last dose of investigational product
-No known history of active tuberculosis (TB) & negative assessment for TB/latent TB

- Diagnosi di CD ileale, ileocolico o colico risalente a un minimo di 3 mesi prima dello screening
- Soggetti ambosessi di età compresa tra 18 e 80 anni, al momento dello screening
- CD da moderatamente a gravemente attivo, come definito da CDAI E evidenza endoscopica di infiammazione
- In terapia con dose stabile di farmaci per CD
- Fallimento di un precedente trattamento con o intolleranza ad almeno un agente anti TNFα
- Contraccezione efficace a partire dallo screening e per 26 settimane dopo l’ultima dose del prodotto sperimentale
- Nessuna anamnesi nota di tubercolosi (TBC) attiva & valutazione negativa per TBC/TBC latente

E.4

Principal exclusion criteria

-Severe underlying immunosuppression
- Severe gastrointestinal complications; e.g., short bowel syndromes, obstructing strictures, recent or planned bowel surgery, Ileostomy and/or colostomy, recent bowel perforation
- Significant infections at screening; Infected abscess, positive for Clostridium difficile, recent infectious hospitalization,
-Recent treatment with approved or investigational biologic therapy for Crohn's disease
- Recent or planned live attenuated vaccine
- History of cancer, except for basal cell carcinoma or CIS of the cervix with apparent cure ≥ 12 months before screening
- Pregnancy/breast feeding
- Drug abuse

- Grave immunosoppressione di base
- Gravi complicazioni gastrointestinali; es, sindrome dell'intestino corto, stenosi ostruttive, chirurgia intestinale recente o prevista, ileostomia
e / o colostomia, recente perforazione intestinale
- Infezioni significative allo screening; Ascessi infetti, positività per Clostridium difficile, recente ricovero infettivo
- Trattamento recente con terapia biologica approvati o in fase di sperimentazione per
Morbo di Crohn
- Somministrazione recente o pianificata di vaccino vivo attenuato
- Anamnesi di tumore, a eccezione di carcinoma basocellulare o carcinoma in situ della cervice trattati con apparente successo mediante terapia curativa ≥ 12 mesi prima dello screening.
- Gravidanza / allattamento
- Abuso di droghe

E.5 End points

E.5.1

Primary end point(s)

Primary endpoint is CDAI remission at Week 8

Endpoint primario è la remissione clinica CDAI alla Settimana 8

E.5.1.1

Timepoint(s) of evaluation of this end point

Week 8

Settimana 8

E.5.2

Secondary end point(s)

Key secondary endpoints (Induction period):
SES-CD Remission
SES-CD Response
PRO2 Remission
PRO2 Response
Key secondary endpoints (Maintenance period):
CDAI remission
SES-CD Remission
PRO2 Remission
CDAI Modified sustained remission
SES-CD Modified sustained remission
PRO2 Modified sustained remission
Safety Endpoints:
Incidence and severity of treatment-emergent adverse events (AEs)
Incidence of treatment-emergent serious AEs (SAEs)
Incidence and severity of treatment-emergent AEs of special interest,
including:
Incidence and severity of infection-related AEs and SAEs
Incidence and severity of infusion/injection-site reactions
Incidence and severity of hypersensitivity reactions
Incidence of AEs leading to study drug discontinuation
Incidence of specific laboratory abnormalities
Incidence of malignancies
Presence of antidrug antibodies in serum to MEDI2070

Endpoint secondari del periodo di induzione:
• remissione SES-CD
• risposta SES-CD
• remissione PRO2
• risposta PRO2
Endpoint secondari del periodo di mantenimento:
• remissione clinica CDAI
• remissione SES-CD
• remissione PRO2
• remissione clinica CDAI sostenuta modificata
• remissione SES-CD sostenuta modificata
• remissione PRO2 sostenuta modificata
Endpoint di sicurezza:
• incidenza e gravità degli eventi avversi emergenti dal trattamento (TEAEs)
• incidenza degli eventi avversi (EA) seri emergenti dal trattamento
• incidenza e gravità degli eventi avversi di speciale interesse (AESI) emergenti dal trattamento, tra cui:
◦ incidenza e gravità di AEs e SAEs correlati a infezione
◦ incidenza e gravità delle reazioni nel sito di iniezione/infusione;
◦ incidenza e gravità delle reazioni da ipersensibilità
• incidenza degli EA che portano a interruzione del prodotto sperimentale;
• incidenza di specifiche anomalie di laboratorio.
◦ incidenza di neoplasie maligne
- presenza di anticorpi anti farmaco nel siero per MEDI2070

E.5.2.1

Timepoint(s) of evaluation of this end point

Week 8, Week 16 Week 28 and Last study visit - Follow up 28 weeks
post last study treatment

Settimana 8, Settimana 16 Settimana 28 e Ultima visita di studio
Follow up 28 settimane dopo l'ultimo trattamento di studio

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

Yes

E.6.8

Bioequivalence

E.6.9

Dose response

Yes

E.6.10

Pharmacogenetic

Yes

E.6.11

Pharmacogenomic

Yes

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

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

Information not present in EudraCT

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

Austria

Belgium

Brazil

Bulgaria

Canada

Czech Republic

France

Germany

Hungary

Israel

Italy

Korea, Republic of

Netherlands

Poland

Russian Federation

Slovakia

Slovenia

Spain

Switzerland

Turkey

Ukraine

United Kingdom

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

Last visit of the last subject undergoing the trial

Ultima visita dell'ultimo oggetto sottoposto alla sperimentazione

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

Information not present in EudraCT

F.1.1.2

Preterm newborn infants (up to gestational age < 37 weeks)

Information not present in EudraCT

F.1.1.3

Newborns (0-27 days)

Information not present in EudraCT

F.1.1.4

Infants and toddlers (28 days-23 months)

Information not present in EudraCT

F.1.1.5

Children (2-11years)

Information not present in EudraCT

F.1.1.6

Adolescents (12-17 years)

Information not present in EudraCT

F.1.2

Adults (18-64 years)

Yes

F.1.2.1

Number of subjects for this age range:

308

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

Yes

F.3.3.2

Women of child-bearing potential using contraception

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

Yes

F.3.3.7.1

Details of other specific vulnerable populations

Elderly

anziani

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

111

F.4.2.2

In the whole clinical trial

342

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)

Standard of care for patients with Moderate to Severe Crohn's Disease

Standard di cura per i pazienti con malattia di Crohn da moderata a grave

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

2016-02-09

Ethics Committee Opinion of the trial application

Favourable

Ethics Committee Opinion: Reason(s) for unfavourable opinion

Date of Ethics Committee Opinion

2016-03-04

P. End of Trial
P.	End of Trial Status	Prematurely Ended
P.	Date of the global end of the trial	2018-01-29

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