Clinical Trials Register

Summary
EudraCT Number:	2009-016488-12
Sponsor's Protocol Code Number:	C13011
National Competent Authority:	Austria - BASG
Clinical Trial Type:	EEA CTA
Trial Status:	Completed
Date on which this record was first entered in the EudraCT database:	2010-11-18
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

Austria - BASG

A.2

EudraCT number

2009-016488-12

A.3

Full title of the trial

A Phase 3, Randomized, Placebo-Controlled, Blinded, Multicenter Study of the Induction of Clinical Response and Remission by Vedolizumab in Patients With Moderate to Severe Crohn’s Disease

A.3.1

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

Study of Vedolizumab in Patients With Moderate to Severe Crohn's Disease

A.4.1

Sponsor's protocol code number

C13011

A.5.2

US NCT (ClinicalTrials.gov registry) number

NCT01224171

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	Millennium Pharmaceuticals, 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	Millennium Pharmaceuticals, 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	Millennium Pharmaceuticals, Inc.
B.5.2	Functional name of contact point	Drug Information Call Center
B.5.3	Address:
B.5.3.1	Street Address	n/a
B.5.3.2	Town/ city	n/a
B.5.3.3	Post code	n/a
B.5.3.4	Country	United States
B.5.4	Telephone number	+1 510 740 2412
B.5.5	Fax number	+1 800 881 6092
B.5.6	E-mail	medical@mlnm.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	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
D.3.2	Product code	MLN0002
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.3.10	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.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 infusion
D.8.4	Route of administration of the placebo	Intravenous use

E. General Information on the Trial

E.1 Medical condition or disease under investigation

E.1.1

Medical condition(s) being investigated

Moderate to Severe Crohn's Disease

E.1.1.1

Medical condition in easily understood language

Crohn’s Disease

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	14.0
E.1.2	Level	LLT
E.1.2	Classification code	10013099
E.1.2	Term	Disease Crohns
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 determine the effect of vedolizumab induction treatment on clinical remission at Week 6 in the subgroup of patients defined as having failed tumour necrosis factor alpha (TNF alpha) antagonist therapy (TNF alpha subpopulation).

E.2.2

Secondary objectives of the trial

To determine the effect of vedolizumab induction treatment on clinical remission at
Week 6 in the entire study population
To determine the effect of vedolizumab induction treatment on clinical remission at
Week 10 in the TNF alpha subpopulation and in the entire study population
To determine the effect of vedolizumab induction treatment on sustained clinical
remission (ie, clinical remission at both Week 6 and Week 10) in the TNF alpha
subpopulation and in the entire study population
To determine the effect of vedolizumab induction treatment on enhanced clinical
response at Week 6 in the TNF alpha subpopulation

E.2.3

Trial contains a sub-study

E.3

Principal inclusion criteria

1. Age 18 to 80.
2. Male or female patient who is voluntarily able to give informed consent.
3. Female patients who:
• Are postmenopausal for at least 1 year before the Screening visit, OR
• Are surgically sterile, OR
• If they are of childbearing potential, agree to practice 2 effective methods of contraception.
Male patients, even if surgically sterilized, who:
• Agree to practice effective barrier contraception during the entire study
treatment period and through 6 months after the last dose of study drug, OR
•Agree to completely abstain from heterosexual intercourse.
4. Diagnosis of CD established at least 3 months before enrollment by clinical and
endoscopic evidence and corroborated by a histopathology report.
5. Moderately to severely active CD as determined by a CDAI score of 220 to 400 within 7 days before enrollment and 1 of the following:
a. CRP level > 2.87 mg/L during the Screening period, OR
b. Ileocolonoscopy with photographic documentation of a minimum of
3 nonanastomotic ulcerations (each > 0.5 cm in diameter) or 10 aphthous
ulcerations (involving a minimum of 10 contiguous cm of intestine)
consistent with CD, within 4 months before enrollment, OR
c. Fecal calprotectin >250 micro g/g stool during the Screening period in
conjunction with computed tomography (CT) enterography, magnetic
resonance (MR) enterography, contrast-enhanced small bowel radiography,
or wireless capsule endoscopy revealing Crohn’s ulcerations (aphthae not
sufficient), within 4 months before screening.
6. CD involvement of the ileum and/or colon, at a minimum.
7. Patients with 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 before enrollment (may be
performed during screening).
8. Patients with a family history of colorectal cancer, personal history of increased
colorectal cancer risk, age >50 years, or other known risk factor must be up-todate
on colorectal cancer surveillance.
9. Demonstrated, over the previous 5-year period, an inadequate response to, loss of response to, or intolerance of at least 1of the following agents as defined below:
• Immunomodulators
o Signs and symptoms of persistently active disease despite a history of
at least one 8-week regimen of oral azathioprine (≥ 1.5 mg/kg) or
6-MP (≥ 0.75 mg/kg), OR
o Signs and symptoms of persistently active disease despite a history of
at least one 8-week regimen of methotrexate (≥ 12.5 mg/week), OR
o History of intolerance of at least 1 immunomodulator.
• TNF alpha antagonists
o Signs and symptoms of persistently active disease despite a history of
at least one 4-week induction regimen of 1 of the following agents:
- Infliximab: 5 mg/kg IV, 2 doses at least 2 weeks apart
- Adalimumab: one 80-mg subcutaneous (SC) dose, followed by
one 40-mg dose, at least 2 weeks apart
- Certolizumab pegol: 400 mg SC, 2 doses at least 2 weeks apart,
OR
o Recurrence of symptoms during scheduled maintenance dosing
following prior clinical benefit, OR
o History of intolerance of at least 1 TNF alpha antagonist.
• Corticosteroids
o Signs and symptoms of persistently active disease despite a history
of at least one 4-week induction regimen that included a dose
equivalent to prednisone 30 mg daily orally for 2 weeks or
intravenously for 1 week, OR
o Two failed attempts to taper corticosteroids to below a dose
equivalent to prednisone 10 mg daily orally on 2 separate occasions,
OR
o History of intolerance of corticosteroids (including, but not limited
to, Cushing’s syndrome, osteopenia/osteoporosis, hyperglycemia,
insomnia, and infection).10. May be receiving a therapeutic dose of the following drugs:
a. Oral 5-ASA compounds provided that the dose has been stable for the
2 weeks immediately before enrollment
b. Oral corticosteroid therapy (prednisone at a stable dose <=30 mg/day,
budesonide at a stable dose <=9 mg/day, or equivalent steroid) provided that
the dose has been stable for the 4 weeks immediately before enrollment if
corticosteroids have just been initiated, or for the 2 weeks immediately before
enrollment if corticosteroids are being tapered
c. Probiotics (eg, Culturelle, Saccharomyces boulardii) provided that the dose
has been stable for the 2 weeks immediately before enrollment
d. Antidiarrheals (eg, loperamide, diphenoxylate with atropine) for control of
chronic diarrhea
e. Azathioprine or 6-MP provided that the dose has been stable for the 8 weeks
immediately before enrollment
f. Methotrexate provided that the dose has been stable for the 8 weeks
immediately before enrollment
g. Antibiotics used for the treatment of CD (ie, ciprofloxacin, metronidazole)
provided that the dose has been stable for the 2 weeks immediately before
enrollment

E.4

Principal exclusion criteria

Gastrointestinal Exclusion Criteria
1. Evidence of abdominal abscess during screening
2. Extensive colonic resection or subtotal or total colectomy
3. History of > 3 small bowel resections or diagnosis of short bowel syndrome
4. Have received tube feeding, defined formula diets, or parenteral alimentation
within 21 days before enrollment
5. Ileostomy, colostomy, or known fixed symptomatic stenosis of the intestine
6. Within 30 days before enrollment, have received any of the following for the
treatment of underlying disease:
a. Nonbiologic therapies (eg, cyclosporine, thalidomide) other than those
specifically listed in Section 6.2.1
b. A nonbiologic investigational therapy
c. An approved nonbiologic therapy in an investigational protocol
d. Adalimumab
7. Within 60 days before enrollment, have received any of the following:
a. Infliximab
b. Certolizumab pegol
c. Any other investigational or approved biological agent, other than local
administration for non-IBD conditions
8. Any prior exposure to natalizumab, efalizumab, or rituximab
9. Use of topical (rectal) treatment with 5-ASA or corticosteroid
enemas/suppositories within 2 weeks before enrollment
10. Evidence of or treatment for C. difficile infection or other intestinal pathogen
within 28 days before enrollment
11. Currently require or are anticipated to require major surgical intervention for CD during the study.
12. History or evidence of adenomatous colonic polyps that have not been removed
13. History or evidence of colonic mucosal dysplasia
14. Diagnosis of ulcerative colitis or indeterminate colitis
Infectious Disease Exclusion Criteria
1. Chronic hepatitis B or C infection
2. Active or latent tuberculosis, regardless of treatment history, as evidenced by any
of the following:
a. History of tuberculosis
b. A positive diagnostic TB test defined as:
i. A positive QuantiFERON test or 2 successive indeterminate
QuantiFERON tests within 1 month before enrollment, OR
ii. A tuberculin skin test reaction => 10 mm ( => 5 mm in patients receiving
the equivalent of > 15 mg/day prednisone) within 3 months before
enrollment
c. Chest X-ray within 3 months before enrollment in which active or latent
pulmonary TB cannot be excluded
3. Any identified congenital or acquired immunodeficiency
4. Any live vaccinations within 30 days before enrollment except for the influenza
vaccine
5. Clinically significant extra-intestinal infection within 30 days before screening or during screening
General Exclusion Criteria
1. Previous exposure to MLN0002.
2. Female patients who are lactating or have a positive serum pregnancy test during
the Screening period or a positive urine pregnancy test on Day 1 before
enrollment.
3. Any unstable or uncontrolled cardiovascular, pulmonary, hepatic, renal, GI,
genitourinary, hematological, coagulation, immunological, endocrine/metabolic,
or other medical disorder that, in the opinion of the investigator, would confound
the study results or compromise patient safety.
4. Had any surgical procedure requiring general anesthesia within 30 days before enrollment or is planning to undergo major surgery during the study period.
5. Any history of malignancy, except for the following: (a) adequately treated
nonmetastatic basal cell skin cancer; (b) squamous cell skin cancer that has been
adequately treated and that has not recurred for at least 1 year before enrollment;
and (c) history of cervical carcinoma in situ that has been adequately treated and
that has not recurred for at least 3 years before enrollment.
6. History of any major neurological disorders including, but not limited to, stroke,
multiple sclerosis, brain tumor, or neurodegenerative disease.
7. Positive PML subjective symptom checklist before enrollment.
8. Any of the following laboratory abnormalities during the Screening period:
a. Hemoglobin level <8 g/dL (80 g/L)
b. White blood cell (WBC) count <3 x10^3/microL (3x10^9/L)
c. Lymphocyte count <0.5x10^3/microL (0.5x10^9/L)
d. Platelet count <100x10^3/microL (100x10^9/L) or >1200x10^3/microL (1200x10^9/L)
e. Alanine aminotransferase (ALT) or aspartate aminotransferase (AST) >3x the upper limit of normal (ULN)
f. Alkaline phosphatase >3x ULN
g. Serum creatinine >2x ULN
h. Albumin <2.0 g/dL (<20 g/L)
9. Current or recent history (within 1 year before enrollment) of alcohol dependence
or illicit drug use.
10. Active psychiatric problems that, in the investigator’s opinion, may interfere with
compliance with the study procedures.
11. Unable to attend all the study visits or comply with study procedures.

E.5 End points

E.5.1

Primary end point(s)

• Proportion of patients in clinical remission at Week 6 in the TNF alpha subpopulation

E.5.1.1

Timepoint(s) of evaluation of this end point

Week 6

E.5.2

Secondary end point(s)

•Proportion of patients in clinical remission
•Proportion of patients with sustained clinical remission
•Proportion of patients with enhanced clinical response
•Safety profile - Adverse events, serious adverse events, results of standard laboratory tests and results of 12-lead electrocardiograms (ECGs)

E.5.2.1

Timepoint(s) of evaluation of this end point

Weeks 6, 10 or 22

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

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

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

Austria

Belgium

Canada

Czech Republic

France

Germany

Hungary

Israel

Italy

Korea, Republic of

Malaysia

Netherlands

New Zealand

Norway

Poland

Slovakia

South Africa

Turkey

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

After the Screening period, enrolled patients will complete the 6 week induction treatment and a follow-up observation visit at Week 10, at which time they may be eligible to receive vedolizumab treatment by enrolling in Study C13008 (long-term safety). Patients who do not enroll in Study C13008 will complete the Final Safety visit for a maximum time on study of 22 weeks. Patients who do not enroll in Study C13008 will participate in a 2 year follow-up survey.

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

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)

F.1.1.6

Adolescents (12-17 years)

F.1.2

Adults (18-64 years)

Yes

F.1.3

Elderly (>=65 years)

Yes

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

137

F.4.2.2

In the whole clinical trial

396

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)

Enrolled patients who complete theinduction treatment and a follow-up observation visit, may be eligible to receive active vedolizumab treatment by enrolling in Study C13008 (long-term safety). Patients who do not enroll in Study C13008 will complete the Final Safety visit (16 weeks after the last dose of study drug) for a maximum time on study of 22 weeks. After the end of the study, patients who do not enroll in Study C13008 will participate in a 2-year follow-up survey.

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

2011-01-05

Ethics Committee Opinion of the trial application

Favourable

Ethics Committee Opinion: Reason(s) for unfavourable opinion

Date of Ethics Committee Opinion

2010-12-07

P. End of Trial
P.	End of Trial Status	Completed
P.	Date of the global end of the trial	2014-01-30

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