Clinical Trials Register

Summary
EudraCT Number:	2015-000481-58
Sponsor's Protocol Code Number:	MLN0002SC-3031
National Competent Authority:	Czechia - SUKL
Clinical Trial Type:	EEA CTA
Trial Status:	Completed
Date on which this record was first entered in the EudraCT database:	2016-01-21
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

Czechia - SUKL

A.2

EudraCT number

2015-000481-58

A.3

Full title of the trial

A Phase 3 Randomized, Double-Blind, Placebo-Controlled Study to Evaluate the Efficacy and Safety of Vedolizumab Subcutaneous as Maintenance Therapy in Subjects With Moderately to Severely Active Crohn’s Disease Who Achieved Clinical Response Following Open-Label Vedolizumab Intravenous Therapy

Randomizované, dvojitě zaslepené, placebem kontrolované klinické
hodnocení fáze 3 hodnotící účinnost a bezpečnost subkutánně podávaného
vedolizumabu jako udržovací léčby u pacientů s mírnou až těžkou aktivní
Crohnovou nemocí, kteří po otevřené léčbě intravenózně podávaným
vedolizumabem dosáhli klinické odpovědi

A.3.1

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

Effectiveness and Safety of Vedolizumab SC as Maintenance Therapy in Crohn’s Disease

A.3.2

Name or abbreviated title of the trial where available

Efficacy and Safety of Vedolizumab SC as Maintenance Therapy in Crohn’s Disease

A.4.1

Sponsor's protocol code number

MLN0002SC-3031

A.5.2

US NCT (ClinicalTrials.gov registry) number

NCT02611817

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	Takeda Development Centre Europe, Ltd.
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	Takeda Development Center Americas, 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	Takeda Development Centre Europe Ltd
B.5.2	Functional name of contact point	Study Manager
B.5.3	Address:
B.5.3.1	Street Address	61 Aldwych
B.5.3.2	Town/ city	London
B.5.3.3	Post code	WC2B 4AE
B.5.3.4	Country	United Kingdom
B.5.4	Telephone number	44203116 8000
B.5.5	Fax number	44203116 8199
B.5.6	E-mail	clinicaloperations@tgrd.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	Yes
D.2.1.1.1	Trade name	Entyvio
D.2.1.1.2	Name of the Marketing Authorisation holder	Takeda Pharma A/S
D.2.1.2	Country which granted the Marketing Authorisation	United Kingdom
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	Vedolizumab IV
D.3.2	Product code	MLN0002
D.3.4	Pharmaceutical form	Powder for concentrate for 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	Vedolizumab
D.3.9.1	CAS number	943609-66-3
D.3.9.3	Other descriptive name	VEDOLIZUMAB
D.3.9.4	EV Substance Code	SUB30452
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	300
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.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	Vedolizumab SC
D.3.2	Product code	MLN0002 SC
D.3.4	Pharmaceutical form	Solution for injection in pre-filled syringe
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	Vedolizumab SC
D.3.9.1	CAS number	943609-66-3
D.3.9.2	Current sponsor code	MLN0002 SC
D.3.9.4	EV Substance Code	SUB30452
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	108
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 in pre-filled syringe
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

Crohn’s Disease

E.1.1.1

Medical condition in easily understood language

Crohn’s Disease

E.1.1.2

Therapeutic area

Diseases [C] - Immune System Diseases [C20]

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

• To assess the effect of vedolizumab SC maintenance treatment on clinical remission at Week 52 in subjects with moderately to severely active Crohn's disease who achieved clinical response at Week 6 following administration of vedolizumab IV at Weeks 0 and 2.

E.2.2

Secondary objectives of the trial

• To determine the effect of vedolizumab SC maintenance treatment on enhanced clinical response at Week 52 in subjects who achieved clinical response at Week 6 following administration of vedolizumab IV at Weeks 0 and 2.
• To determine the effect of vedolizumab SC maintenance treatment on corticosteroid-free remission at Week 52 in subjects who achieved clinical response at Week 6 following administration of vedolizumab IV at Weeks 0 and 2.
• To assess the effect of vedolizumab SC maintenance treatment on clinical remission at Week 52 in subjects who are naïve to TNF-alpha antagonist exposure, and achieved clinical response at Week 6 following administration of vedolizumab IV at Weeks 0 and 2.

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

Ileonoscopy Sub-study (Version and Date per Main Study)

Related objective: To determine the effect of vedolizumab SC maintenance treatment on clinical remission at Week 52 in subjects who achieved clinical response at Week 6 following administration of vedolizumab IV at Weeks 0 and 2, using an alternate definition of clinical remission based on endoscopy (using simple endoscopic score for Crohn’s Disease [SES-CD]), abdominal pain (using the CDAI component) and loose/watery stool frequency (using the CDAI component).

Ileocolonoscopy assessments will be performed at sites with appropriate capabilities, in subjects who volunteer at screening. The purpose of this assessment is to explore an alternate definition of clinical remission at Week 52 based on endoscopy (using SES-CD), abdominal pain (using the CDAI component) and loose/watery stool frequency (using the CDAI
component). Ileocolonoscopy assessments (including terminal ileum plus ascending, traverse, decending and sigmoid colon and rectum) will be performed prior to Week 0 dosing and at Week 52 by a local endoscopist.

E.3

Principal inclusion criteria

1. The subject has a diagnosis of Crohn's disease (CD) established at least 3 months prior to screening, by clinical and endoscopic evidence and corroborated by a histopathology report.
2. The subject has moderately to severely active CD.
3. The subject has CD involvement of the ileum and/or colon, at a minimum.
4. The subject has extensive colitis or pancolitis of >8 years duration or limited colitis of >12 years duration must have documented evidence that a surveillance colonoscopy was performed within 12 months of the initial screening visit.
5. Subjects with a family history of colorectal cancer, personal history of increased colorectal cancer risk, age >50 years, or other known risk factors must be up-to-date on colorectal cancer surveillance at screening.
6. The subject has demonstrated an inadequate response to, loss of response to, or intolerance of at least 1 of the following agents: immunomodulators, corticosteroids, or TNF-alpha antagonists.

E.4

Principal exclusion criteria

1. The subject has evidence of abdominal abscess at the initial Screening Visit.
2. The subject has had extensive colonic resection, subtotal or total colectomy.
3. The subject has a history of >3 small bowel resections or diagnosis of short bowel syndrome.
4. The subject has received tube feeding, defined formula diets, or parenteral alimentation within 28 days prior to the administration of the first dose of study drug.
5. The subject has ileostomy, colostomy, or known fixed symptomatic stenosis of the intestine.
6. The subject has received any of the investigational or approved non-biologic therapies (eg, cyclosporine, tacrolimus, thalidomide, methotrexate, or tofacitinib except for those specifically listed in the protocol) for the treatment of underlying disease within 30 days or 5 half-lives of screening (which ever is longer).
7. The subject has received any investigational or approved biologic or biosimilar agent within 60 days or 5 half-lives of screening (which ever is longer).
8. The subject has used topical (rectal) treatment with 5-ASA or corticosteroid enemas/suppositories within 2 weeks of the administration of the first dose of study drug.
9. The subject requires currently or is anticipated to require surgical intervention for CD during the study.
10. The subject has a history or evidence of adenomatous colonic polyps that have not been removed.
11. The subject has a history or evidence of colonic mucosal dysplasia.
12. The subject has a suspected or confirmed diagnosis of ulcerative colitis, indeterminate colitis, ischaemic colitis, radiation colitis, diverticular disease associated with colitis, or microscopic colitis.
13. The subject has evidence of an active infection during the Screening Period.
14. The subject has evidence of, or treatment for, C. difficile infection or other intestinal pathogen with 28 days prior to first dose of study drug.
15. The subject has chronic hepatitis B virus (HBV) infection* or chronic hepatitis C virus (HCV) infection.
* HBV immune subjects (ie, being hepatitis B surface antigen [HBsAg] negative and hepatitis B surface antibody [HBsAb] positive) may, however, be included.
16. The subject has active or latent TB as evidenced by the following:
i. A positive diagnostic TB test within 30 days prior to screening or during the screening period, defined as: 1. A positive QuantiFERON test or 2 successive indeterminate QuantiFERON tests, (or, A positive T-SPOT TB test [Japan only]), OR,
Vedolizumab SC 2. A tuberculin skin test reaction ≥5 mm.
Note: if subjects have received BCG vaccine then a QuantiFERON TB Gold text should be performed instead of the tuberculin skin text
ii. Chest X-ray within 3 months prior to Week 0 which is suspicious for pulmonary TB, and a positive or 2 successive indeterminate QuantiFERON tests (or, A positive T-SPOT TB test [Japan only]) within 30 days prior to Screening or during the Screening Period.
Note: subjects with documented previously treated TB with a negative QuantiFERON text can be included in the study.
17. The subject has any identified congenital or acquired immunodeficiency (eg, common variable immunodeficiency, human immunodeficiency virus [HIV] infection, organ transplantation).
18. The subject has received any live vaccinations within 30 days prior to screening.
19. The subject has clinically significant infection (eg, pneumonia, pyelonephritis) within 30 days prior to screening, or ongoing chronic infection.

E.5 End points

E.5.1

Primary end point(s)

• Proportion of subjects with clinical remission, defined as Crohn’s Disease Activity Index (CDAI) score ≤150, at Week 52.

E.5.1.1

Timepoint(s) of evaluation of this end point

Week 52

E.5.2

Secondary end point(s)

• Proportion of subjects with enhanced clinical response, defined as a ≥100 point decrease in CDAI score from Baseline (Week 0), at Week 52.
• Proportion of subjects with corticosteroid-free remission, defined as subjects using oral corticosteroids at Baseline (Week 0) who have discontinued oral corticosteroids and are in clinical remission at Week 52.
• Proportion of TNF-alpha antagonist naïve subjects who achieved clinical remission, defined as CDAI score ≤150, at Week 52.

E.5.2.1

Timepoint(s) of evaluation of this end point

Week 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

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

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)

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

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

135

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

Argentina

Australia

Belgium

Bosnia and Herzegovina

Brazil

Bulgaria

Canada

Czech Republic

Denmark

Estonia

Germany

Hungary

Israel

Italy

Japan

Korea, Republic of

Lithuania

Mexico

Netherlands

Poland

Romania

Russian Federation

Serbia

Slovakia

South Africa

Spain

Sweden

Taiwan

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

End of trial will be the date of the last visit of the last subject at the Week 68 Follow-up visit

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.1.1.1

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:

799

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

308

F.4.2.2

In the whole clinical trial

824

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)

Eligible subjects will be enrolled into an open-label extension (OLE) study and receive Vedolizumab SC treatment. This includes subjects who enter the Maintenance Period (clinical response at Week 6), plus subjects achieving a response by Week 14 who do not enter the Maintenance Period.
The study medication will not be available to subjects not participating in the OLE trial or who are discontinued. The subject should be returned to the care of a physician and standard therapies as required.

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

2016-04-13

Ethics Committee Opinion of the trial application

Favourable

Ethics Committee Opinion: Reason(s) for unfavourable opinion

Date of Ethics Committee Opinion

2016-02-10

P. End of Trial
P.	End of Trial Status	Completed
P.	Date of the global end of the trial	2019-10-14

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