Study of Vedolizumab in Patients With Moderate to Severe Crohn's Disease (GEMINI III)

• Sponsor: Millennium Pharmaceuticals, Inc.
• Information provided by (Responsible Party): Millennium Pharmaceuticals, Inc.

Study Type	Interventional
Study Design	Allocation: Randomized; Intervention Model: Parallel Assignment; Masking: Triple (Participant, Care Provider, Investigator); Primary Purpose: Treatment
Condition	Crohn's Disease
Interventions	Drug: vedolizumab; Other: Placebo
Enrollment	416

Participant Flow

Recruitment Details	Participants with moderately to severely active Crohn's Disease took part in the study at 107 sites worldwide from 24 November 2010 to 12 April 2012. Approximately 75% of participants were to have previously failed tumor necrosis factor alpha (TNFα) antagonist therapy and approximately 25% were to have been naïve to TNFα antagonist therapy.
Pre-assignment Details	Participants were randomized 1:1 to receive either 300 mg vedolizumab or placebo. Randomization to treatment assignment was stratified by the presence or absence of previous failure of TNFα antagonist therapy or naïve to TNFα antagonist therapy, concomitant use of oral corticosteroids and concomitant use of immunomodulators.

Arm/Group Title	Placebo	Vedolizumab
Arm/Group Description	Participants received placebo intravenous infusion at Weeks 0, 2 and 6.	Participants received 300 mg intravenous vedolizumab at Weeks 0, 2, and 6.
Period Title: Overall Study
Started	207	209
TNFα Antagonist Failure Population	157 [1]	158 [1]
Completed	192 [2]	196 [2]
Not Completed	15	13
Reason Not Completed
Adverse Event	8	4
Protocol Violation	0	1
Lack of Efficacy	5	1
Withdrawal of Consent	2	4
Lost to Follow-up	0	3
[1] Previously failed (inadequate response, loss of response, or intolerance) TNFα antagonist therapy; [2] Completed study is defined as patients who completed the Week 10 assessments.

Baseline Characteristics

Arm/Group Title		Placebo	Vedolizumab	Total
Arm/Group Description		Participants received placebo intravenous infusion at Weeks 0, 2 and 6.	Participants received 300 mg intravenous vedolizumab at Weeks 0, 2, and 6.	Total of all reporting groups
Overall Number of Baseline Participants		207	209	416
Baseline Analysis Population Description		The Overall Intent-to-treat (ITT) Population consisted of all randomized participants who received any amount of blinded study drug.
Age, Continuous; Mean (Standard Deviation); Unit of measure: Years
	Number Analyzed	207 participants	209 participants	416 participants
		37.1 (13.15)	38.6 (12.14)	37.9 (12.66)
Age, Customized; Measure Type: Number; Unit of measure: Participants	Number Analyzed	207 participants	209 participants	416 participants
< 35 years		105	88	193
≥ 35 years		102	121	223
Age, Customized; Measure Type: Number; Unit of measure: Participants	Number Analyzed	207 participants	209 participants	416 participants
< 65 years		202	206	408
≥ 65 years		5	3	8
Sex: Female, Male; Measure Type: Count of Participants; Unit of measure: Participants
	Number Analyzed	207 participants	209 participants	416 participants
	Female	118 57.0%	118 56.5%	236 56.7%
	Male	89 43.0%	91 43.5%	180 43.3%
Ethnicity (NIH/OMB); Measure Type: Count of Participants; Unit of measure: Participants
	Number Analyzed	207 participants	209 participants	416 participants
	Hispanic or Latino	4 1.9%	4 1.9%	8 1.9%
	Not Hispanic or Latino	199 96.1%	204 97.6%	403 96.9%
	Unknown or Not Reported	4 1.9%	1 0.5%	5 1.2%
Race/Ethnicity, Customized; Measure Type: Number; Unit of measure: Participants	Number Analyzed	207 participants	209 participants	416 participants
White		186	188	374
Black		5	4	9
Asian		9	9	18
Other		7	6	13
Not Reported		0	2	2
Body Weight; Mean (Standard Deviation); Unit of measure: Kg
	Number Analyzed	207 participants	209 participants	416 participants
		71.3 (19.22)	69.5 (17.76)	70.4 (18.50)
Body Mass Index; Mean (Standard Deviation); Unit of measure: Kg/m^2
	Number Analyzed	207 participants	209 participants	416 participants
		24.6 (6.13)	24.0 (5.13)	24.3 (5.65)
Geographic Region; Measure Type: Number; Unit of measure: Participants	Number Analyzed	207 participants	209 participants	416 participants
North America		95	102	197
Western/Northern Europe		37	38	75
Central Europe		46	41	87
Eastern Europe		15	10	25
Asia/Australia/Africa		14	18	32
Duration of Crohn's Disease (CD); Mean (Standard Deviation); Unit of measure: Years
	Number Analyzed	207 participants	209 participants	416 participants
		10.0 (7.98)	10.6 (8.75)	10.3 (8.37)
Duration of Crohn's Disease - Categorical; Measure Type: Number; Unit of measure: Participants	Number Analyzed	207 participants	209 participants	416 participants
< 1 year		12	11	23
≥ 1 to < 3 years		25	28	53
≥ 3 to < 7 years		52	52	104
≥ 7 years		118	118	236
Baseline Disease Activity – Crohn’s Disease Activity Index (CDAI) [1]; Mean (Standard Deviation); Unit of measure: Units on a scale
	Number Analyzed	207 participants	209 participants	416 participants
		301.3 (54.97)	313.9 (53.17)	307.7 (54.38)
		[1] Measure Description: Baseline disease activity represents the baseline CDAI score. The CDAI is a numerical calculation derived from the sum of products from a list of 8 disease variables: number of liquid stools, extent of abdominal pain, general well-being, occurrence of extraintestinal symptoms, need for antidiarrheal drugs, presence of abdominal masses, hematocrit, and body weight. CDAI scores range from 0 to ~600 points with lower scores indicating disease remission and higher scores indicating disease worsening.
Baseline Disease Activity – Categorical; Measure Type: Number; Unit of measure: Participants	Number Analyzed	207 participants	209 participants	416 participants
CDAI ≤ 330		148	132	280
CDAI > 330		59	77	136
C-reactive Protein (CRP); Mean (Standard Deviation); Unit of measure: mg/L
	Number Analyzed	207 participants	209 participants	416 participants
		18.5 (21.98)	19.0 (23.17)	18.8 (22.56)
CRP - Categorical; Measure Type: Number; Unit of measure: Participants	Number Analyzed	207 participants	209 participants	416 participants
≤ 2.87 mg/L		41	46	87
> 2.87 to ≤ 5 mg/L		19	14	33
> 5 to ≤ 10 mg/L		42	48	90
> 10 mg/L		105	101	206
Fecal Calprotectin [1]; Mean (Standard Deviation); Unit of measure: μg/g
	Number Analyzed	207 participants	209 participants	416 participants
		1426.5 (2357.76)	1148.1 (1878.58)	1288.0 (2134.79)
		[1] Measure Description: Number of participants for whom baseline fecal calprotectin data were available were 206 and 204, respectively.
Fecal Calprotectin - Categorical; Measure Type: Number; Unit of measure: Participants	Number Analyzed	207 participants	209 participants	416 participants
≤ 250 μg/g		47	52	99
> 250 to ≤ 500 μg/g		35	35	70
> 500 μg/g		124	117	241
Missing		1	5	6
Disease Localization; Measure Type: Number; Unit of measure: Participants	Number Analyzed	207 participants	209 participants	416 participants
Ileum only		29	33	62
Colon only		52	48	100
Ileocolonic (both ileum and colon)		126	128	254
History of Prior Surgery for Crohn's Disease; Measure Type: Number; Unit of measure: Participants	Number Analyzed	207 participants	209 participants	416 participants
Yes		89	92	181
No		118	117	235
Smoking Status; Measure Type: Number; Unit of measure: Participants	Number Analyzed	207 participants	209 participants	416 participants
Current Smoker		58	65	123
Never Smoked		102	93	195
Former Smoker		47	51	98
History of Fistulizing Disease; Measure Type: Number; Unit of measure: Participants	Number Analyzed	207 participants	209 participants	416 participants
Yes		77	71	148
No		130	138	268
Draining Fistula at Baseline; Measure Type: Number; Unit of measure: Participants	Number Analyzed	207 participants	209 participants	416 participants
Yes		25	25	50
All Closed		0	1	1
No Fistula		182	183	365
Extraintestinal Manifestations at Baseline; Measure Type: Number; Unit of measure: Participants	Number Analyzed	207 participants	209 participants	416 participants
Yes		130	116	246
No		77	93	170

Outcome Measures

1. Primary Outcome

Title	Percentage of Participants in Clinical Remission in the Tumor Necrosis Factor Alpha (TNFα) Antagonist Failure Subpopulation
Description	Clinical remission is defined as a Crohn’s Disease Activity Index (CDAI) score ≤ 150 points. The CDAI is used to quantify the symptoms of patients with Crohn's disease and consists of eight factors, each summed after adjustment with a weighting factor. The components of the CDAI are: Number of liquid or soft stools each day for 7 days;; Abdominal pain (graded from 0-3 on severity) each day for 7 days;; General well-being, subjectively assessed from 0 (well) to 4 (terrible) each day for 7 days;; Presence of complications;; Taking Lomotil or opiates for diarrhea;; Presence of an abdominal mass (0 as none, 2 as questionable, 5 as definite);; Hematocrit of < 0.47 in men and < 0.42 in women;; Percentage deviation from standard weight. The total score ranges from 0 to approximately 600 and with higher scores indicating greater disease activity. All participants who prematurely discontinued for any reason were considered as not achieving clinical remission.
Time Frame	Week 6

Outcome Measure Data

Analysis Population Description

TNFα Antagonist Failure Intent-to-treat (ITT) subpopulation which consisted of all randomized participants who received any amount of blinded study drug who met the TNFα antagonist failure criterion.

Arm/Group Title	Placebo	Vedolizumab
Arm/Group Description:	Participants received placebo intravenous infusion at Weeks 0, 2 and 6.	Participants received 300 mg intravenous vedolizumab at Weeks 0, 2, and 6.
Overall Number of Participants Analyzed	157	158
Measure Type: Number; Number (95% Confidence Interval); Unit of Measure: percentage of participants
	12.1; (7.0 to 17.2)	15.2; (9.6 to 20.8)

Statistical Analysis 1

Statistical Analysis Overview	Comparison Group Selection	Placebo, Vedolizumab
	Comments	Clinical remission was tested using the Cochran-Mantel-Haenszel (CMH) chi-square test at a 5% significance level with stratification according to concomitant use of oral corticosteroids and concomitant use of immunomodulators (6-mercaptopurine [6-MP], azathioprine, or methotrexate) for the TNFα antagonist failure subpopulation.
	Type of Statistical Test	Superiority or Other
	Comments	[Not Specified]
Statistical Test of Hypothesis	P-Value	0.4332
	Comments	[Not Specified]
	Method	Cochran-Mantel-Haenszel
	Comments	[Not Specified]
Method of Estimation	Estimation Parameter	Risk Difference (RD)
	Estimated Value	3.0
	Confidence Interval	(2-Sided) 95%; -4.5 to 10.5
	Estimation Comments	Risk Difference = adjusted (for stratification factors) percent vedolizumab - adjusted percent placebo

2. Secondary Outcome

Title	Percentage of Participants in Clinical Remission at Week 6 in the Overall Population
Description	Clinical remission is defined as a Crohn's Disease Activity Index (CDAI) score ≤ 150 points. The CDAI is used to quantify the symptoms of patients with Crohn's disease and consists of eight factors, each summed after adjustment with a weighting factor. The components of the CDAI are: Number of liquid or soft stools each day for 7 days;; Abdominal pain (graded from 0-3 on severity) each day for 7 days;; General well-being, subjectively assessed from 0 (well) to 4 (terrible) each day for 7 days;; Presence of complications;; Taking Lomotil or opiates for diarrhea;; Presence of an abdominal mass (0 as none, 2 as questionable, 5 as definite);; Hematocrit of < 0.47 in men and < 0.42 in women;; Percentage deviation from standard weight. The total score ranges from 0 to approximately 600 and with higher scores indicating greater disease activity. All participants who prematurely discontinued for any reason were considered as not achieving clinical remission.
Time Frame	Week 6

Outcome Measure Data

Analysis Population Description

Overall ITT population, consisting of all randomized participants who received any amount of blinded study drug.

Arm/Group Title	Placebo	Vedolizumab
Arm/Group Description:	Participants received placebo intravenous infusion at Weeks 0, 2 and 6.	Participants received 300 mg intravenous vedolizumab at Weeks 0, 2, and 6.
Overall Number of Participants Analyzed	207	209
Measure Type: Number; Number (95% Confidence Interval); Unit of Measure: percentage of participants
	12.1; (7.6 to 16.5)	19.1; (13.8 to 24.5)

3. Secondary Outcome

Title	Percentage of Participants in Clinical Remission at Week 10 in the TNFα Antagonist Failure Subpopulation
Description	Clinical remission is defined as a Crohn’s Disease Activity Index (CDAI) score ≤ 150 points. The CDAI is used to quantify the symptoms of patients with Crohn's disease and consists of eight factors, each summed after adjustment with a weighting factor. The components of the CDAI are: Number of liquid or soft stools each day for 7 days;; Abdominal pain (graded from 0-3 on severity) each day for 7 days;; General well-being, subjectively assessed from 0 (well) to 4 (terrible) each day for 7 days;; Presence of complications;; Taking Lomotil or opiates for diarrhea;; Presence of an abdominal mass (0 as none, 2 as questionable, 5 as definite);; Hematocrit of < 0.47 in men and < 0.42 in women;; Percentage deviation from standard weight. The total score ranges from 0 to approximately 600 and with higher scores indicating greater disease activity. All participants who prematurely discontinued for any reason were considered as not achieving clinical remission.
Time Frame	Week 10

Outcome Measure Data

Analysis Population Description

TNFα Antagonist Failure Intent-to-treat (ITT) Subpopulation

Arm/Group Title	Placebo	Vedolizumab
Arm/Group Description:	Participants received placebo intravenous infusion at Weeks 0, 2 and 6.	Participants received 300 mg intravenous vedolizumab at Weeks 0, 2, and 6.
Overall Number of Participants Analyzed	157	158
Measure Type: Number; Number (95% Confidence Interval); Unit of Measure: percentage of participants
	12.1; (7.0 to 17.2)	26.6; (19.7 to 33.5)

4. Secondary Outcome

Title	Percentage of Participants in Clinical Remission at Week 10 in the Overall Population
Description	Clinical remission is defined as a Crohn's Disease Activity Index (CDAI) score ≤ 150 points. The CDAI is used to quantify the symptoms of patients with Crohn's disease and consists of eight factors, each summed after adjustment with a weighting factor. The components of the CDAI are: Number of liquid or soft stools each day for 7 days;; Abdominal pain (graded from 0-3 on severity) each day for 7 days;; General well-being, subjectively assessed from 0 (well) to 4 (terrible) each day for 7 days;; Presence of complications;; Taking Lomotil or opiates for diarrhea;; Presence of an abdominal mass (0 as none, 2 as questionable, 5 as definite);; Hematocrit of < 0.47 in men and < 0.42 in women;; Percentage deviation from standard weight. The total score ranges from 0 to approximately 600 and with higher scores indicating greater disease activity. All participants who prematurely discontinued for any reason were considered as not achieving clinical remission.
Time Frame	Week 10

Outcome Measure Data

Analysis Population Description

Overall ITT population

Arm/Group Title	Placebo	Vedolizumab
Arm/Group Description:	Participants received placebo intravenous infusion at Weeks 0, 2 and 6.	Participants received 300 mg intravenous vedolizumab at Weeks 0, 2, and 6.
Overall Number of Participants Analyzed	207	209
Measure Type: Number; Number (95% Confidence Interval); Unit of Measure: percentage of participants
	13.0; (8.5 to 17.6)	28.7; (22.6 to 34.8)

5. Secondary Outcome

Title	Percentage of Participants With Sustained Clinical Remission in the TNFα Antagonist Failure Population
Description	Sustained clinical remission is defined as a CDAI score ≤ 150 points at both Week 6 and Week 10. The CDAI is used to quantify the symptoms of patients with Crohn's disease and consists of eight factors, each summed after adjustment with a weighting factor. The components of the CDAI are: Number of liquid or soft stools each day for 7 days;; Abdominal pain (graded from 0-3 on severity) each day for 7 days;; General well-being, subjectively assessed from 0 (well) to 4 (terrible) each day for 7 days;; Presence of complications;; Taking Lomotil or opiates for diarrhea;; Presence of an abdominal mass (0 as none, 2 as questionable, 5 as definite);; Hematocrit of < 0.47 in men and < 0.42 in women;; Percentage deviation from standard weight. The total score ranges from 0 to approximately 600 and with higher scores indicating greater disease activity. All participants who prematurely discontinued for any reason were considered as not achieving sustained clinical remission.
Time Frame	Week 6 and Week 10

Outcome Measure Data

Analysis Population Description

TNFα Antagonist Failure ITT Subpopulation

Arm/Group Title	Placebo	Vedolizumab
Arm/Group Description:	Participants received placebo intravenous infusion at Weeks 0, 2 and 6.	Participants received 300 mg intravenous vedolizumab at Weeks 0, 2, and 6.
Overall Number of Participants Analyzed	157	158
Measure Type: Number; Number (95% Confidence Interval); Unit of Measure: percentage of participants
	8.3; (4.0 to 12.6)	12.0; (7.0 to 17.1)

6. Secondary Outcome

Title	Percentage of Participants With Sustained Clinical Remission in the Overall Population
Description	Sustained clinical remission is defined as a CDAI score ≤ 150 points at both Week 6 and Week 10. The CDAI is used to quantify the symptoms of patients with Crohn's disease and consists of eight factors, each summed after adjustment with a weighting factor. The components of the CDAI are: Number of liquid or soft stools each day for 7 days;; Abdominal pain (graded from 0-3 on severity) each day for 7 days;; General well-being, subjectively assessed from 0 (well) to 4 (terrible) each day for 7 days;; Presence of complications;; Taking Lomotil or opiates for diarrhea;; Presence of an abdominal mass (0 as none, 2 as questionable, 5 as definite);; Hematocrit of < 0.47 in men and < 0.42 in women;; Percentage deviation from standard weight. The total score ranges from 0 to approximately 600 and with higher scores indicating greater disease activity. All participants who prematurely discontinued for any reason were considered as not achieving sustained clinical remission.
Time Frame	Week 6 and Week 10

Outcome Measure Data

Analysis Population Description

Overall ITT population

Arm/Group Title	Placebo	Vedolizumab
Arm/Group Description:	Participants received placebo intravenous infusion at Weeks 0, 2 and 6.	Participants received 300 mg intravenous vedolizumab at Weeks 0, 2, and 6.
Overall Number of Participants Analyzed	207	209
Measure Type: Number; Number (95% Confidence Interval); Unit of Measure: percentage of participants
	8.2; (4.5 to 12.0)	15.3; (10.4 to 20.2)

7. Secondary Outcome

Title	Percentage of Participants With Enhanced Clinical Response at Week 6 in the TNFα Antagonist Failure Subpopulation
Description	Enhanced clinical response is defined as a ≥ 100-point decrease in CDAI score from Baseline. The CDAI is used to quantify the symptoms of patients with Crohn's disease and consists of eight factors, each summed after adjustment with a weighting factor. The components of the CDAI are: Number of liquid or soft stools each day for 7 days;; Abdominal pain (graded from 0-3 on severity) each day for 7 days;; General well-being, subjectively assessed from 0 (well) to 4 (terrible) each day for 7 days;; Presence of complications;; Taking Lomotil or opiates for diarrhea;; Presence of an abdominal mass (0 as none, 2 as questionable, 5 as definite);; Hematocrit of < 0.47 in men and < 0.42 in women;; Percent deviation from standard weight. The total score ranges from 0 to approximately 600 and with higher scores indicating greater disease activity. All participants who prematurely discontinued for any reason were considered as not achieving enhanced clinical response.
Time Frame	Baseline and Week 6

Outcome Measure Data

Analysis Population Description

TNFα Antagonist Failure ITT Subpopulation

Arm/Group Title	Placebo	Vedolizumab
Arm/Group Description:	Participants received placebo intravenous infusion at Weeks 0, 2 and 6.	Participants received 300 mg intravenous vedolizumab at Weeks 0, 2, and 6.
Overall Number of Participants Analyzed	157	158
Measure Type: Number; Number (95% Confidence Interval); Unit of Measure: percentage of participants
	22.3; (15.8 to 28.8)	39.2; (31.6 to 46.9)

8. Secondary Outcome

Title	Number of Participants With Adverse Events (AEs)
Description	An AE was defined as any untoward medical occurrence in a patient administered a pharmaceutical product, which did not necessarily have a causal relationship with the treatment. A serious adverse event (SAE) was any AE, occurring at any dose and regardless of causality that resulted in death, was life-threatening, required inpatient hospitalization or prolongation of existing hospitalization, resulted in persistent or significant disability/incapacity, was a congenital anomaly/birth defect, was an important medical event based upon appropriate medical judgment that may have jeopardized the patient and may have required medical or surgical intervention to prevent 1 of the outcomes listed above, or any diagnosis of progressive multifocal leukoencephalopathy (PML). Relationship to study drug administration was determined by the investigator responding yes or no to the question: Is there a reasonable possibility that the AE is associated with the study drug?
Time Frame	From the date of first study drug administration to Week 22, through the 14 March 2012 database lock date. At the time of this database lock, 7 patients had completed Week 10 or early termination assessments but not Week 22 assessments.

Outcome Measure Data

Analysis Population Description

Overall Safety Population

Arm/Group Title	Placebo	Vedolizumab
Arm/Group Description:	Participants received placebo intravenous infusion at Weeks 0, 2 and 6.	Participants received 300 mg intravenous vedolizumab at Weeks 0, 2, and 6.
Overall Number of Participants Analyzed	207	209
Measure Type: Number; Unit of Measure: participants
Any adverse event	124	117
Drug-related adverse event	34	34
Adverse event resulting in study discontinuation	8	4
Serious adverse event	16	13
Serious infection adverse event	0	2
Drug-related serious adverse event	1	1
Serious adverse event resulting in discontinuation	5	4
Death	0	0

Adverse Events

Time Frame	From the date of first study drug administration to Week 22, through the 14 March 2012 database lock date. At the time of this database lock, 7 patients had completed Week 10 or early termination assessments but not Week 22 assessments.
Adverse Event Reporting Description	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.
Arm/Group Title	Placebo	Vedolizumab
Arm/Group Description	Participants received placebo intravenous infusion at Weeks 0, 2 and 6.	Participants received 300 mg intravenous vedolizumab at Weeks 0, 2, and 6.
All-Cause Mortality
	Placebo	Vedolizumab
	Affected / at Risk (%)	Affected / at Risk (%)
Total	--/--	--/--
Serious Adverse Events
	Placebo	Vedolizumab
	Affected / at Risk (%)	Affected / at Risk (%)
Total	16/207 (7.73%)	13/209 (6.22%)
Blood and lymphatic system disorders
Anaemia † 1	0/207 (0.00%)	1/209 (0.48%)
Gastrointestinal disorders
Crohn’s disease † 1	11/207 (5.31%)	2/209 (0.96%)
Abdominal pain † 1	1/207 (0.48%)	1/209 (0.48%)
Pancreatitis † 1	0/207 (0.00%)	1/209 (0.48%)
Small intestinal obstruction † 1	0/207 (0.00%)	1/209 (0.48%)
Gastric ulcer † 1	0/207 (0.00%)	1/209 (0.48%)
Gastritis † 1	0/207 (0.00%)	1/209 (0.48%)
General disorders
General physical health deterioration † 1	1/207 (0.48%)	0/209 (0.00%)
Hepatobiliary disorders
Cholecystitis acute † 1	0/207 (0.00%)	1/209 (0.48%)
Infections and infestations
Anal abscess † 1	0/207 (0.00%)	1/209 (0.48%)
Urinary tract infection † 1	0/207 (0.00%)	1/209 (0.48%)
Metabolism and nutrition disorders
Hypokalaemia † 1	0/207 (0.00%)	1/209 (0.48%)
Dehydration † 1	1/207 (0.48%)	0/209 (0.00%)
Musculoskeletal and connective tissue disorders
Joint effusion † 1	0/207 (0.00%)	1/209 (0.48%)
Polyarthritis † 1	1/207 (0.48%)	0/209 (0.00%)
Neoplasms benign, malignant and unspecified (incl cysts and polyps)
Ependymoma † 1	0/207 (0.00%)	1/209 (0.48%)
Nervous system disorders
Demyelination † 1	1/207 (0.48%)	0/209 (0.00%)
Skin and subcutaneous tissue disorders
Urticaria † 1	1/207 (0.48%)	0/209 (0.00%)
† Indicates events were collected by systematic assessment; 1 Term from vocabulary, MedDRA (14.0)
Other (Not Including Serious) Adverse Events
Frequency Threshold for Reporting Other Adverse Events	5%
	Placebo	Vedolizumab
	Affected / at Risk (%)	Affected / at Risk (%)
Total	29/207 (14.01%)	25/209 (11.96%)
Gastrointestinal disorders
Nausea † 1	5/207 (2.42%)	12/209 (5.74%)
General disorders
Pyrexia † 1	13/207 (6.28%)	7/209 (3.35%)
Nervous system disorders
Headache † 1	15/207 (7.25%)	11/209 (5.26%)
† Indicates events were collected by systematic assessment; 1 Term from vocabulary, MedDRA (14.0)

Limitations and Caveats

[Not Specified]

More Information

Certain Agreements

Principal Investigators are NOT employed by the organization sponsoring the study.

There IS an agreement between Principal Investigators and the Sponsor (or its agents) that restricts the PI's rights to discuss or publish trial results after the trial is completed.

The first study related publication will be a multi-center publication submitted within 24 months after conclusion or termination of a study at all sites. After such multi site publication, all proposed site publications and presentations will be submitted to sponsor for review 60 days in advance of publication. Site will remove Sponsor confidential information unrelated to study results. Sponsor can delay a proposed publication for another 60 days to preserve intellectual property.

Results Point of Contact

Name/Title: Medical Director

Organization: Millennium Pharmaceuticals Inc.

Phone: 800-778-2860

EMail: clinicaltrialregistry@tpna.com

Publications automatically indexed to this study by ClinicalTrials.gov Identifier (NCT Number):

Feagan BG, Sandborn WJ, Colombel JF, Byrne SO, Khalid JM, Kempf C, Geransar P, Bhayat F, Rubin DT. Incidence of Arthritis/Arthralgia in Inflammatory Bowel Disease with Long-term Vedolizumab Treatment: Post Hoc Analyses of the GEMINI Trials. J Crohns Colitis. 2019 Jan 1;13(1):50-57. doi: 10.1093/ecco-jcc/jjy125.

Feagan BG, Lasch K, Lissoos T, Cao C, Wojtowicz AM, Khalid JM, Colombel JF. Rapid Response to Vedolizumab Therapy in Biologic-Naive Patients With Inflammatory Bowel Diseases. Clin Gastroenterol Hepatol. 2019 Jan;17(1):130-138.e7. doi: 10.1016/j.cgh.2018.05.026. Epub 2018 May 29.

Colombel JF, Sands BE, Rutgeerts P, Sandborn W, Danese S, D'Haens G, Panaccione R, Loftus EV Jr, Sankoh S, Fox I, Parikh A, Milch C, Abhyankar B, Feagan BG. The safety of vedolizumab for ulcerative colitis and Crohn's disease. Gut. 2017 May;66(5):839-851. doi: 10.1136/gutjnl-2015-311079. Epub 2016 Feb 18.

Rosario M, Dirks NL, Gastonguay MR, Fasanmade AA, Wyant T, Parikh A, Sandborn WJ, Feagan BG, Reinisch W, Fox I. Population pharmacokinetics-pharmacodynamics of vedolizumab in patients with ulcerative colitis and Crohn's disease. Aliment Pharmacol Ther. 2015 Jul;42(2):188-202. doi: 10.1111/apt.13243. Epub 2015 May 20. Erratum in: Aliment Pharmacol Ther. 2015 Nov;42(9):1135.

Sands BE, Feagan BG, Rutgeerts P, Colombel JF, Sandborn WJ, Sy R, D'Haens G, Ben-Horin S, Xu J, Rosario M, Fox I, Parikh A, Milch C, Hanauer S. Effects of vedolizumab induction therapy for patients with Crohn's disease in whom tumor necrosis factor antagonist treatment failed. Gastroenterology. 2014 Sep;147(3):618-627.e3. doi: 10.1053/j.gastro.2014.05.008. Epub 2014 May 21.

Responsible Party:	Millennium Pharmaceuticals, Inc.
ClinicalTrials.gov Identifier:	NCT01224171 History of Changes
Other Study ID Numbers:	C13011; U1111-1158-2581 ( Registry Identifier: WHO ); 2009-016488-12 ( EudraCT Number ); NL34356.078.10 ( Registry Identifier: CCMO )
First Submitted:	October 18, 2010
First Posted:	October 19, 2010
Results First Submitted:	June 19, 2014
Results First Posted:	July 21, 2014
Last Update Posted:	July 21, 2014