ICH GCP - EU Clinical trials Registry - 2019-001866-14 (IT)

Summary
EudraCT Number:	2019-001866-14
Sponsor's Protocol Code Number:	D5271C00002
National Competent Authority:	Italy - Italian Medicines Agency
Clinical Trial Type:	EEA CTA
Trial Status:	Ongoing
Date on which this record was first entered in the EudraCT database:	2021-10-12
Trial 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

B. Sponsor Information
B.Sponsor: 1
B.1.1	Name of Sponsor	ASTRAZENECA AB
B.1.3.4	Country	Sweden
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
B.4.2	Country
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	Clinical Study Information Center
B.5.3	Address:
B.5.3.1	Street Address	N/A
B.5.3.2	Town/ city	N/A
B.5.3.3	Post code	N/A
B.5.3.4	Country	United States
B.5.4	Telephone number	000000
B.5.5	Fax number	000000
B.5.6	E-mail	information.center@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	Brazikumab
D.3.2	Product code	[MEDI2070]
D.3.4	Pharmaceutical form	Concentrate and solvent for 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	( L ) ASCORBATO DI CALCIO
D.3.9.1	CAS number	1610353-18-8
D.3.9.2	Current sponsor code	NA
D.3.9.3	Other descriptive name	Anti-Interleukin-23 Immunoglobulin G2 (IgG2) Human Monoclonal Antibody; also referred to as MED2070
D.3.9.4	EV Substance Code	SUB188673
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	120
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	Yes
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.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	Brazikumab
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	Intravenous use
D.3.8 to D.3.10 IMP Identification Details (Active Substances)
D.3.8	INN - Proposed INN	( L ) ASCORBATO DI CALCIO
D.3.9.1	CAS number	1610353-18-8
D.3.9.2	Current sponsor code	NA
D.3.9.3	Other descriptive name	Anti-Interleukin-23 Immunoglobulin G2 (IgG2) Human Monoclonal Antibody; also referred to as MEDI2070
D.3.9.4	EV Substance Code	SUB188673
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	720
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

E. General Information on the Trial

E.1 Medical condition or disease under investigation

E.1.1

Medical condition(s) being investigated

Moderately to Severely Active Crohn's Disease.

Malattia di Crohn da moderatamente a gravemente attiva.

E.1.1.1

Medical condition in easily understood language

Crohn's disease is a condition that affects the lining of the digestive tract due to inflammation and may result in ulcers and/or strictures.

La malattia di Crohn è una condizione che colpisce il rivestimento del tubo digerente tramite l'infiammazione e può provocare ulcere e/o stenosi.

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	LLT
E.1.2	Classification code	10011402
E.1.2	Term	Crohn's disease (colon)
E.1.2	System Organ Class	100000004856

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 assess the safety of long-term treatment with brazikumab in participants who previously completed Study D5271C00001 (Legacy #3150- 301-008) or discontinued from the study at or after Week 12 due to lack of efficacy.

Per valutare la sicurezza del trattamento a lungo termine con brazikumab nei partecipanti che hanno precedentemente completato lo Studio D5271C00001 (precedente #3150-301-008) o interrotto la partecipazione allo studio dopo la settimana 12 a causa di una mancanza di efficacia.

E.2.2

Secondary objectives of the trial

Not applicable.

Non applicabile.

E.2.3

Trial contains a sub-study

E.3

Principal inclusion criteria

1 Male or female participants with successful completion or early termination due to lack of efficacy from Study D5271C00001 (Legacy # 3150-301-008).
2 No known history of active TB or latent TB without completion of appropriate intervention.
3 Each participant must have had the ileocolonoscopic procedure at the final visit (Week 52, Week 12, or early termination after Week 12 of Study D5271C00001 (Legacy # 3150-301-008).
4 Female participants of childbearing potential must have a negative urine pregnancy test prior to administration of study intervention and must agree to use a highly effective method of birth control (confirmed by the investigator) from randomization throughout the study duration and for at least 18 weeks after last dose of study intervention.
5 Nonsterilized males who are sexually active with a female partner of childbearing potential must comply with the methods of contraception during treatment and until the end of relevant systemic exposure in the male participant, plus a further 18 weeks.
6 Capable of giving signed informed consent which includes compliance with the requirements and restrictions listed in the ICF and in this protocol.
7 Written informed consent from the participant has been obtained prior to any study related procedures.
8 Demonstration of adequate compliance with the study procedures in Study D5271C00001 (Legacy #3150 301-008) in the opinion of the investigator and/or sponsor.
9 Willingness and ability to attend all study visits, comply with the study procedures, read and write in order to complete questionnaires, and be able to complete the study.
The complete list of eligibility criteria are outlined in the study protocol

1. Partecipanti maschi o femmine che hanno completato con successo o interrotto anticipatamente per mancanza di efficacia lo Studio D5271C00001 (precedente #3150-301-008).
2. Nessuna storia nota di TB attiva o TB latente senza il completamento di un intervento appropriato.
3. Ogni partecipante deve aver subito la procedura ileocolonoscopica nella visita finale (settimana 52, settimana 12 o interruzione anticipata dopo la settimana 12 dello Studio D5271C00001 (precedente # 3150-301-008).
4. Le partecipanti in età fertile devono avere un test di gravidanza sulle urine negativo prima della somministrazione del trattamento di studio e devono accettare di utilizzare un metodo contraccettivo altamente efficace (confermato dallo sperimentatore) a partire dalla randomizzazione, per tutta la durata dello studio e per almeno 18 settimane dopo l'ultima dose di trattamento dello studio.
5. Maschi non sterilizzati che sono sessualmente attivi con una partner femminile in età fertile devono rispettare i metodi di contraccezione durante il trattamento e fino alla fine della relativa esposizione sistemica del partecipante maschio, più altre 18 settimane.
6. In grado di fornire un consenso informato firmato che include la conformità con i requisiti e le restrizioni elencate nell'ICF e in questo protocollo.
7. Il consenso informato scritto del partecipante è stato ottenuto prima di qualsiasi procedura relativa allo studio.
8. Dimostrazione di un adeguato rispetto delle procedure di studio nello Studio D5271C00001 (precedente #3150 301-008) secondo il parere dello sperimentatore e/o dello sponsor.
9. Disponibilità e capacità di partecipare a tutte le visite dello studio, rispettare le procedure di studio, leggere e scrivere in modo da completare i questionari, ed essere grado di completare lo studio.
L'elenco completo dei criteri di eleggibilità è delineato nel protocollo di studio.

E.4

Principal exclusion criteria

1 Any participant with an unresolved AE from the Study D5271C00001 (Legacy #3150 301-008) that would limit the participant's ability to participate in or complete this study.
2 Current diagnosis of ischemic colitis, colonic mucosal dysplasia, or primary sclerosing cholangitis.
3 Organ or cell-based transplantation (eg, islet cell transplantation or autologous stem cell transplantation) with the exception of corneal transplant.
4 Any other condition or finding that, in the investigator's or sponsor's opinion, would either confound proper interpretation of the study or expose a participant to unacceptable risk.
5 History of cancer except for basal cell and/or squamous cell carcinoma of the skin, and carcinoma in situ of the cervix within 12 months of screening.
6 Participant meets criteria for discontinuation of study intervention during prior the D5271C00001 (Legacy #3150 301-008) study (excluding lack of efficacy).
7 Chronic hepatitis B or C infection.
8 Known history of primary immunodeficiency, splenectomy, or any underlying condition that predisposes the subject to infection, including HIV infection.
9 Prolonged QTcF interval (QTc >450 msec or QTC >480 for participants with bundle branch block; determined by central ECG), or conditions leading to additional risk for QT prolongation (eg, congenital long-QT syndrome).
10 Participant requires additional immunosuppressive therapy (aside from permitted concomitant medication), biological treatment, or prohibited treatment.
11 Participant received a Bacille Calmette-Guérin vaccination within 12 months of Week 0 (Visit 1) or any other live vaccine < 4 weeks prior to Week 0 (Visit 1) or is planning to receive any such vaccine over the course of the study.
12 Participant received a prohibited medication during participation in the lead-in study or during screening for this study.
13 Participant is planning to receive an investigational drug (other than study intervention) or investigational device at any time during Study D5271C00002 (Legacy #3150-303-008) with the exception of "registry" or "cohort" trials.
14 Participants with a known hypersensitivity to brazikumab or any of the excipients of the product.
15 Protocol-defined abnormal laboratory results at screening.
The complete list of eligibility criteria are outlined in the study protocol.

1. Qualsiasi partecipante con un evento avverso irrisolto nello studio D5271C00001 (precedente #3150 301-008) che limiterebbe la capacità del partecipante di partecipare o di completare questo studio.
2. Diagnosi attuale di colite ischemica, displasia della mucosa del colon, o colangite sclerosante primitiva.
3. Trapianto di organi o cellule (ad es., trapianto di cellule insulari o trapianto autologo di cellule staminali) ad eccezione del trapianto della cornea.
4. Qualsiasi altra condizione o accertamento che, a giudizio dello sperimentatore o dello sponsor, confonderebbe la corretta interpretazione dello studio o esporrebbe il partecipante a un rischio inaccettabile.
5. Storia di tumore ad eccezione del carcinoma della pelle basocellulare e/o alle cellule squamose e del carcinoma in situ della cervice entro 12 mesi dallo screening.
6. Il partecipante soddisfa i criteri per l'interruzione del trattamento dello studio D5271C00001 (precedente #3150 301-008) (esclusa la mancanza di efficacia).
7. Infezione cronica da epatite B o C.
8. Anamnesi nota di immunodeficienza primaria, splenectomia o altra condizione sottostante che predispone il soggetto all'infezione, tra cui l' infezione da HIV.
9. Intervallo QTcF prolungato (QTc >450 msec o QTC >480 per i partecipanti con blocco di branca; determinato dall'ECG centrale), o condizioni che portano a un rischio aggiuntivo di prolungamento dell'intervallo QT (ad es., sindrome congenita del tratto QT lungo).
10. Il partecipante richiede una terapia immunosoppressiva aggiuntiva (a parte i farmaci concomitanti consentiti), un trattamento biologico, o un trattamento vietato.
11. Il partecipante ha ricevuto una vaccinazione Bacille Calmette-Guérin entro 12 mesi della settimana 0 (visita 1) o qualsiasi altro vaccino vivo entro 4 settimane prima della settimana 0 (Visita 1) o sta pianificando di ricevere un vaccino di questo tipo nel corso dello studio.
12. Il partecipante ha ricevuto un farmaco proibito durante la partecipazione allo studio iniziale o durante lo screening per questo studio.
13. Il partecipante sta pianificando di ricevere un farmaco sperimentale (diverso dal trattamento dello studio) o un dispositivo sperimentale in qualsiasi momento durante lo Studio D5271C00002 (precedente #3150-303-008) con l'eccezione di studi di "registro" o di "coorte".
14. Partecipanti con nota ipersensibilità al brazikumab o ad uno qualsiasi degli eccipienti presenti nel prodotto.
15. Risultati di laboratorio anormali definiti dal protocollo allo screening.
L'elenco completo dei criteri di eleggibilità è delineato nel protocollo di studio.

E.5 End points

E.5.1

Primary end point(s)

a. AE/SAE
b. Clinical laboratory values
c. Vital signs
d. ECG

a. AE/SAE
b. Valori clinici di laboratorio
c. Segni vitali
d. ECG

E.5.1.1

Timepoint(s) of evaluation of this end point

a. across the 52-week treatment period
b. across the 52-week treatment period
c. across the 52-week treatment period
d. across the 52-week treatment period

a. durante il periodo di trattamento di 52 settimane
b. durante il periodo di trattamento di 52 settimane
c. durante il periodo di trattamento di 52 settimane
d. durante il periodo di trattamento di 52 settimane

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

Yes

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)

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

E.8.1.1

Randomised

E.8.1.2

Open

E.8.1.3

Single blind

E.8.1.4

Double blind

E.8.1.5

Parallel group

E.8.1.6

Cross over

E.8.1.7

Other

Yes

E.8.1.7.1

Other trial design description

Studio di estensione

Extension study

E.8.2

Comparator of controlled trial

E.8.2.1

Other medicinal product(s)

E.8.2.2

Placebo

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

Canada

India

Israel

Korea, Republic of

Russian Federation

South Africa

Taiwan

Ukraine

United States

Austria

France

Germany

Hungary

Italy

Poland

Slovakia

Spain

United Kingdom

Czechia

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

Page Nct des essais cliniques

Sponsors et collaborateurs

Les conditions médicales

Interventions en matière de drogue