Clinical Trials Register

Summary
EudraCT Number:	2020-004301-31
Sponsor's Protocol Code Number:	MLN0002-3025
National Competent Authority:	Croatia - MIZ
Clinical Trial Type:	EEA CTA
Trial Status:	Trial now transitioned
Date on which this record was first entered in the EudraCT database:	2021-09-02
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

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A. Protocol Information

A.1

Member State Concerned

Croatia - MIZ

A.2

EudraCT number

2020-004301-31

A.3

Full title of the trial

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

A.3.1

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

A study to evaluate efficacy and safety of Vedolizumab in pediatric subjects with moderately to severely active Crohn's disease

A.4.1

Sponsor's protocol code number

MLN0002-3025

A.5.4

Other Identifiers

Name:

IND

Number:

009125

A.7

Trial is part of a Paediatric Investigation Plan

Yes

A.8

EMA Decision number of Paediatric Investigation Plan

P/361/2020

B. Sponsor Information
B.Sponsor: 1
B.1.1	Name of Sponsor	Takeda Development Center Americas, Inc.
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 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 Center Americas, Inc.
B.5.2	Functional name of contact point	Director, Clinical Operations
B.5.3	Address:
B.5.3.1	Street Address	40 Landsdowne Street
B.5.3.2	Town/ city	Cambridge, Massachusetts
B.5.3.3	Post code	02139
B.5.3.4	Country	United States
B.5.4	Telephone number	+1617.444.1281
B.5.6	E-mail	mark.patti@takeda.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
D.3.4	Pharmaceutical form	Powder for concentrate for solution for infusion
D.3.4.1	Specific paediatric formulation	Yes
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	MLN0002
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	range
D.3.10.3	Concentration number	100 to 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.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

Moderately to severely active Crohn’s disease (CD)

E.1.1.1

Medical condition in easily understood language

Moderately to severely active Crohn’s disease. Crohn’s disease is a disease that causes inflammation of the digestive system.

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	20.1
E.1.2	Level	LLT
E.1.2	Classification code	10058815
E.1.2	Term	Crohn's disease acute episode
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 evaluate the efficacy of 2 different dose regimens of vedolizumab IV in pediatric subjects with moderately to severely active CD during maintenance therapy, based on clinical and endoscopic assessments at Week 54.

E.2.2

Secondary objectives of the trial

• To evaluate the efficacy of high and low doses of vedolizumab IV as measured by clinical and endoscopic remission at Weeks 14 and 54.
• To evaluate the effect of high and low doses of vedolizumab IV in each weight group on achieving corticosteroid-free remission at Week 54.
• To evaluate the effect of vedolizumab IV in each weight group on clinical response and clinical remission over time up to Week 54.
• To characterize the exposure of 2 different dose regimens of vedolizumab in pediatric subjects with moderately to severely active CD after IV administration.
• To evaluate safety in pediatric subjects on maintenance therapy up to Week 54.
• To evaluate the immunogenicity of vedolizumab in pediatric subjects with moderately to severely active CD treated with vedolizumab IV.
• To evaluate the effect of vedolizumab on patterns of growth and pubertal development in pediatric subjects with moderately to severely active CD during their participation in the study.

E.2.3

Trial contains a sub-study

E.3

Principal inclusion criteria

1. Subjects male or female aged 2 to 17 years, inclusive, who weigh ≥10 kg at the time of screening and enrollment into the study.
2. Subjects with moderately to severely active CD diagnosed at least 1 month before screening, defined by a PCDAI >30 and an SES-CD >6 (or an SES-CD ≥4 if disease is confined to terminal ileum).
3. Subjects who have failed, lost response to, or been intolerant to treatment with at least 1 of the following agents: corticosteroids, immunomodulators (eg, AZA, 6-mercaptopurine, methotrexate), and/or TNF-α antagonist therapy (eg, infliximab, adalimumab). This includes subjects who are dependent on corticosteroids or exclusive or partial enteral nutrition to control symptoms and who are experiencing worsening of disease in the moderate-to-severe range when attempting to wean off corticosteroids or discontinue exclusive enteral nutrition.
4. Subjects with extensive colitis or pancolitis of >8 years’ duration or left-sided colitis of >12 years’ duration must have documented evidence of a negative surveillance colonoscopy within 12 months before screening.
5. Subjects with vaccinations that are up-to-date based on the countrywide accepted schedule of childhood vaccines.

E.4

Principal exclusion criteria

1. Subjects who have 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.
2. Subjects who have had prior exposure to vedolizumab.
3. Subjects with hypersensitivity or allergies to any of the vedolizumab excipients.
4. Subjects who have received either (1) an investigational biologic (other than those listed in Exclusion Criterion #1) within 60 days or 5 half-lives before screening (whichever is longer); or (2) an approved biologic or biosimilar agent within 2 weeks before the first dose of study drug or at any time during the screening period.
5. Subjects with active cerebral/meningeal disease, signs/symptoms or history of progressive multifocal leukoencephalopathy (PML) or any other major neurological disorders including stroke, multiple sclerosis, brain tumor or neurodegenerative disease.
6. Subjects who currently require surgical intervention or are anticipated to require surgical intervention for CD during this study.
7. Subjects who have had subtotal or total colectomy or have a jejunostomy, ileostomy, colostomy, ileo-anal pouch, known fixed stenosis of the intestine, short bowel syndrome, or >3 small intestine resections.
8. Subjects with a current diagnosis of indeterminate colitis.
9. Subjects with clinical features suggesting monogenic very early-onset inflammatory bowel disease.

E.5 End points

E.5.1

Primary end point(s)

• Coprimary 1 (based on PCDAI): Clinical remission defined as a PCDAI ≤10 at Week 54.
• Coprimary 2 (based on SES-CD): Endoscopic response at Week 54, where a subject achieves endoscopic response if he or she has a 50% reduction in SES-CD score from baseline.

E.5.1.1

Timepoint(s) of evaluation of this end point

The end of study is defined as the Week 54 study visit.

E.5.2

Secondary end point(s)

• Clinical and endoscopic remission at Week 14, where a subject achieves both clinical and endoscopic remission if he or she meets the following definition: PCDAI ≤10 and SES-CD ≤4 with at least a 2-point reduction from baseline and no subscore >1.
• Clinical and endoscopic remission at Week 54, where a subject achieves clinical and endoscopic remission if he or she meets the following definition: PCDAI ≤10 and SES-CD ≤4 with at least a 2-point reduction from baseline and no subscore >1.
• Sustained clinical and endoscopic remission at Week 54, where a subject achieves sustained clinical and endoscopic remission if he or she achieved clinical and endoscopic remission (based on PCDAI and SES-CD) at Week 14 and at Week 54.
• Corticosteroid-free remission at Week 54, where a subject achieves corticosteroid-free clinical remission based on PCDAI at Week 54 and he or she has been off corticosteroids at least 12 weeks prior to Week 54.
• Sustained endoscopic remission, where a subject achieves sustained endoscopic remission if he or she meets the following definition: SES-CD ≤4 with at least a 2 point reduction from baseline and no subscore >1, achieved at both Weeks 14 and 54.
• Sustained clinical remission at Week 54, where a subject achieves sustained clinical remission if he or she achieved clinical remission (based on PCDAI) at Week 14 and at Week 54.
• Serum trough concentrations of vedolizumab over time.
• Positive antivedolizumab antibodies and positive neutralizing antivedolizumab antibodies during the study.
• Sustained clinical response of subjects at Weeks 14 and 54, where a subject meets clinical response of if he or she has a PCDAI score <30 and reduction of the PCDAI by ≥15 points from baseline.
• Clinical remission at Weeks 2, 6, 10, 14, 22, 30, 38, 46, and 54 where a subject achieves clinical remission if he or she meets the following definition: PCDAI ≤10.
• Clinical response at Weeks 2, 6, 10, 14, 22, 30, 38, 46, and 54 where a subject achieves clinical response if he or she meets the following definition: PCDAI <30 with reduction in the PCDAI of ≥15 points from baseline.
• Safety assessments: Descriptions of adverse events (AEs); serious adverse events (SAEs) and AEs of special interest (AESIs), including evaluation of opportunistic infection, such as PML, and liver injury, malignancies, infusion-related reactions, and hypersensitivity.
• Change from baseline in weight gain and linear growth z-score during the course of dosing with vedolizumab.
• Tanner Stage V at Week 54, where a subject achieves Tanner Stage V at Week 54 based on progression of pubertal changes from baseline.

E.5.2.1

Timepoint(s) of evaluation of this end point

LVLS

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

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)

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

Yes

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

Different doses of IMP are used in treatment arms

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

100

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

Bosnia and Herzegovina

Canada

China

Israel

Japan

New Zealand

Russian Federation

Ukraine

United States

Austria

Belgium

Croatia

France

Germany

Hungary

Italy

Lithuania

Poland

Romania

Slovakia

Spain

United Kingdom

Czechia

Greece

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

The end of study is defined as the Week 54 study 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

Yes

F.1.1

Number of subjects for this age range:

120

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 For clinical trials recorded in the database before the 10th March 2011 this question read: "Women of childbearing potential" and did not include the words "not using contraception". An answer of yes could have included women of child bearing potential whether or not they would be using contraception. The answer should therefore be understood in that context. This trial was recorded in the database on 2021-09-02.

Yes

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

Yes

F.3.3.6.1

Details of subjects incapable of giving consent

Children & adolescents (2-17)

F.3.3.7

Others

Yes

F.3.3.7.1

Details of other specific vulnerable populations

Pediatric patients

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

120

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)

Follow-up safety visit 18 weeks after the last dose of study drug and a final LTFU safety survey phone call every 6 months for 2 years after the last dose of study drug for all subjects who do not continue into the extension study and for subjects who discontinue study drug at any time during the study.

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

2021-08-17

Ethics Committee Opinion of the trial application

Favourable

Ethics Committee Opinion: Reason(s) for unfavourable opinion

Date of Ethics Committee Opinion

2021-07-08

P. End of Trial
P.	End of Trial Status	Trial now transitioned

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