Clinical Trials Register

Summary
EudraCT Number:	2016-000678-40
Sponsor's Protocol Code Number:	Vedolizumab-4013
National Competent Authority:	Latvia - SAM
Clinical Trial Type:	EEA CTA
Trial Status:	Completed
Date on which this record was first entered in the EudraCT database:	2016-05-10
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

Latvia - SAM

A.2

EudraCT number

2016-000678-40

A.3

Full title of the trial

Entyvio (Vedolizumab IV) Extended Access Program in Ulcerative Colitis and Crohn’s Disease

A.3.1

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

Program to allow continuation of treatment with Entyvio (Vedolizumab IV) for patients with ulcerative colitis and Chron´s disease who previously participated in a clinical trial with this same treatment

A.4.1

Sponsor's protocol code number

Vedolizumab-4013

A.5.2

US NCT (ClinicalTrials.gov registry) number

NCT02743806

A.5.3

WHO Universal Trial Reference Number (UTRN)

U1111-1180-9339

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 Limited
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 Centre 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 Limited
B.5.2	Functional name of contact point	Global Medical Affairs
B.5.3	Address:
B.5.3.1	Street Address	1 Kingdom Street
B.5.3.2	Town/ city	London
B.5.3.3	Post code	W2 6BD
B.5.3.4	Country	United Kingdom
B.5.4	Telephone number	0044(0)1256 894003
B.5.6	E-mail	Stephen.Jones@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.3.4	Pharmaceutical form	Powder 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	20.1
E.1.2	Level	LLT
E.1.2	Classification code	10045365
E.1.2	Term	Ulcerative colitis
E.1.2	System Organ Class	100000004856

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	10013099
E.1.2	Term	Disease Crohns
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 monitor ongoing safety in subjects with ulcerative colitis and Crohn´s disease and to provide access to vedolizumab for qualifying subjects who, in the opinion of the investigator, continue to derive benefit from vedolizumab and for whom continued treatment with vedolizumab is desired because there is no other comparable product available or the subject may be expected to develop worsening of disease if they were to modify treatment

E.2.2

Secondary objectives of the trial

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

XAP-PK Substudy (Protocol Amendment 5, 07-Feb-17):
Subjects entering the Vedolizumab-4013 extended access program (XAP) from the C13008 clinical study will undergo a decrease in dosing frequency from every 4-week (Q4W) dosing to an every 8-week (Q8W) dosing regimen. Subjects making the transition between the two studies and moving to Q8W dosing may consent to take part in a pharmacokinetic (PK) sub-study (XAP-PK). The XAP-PK sub-study will assess the PK of vedolizumab (serum vedolizumab concentration and anti-vedolizumab antibodies [AVAs]) in subjects who move from Q4W dosing to Q8W dosing. Trough PK samples will be drawn immediately before the last dose in the C13008 study (T0), and in addition, before the first Q8W dose at Week 8 (T+1) and the second Q8W dose (T+2) at Week 16 to quantify PK at the new steady state for Q8W dosing. Should the subject lose clinical response to vedolizumab over time after the transition to Q8W dosing, further trough blood samples will be drawn for PK immediately prior to first dose after decision to return to Q4W dosing (T’0) and in addition before the next 2 doses (T’+1, T’+2), to quantify PK at the new steady state for Q4W dosing. The XAP-PK sub-study will also assess the proportion of subjects who move from Q4W dosing to Q8W dosing and remain on Q8W dosing through to Week 56. Vedolizumab PK will also be described based on trough concentrations by baseline subject factors influencing variability in subjects who remain on Q8W dosing, as well as those who return to Q4W dosing, either regaining response or not.

XAP-PK Substudy Objectives:
* To assess drug concentration during changes in dosing regimens.
* To understand the effects of AVAs on a subject’s ability to maintain or regain clinical response during changes in dosing regimens.
* To understand the proportion of subjects who maintain clinical response during a change in dosing regimen .
* To describe vedolizumab PK based on trough concentrations by baseline subject characteristics influencing variability.
* To assess pre-dose serum drug concentration and AVA in relation to efficacy and safety.

E.3

Principal inclusion criteria

Any subject who meets the inclusion criteria for the qualifying vedolizumab clinical studies and meets any of the following criteria will qualify for entry into the study:
1. Received vedolizumab (excluding comparator or placebo subjects) during participation in a qualifying vedolizumab study.
2. In the opinion of the investigator, the subject is continuing to derive benefit from vedolizumab and continued treatment with vedolizumab is desired because there is no other comparable product available or the subject may be expected to develop worsening of disease if they were to modify treatment.
3. A male subject who is nonsterilized and sexually active with a female partner of childbearing potential agrees to use adequate contraception from signing of informed consent throughout the duration of the study and for 18 weeks after last dose.
4. A female subject of childbearing potential who is sexually active with a nonsterilized male partner agrees to use routinely adequate contraception from signing of informed consent throughout the duration of the study and for 18 weeks after last dose.

PK Substudy:
5. Received vedolizumab during participation in the C13008 protocol.
6. The subject will start the main XAP study on Q8W dosing.
7. The subject or, when applicable, the subject’s legally acceptable representative, has signed and dated a written ICF for the procedures related to the XAP-PK substudy.

E.4

Principal exclusion criteria

Any subject who meets any of the exclusion following criteria will not qualify for entry into the study:
1. For the subject’s particular clinical scenario, vedolizumab is currently available to the subject through commercial channels, including reimbursement.
2. Subject has any clinical condition or prior therapy that, in the opinion of the investigator, would make the subject unsuitable for the study or unable to comply with the dosing requirements or poses a risk to the subject being in the study.
3. If female, the subject is pregnant or lactating or intending to become pregnant before, during, or within 18 weeks after participating in this study; or intending to donate ova during such time period.
4. If male, the subject intends to donate sperm during the course of this study or for 18 weeks thereafter.
5. Subject has received a live vaccine in the last 18 weeks or is in need of a live vaccine during the study or up to 18 weeks after the last study dose.

E.5 End points

E.5.1

Primary end point(s)

* Number and percentage of subjects with adverse events (AEs) and serious AEs (SAEs)
* Number and percentage of subjects with adverse events of special interest (AESIs)

E.5.1.1

Timepoint(s) of evaluation of this end point

Continuous

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

Yes

E.6.4

Safety

Yes

E.6.5

Efficacy

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

Continue to provide access to vedolizumab for qualifying subjects (extended access program)

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)

E.7.4

Therapeutic use (Phase IV)

Yes

E.8 Design of the trial

E.8.1

Controlled

E.8.1.1

Randomised

E.8.1.2

Open

Yes

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

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

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

Bulgaria

Czech Republic

Estonia

Hungary

India

Italy

Korea, Republic of

Latvia

Malaysia

New Zealand

Poland

Romania

Russian Federation

Serbia

Slovakia

South Africa

Taiwan

Turkey

Ukraine

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

Subjects will remain in the study until vedolizumab is available to the subject through commercial channels, including reimbursement, for the subject’s clinical scenario or until subject withdrawal, whichever is sooner. Subjects will return 18 weeks after their final study infusion for a safety follow-up visit regardless of whether they remain on vedolizumab after the study (ie, they left the study due the availability of vedolizumab or they withdrew from the study for other reasons).

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:

380

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

239

F.4.2.2

In the whole clinical trial

385

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)

Subjects will be allowed to remain in the study until vedolizumab is available to the subject through commercial channels, including reimbursement, for the subject’s clinical scenario or until subject withdrawal, whichever is sooner.

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

2016-08-15

Ethics Committee Opinion of the trial application

Favourable

Ethics Committee Opinion: Reason(s) for unfavourable opinion

Date of Ethics Committee Opinion

2016-08-19

P. End of Trial
P.	End of Trial Status	Completed
P.	Date of the global end of the trial	2023-01-03

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