Study of Vedolizumab (MLN0002) in Patients With Moderate to Severe Ulcerative Colitis (GEMINI I)

• ClinicalTrials.gov Identifier: NCT00783718
• Recruitment Status: Completed
• First Posted: November 2, 2008
• Results First Posted: July 18, 2014
• Last Update Posted: July 18, 2014
• 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: Ulcerative Colitis
• Interventions: Drug: vedolizumab; Other: Placebo
• Enrollment: 895

Participant Flow

Recruitment Details	Participants took part in the study at 211 investigative sites worldwide. The Induction Phase contained 2 cohorts. The eligibility criteria for both cohorts were identical. The purpose of Cohort 2 was to provide enough responders to power the Maintenance Phase primary efficacy analysis.
Pre-assignment Details	In Cohort 1, eligible patients who met entry criteria were randomized to treatment with double-blind vedolizumab 300 mg or placebo in a 3:2 ratio. All Cohort 2 patients were treated with open-label vedolizumab. In the Maintenance Phase participants were assigned to treatment groups based on their Induction Phase treatment and response to therapy.

Arm/Group Title	Placebo	Induction Phase: DB Vedolizumab	Induction Phase: OL Vedolizumab	Maintenance Phase: Placebo	Maintenance Phase: Vedolizumab Q8W	Maintenance Phase: Vedolizumab Q4W	Maintenance Phase: Non-responders
Arm/Group Description	In the Induction Phase participants in Cohort 1 were randomized to receive double-blind placebo intravenous infusions at Week 0 and Week 2. Participants continued to receive placebo every 4 weeks from Week 6 through Week 50 during the Maintenance Phase, regardless of treatment response during induction.	In the Induction Phase participants in Cohort 1 were randomized to receive double-blind (DB) vedolizumab 300 mg, administered by intravenous infusion at Week 0 and Week 2.	In the Induction Phase participants in Cohort 2 received open-label (OL) vedolizumab 300 mg, administered by intravenous infusion at Week 0 and Week 2.	Participants who received vedolizumab during the Induction Phase and demonstrated a clinical response at Week 6 were then randomized to receive double-blind treatment with placebo every 4 weeks up to Week 50 during the Maintenance Phase.	Participants who received vedolizumab during the Induction Phase and demonstrated a clinical response at Week 6 were then randomized to receive double-blind treatment with vedolizumab 300 mg every 8 weeks (Q8W) at Weeks 6, 14, 22, 30, 38, and 46, and, to maintain blinding, placebo infusions at Weeks 10, 18, 26, 34, 42, and 50.	Participants who received vedolizumab during the Induction Phase and demonstrated a clinical response at Week 6 were then randomized to receive double-blind treatment with vedolizumab 300 mg every 4 weeks (Q4W) from Week 6 to Week 50.	Participants who received vedolizumab during the Induction Phase who did not demonstrate a clinical response at Week 6 received open-label treatment with vedolizumab 300 mg every 4 weeks from Week 6 to Week 50.
Period Title: Induction Phase
Started	149	225	521	0	0	0	0
Completed	135	218	485	0	0	0	0
Not Completed	14	7	36	0	0	0	0
Reason Not Completed
Adverse Event	4	0	7	0	0	0	0
Protocol Violation	1	1	6	0	0	0	0
Lack of Efficacy	5	2	14	0	0	0	0
Withdrawal by Subject	3	4	8	0	0	0	0
Lost to Follow-up	1	0	1	0	0	0	0
Period Title: Maintenance Phase
Started	135	0	0	126	122	125	330
Completed	30	0	0	48	77	84	135
Not Completed	105	0	0	78	45	41	195
Reason Not Completed
Adverse Event	12	0	0	15	7	6	16
Protocol Violation	1	0	0	0	0	0	2
Lack of Efficacy	83	0	0	61	31	33	155
Withdrawal by Subject	6	0	0	2	5	2	20
Lost to Follow-up	3	0	0	0	2	0	2

Baseline Characteristics

Arm/Group Title		Placebo	Induction Phase: DB Vedolizumab	Induction Phase: OL Vedolizumab	Total
Arm/Group Description		In the Induction Phase participants in Cohort 1 were randomized to receive double-blind placebo intravenous infusions at Week 0 and Week 2. Participants continued to receive placebo every 4 weeks from Week 6 through Week 50 during the Maintenance Phase, regardless of treatment response during induction.	In the Induction Phase participants in Cohort 1 were randomized to receive double-blind vedolizumab 300 mg, administered by intravenous infusion at Week 0 and Week 2.	In the Induction Phase participants in Cohort 2 received open-label vedolizumab 300 mg, administered by intravenous infusion at Week 0 and Week 2.	Total of all reporting groups
Overall Number of Baseline Participants		149	225	521	895
Baseline Analysis Population Description		Baseline characteristics are provided for the Induction Phase Safety Population, defined as all participants, in both Cohort 1 and Cohort 2, who received any amount of study drug in the Induction Phase (Weeks 0-6), according to the actual study drug received.
Age, Continuous; Mean (Standard Deviation); Unit of measure: Years
	Number Analyzed	149 participants	225 participants	521 participants	895 participants
		41.2 (12.50)	40.1 (13.11)	40.1 (13.27)	40.3 (13.09)
Age, Customized; Measure Type: Number; Unit of measure: Participants	Number Analyzed	149 participants	225 participants	521 participants	895 participants
< 35		53	86	214	353
≥ 35		96	139	307	542
Age, Customized; Measure Type: Number; Unit of measure: Participants	Number Analyzed	149 participants	225 participants	521 participants	895 participants
< 65		142	217	503	862
≥ 65		7	8	18	33
Sex: Female, Male; Measure Type: Count of Participants; Unit of measure: Participants
	Number Analyzed	149 participants	225 participants	521 participants	895 participants
	Female	57 38.3%	93 41.3%	220 42.2%	370 41.3%
	Male	92 61.7%	132 58.7%	301 57.8%	525 58.7%
Race/Ethnicity, Customized; Measure Type: Number; Unit of measure: Participants	Number Analyzed	149 participants	225 participants	521 participants	895 participants
White		115	183	436	734
Black		2	5	5	12
Asian		32	36	67	135
Other		0	1	13	14
Race/Ethnicity, Customized; Measure Type: Number; Unit of measure: Participants	Number Analyzed	149 participants	225 participants	521 participants	895 participants
Hispanic or Latino		5	10	31	46
Not Hispanic or Latino		140	211	481	832
Not reported		4	4	9	17
Region of Enrollment; Measure Type: Number; Unit of measure: Participants	Number Analyzed	149 participants	225 participants	521 participants	895 participants
Australia		7	17	29	53
Austria		4	3	12	19
Belgium		7	14	35	56
Bulgaria		2	1	3	6
Canada		16	14	62	92
Czech Republic		7	12	19	38
Denmark		2	7	5	14
Estonia		1	4	5	10
France		1	3	13	17
Germany		0	1	16	17
Greece		0	1	4	5
Hong Kong		0	0	1	1
Hungary		2	6	8	16
Iceland		0	1	2	3
India		18	16	24	58
Ireland		0	0	1	1
Israel		0	1	1	2
Italy		1	9	11	21
Korea, Republic of		5	10	26	41
Latvia		1	2	0	3
Malaysia		5	2	2	9
Netherlands		1	0	2	3
New Zealand		0	5	6	11
Norway		2	1	6	9
Poland		2	6	52	60
Russian Federation		9	15	25	49
Singapore		0	0	1	1
South Africa		4	5	10	19
Spain		0	0	2	2
Switzerland		2	1	3	6
Turkey		0	3	3	6
United Kingdom		2	0	4	6
United States		47	64	127	238
Body Weight [1]; Mean (Standard Deviation); Unit of measure: Kg
	Number Analyzed	149 participants	225 participants	521 participants	895 participants
		72.4 (17.65)	72.4 (17.11)	74.2 (19.32)	73.4 (18.51)
		[1] Measure Description: Body weight data only available for 148 participants in the placebo arm.
Body Mass Index (BMI) [1]; Mean (Standard Deviation); Unit of measure: Kg/m^2
	Number Analyzed	149 participants	225 participants	521 participants	895 participants
		24.6 (5.11)	24.9 (4.85)	25.3 (6.05)	25.1 (5.62)
		[1] Measure Description: BMI data only available for 148 participants in the placebo arm.
Duration of Ulcerative Colitis [1]; Mean (Standard Deviation); Unit of measure: Years
	Number Analyzed	149 participants	225 participants	521 participants	895 participants
		7.1 (7.25)	6.1 (5.08)	7.2 (6.61)	6.9 (6.39)
		[1] Measure Description: Duration of ulcerative colitis data only available for 519 participants in the Induction Phase: OL Vedolizumab arm.
Categorical Duration of Ulcerative Colitis; Measure Type: Number; Unit of measure: Participants	Number Analyzed	149 participants	225 participants	521 participants	895 participants
< 1 year		13	13	38	64
≥1 - < 3 years		44	63	121	228
≥ 3 - < 7 years		39	77	163	279
≥ 7 years		53	72	197	322
Missing		0	0	2	2
Baseline Mayo Score [1]; Mean (Standard Deviation); Unit of measure: Units on a scale
	Number Analyzed	149 participants	225 participants	521 participants	895 participants
		8.6 (1.68)	8.5 (1.78)	8.6 (1.76)	8.6 (1.75)
		[1] Measure Description: The Mayo Score is a standard assessment tool to measure ulcerative colitis disease activity in clinical trials. The index consists of 4 components: two that are patient reported (rectal bleeding and stool frequency), a global assessment by the physician, and an endoscopic subscore. Each component is scored on a scale from 0 to 3 and the complete score ranges from 1 to 12 (higher scores indicate greater disease activity).
Baseline Disease Activity; Measure Type: Number; Unit of measure: Participants	Number Analyzed	149 participants	225 participants	521 participants	895 participants
Complete Mayo score < 6		5	6	14	25
Complete Mayo score of 6 to 8 (inclusive)		70	105	249	424
Complete Mayo score of 9 to 12 (inclusive)		74	114	258	446
Baseline Fecal Calprotectin [1]; Mean (Standard Deviation); Unit of measure: μg/g
	Number Analyzed	149 participants	225 participants	521 participants	895 participants
		2369.9 (3258.82)	2552.2 (3800.36)	1442.7 (1855.61)	1868.8 (2753.28)
		[1] Measure Description: Number of participants for whom baseline fecal calprotectin data were available were 139, 213, and 505, respectively.
Categorical Baseline Fecal Calprotectin; Measure Type: Number; Unit of measure: Participants	Number Analyzed	149 participants	225 participants	521 participants	895 participants
≤ 250 μg/g		27	37	94	158
> 250 to ≤ 500 μg/g		20	20	82	122
> 500 μg/g		92	156	329	577
Missing		10	12	16	38
Disease Localization; Measure Type: Number; Unit of measure: Participants	Number Analyzed	149 participants	225 participants	521 participants	895 participants
Proctosigmoiditis		22	25	69	116
Left-sided colitis		59	92	188	339
Extensive colitis		18	25	66	109
Pancolitis		50	83	198	331
Smoking Status; Measure Type: Number; Unit of measure: Participants	Number Analyzed	149 participants	225 participants	521 participants	895 participants
Current smoker		11	12	32	55
Nonsmoker		88	145	322	555
Former smoker		50	68	167	285
History of Extraintestinal Manifestations; Measure Type: Number; Unit of measure: Participants	Number Analyzed	149 participants	225 participants	521 participants	895 participants
Yes		44	74	180	298
No		105	151	341	597

Outcome Measures

1. Primary Outcome

Title	Induction Phase: Percentage of Participants With a Clinical Response at Week 6
Description	Clinical response is defined as a reduction in complete Mayo score 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. The Mayo Score is a standard assessment tool to measure ulcerative colitis disease activity in clinical trials. The index consists of 4 components: two that are patient reported (rectal bleeding and stool frequency), a global assessment by the physician, and an endoscopic subscore. Each component is scored on a scale from 0 to 3 and the complete score ranges from 1 to 12 (higher scores indicate greater disease activity). All participants who prematurely discontinued for any reason were considered as not achieving clinical response.
Time Frame	Baseline and Week 6

Outcome Measure Data

Analysis Population Description

Induction Study Intent-to-treat (ITT) population which consisted of all randomized patients in Cohort 1 who received any amount of blinded study drug.

Arm/Group Title	Placebo	DB Vedolizumab
Arm/Group Description:	Participants in Cohort 1 received double-blind placebo intravenous infusions at Week 0 and Week 2 in the Induction Phase.	Participants in Cohort 1 received double-blind vedolizumab 300 mg, administered by intravenous infusion at Week 0 and Week 2 in the Induction Phase.
Overall Number of Participants Analyzed	149	225
Measure Type: Number; Number (95% Confidence Interval); Unit of Measure: percentage of participants
	25.5; (18.5 to 32.5)	47.1; (40.6 to 53.6)

Statistical Analysis 1

Statistical Analysis Overview	Comparison Group Selection	Placebo, DB Vedolizumab
	Comments	The primary comparison of the Induction Phase was tested using the Cochran-Mantel-Haenszel (CMH) chi-square test at a 5% significance level, with stratification according to the stratification factors (concomitant use of oral corticosteroids and previous exposure to tumor necrosis factor alpha (TNFα) antagonists or concomitant immunomodulator [6-mercaptopurine or azathioprine] use).
	Type of Statistical Test	Superiority or Other
	Comments	[Not Specified]
Statistical Test of Hypothesis	P-Value	< 0.0001
	Comments	[Not Specified]
	Method	Cochran-Mantel-Haenszel
	Comments	[Not Specified]
Method of Estimation	Estimation Parameter	Risk Difference (RD)
	Estimated Value	21.7
	Confidence Interval	(2-Sided) 95%; 11.6 to 31.7
	Estimation Comments	[Not Specified]

2. Primary Outcome

Title	Maintenance Phase: Percentage of Participants in Clinical Remission at Week 52
Description	Clinical Remission is defined as a complete Mayo score of ≤ 2 points and no individual subscore > 1 point. The Mayo Score is a standard assessment tool to measure ulcerative colitis disease activity in clinical trials. The index consists of 4 components: two that are patient reported (rectal bleeding and stool frequency), a global assessment by the physician, and an endoscopic subscore. Each component is scored on a scale from 0 to 3 and the complete score ranges from 1 to 12 (higher scores indicate greater disease activity). All participants who prematurely discontinued for any reason were considered as not achieving clinical remission.
Time Frame	Week 52

Outcome Measure Data

Analysis Population Description

Maintenance Study ITT Population, defined as all randomized participants who received vedolizumab during the Induction Phase and met the protocol definition of clinical response at Week 6, as assessed by the investigator, were randomized, and received any amount of double-blind study drug in the Maintenance Phase.

Arm/Group Title	Placebo	Vedolizumab Q8W	Vedolizumab Q4W
Arm/Group Description:	Participants who received vedolizumab during the Induction Phase and demonstrated a clinical response at Week 6 were randomized to receive double-blind treatment with placebo every 4 weeks up to Week 50 during the Maintenance Phase.	Participants who received vedolizumab during the Induction Phase and demonstrated a clinical response at Week 6 were randomized to receive double-blind treatment with vedolizumab 300 mg every 8 weeks (Q8W) from Week 6 to Week 50.	Participants who received vedolizumab during the Induction Phase and demonstrated a clinical response at Week 6 were randomized to receive double-blind treatment with vedolizumab 300 mg every 4 weeks (Q4W) from Week 6 to Week 50.
Overall Number of Participants Analyzed	126	122	125
Measure Type: Number; Number (95% Confidence Interval); Unit of Measure: percentage of participants
	15.9; (9.5 to 22.3)	41.8; (33.1 to 50.6)	44.8; (36.1 to 53.5)

Statistical Analysis 1

Statistical Analysis Overview	Comparison Group Selection	Placebo, Vedolizumab Q8W
	Comments	The Hochberg method was applied to control the overall Type I error rate at a 5% significance level. If both P-values were ≤ 0.05, both dose regimens were to be declared significant. If 1 of the P-values for the 2 dose comparisons was > 0.05, the other P-value was to be tested at the 0.025 level and declared significant only if the P-value was ≤ 0.025. If neither dose was declared significant for the primary endpoint, no further testing was to be conducted.
	Type of Statistical Test	Superiority or Other
	Comments	[Not Specified]
Statistical Test of Hypothesis	P-Value	< 0.0001
	Comments	P-value is based on the CMH chi-square test, with 3 stratification factors: concomitant use of oral corticosteroids; previous exposure to TNFα antagonists or concomitant immunomodulator use; enrollment in Cohort 1 or 2 in the Induction Phase.
	Method	Cochran-Mantel-Haenszel
	Comments	[Not Specified]
Method of Estimation	Estimation Parameter	Risk Difference (RD)
	Estimated Value	26.1
	Confidence Interval	(2-Sided) 95%; 14.9 to 37.2
	Estimation Comments	[Not Specified]

Statistical Analysis 2

Statistical Analysis Overview	Comparison Group Selection	Placebo, Vedolizumab Q4W
	Comments	The Hochberg method was applied to control the overall Type I error rate at a 5% significance level. If both P-values were ≤ 0.05, both dose regimens were to be declared significant. If 1 of the P-values for the 2 dose comparisons was > 0.05, the other P-value was to be tested at the 0.025 level and declared significant only if the P-value was ≤ 0.025. If neither dose was declared significant for the primary endpoint, no further testing was to be conducted.
	Type of Statistical Test	Superiority or Other
	Comments	[Not Specified]
Statistical Test of Hypothesis	P-Value	< 0.0001
	Comments	P-value is based on the CMH chi-square test, with 3 stratification factors: concomitant use of oral corticosteroids; previous exposure to TNFα antagonists or concomitant immunomodulator use; enrollment in Cohort 1 or 2 in the Induction Phase.
	Method	Cochran-Mantel-Haenszel
	Comments	[Not Specified]
Method of Estimation	Estimation Parameter	Risk Difference (RD)
	Estimated Value	29.1
	Confidence Interval	(2-Sided) 95%; 17.9 to 40.4
	Estimation Comments	[Not Specified]

3. Secondary Outcome

Title	Induction Phase: Percentage of Participants in Clinical Remission at Week 6
Description	Clinical Remission is defined as a complete Mayo score of ≤ 2 points and no individual subscore > 1 point. The Mayo Score is a standard assessment tool to measure ulcerative colitis disease activity in clinical trials. The index consists of 4 components: two that are patient reported (rectal bleeding and stool frequency), a global assessment by the physician, and an endoscopic subscore. Each component is scored on a scale from 0 to 3 and the complete score ranges from 1 to 12 (higher scores indicate 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

Induction Study ITT Population

Arm/Group Title	Placebo	DB Vedolizumab
Arm/Group Description:	Participants in Cohort 1 received double-blind placebo intravenous infusions at Week 0 and Week 2 in the Induction Phase.	Participants in Cohort 1 received double-blind vedolizumab 300 mg, administered by intravenous infusion at Week 0 and Week 2 in the Induction Phase.
Overall Number of Participants Analyzed	149	225
Measure Type: Number; Number (95% Confidence Interval); Unit of Measure: percentage of participants
	5.4; (1.7 to 9.0)	16.9; (12.0 to 21.8)

Statistical Analysis 1

Statistical Analysis Overview	Comparison Group Selection	Placebo, DB Vedolizumab
	Comments	To maintain the overall Type I error rate at 5%, the key secondary assessments were performed sequentially (closed sequential method). The first secondary endpoint was to be tested only if the primary comparison was significant and the second key secondary endpoint was to be tested only if the first secondary endpoint was significant for vedolizumab.
	Type of Statistical Test	Superiority or Other
	Comments	[Not Specified]
Statistical Test of Hypothesis	P-Value	0.0009
	Comments	P-value is based on the CMH chi-square test, with stratification according to: 1) concomitant use of oral corticosteroids (yes/no); and 2) previous exposure to TNFα antagonists or concomitant immunomodulator use (yes/no).
	Method	Cochran-Mantel-Haenszel
	Comments	[Not Specified]
Method of Estimation	Estimation Parameter	Risk Difference (RD)
	Estimated Value	11.5
	Confidence Interval	(2-Sided) 95%; 4.7 to 18.3
	Estimation Comments	[Not Specified]

4. Secondary Outcome

Title	Induction Phase: Percentage of Participants With Mucosal Healing at Week 6
Description	Mucosal healing is defined as a Mayo endoscopic subscore of ≤ 1 point. The Mayo Score is a standard assessment tool to measure ulcerative colitis disease activity in clinical trials. The index consists of 4 components: two that are patient reported (rectal bleeding and stool frequency), a global assessment by the physician, and an endoscopic subscore. Endoscopic findings were scored on a scale from 0 to 3 as follows: 0 = Normal or inactive disease; 1 = Mild disease (erythema, decreased vascular pattern, mild friability); 2 = Moderate disease (marked erythema, lack of vascular pattern, friability, erosions); 3 = Severe disease (spontaneous bleeding, ulceration). All participants who prematurely discontinued for any reason were considered as not achieving mucosal healing.
Time Frame	Week 6

Outcome Measure Data

Analysis Population Description

Induction Study ITT Population

Arm/Group Title	Placebo	DB Vedolizumab
Arm/Group Description:	Participants in Cohort 1 received double-blind placebo intravenous infusions at Week 0 and Week 2 in the Induction Phase.	Participants in Cohort 1 received double-blind vedolizumab 300 mg, administered by intravenous infusion at Week 0 and Week 2 in the Induction Phase.
Overall Number of Participants Analyzed	149	225
Measure Type: Number; Number (95% Confidence Interval); Unit of Measure: percentage of participants
	24.8; (17.9 to 31.8)	40.9; (34.5 to 47.3)

Statistical Analysis 1

Statistical Analysis Overview	Comparison Group Selection	Placebo, DB Vedolizumab
	Comments	To maintain the overall Type I error rate at 5%, the key secondary assessments were performed sequentially (closed sequential method). The first secondary endpoint was to be tested only if the primary comparison was significant and the second key secondary endpoint was to be tested only if the first secondary endpoint was significant for vedolizumab.
	Type of Statistical Test	Superiority or Other
	Comments	[Not Specified]
Statistical Test of Hypothesis	P-Value	0.0012
	Comments	P-value is based on the CMH chi-square test, with stratification according to: 1) concomitant use of oral corticosteroids (yes/no); and 2) previous exposure to TNFα antagonists or concomitant immunomodulator use (yes/no).
	Method	Cochran-Mantel-Haenszel
	Comments	[Not Specified]
Method of Estimation	Estimation Parameter	Risk Difference (RD)
	Estimated Value	16.1
	Confidence Interval	95%; 6.4 to 25.9
	Estimation Comments	[Not Specified]

5. Secondary Outcome

Title	Maintenance Phase: Percentage of Participants With Durable Clinical Response
Description	Durable clinical response is defined as reduction in complete Mayo score of ≥ 3 points and ≥ 30% from Baseline (Week 0) with an accompanying decrease in rectal bleeding subscore of ≥ 1 point or absolute rectal bleeding subscore of ≤ 1 point at both Weeks 6 and 52. The Mayo Score is a standard assessment tool to measure ulcerative colitis disease activity in clinical trials. The index consists of 4 components: two that are patient reported (rectal bleeding and stool frequency), a global assessment by the physician, and an endoscopic subscore. Each component is scored on a scale from 0 to 3 and the complete score ranges from 1 to 12 (higher scores indicate greater disease activity). All participants who prematurely discontinued for any reason were considered as not achieving durable clinical response.
Time Frame	Baseline, Week 6 and Week 52

Outcome Measure Data

Analysis Population Description

Maintenance Study ITT Population

Arm/Group Title	Placebo	Vedolizumab Q8W	Vedolizumab Q4W
Arm/Group Description:	Participants who received vedolizumab during the Induction Phase and demonstrated a clinical response at Week 6 were randomized to receive double-blind treatment with placebo every 4 weeks up to Week 50 during the Maintenance Phase.	Participants who received vedolizumab during the Induction Phase and demonstrated a clinical response at Week 6 were randomized to receive double-blind treatment with vedolizumab 300 mg every 8 weeks (Q8W) from Week 6 to Week 50.	Participants who received vedolizumab during the Induction Phase and demonstrated a clinical response at Week 6 were randomized to receive double-blind treatment with vedolizumab 300 mg every 4 weeks (Q4W) from Week 6 to Week 50.
Overall Number of Participants Analyzed	126	122	125
Measure Type: Number; Number (95% Confidence Interval); Unit of Measure: percentage of participants
	23.8; (16.4 to 31.2)	56.6; (47.8 to 65.4)	52.0; (43.2 to 60.8)

Statistical Analysis 1

Statistical Analysis Overview	Comparison Group Selection	Placebo, Vedolizumab Q8W
	Comments	To maintain the overall Type I error rate at 5% for the 2 dose regimen comparisons for each key secondary endpoint, the Hochberg method was used as described for the primary outcome measure. To further maintain the overall Type I error rate at 5%, the key secondary endpoints were also performed sequentially. The first was tested only if 1 or both of the primary comparisons were significant and the next endpoint was tested only if the previous endpoint was significant for at least 1 dose.
	Type of Statistical Test	Superiority or Other
	Comments	[Not Specified]
Statistical Test of Hypothesis	P-Value	< 0.0001
	Comments	P-value is based on the CMH chi-square test, with 3 stratification factors: concomitant use of oral corticosteroids; previous exposure to TNFα antagonists or concomitant immunomodulator use; enrollment in Cohort 1 or 2 in the Induction Phase.
	Method	Cochran-Mantel-Haenszel
	Comments	[Not Specified]
Method of Estimation	Estimation Parameter	Risk Difference (RD)
	Estimated Value	32.8
	Confidence Interval	(2-Sided) 95%; 20.8 to 44.7
	Estimation Comments	[Not Specified]

Statistical Analysis 2

Statistical Analysis Overview	Comparison Group Selection	Placebo, Vedolizumab Q4W
	Comments	To maintain the overall Type I error rate at 5% for the 2 dose regimen comparisons for each key secondary endpoint, the Hochberg method was used as described for the primary outcome measure. To further maintain the overall Type I error rate at 5%, the key secondary endpoints were also performed sequentially. The first was tested only if 1 or both of the primary comparisons were significant and the next endpoint was tested only if the previous endpoint was significant for at least 1 dose.
	Type of Statistical Test	Superiority or Other
	Comments	[Not Specified]
Statistical Test of Hypothesis	P-Value	< 0.0001
	Comments	P-value is based on the CMH chi-square test, with 3 stratification factors: concomitant use of oral corticosteroids; previous exposure to TNFα antagonists or concomitant immunomodulator use; enrollment in Cohort 1 or 2 in the Induction Phase.
	Method	Cochran-Mantel-Haenszel
	Comments	[Not Specified]
Method of Estimation	Estimation Parameter	Risk Difference (RD)
	Estimated Value	28.5
	Confidence Interval	(2-Sided) 95%; 16.7 to 40.3
	Estimation Comments	[Not Specified]

6. Secondary Outcome

Title	Maintenance Phase: Percentage of Participants With Mucosal Healing at Week 52
Description	Mucosal healing is defined as a Mayo endoscopic subscore of ≤ 1 point. The Mayo Score is a standard assessment tool to measure ulcerative colitis disease activity in clinical trials. The index consists of 4 components: two that are patient reported (rectal bleeding and stool frequency), a global assessment by the physician, and an endoscopic subscore. Endoscopic findings were scored on a scale from 0 to 3 as follows: 0 = Normal or inactive disease; 1 = Mild disease (erythema, decreased vascular pattern, mild friability); 2 = Moderate disease (marked erythema, lack of vascular pattern, friability, erosions); 3 = Severe disease (spontaneous bleeding, ulceration). All participants who prematurely discontinued for any reason were considered as not achieving mucosal healing.
Time Frame	Week 52

Outcome Measure Data

Analysis Population Description

Maintenance Study ITT Population

Arm/Group Title	Placebo	Vedolizumab Q8W	Vedolizumab Q4W
Arm/Group Description:	Participants who received vedolizumab during the Induction Phase and demonstrated a clinical response at Week 6 were randomized to receive double-blind treatment with placebo every 4 weeks up to Week 50 during the Maintenance Phase.	Participants who received vedolizumab during the Induction Phase and demonstrated a clinical response at Week 6 were randomized to receive double-blind treatment with vedolizumab 300 mg every 8 weeks (Q8W) from Week 6 to Week 50.	Participants who received vedolizumab during the Induction Phase and demonstrated a clinical response at Week 6 were randomized to receive double-blind treatment with vedolizumab 300 mg every 4 weeks (Q4W) from Week 6 to Week 50.
Overall Number of Participants Analyzed	126	122	125
Measure Type: Number; Number (95% Confidence Interval); Unit of Measure: percentage of participants
	19.8; (12.9 to 26.8)	51.6; (42.8 to 60.5)	56.0; (47.3 to 64.7)

Statistical Analysis 1

Statistical Analysis Overview	Comparison Group Selection	Placebo, Vedolizumab Q8W
	Comments	To maintain the overall Type I error rate at 5% for the 2 dose regimen comparisons for each key secondary endpoint, the Hochberg method was used as described for the primary outcome measure. To further maintain the overall Type I error rate at 5%, the key secondary endpoints were also performed sequentially. The first was tested only if 1 or both of the primary comparisons were significant and the next endpoint was tested only if the previous endpoint was significant for at least 1 dose.
	Type of Statistical Test	Superiority or Other
	Comments	[Not Specified]
Statistical Test of Hypothesis	P-Value	< 0.0001
	Comments	P-value is based on the CMH chi-square test, with 3 stratification factors: concomitant use of oral corticosteroids; previous exposure to TNFα antagonists or concomitant immunomodulator use; enrollment in Cohort 1 or 2 in the Induction Phase.
	Method	Cochran-Mantel-Haenszel
	Comments	[Not Specified]
Method of Estimation	Estimation Parameter	Risk Difference (RD)
	Estimated Value	32.0
	Confidence Interval	(2-Sided) 95%; 20.3 to 43.8
	Estimation Comments	[Not Specified]

Statistical Analysis 2

Statistical Analysis Overview	Comparison Group Selection	Placebo, Vedolizumab Q4W
	Comments	To maintain the overall Type I error rate at 5% for the 2 dose regimen comparisons for each key secondary endpoint, the Hochberg method was used as described for the primary outcome measure. To further maintain the overall Type I error rate at 5%, the key secondary endpoints were also performed sequentially. The first was tested only if 1 or both of the primary comparisons were significant and the next endpoint was tested only if the previous endpoint was significant for at least 1 dose.
	Type of Statistical Test	Superiority or Other
	Comments	[Not Specified]
Statistical Test of Hypothesis	P-Value	< 0.0001
	Comments	P-value is based on the CMH chi-square test, with 3 stratification factors: concomitant use of oral corticosteroids; previous exposure to TNFα antagonists or concomitant immunomodulator use; enrollment in Cohort 1 or 2 in the Induction Phase.
	Method	Cochran-Mantel-Haenszel
	Comments	[Not Specified]
Method of Estimation	Estimation Parameter	Risk Difference (RD)
	Estimated Value	36.3
	Confidence Interval	(2-Sided) 95%; 24.4 to 48.3
	Estimation Comments	[Not Specified]

7. Secondary Outcome

Title	Maintenance Phase: Percentage of Participants With Durable Clinical Remission
Description	Durable clinical remission is defined as complete Mayo score of ≤ 2 points and no individual subscore > 1 point at both Weeks 6 and 52. The Mayo Score is a standard assessment tool to measure ulcerative colitis disease activity in clinical trials. The index consists of 4 components: two that are patient reported (rectal bleeding and stool frequency), a global assessment by the physician, and an endoscopic subscore. Each component is scored on a scale from 0 to 3 and the complete score ranges from 1 to 12 (higher scores indicate greater disease activity). All participants who prematurely discontinued for any reason were considered as not achieving durable clinical remission.
Time Frame	Week 6 and Week 52

Outcome Measure Data

Analysis Population Description

Maintenance Study ITT Population

Arm/Group Title	Placebo	Vedolizumab Q8W	Vedolizumab Q4W
Arm/Group Description:	Participants who received vedolizumab during the Induction Phase and demonstrated a clinical response at Week 6 were randomized to receive double-blind treatment with placebo every 4 weeks up to Week 50 during the Maintenance Phase.	Participants who received vedolizumab during the Induction Phase and demonstrated a clinical response at Week 6 were randomized to receive double-blind treatment with vedolizumab 300 mg every 8 weeks (Q8W) from Week 6 to Week 50.	Participants who received vedolizumab during the Induction Phase and demonstrated a clinical response at Week 6 were randomized to receive double-blind treatment with vedolizumab 300 mg every 4 weeks (Q4W) from Week 6 to Week 50.
Overall Number of Participants Analyzed	126	122	125
Measure Type: Number; Number (95% Confidence Interval); Unit of Measure: percentage of participants
	8.7; (3.8 to 13.7)	20.5; (13.3 to 27.7)	24.0; (16.5 to 31.5)

Statistical Analysis 1

Statistical Analysis Overview	Comparison Group Selection	Placebo, Vedolizumab Q8W
	Comments	To maintain the overall Type I error rate at 5% for the 2 dose regimen comparisons for each key secondary endpoint, the Hochberg method was used as described for the primary outcome measure. To further maintain the overall Type I error rate at 5%, the key secondary endpoints were also performed sequentially. The first was tested only if 1 or both of the primary comparisons were significant and the next endpoint was tested only if the previous endpoint was significant for at least 1 dose.
	Type of Statistical Test	Superiority or Other
	Comments	[Not Specified]
Statistical Test of Hypothesis	P-Value	0.0079
	Comments	P-value is based on the CMH chi-square test, with 3 stratification factors: concomitant use of oral corticosteroids; previous exposure to TNFα antagonists or concomitant immunomodulator use; enrollment in Cohort 1 or 2 in the Induction Phase.
	Method	Cochran-Mantel-Haenszel
	Comments	[Not Specified]
Method of Estimation	Estimation Parameter	Risk Difference (RD)
	Estimated Value	11.8
	Confidence Interval	(2-Sided) 95%; 3.1 to 20.5
	Estimation Comments	[Not Specified]

Statistical Analysis 2

Statistical Analysis Overview	Comparison Group Selection	Placebo, Vedolizumab Q4W
	Comments	To maintain the overall Type I error rate at 5% for the 2 dose regimen comparisons for each key secondary endpoint, the Hochberg method was used as described for the primary outcome measure. To further maintain the overall Type I error rate at 5%, the key secondary endpoints were also performed sequentially. The first was tested only if 1 or both of the primary comparisons were significant and the next endpoint was tested only if the previous endpoint was significant for at least 1 dose.
	Type of Statistical Test	Superiority or Other
	Comments	[Not Specified]
Statistical Test of Hypothesis	P-Value	0.0009
	Comments	P-value is based on the CMH chi-square test, with 3 stratification factors: concomitant use of oral corticosteroids; previous exposure to TNFα antagonists or concomitant immunomodulator use; enrollment in Cohort 1 or 2 in the Induction Phase.
	Method	Cochran-Mantel-Haenszel
	Comments	[Not Specified]
Method of Estimation	Estimation Parameter	Risk Difference (RD)
	Estimated Value	15.3
	Confidence Interval	(2-Sided) 95%; 6.2 to 24.4
	Estimation Comments	[Not Specified]

8. Secondary Outcome

Title	Maintenance Phase: Percentage of Participants With Corticosteroid-free Remission at Week 52
Description	Clinical Remission is defined as a complete Mayo score of ≤ 2 points and no individual subscore > 1 point. Corticosteroid-free clinical remission is defined as participants using oral corticosteroids at baseline (Week 0) who discontinued corticosteroids and were in clinical remission at Week 52. The Mayo Score is a standard assessment tool to measure ulcerative colitis disease activity in clinical trials. The index consists of 4 components: two that are patient reported (rectal bleeding and stool frequency), a global assessment by the physician, and an endoscopic subscore. Each component is scored on a scale from 0 to 3 and the complete score ranges from 1 to 12 (higher scores indicate greater disease activity). All participants who prematurely discontinued for any reason were considered as not achieving corticosteroid-free remission.
Time Frame	Week 52

Outcome Measure Data

Analysis Population Description

Maintenance Study ITT Population, participants who were on corticosteroids at Baseline.

Arm/Group Title	Placebo	Vedolizumab Q8W	Vedolizumab Q4W
Arm/Group Description:	Participants who received vedolizumab during the Induction Phase and demonstrated a clinical response at Week 6 were randomized to receive double-blind treatment with placebo every 4 weeks up to Week 50 during the Maintenance Phase.	Participants who received vedolizumab during the Induction Phase and demonstrated a clinical response at Week 6 were randomized to receive double-blind treatment with vedolizumab 300 mg every 8 weeks (Q8W) from Week 6 to Week 50.	Participants who received vedolizumab during the Induction Phase and demonstrated a clinical response at Week 6 were randomized to receive double-blind treatment with vedolizumab 300 mg every 4 weeks (Q4W) from Week 6 to Week 50.
Overall Number of Participants Analyzed	72	70	73
Measure Type: Number; Number (95% Confidence Interval); Unit of Measure: percentage of participants
	13.9; (5.9 to 21.9)	31.4; (20.6 to 42.3)	45.2; (33.8 to 56.6)

Statistical Analysis 1

Statistical Analysis Overview	Comparison Group Selection	Placebo, Vedolizumab Q8W
	Comments	To maintain the overall Type I error rate at 5% for the 2 dose regimen comparisons for each key secondary endpoint, the Hochberg method was used as described for the primary outcome measure. To further maintain the overall Type I error rate at 5%, the key secondary endpoints were also performed sequentially. The first was tested only if 1 or both of the primary comparisons were significant and the next endpoint was tested only if the previous endpoint was significant for at least 1 dose.
	Type of Statistical Test	Superiority or Other
	Comments	[Not Specified]
Statistical Test of Hypothesis	P-Value	0.0120
	Comments	P-value based on the CMH chi-square test, with 3 stratification factors: concomitant use of oral corticosteroids; previous exposure to TNFα antagonists or concomitant immunomodulator use; enrollment in Cohort 1 or 2 in the Induction Phase.
	Method	Cochran-Mantel-Haenszel
	Comments	[Not Specified]
Method of Estimation	Estimation Parameter	Risk Difference (RD)
	Estimated Value	17.6
	Confidence Interval	(2-Sided) 95%; 3.9 to 31.3
	Estimation Comments	[Not Specified]

Statistical Analysis 2

Statistical Analysis Overview	Comparison Group Selection	Placebo, Vedolizumab Q4W
	Comments	To maintain the overall Type I error rate at 5% for the 2 dose regimen comparisons for each key secondary endpoint, the Hochberg method was used as described for the primary outcome measure. To further maintain the overall Type I error rate at 5%, the key secondary endpoints were also performed sequentially. The first was tested only if 1 or both of the primary comparisons were significant and the next endpoint was tested only if the previous endpoint was significant for at least 1 dose.
	Type of Statistical Test	Superiority or Other
	Comments	[Not Specified]
Statistical Test of Hypothesis	P-Value	< 0.0001
	Comments	P-value is based on the CMH chi-square test, with 3 stratification factors: concomitant use of oral corticosteroids; previous exposure to TNFα antagonists or concomitant immunomodulator use; enrollment in Cohort 1 or 2 in the Induction Phase.
	Method	Cochran-Mantel-Haenszel
	Comments	[Not Specified]
Method of Estimation	Estimation Parameter	Risk Difference (RD)
	Estimated Value	31.4
	Confidence Interval	(2-Sided) 95%; 16.6 to 46.2
	Estimation Comments	[Not Specified]

Adverse Events

Time Frame	From the start of the Induction Phase until a final on-study safety assessment at Week 66 (or Final Safety visit 16 weeks after the last dose).
Adverse Event Reporting Description	[Not Specified]
Arm/Group Title	Placebo	Vedolizumab Then Placebo	Vedolizumab
Arm/Group Description	Participants who received double-blind placebo intravenous infusions in the Induction Phase and continued to receive placebo during the Maintenance Phase.	Participants who received vedolizumab during the Induction Phase and were then randomized to receive placebo during the Maintenance Phase.	Participants who received vedolizumab during the Induction Phase and continued to receive vedolizumab during the Maintenance Phase. This includes participants who had a clinical response at Week 6 and were randomized to vedolizumab every 4 weeks or every 8 weeks in the Maintenance Phase, participants who did not achieve a clinical response at Week 6 and continued to receive vedolizumab every 4 weeks for the duration of the study, and participants who withdrew during the Induction phase.
All-Cause Mortality
	Placebo	Vedolizumab Then Placebo	Vedolizumab
	Affected / at Risk (%)	Affected / at Risk (%)	Affected / at Risk (%)
Total	--/--	--/--	--/--
Serious Adverse Events
	Placebo	Vedolizumab Then Placebo	Vedolizumab
	Affected / at Risk (%)	Affected / at Risk (%)	Affected / at Risk (%)
Total	17/149 (11.41%)	20/126 (15.87%)	77/620 (12.42%)
Blood and lymphatic system disorders
Anaemia † 1	1/149 (0.67%)	1/126 (0.79%)	1/620 (0.16%)
Cardiac disorders
Arteriosclerosis coronary artery † 1	0/149 (0.00%)	0/126 (0.00%)	1/620 (0.16%)
Atrial fibrillation † 1	0/149 (0.00%)	0/126 (0.00%)	1/620 (0.16%)
Aortic valve stenosis † 1	0/149 (0.00%)	1/126 (0.79%)	0/620 (0.00%)
Ear and labyrinth disorders
Vertigo positional † 1	0/149 (0.00%)	0/126 (0.00%)	1/620 (0.16%)
Gastrointestinal disorders
Colitis ulcerative † 1	10/149 (6.71%)	7/126 (5.56%)	47/620 (7.58%)
Abdominal pain † 1	1/149 (0.67%)	0/126 (0.00%)	2/620 (0.32%)
Small intestinal obstruction † 1	1/149 (0.67%)	0/126 (0.00%)	1/620 (0.16%)
Abdominal pain upper † 1	0/149 (0.00%)	0/126 (0.00%)	1/620 (0.16%)
Ileus † 1	0/149 (0.00%)	0/126 (0.00%)	1/620 (0.16%)
Nausea † 1	0/149 (0.00%)	0/126 (0.00%)	1/620 (0.16%)
Peritoneal haemorrhage † 1	0/149 (0.00%)	0/126 (0.00%)	1/620 (0.16%)
Subileus † 1	0/149 (0.00%)	0/126 (0.00%)	1/620 (0.16%)
Upper gastrointestinal haemorrhage † 1	0/149 (0.00%)	0/126 (0.00%)	1/620 (0.16%)
Colon dysplasia † 1	0/149 (0.00%)	1/126 (0.79%)	0/620 (0.00%)
Pancreatitis acute † 1	1/149 (0.67%)	0/126 (0.00%)	0/620 (0.00%)
Rectal haemorrhage † 1	0/149 (0.00%)	1/126 (0.79%)	0/620 (0.00%)
General disorders
Fatigue † 1	0/149 (0.00%)	0/126 (0.00%)	1/620 (0.16%)
Multi-organ failure † 1	0/149 (0.00%)	0/126 (0.00%)	1/620 (0.16%)
Pyrexia † 1	0/149 (0.00%)	1/126 (0.79%)	0/620 (0.00%)
Hepatobiliary disorders
Bile duct stone † 1	0/149 (0.00%)	0/126 (0.00%)	1/620 (0.16%)
Cholangitis sclerosing † 1	0/149 (0.00%)	0/126 (0.00%)	1/620 (0.16%)
Hepatitis acute † 1	0/149 (0.00%)	0/126 (0.00%)	1/620 (0.16%)
Immune system disorders
Sarcoidosis † 1	1/149 (0.67%)	0/126 (0.00%)	0/620 (0.00%)
Infections and infestations
Anal abscess † 1	0/149 (0.00%)	0/126 (0.00%)	2/620 (0.32%)
Wound infection † 1	0/149 (0.00%)	0/126 (0.00%)	2/620 (0.32%)
Perirectal abscess † 1	1/149 (0.67%)	0/126 (0.00%)	1/620 (0.16%)
Sepsis † 1	1/149 (0.67%)	0/126 (0.00%)	1/620 (0.16%)
Urinary tract infection † 1	1/149 (0.67%)	0/126 (0.00%)	1/620 (0.16%)
Bronchitis † 1	0/149 (0.00%)	0/126 (0.00%)	1/620 (0.16%)
Cellulitis † 1	0/149 (0.00%)	0/126 (0.00%)	1/620 (0.16%)
Cholangitis suppurative † 1	0/149 (0.00%)	0/126 (0.00%)	1/620 (0.16%)
Klebsiella infection † 1	0/149 (0.00%)	0/126 (0.00%)	1/620 (0.16%)
Lower respiratory tract infection † 1	0/149 (0.00%)	0/126 (0.00%)	1/620 (0.16%)
Pulpitis dental † 1	0/149 (0.00%)	0/126 (0.00%)	1/620 (0.16%)
Tonsillitis † 1	0/149 (0.00%)	0/126 (0.00%)	1/620 (0.16%)
Appendicitis † 1	0/149 (0.00%)	2/126 (1.59%)	0/620 (0.00%)
Infection † 1	0/149 (0.00%)	1/126 (0.79%)	0/620 (0.00%)
Pelvic abscess † 1	1/149 (0.67%)	0/126 (0.00%)	0/620 (0.00%)
Pericoronitis † 1	1/149 (0.67%)	0/126 (0.00%)	0/620 (0.00%)
Pneumonia † 1	0/149 (0.00%)	1/126 (0.79%)	0/620 (0.00%)
Injury, poisoning and procedural complications
Accidental poisoning † 1	0/149 (0.00%)	0/126 (0.00%)	1/620 (0.16%)
Fall † 1	0/149 (0.00%)	0/126 (0.00%)	1/620 (0.16%)
Fibula fracture † 1	0/149 (0.00%)	0/126 (0.00%)	1/620 (0.16%)
Gastrointestinal stoma complication † 1	0/149 (0.00%)	0/126 (0.00%)	1/620 (0.16%)
Wrist fracture † 1	0/149 (0.00%)	0/126 (0.00%)	1/620 (0.16%)
Concussion † 1	0/149 (0.00%)	1/126 (0.79%)	0/620 (0.00%)
Pubis fracture † 1	0/149 (0.00%)	1/126 (0.79%)	0/620 (0.00%)
Investigations
Haemoglobin decrease † 1	0/149 (0.00%)	1/126 (0.79%)	1/620 (0.16%)
Lipase increased † 1	1/149 (0.67%)	0/126 (0.00%)	0/620 (0.00%)
Weight decreased † 1	0/149 (0.00%)	1/126 (0.79%)	0/620 (0.00%)
Metabolism and nutrition disorders
Dehydration † 1	1/149 (0.67%)	0/126 (0.00%)	2/620 (0.32%)
Musculoskeletal and connective tissue disorders
Osteoporosis † 1	0/149 (0.00%)	1/126 (0.79%)	0/620 (0.00%)
Neoplasms benign, malignant and unspecified (incl cysts and polyps)
Colon cancer † 1	0/149 (0.00%)	1/126 (0.79%)	1/620 (0.16%)
Transitional cell carcinoma † 1	0/149 (0.00%)	1/126 (0.79%)	0/620 (0.00%)
Nervous system disorders
Syncope † 1	0/149 (0.00%)	0/126 (0.00%)	1/620 (0.16%)
Pregnancy, puerperium and perinatal conditions
Abortion spontaneous † 1	0/149 (0.00%)	0/126 (0.00%)	1/620 (0.16%)
Renal and urinary disorders
Renal failure † 1	0/149 (0.00%)	0/126 (0.00%)	1/620 (0.16%)
Tubulointerstitial nephritis † 1	0/149 (0.00%)	0/126 (0.00%)	1/620 (0.16%)
Reproductive system and breast disorders
Menorrhagia † 1	0/149 (0.00%)	0/126 (0.00%)	1/620 (0.16%)
Benign prostatic hyperplasia † 1	0/149 (0.00%)	1/126 (0.79%)	0/620 (0.00%)
Respiratory, thoracic and mediastinal disorders
Pulmonary embolism † 1	1/149 (0.67%)	0/126 (0.00%)	2/620 (0.32%)
Pneumothorax † 1	0/149 (0.00%)	0/126 (0.00%)	1/620 (0.16%)
Pleural effusion † 1	0/149 (0.00%)	1/126 (0.79%)	0/620 (0.00%)
Skin and subcutaneous tissue disorders
Pemphigoid † 1	0/149 (0.00%)	0/126 (0.00%)	1/620 (0.16%)
Rash † 1	0/149 (0.00%)	0/126 (0.00%)	1/620 (0.16%)
Vascular disorders
Deep vein thrombosis † 1	0/149 (0.00%)	0/126 (0.00%)	1/620 (0.16%)
Arteriosclerosis obliterans † 1	1/149 (0.67%)	0/126 (0.00%)	0/620 (0.00%)
Venous thrombosis † 1	0/149 (0.00%)	1/126 (0.79%)	0/620 (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 Then Placebo	Vedolizumab
	Affected / at Risk (%)	Affected / at Risk (%)	Affected / at Risk (%)
Total	67/149 (44.97%)	69/126 (54.76%)	321/620 (51.77%)
Blood and lymphatic system disorders
Anaemia † 1	10/149 (6.71%)	4/126 (3.17%)	35/620 (5.65%)
Gastrointestinal disorders
Colitis ulcerative † 1	20/149 (13.42%)	22/126 (17.46%)	57/620 (9.19%)
Nausea † 1	11/149 (7.38%)	8/126 (6.35%)	38/620 (6.13%)
Abdominal pain † 1	7/149 (4.70%)	2/126 (1.59%)	34/620 (5.48%)
General disorders
Fatigue † 1	5/149 (3.36%)	5/126 (3.97%)	32/620 (5.16%)
Infections and infestations
Nasopharyngitis † 1	11/149 (7.38%)	15/126 (11.90%)	80/620 (12.90%)
Upper respiratory tract infection † 1	8/149 (5.37%)	13/126 (10.32%)	52/620 (8.39%)
Bronchitis † 1	5/149 (3.36%)	7/126 (5.56%)	23/620 (3.71%)
Musculoskeletal and connective tissue disorders
Arthralgia † 1	10/149 (6.71%)	15/126 (11.90%)	56/620 (9.03%)
Nervous system disorders
Headache † 1	13/149 (8.72%)	15/126 (11.90%)	80/620 (12.90%)
Respiratory, thoracic and mediastinal disorders
Cough † 1	7/149 (4.70%)	6/126 (4.76%)	36/620 (5.81%)
† 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 of Results:

Feagan BG, Rutgeerts P, Sands BE, Hanauer S, Colombel JF, Sandborn WJ, Van Assche G, Axler J, Kim HJ, Danese S, Fox I, Milch C, Sankoh S, Wyant T, Xu J, Parikh A; GEMINI 1 Study Group. Vedolizumab as induction and maintenance therapy for ulcerative colitis. N Engl J Med. 2013 Aug 22;369(8):699-710. doi: 10.1056/NEJMoa1215734.

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

Dulai PS, Feagan BG, Sands BE, Chen J, Lasch K, Lirio RA. Prognostic Value of Fecal Calprotectin to Inform Treat-to-Target Monitoring in Ulcerative Colitis. Clin Gastroenterol Hepatol. 2023 Feb;21(2):456-466.e7. doi: 10.1016/j.cgh.2022.07.027. Epub 2022 Aug 4.

Wyant T, Yang L, Rosario M. Comparison of the ELISA and ECL Assay for Vedolizumab Anti-drug Antibodies: Assessing the Impact on Pharmacokinetics and Safety Outcomes of the Phase 3 GEMINI Trials. AAPS J. 2020 Nov 16;23(1):3. doi: 10.1208/s12248-020-00518-0.

Okamoto H, Dirks NL, Rosario M, Hori T, Hibi T. Population pharmacokinetics of vedolizumab in Asian and non-Asian patients with ulcerative colitis and Crohn's disease. Intest Res. 2021 Jan;19(1):95-105. doi: 10.5217/ir.2019.09167. Epub 2020 Jul 10.

Loftus EV Jr, Sands BE, Colombel JF, Dotan I, Khalid JM, Tudor D, Geransar P. Sustained Corticosteroid-Free Clinical Remission During Vedolizumab Maintenance Therapy in Patients with Ulcerative Colitis on Stable Concomitant Corticosteroids During Induction Therapy: A Post Hoc Analysis of GEMINI 1. Clin Exp Gastroenterol. 2020 Jun 11;13:211-220. doi: 10.2147/CEG.S248597. eCollection 2020.

Dulai PS, Singh S, Vande Casteele N, Meserve J, Winters A, Chablaney S, Aniwan S, Shashi P, Kochhar G, Weiss A, Koliani-Pace JL, Gao Y, Boland BS, Chang JT, Faleck D, Hirten R, Ungaro R, Lukin D, Sultan K, Hudesman D, Chang S, Bohm M, Varma S, Fischer M, Shmidt E, Swaminath A, Gupta N, Rosario M, Jairath V, Guizzetti L, Feagan BG, Siegel CA, Shen B, Kane S, Loftus EV Jr, Sandborn WJ, Sands BE, Colombel JF, Lasch K, Cao C. Development and Validation of Clinical Scoring Tool to Predict Outcomes of Treatment With Vedolizumab in Patients With Ulcerative Colitis. Clin Gastroenterol Hepatol. 2020 Dec;18(13):2952-2961.e8. doi: 10.1016/j.cgh.2020.02.010. Epub 2020 Feb 13.

Feagan BG, Schreiber S, Wolf DC, Axler JL, Kaviya A, James A, Curtis RI, Geransar P, Stallmach A, Ehehalt R, Bokemeyer B, Khalid JM, O'Byrne S. Sustained Clinical Remission With Vedolizumab in Patients With Moderate-to-Severe Ulcerative Colitis. Inflamm Bowel Dis. 2019 May 4;25(6):1028-1035. doi: 10.1093/ibd/izy323.

Sandborn WJ, Colombel JF, Panaccione R, Dulai PS, Rosario M, Cao C, Barocas M, Lasch K. Deep Remission With Vedolizumab in Patients With Moderately to Severely Active Ulcerative Colitis: A GEMINI 1 post hoc Analysis. J Crohns Colitis. 2019 Feb 1;13(2):172-181. doi: 10.1093/ecco-jcc/jjy149.

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. Erratum In: Clin Gastroenterol Hepatol. 2020 Mar;18(3):759.

Arijs I, De Hertogh G, Lemmens B, Van Lommel L, de Bruyn M, Vanhove W, Cleynen I, Machiels K, Ferrante M, Schuit F, Van Assche G, Rutgeerts P, Vermeire S. Effect of vedolizumab (anti-alpha4beta7-integrin) therapy on histological healing and mucosal gene expression in patients with UC. Gut. 2018 Jan;67(1):43-52. doi: 10.1136/gutjnl-2016-312293. Epub 2016 Oct 7.

Feagan BG, Rubin DT, Danese S, Vermeire S, Abhyankar B, Sankoh S, James A, Smyth M. Efficacy of Vedolizumab Induction and Maintenance Therapy in Patients With Ulcerative Colitis, Regardless of Prior Exposure to Tumor Necrosis Factor Antagonists. Clin Gastroenterol Hepatol. 2017 Feb;15(2):229-239.e5. doi: 10.1016/j.cgh.2016.08.044. Epub 2016 Sep 14.

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.

• Responsible Party: Millennium Pharmaceuticals, Inc.
• ClinicalTrials.gov Identifier: NCT00783718
• Other Study ID Numbers: C13006; U1111-1156-8422 ( Registry Identifier: WHO ); 2008-002782-32 ( EudraCT Number ); NL25207.096.08 ( Registry Identifier: CCMO ); CTRI/2009/091/000128 ( Registry Identifier: CTRI ); NMRR-08-1046-2201 ( Registry Identifier: NMRR ); C13006CTIL ( Other Identifier: Israel MoH ); 09/H1102/66 ( Registry Identifier: NRES )
• First Submitted: October 31, 2008
• First Posted: November 2, 2008
• Results First Submitted: June 19, 2014
• Results First Posted: July 18, 2014
• Last Update Posted: July 18, 2014