Clinical Trials Register

Summary
EudraCT Number:	2020-004300-34
Sponsor's Protocol Code Number:	MLN0002-3024
National Competent Authority:	Lithuania - SMCA
Clinical Trial Type:	EEA CTA
Trial Status:	Completed
Date on which this record was first entered in the EudraCT database:	2021-04-21
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

Lithuania - SMCA

A.2

EudraCT number

2020-004300-34

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 Ulcerative Colitis 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 Ulcerative Colitis

A.4.1

Sponsor's protocol code number

MLN0002-3024

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 Ulcerative Colitis (UC)

E.1.1.1

Medical condition in easily understood language

Moderately to severely active Ulcerative Colitis. UC is a long-term condition that results in inflammation and ulcers of the colon and rectum

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	10066678
E.1.2	Term	Acute ulcerative colitis
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 UC during maintenance therapy, based on clinical remission at Week 54.

E.2.2

Secondary objectives of the trial

To Evaluate Efficacy of high & low doses of vedolizumab IV:
-In paediatric subjects with moderately to severely active UC, based on clinical remission at W14
-As measured by sustained clinical remission at W14&54
-As measured by sustained clinical response at W14&54
-As measured by sustained endoscopic remission at W14&54
-On achieving corticosteroid-free remission at W54
-Effect of high & low doses of vedolizumab IV on clinical response and clinical remission over time up to W54
To Evaluate:
-Vedolizumab PK in paediatric subjects with moderately to severely active UC after IV admin
-Safety in ped subjects on maintenance therapy up to W54
-The immunogenicity of vedolizumab in paediatric subjects with moderately to severely active UC treated with vedolizumab IV
-The effect of vedolizumab on patterns of growth and pubertal development in paediatric subjects with moderately to severely active UC during their study participation

E.2.3

Trial contains a sub-study

E.3

Principal inclusion criteria

1. The subjects aged 2 to 17 years, inclusive, at the time of screening and enrollment into the maintenance phase of the study.
2. The subject weighs ≥10 kg at the time of screening and enrollment into the study.
3. Subjects with moderately to severely active UC diagnosed at least 1 month before screening, defined by a modified Mayo score of 5 to 9 (sum of Mayo endoscopic subscore, stool frequency subscore, and rectal bleeding subscore) with a Mayo endoscopic subscore of ≥2 (with the presence of mucosal friability excluding an endoscopic subscore of 1 and mandating a score of at least 2).
4. Subjects who have failed, lost response to, or been intolerant to treatment with at least 1 of the following agents: corticosteroids, immunomodulators (eg, azathioprine, 6-mercaptopurine, methotrexate), and/or TNF-α antagonist therapy (eg, infliximab, adalimumab). This includes subjects who are dependent on corticosteroids to control symptoms and who are experiencing worsening of disease when attempting to wean off corticosteroids.
5. Subjects with evidence of UC extending proximal to the rectum (ie, not limited to proctitis), at a minimum.
6. 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.
7. 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 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 UC during this study.
7. Subjects who have had subtotal or total colectomy or have a jejunostomy, ileostomy, colostomy, ileo-anal pouch, or known fixed stenosis of the intestine.
8. Subjects with a current diagnosis of indeterminate colitis.
9. Subjects with clinical features suggesting monogenic very early onset inflammatory bowel disease.
10. 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)

The primary endpoint is clinical remission at Week 54, where clinical remission based on the modified Mayo score is defined as:
• stool frequency subscore 0 to 1 and a decrease of 1 or more from baseline;
• rectal bleeding subscore of 0;
• endoscopy subscore 0 to 1 (modified so that a score of 1 does not include friability).

E.5.1.1

Timepoint(s) of evaluation of this end point

Week 54

E.5.2

Secondary end point(s)

• Clinical remission at Week 14, where a subject achieves clinical remission if he or she meets the definition described in the primary endpoint.
• Sustained clinical remission at Week 54, where a subject achieves sustained clinical remission if he or she achieved clinical remission (as defined by primary endpoint) at Week 14 and at Week 54.
• Sustained endoscopic remission, defined as Mayo endoscopic score (MES) of ≤1 point, at Week 14 and at Week 54.
• Endoscopic response, defined as a decrease in MES ≥1 grade at Week 14 and at Week 54.
• Corticosteroid-free clinical remission at Week 54, where a subject achieves corticosteroid-free clinical remission at Week 54 if he or she meets the definition described in the primary endpoint and was off corticosteroids at least 12 weeks before Week 54.
• Clinical remission based on complete Mayo score at Week 54, where a subject achieves clinical remission if he or she achieved a complete Mayo score ≤2 points with no individual subscore >1 at Week 54.
• Serum trough concentrations of vedolizumab over time.
• Positive antivedolizumab antibodies (AVA) and positive neutralizing AVA during the study.
• Sustained clinical response of subjects at Weeks 14 and 54, where a subject meets clinical response if he or she has a reduction in complete Mayo score (see Appendix G) of ≥3 points and ≥30% from baseline with an accompanying decrease in rectal bleeding subscore of ≥1 point or absolute rectal bleeding subscore of ≤1 point.
• 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:
• Reduction of ≥2 points and ≥25% from the baseline partial Mayo score, including a ≥1-point decrease in the Mayo stool frequency subscore and a ≥1-point reduction in the rectal bleeding subscore or absolute rectal bleeding subscore of ≤1 point;
• Safety assessments: descriptions of adverse events (AEs); serious adverse events (SAEs); and adverse events of special interest (AESIs), including evaluation of opportunistic infection, such as PML, 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

Timepoints of secondary end points are provided in E.5.2.

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

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

Belgium

Canada

China

Croatia

Czechia

Greece

Hungary

Israel

Italy

Japan

Korea, Republic of

Lithuania

Poland

Russian Federation

Slovakia

Spain

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

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

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 2021-04-21.

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.
Eligible subjects may participate in the extension study MLN0002-3029.

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

2021-06-25

Ethics Committee Opinion of the trial application

Favourable

Ethics Committee Opinion: Reason(s) for unfavourable opinion

Date of Ethics Committee Opinion

2021-06-21

P. End of Trial
P.	End of Trial Status	Completed

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IMP with orphan designation in the indication
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