Clinical Trials Register

Summary
EudraCT Number:	2017-002231-41
Sponsor's Protocol Code Number:	MLN0002-2003
National Competent Authority:	Poland - Office for Medicinal Products
Clinical Trial Type:	EEA CTA
Trial Status:	Completed
Date on which this record was first entered in the EudraCT database:	2017-10-13
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

Poland - Office for Medicinal Products

A.2

EudraCT number

2017-002231-41

A.3

Full title of the trial

A Phase 2, Randomized, Double-Blind, Dose-Ranging Study to Determine the Pharmacokinetics, Safety and Tolerability of Vedolizumab IV in Pediatric Subjects With Ulcerative Colitis or Crohn’s Disease
(A Phase 2, Randomized, Double-Blind, Dose-Ranging Study With Vedolizumab IV in Pediatric Subjects With Ulcerative Colitis or Crohn’s Disease)

A.3.1

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

A study to investigate how the body responds to the study drug Vedolizumab in child patients with Ulcerative Colitis or Crohn’s Disease

A.3.2

Name or abbreviated title of the trial where available

Hubble

A.4.1

Sponsor's protocol code number

MLN0002-2003

A.5.3

WHO Universal Trial Reference Number (UTRN)

U1111-1176-5741

A.5.4

Other Identifiers

Name:

IND number

Number:

009125

A.7

Trial is part of a Paediatric Investigation Plan

Yes

A.8

EMA Decision number of Paediatric Investigation Plan

P/146/2017

B. Sponsor Information
B.Sponsor: 1
B.1.1	Name of Sponsor	Takeda Development Centre Europe, Ltd.
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	Takeda Development Centre Europe, Ltd.
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	Takeda
B.5.2	Functional name of contact point	Takeda Study Registration Call Cent
B.5.3	Address:
B.5.3.1	Street Address	Unknown
B.5.3.2	Town/ city	Unknown
B.5.3.3	Post code	Unknown
B.5.3.4	Country	United States
B.5.4	Telephone number	+1877825-3327
B.5.6	E-mail	medicalinformation@tpna.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	European Union
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.3.9.2	Current sponsor code	MLN0002
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)	Yes
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

E. General Information on the Trial

E.1 Medical condition or disease under investigation

E.1.1

Medical condition(s) being investigated

Ulcerative Colitis and Crohn’s Disease

E.1.1.1

Medical condition in easily understood language

Ulcerative colitis is an inflammatory disease of the large bowel. Crohn’s disease is an inflammatory disease of the gastrointestinal tract.

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.1.2 Medical condition or disease under investigation

E.1.2	Version	20.1
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 vedolizumab PK in pediatric subjects with UC or CD.

E.2.2

Secondary objectives of the trial

- To assess the efficacy of vedolizumab IV in pediatric subjects with UC or CD.
- To characterize the dose-response relationships of vedolizumab IV in pediatric subjects with UC or CD.

E.2.3

Trial contains a sub-study

E.3

Principal inclusion criteria

-The subject is male or female; weighs ≥10 kg and 2 to 17 years, inclusive, at the time of randomization with moderately to severely active UC or CD diagnosed at least 3 months prior to Screening by clinical and endoscopic evidence and corroborated by a histopathology report, and who have demonstrated an inadequate response to, loss of response to, or intolerance of at least 1 of the following agents: corticosteroids, immunomodulators, and/or TNF-α antagonist therapy.
-The subject has a medical history of moderately to severely active UC during Screening defined as a complete Mayo score of 6 to 12, and a total of Mayo subscores of stool frequency and rectal bleeding ≥4 and Mayo endoscopy subscore ≥2, or has moderately to severely active CD defined as simple endoscopic score for Crohn’s disease (SES-CD) ≥7, and the Crohn’s Disease Activity Index (CDAI) components of average daily Abdominal Pain Score of >1 for the 7 days prior, and total number of liquid/very soft stools >10 for the 7 days prior to the first dose of study drug.
-The subject has evidence of UC extending proximal to the rectum (ie, not limited to proctitis) or evidence of CD involving the ileum and/or colon, at a minimum.
-Subjects with extensive colitis or pancolitis of >8 years duration or left-sided colitis of >12 years duration must have documented evidence that a surveillance colonoscopy was performed within 12 months prior to their first dose of study drug.

E.4

Principal exclusion criteria

-The subject has had previous exposure to approved or investigational anti-integrins including, but not limited to, natalizumab, efalizumab, etrolizumab, or AMG 181 or mucosal addressin cell adhesion molecule-1 (MAdCAM-1) antagonists, or rituximab.
-The subject has had prior exposure to vedolizumab.
-The subject has had hypersensitivity or allergies to any of the vedolizumab excipients.
-The subject has received
a)any investigational biologic (other than those listed in Exclusion
Criterion #1) within 60 days or 5 half-lives prior to Screening (whichever
is longer).
b) an approved biologic or biosimilar agent within 2 weeks prior to the
first dose of the study drug or at any time during the Screening period.
-The subject has a positive progressive multifocal leukoencephalopathy (PML) subjective symptom checklist prior to the administration of the first dose of study drug.
-The subject currently requires surgical intervention for UC or CD, or is anticipated to require surgical intervention for UC or CD during this study.
-The subject has other serious comorbidities that will limit his or her ability to complete the study.

E.5 End points

E.5.1

Primary end point(s)

- PK parameters - area under the serum concentration-time curve at Week 14 (AUC Wk 14).
- Average serum concentration during a dosing interval at Week 14 (Cav, Wk 14).
- Observed serum concentration at the end of a dosing interval at Week 14 (Ctrough, Wk 14)

E.5.1.1

Timepoint(s) of evaluation of this end point

Week 14

E.5.2

Secondary end point(s)

The secondary endpoints for this study are:
-Percentage of UC subjects who achieve clinical response based on complete Mayo score at Week 14.
-Percentage of CD subjects who achieve clinical response based on CDAI as defined by a ≥70 point decrease from baseline in CDAI score at Week 14.

E.5.2.1

Timepoint(s) of evaluation of this end point

Week 14

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

E.6.12

Pharmacoeconomic

E.6.13

Others

Yes

E.6.13.1

Other scope of the trial description

Tolerability;
Immunogenicity

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

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

E.8.2.3

Other

Yes

E.8.2.3.1

Comparator description

Vedolizumab to be tested at doses of 300mg, 200mg, 150 mg and 100mg

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

Belgium

Canada

France

Germany

Hungary

Israel

Netherlands

Poland

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

LPLV (aka LSO) is defined as the last subject visit for any subject in the study. Therefore, this will be Week 32 Final Safety Visit for a subject who is not enrolling into the extension study, OR the Week 22 visit for a subject that does enroll into the extension study, OR an Early Termination visit – whichever is the latest.

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

F. Population of Trial Subjects

F.1 Age Range

F.1.1

Trial has subjects under 18

Yes

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)

Yes

F.1.1.5.1

Number of subjects for this age range:

F.1.1.6

Adolescents (12-17 years)

Yes

F.1.1.6.1

Number of subjects for this age range:

F.1.2

Adults (18-64 years)

F.1.3

Elderly (>=65 years)

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

F.4.2.2

In the whole clinical trial

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)

After completing the Week 22 Visit, eligible subjects may enter an extension study: protocol Vedolizumab-2005. Those subjects who do not enter an extention study will have a Final Safety Visit 18 weeks after their last dose and participate in a long-term follow-up safety survey by telephone, 6 months after their last dose. Following this the subjects should return to the care of a physician and use 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

2018-01-17

Ethics Committee Opinion of the trial application

Favourable

Ethics Committee Opinion: Reason(s) for unfavourable opinion

Date of Ethics Committee Opinion

2017-11-02

P. End of Trial
P.	End of Trial Status	Completed
P.	Date of the global end of the trial	2020-05-26

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