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Clinical Trial Results:
A Phase 3, Open-label Study to Determine the Long-term Safety and Efficacy of Vedolizumab (MLN0002) in Subjects with Ulcerative Colitis and Crohn’s Disease

Summary
EudraCT number	2008-002784-14
Trial protocol	EE HU AT SK IE LV CZ NL IS PT FR BE ES MT BG SE IT DE GR GB
Global end of trial date	31 Oct 2017

Results information
Results version number	v1(current)
This version publication date	09 Nov 2018
First version publication date	09 Nov 2018
Other versions

Trial Information
Subject Disposition
Baseline Characteristics
End Points
Adverse Events
More Information

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Trial information

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Sponsor protocol code

C13008

ISRCTN number

US NCT number

NCT00790933

WHO universal trial number (UTN)

Sponsor organisation name

Takeda

Sponsor organisation address

One Takeda Parkway, Deerfield, IL, United States, 60015

Public contact

Medical Director, Takeda, +1 8778253327, trialdisclosures@takeda.com

Scientific contact

Medical Director, Takeda, +1 8778253327, trialdisclosures@takeda.com

Is trial part of an agreed paediatric investigation plan (PIP)

Does article 45 of REGULATION (EC) No 1901/2006 apply to this trial?

Does article 46 of REGULATION (EC) No 1901/2006 apply to this trial?

Analysis stage

Final

Date of interim/final analysis

31 Oct 2017

Is this the analysis of the primary completion data?

Global end of trial reached?

Yes

Global end of trial date

31 Oct 2017

Was the trial ended prematurely?

Main objective of the trial

The purpose of this study is to determine the safety profile of long-term vedolizumab treatment

Protection of trial subjects

At each visit, the investigator had to document any occurrence of adverse events and abnormal laboratory findings. Any event spontaneously reported by the participant or observed by the investigator was recorded, irrespective of the relation to study treatment.

Background therapy

Evidence for comparator

Actual start date of recruitment

22 May 2009

Long term follow-up planned

Yes

Long term follow-up rationale

Safety

Long term follow-up duration

4 Months

Independent data monitoring committee (IDMC) involvement?

Yes

Number of subjects enrolled per country

Country: Number of subjects enrolled

Hong Kong: 3

Country: Number of subjects enrolled

India: 63

Country: Number of subjects enrolled

Australia: 100

Country: Number of subjects enrolled

Malaysia: 17

Country: Number of subjects enrolled

New Zealand: 26

Country: Number of subjects enrolled

Singapore: 2

Country: Number of subjects enrolled

South Africa: 36

Country: Number of subjects enrolled

Korea, Republic of: 59

Country: Number of subjects enrolled

Taiwan: 4

Country: Number of subjects enrolled

Czech Republic: 206

Country: Number of subjects enrolled

Greece: 5

Country: Number of subjects enrolled

Hungary: 98

Country: Number of subjects enrolled

Poland: 82

Country: Number of subjects enrolled

Romania: 4

Country: Number of subjects enrolled

Serbia: 2

Country: Number of subjects enrolled

Slovakia: 31

Country: Number of subjects enrolled

Bulgaria: 11

Country: Number of subjects enrolled

Estonia: 14

Country: Number of subjects enrolled

Israel: 56

Country: Number of subjects enrolled

Latvia: 1

Country: Number of subjects enrolled

Russian Federation: 85

Country: Number of subjects enrolled

Turkey: 9

Country: Number of subjects enrolled

Ukraine: 9

Country: Number of subjects enrolled

Canada: 355

Country: Number of subjects enrolled

United States: 591

Country: Number of subjects enrolled

Austria: 25

Country: Number of subjects enrolled

Belgium: 175

Country: Number of subjects enrolled

Denmark: 2

Country: Number of subjects enrolled

France: 46

Country: Number of subjects enrolled

Germany: 44

Country: Number of subjects enrolled

Iceland: 6

Country: Number of subjects enrolled

Ireland: 2

Country: Number of subjects enrolled

Italy: 23

Country: Number of subjects enrolled

Netherlands: 19

Country: Number of subjects enrolled

Norway: 14

Country: Number of subjects enrolled

Spain: 5

Country: Number of subjects enrolled

Sweden: 5

Country: Number of subjects enrolled

Switzerland: 6

Country: Number of subjects enrolled

United Kingdom: 2

Worldwide total number of subjects

2243

EEA total number of subjects

820

Number of subjects enrolled per age group

In utero

Preterm newborn - gestational age < 37 wk

Newborns (0-27 days)

Infants and toddlers (28 days-23 months)

Children (2-11 years)

Adolescents (12-17 years)

Adults (18-64 years)

2167

From 65 to 84 years

85 years and over

Subject disposition

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Recruitment details

Participants took part in study at 298 sites in North America, Western/Northern Europe, Central Europe, Eastern Europe, Asia, Australia and Africa from 22 May 2009 to 31 October 2017.

Screening details

Participants with a diagnosis of ulcerative colitis and Crohn's disease who participated in previous studies: C13004 (NCT00619489), C13006 (NCT00783718), C13007 (NCT00783692) and C13011 (NCT01224171) and DeNovo participants were enrolled into 1 treatment group, vedolizumab 300 mg, 30-minute intravenous (IV) infusion, every 4 weeks (Q4W).

Period 1 title

Overall Study (overall period)

Is this the baseline period?

Yes

Allocation method

Not applicable

Blinding used

Not blinded

Are arms mutually exclusive

Yes

Vedolizumab 300 mg (C13006)

Arm description

Vedolizumab 300 mg, 30-minute IV infusion, Q4W in this study. Treatment duration was up to approximately 430 weeks including treatment in the previous study. In study C13006: participants received either vedolizumab matching placebo or vedolizumab every Q4W or vedolizumab every 8 weeks (Q8W), IV infusion up to Week 52.

Arm type

Experimental

Investigational medicinal product name

Vedolizumab

Investigational medicinal product code

Other name

Pharmaceutical forms

Solution for injection/infusion

Routes of administration

Intravenous use

Dosage and administration details

Vedolizumab Intravenous Infusion

Investigational medicinal product name

Vedolizumab Matching Placebo

Investigational medicinal product code

Other name

Pharmaceutical forms

Solution for injection/infusion

Routes of administration

Intravenous use

Dosage and administration details

Vedolizumab Matching Placebo Intravenous Infusion

Vedolizumab 300 mg (C13007)

Arm description

Vedolizumab 300 mg, 30-minute IV infusion, Q4W in this study. Treatment duration was up to approximately 429 weeks including treatment in the previous study. In study C13007: participants received either vedolizumab matching placebo or vedolizumab Q4W or vedolizumab Q8W, IV infusion up to Week 52.

Arm type

Experimental

Investigational medicinal product name

Vedolizumab Matching Placebo

Investigational medicinal product code

Other name

Pharmaceutical forms

Solution for injection/infusion

Routes of administration

Intravenous use

Dosage and administration details

Vedolizumab Matching Placebo Intravenous Infusion

Investigational medicinal product name

Vedolizumab

Investigational medicinal product code

Other name

Pharmaceutical forms

Solution for injection/infusion

Routes of administration

Intravenous use

Dosage and administration details

Vedolizumab Intravenous Infusion

Vedolizumab 300 mg (C13011)

Arm description

Vedolizumab 300 mg, 30-minute IV infusion, Q4W in this study. Treatment duration was up to approximately 315 weeks including treatment in the previous study. In study C13011: participants received either vedolizumab matching placebo or vedolizumab 300 mg, IV infusion, at Weeks 0, 2 and 6.

Arm type

Experimental

Investigational medicinal product name

Vedolizumab Matching Placebo

Investigational medicinal product code

Other name

Pharmaceutical forms

Solution for injection/infusion

Routes of administration

Intravenous use

Dosage and administration details

Vedolizumab Matching Placebo Intravenous Infusion

Investigational medicinal product name

Vedolizumab

Investigational medicinal product code

Other name

Pharmaceutical forms

Solution for injection/infusion

Routes of administration

Intravenous use

Dosage and administration details

Vedolizumab Intravenous Infusion

Vedolizumab 300 mg (C13004)

Arm description

Vedolizumab 300 mg, 30-minute IV infusion, Q4W in this study. Treatment duration was up to approximately 510 weeks including treatment in the previous study. In study C13004: participants received either vedolizumab 2 mg/kg or 6 mg/kg, IV infusion Q8W up to Week 78.

Arm type

Experimental

Investigational medicinal product name

Vedolizumab

Investigational medicinal product code

Other name

Pharmaceutical forms

Solution for injection/infusion

Routes of administration

Intravenous use

Dosage and administration details

Vedolizumab Intravenous Infusion

Vedolizumab 300 mg (C13008 De Novo Participants)

Arm description

Vedolizumab 300 mg, 30-minute IV infusion, Q4W in this study. Treatment duration was up to approximately 260 weeks in participants with Crohn’s disease (CD) or ulcerative colitis (UC) not treated in a previous study.

Arm type

Experimental

Investigational medicinal product name

Vedolizumab

Investigational medicinal product code

Other name

Pharmaceutical forms

Solution for injection/infusion

Routes of administration

Intravenous use

Dosage and administration details

Vedolizumab Intravenous Infusion

Number of subjects in period 1	Vedolizumab 300 mg (C13006)	Vedolizumab 300 mg (C13007)	Vedolizumab 300 mg (C13011)	Vedolizumab 300 mg (C13004)	Vedolizumab 300 mg (C13008 De Novo Participants)
Started	675	726	384	37	421
Completed	237	246	115	23	145
Not completed	438	480	269	14	276
Consent withdrawn by subject	123	120	52	6	50
Adverse event, non-fatal	94	119	65	5	69
Reason Not Specified	8	16	4	1	9
Study Terminated by Sponsor	-	-	1	-	-
Lost to follow-up	13	31	10	1	15
Lack of efficacy	192	176	130	1	121
Protocol Violation(s)	8	18	7	-	12

Baseline characteristics

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Reporting group title

Vedolizumab 300 mg (C13006)

Reporting group description

Reporting group title

Vedolizumab 300 mg (C13007)

Reporting group description

Reporting group title

Vedolizumab 300 mg (C13011)

Reporting group description

Reporting group title

Vedolizumab 300 mg (C13004)

Reporting group description

Reporting group title

Vedolizumab 300 mg (C13008 De Novo Participants)

Reporting group description

Reporting group values	Vedolizumab 300 mg (C13006)	Vedolizumab 300 mg (C13007)	Vedolizumab 300 mg (C13011)	Vedolizumab 300 mg (C13004)	Vedolizumab 300 mg (C13008 De Novo Participants)	Total
Number of subjects	675	726	384	37	421	2243
Age, Customized
Units: Subjects
<65	646	710	376	35	400	2167
>=65	29	16	8	2	21	76
Age Continuous
Units: years
arithmetic mean (standard deviation)	41.2 ( 13.27 )	37.3 ( 12.26 )	38.3 ( 12.87 )	43.9 ( 14.24 )	39.3 ( 14.23 )	-
Sex: Female, Male
Units: Subjects
Female	280	384	216	20	215	1115
Male	395	342	168	17	206	1128
Race/Ethnicity, Customized
Units: Subjects
White	557	641	349	36	398	1981
Black	10	17	7	0	8	42
Native Hawaiian or Other Pacific Islander	2	0	1	0	0	3
Asian	98	66	14	0	9	187
American Indian or Alaskan Native	2	0	0	1	0	3
Other	6	2	11	0	5	24
Not Reported	0	0	2	0	1	3
Ethnicity (NIH/OMB)
Units: Subjects
Hispanic or Latino	29	12	7	0	19	67
Not Hispanic or Latino	631	700	372	36	400	2139
Unknown or Not Reported	15	14	5	1	2	37
Region of Enrollment
Units: Subjects
Australia	41	30	8	0	21	100
Hong Kong	1	2	0	0	0	3
India	39	24	0	0	0	63
Malaysia	8	6	3	0	0	17
New Zealand	9	8	1	0	8	26
Singapore	1	1	0	0	0	2
South Africa	13	15	8	0	0	36
Korea, Republic Of	34	18	7	0	0	59
Taiwan, Province Of China	1	3	0	0	0	4
Czech Republic	34	67	36	0	69	206
Greece	5	0	0	0	0	5
Hungary	12	47	22	0	17	98
Poland	53	20	9	0	0	82
Romania	0	4	0	0	0	4
Serbia	0	2	0	0	0	2
Slovakia	0	14	17	0	0	31
Bulgaria	5	6	0	0	0	11
Estonia	9	5	0	0	0	14
Israel	2	12	21	0	21	56
Latvia	0	1	0	0	0	1
Russia	46	24	0	15	0	85
Turkey	6	3	0	0	0	9
Ukraine	0	9	0	0	0	9
Canada	73	98	75	22	87	355
United States	169	166	109	0	147	591
Austria	13	9	3	0	0	25
Belgium	48	48	33	0	46	175
Denmark	2	0	0	0	0	2
France	11	25	10	0	0	46
Germany	10	25	4	0	5	44
Iceland	3	3	0	0	0	6
Ireland	1	1	0	0	0	2
Italy	12	7	4	0	0	23
Netherlands	2	5	12	0	0	19
Norway	7	5	2	0	0	14
Spain	1	4	0	0	0	5
Sweden	0	5	0	0	0	5
Switzerland	2	4	0	0	0	6
United Kingdom	2	0	0	0	0	2
Body Weight
Units: kg
arithmetic mean (standard deviation)	74.10 ( 17.934 )	71.70 ( 19.600 )	71.29 ( 18.951 )	77.66 ( 18.907 )	75.45 ( 18.814 )	-
BMI
Body Mass Index = weight (kg)/[height (m)^2]. 999999 = BMI was not calculated for de novo participants as height was not collected for these participants. BMI data was available for only 1822 participants.
Units: kg/m^2
arithmetic mean (standard deviation)	25.39 ( 5.391 )	24.61 ( 6.039 )	24.56 ( 5.783 )	27.11 ( 6.523 )	999999 ( 999999 )	-

End points

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Reporting group title

Vedolizumab 300 mg (C13006)

Reporting group description

Reporting group title

Vedolizumab 300 mg (C13007)

Reporting group description

Reporting group title

Vedolizumab 300 mg (C13011)

Reporting group description

Reporting group title

Vedolizumab 300 mg (C13004)

Reporting group description

Reporting group title

Vedolizumab 300 mg (C13008 De Novo Participants)

Reporting group description

Subject analysis set title

Vedolizumab 300 mg (UC)

Subject analysis set type

Safety analysis