Trial Outcomes & Findings for Study of Vedolizumab (MLN0002) in Patients With Moderate to Severe Ulcerative Colitis (NCT NCT00783718)

Last Updated: 2014-07-18

Results Overview

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.

Recruitment status

COMPLETED

Study phase

PHASE3

Target enrollment

895 participants

Primary outcome timeframe

Baseline and Week 6

Results posted on

2014-07-18

Participant Flow

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.

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.

Participant milestones

Participant milestones
Measure	Placebo 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.	Induction Phase: DB Vedolizumab 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.	Induction Phase: OL Vedolizumab 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.	Maintenance Phase: Placebo 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.	Maintenance Phase: Vedolizumab Q8W 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.	Maintenance Phase: Vedolizumab Q4W 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.	Maintenance Phase: Non-responders 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.
Induction Phase STARTED	149	225	521	0	0	0	0
Induction Phase COMPLETED	135	218	485	0	0	0	0
Induction Phase NOT COMPLETED	14	7	36	0	0	0	0
Maintenance Phase STARTED	135	0	0	126	122	125	330
Maintenance Phase COMPLETED	30	0	0	48	77	84	135
Maintenance Phase NOT COMPLETED	105	0	0	78	45	41	195

Reasons for withdrawal

Reasons for withdrawal
Measure	Placebo 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.	Induction Phase: DB Vedolizumab 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.	Induction Phase: OL Vedolizumab 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.	Maintenance Phase: Placebo 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.	Maintenance Phase: Vedolizumab Q8W 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.	Maintenance Phase: Vedolizumab Q4W 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.	Maintenance Phase: Non-responders 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.
Induction Phase Adverse Event	4	0	7	0	0	0	0
Induction Phase Protocol Violation	1	1	6	0	0	0	0
Induction Phase Lack of Efficacy	5	2	14	0	0	0	0
Induction Phase Withdrawal by Subject	3	4	8	0	0	0	0
Induction Phase Lost to Follow-up	1	0	1	0	0	0	0
Maintenance Phase Adverse Event	12	0	0	15	7	6	16
Maintenance Phase Protocol Violation	1	0	0	0	0	0	2
Maintenance Phase Lack of Efficacy	83	0	0	61	31	33	155
Maintenance Phase Withdrawal by Subject	6	0	0	2	5	2	20
Maintenance Phase Lost to Follow-up	3	0	0	0	2	0	2

Baseline Characteristics

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

Baseline characteristics by cohort

Baseline characteristics by cohort
Measure	Placebo n=149 Participants 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.	Induction Phase: DB Vedolizumab n=225 Participants 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.	Induction Phase: OL Vedolizumab n=521 Participants 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 n=895 Participants Total of all reporting groups
Age, Continuous	41.2 years STANDARD_DEVIATION 12.50 • n=5 Participants	40.1 years STANDARD_DEVIATION 13.11 • n=7 Participants	40.1 years STANDARD_DEVIATION 13.27 • n=5 Participants	40.3 years STANDARD_DEVIATION 13.09 • n=4 Participants
Age, Customized < 35	53 participants n=5 Participants	86 participants n=7 Participants	214 participants n=5 Participants	353 participants n=4 Participants
Age, Customized ≥ 35	96 participants n=5 Participants	139 participants n=7 Participants	307 participants n=5 Participants	542 participants n=4 Participants
Age, Customized < 65	142 participants n=5 Participants	217 participants n=7 Participants	503 participants n=5 Participants	862 participants n=4 Participants
Age, Customized ≥ 65	7 participants n=5 Participants	8 participants n=7 Participants	18 participants n=5 Participants	33 participants n=4 Participants
Sex: Female, Male Female	57 Participants n=5 Participants	93 Participants n=7 Participants	220 Participants n=5 Participants	370 Participants n=4 Participants
Sex: Female, Male Male	92 Participants n=5 Participants	132 Participants n=7 Participants	301 Participants n=5 Participants	525 Participants n=4 Participants
Race/Ethnicity, Customized White	115 participants n=5 Participants	183 participants n=7 Participants	436 participants n=5 Participants	734 participants n=4 Participants
Race/Ethnicity, Customized Black	2 participants n=5 Participants	5 participants n=7 Participants	5 participants n=5 Participants	12 participants n=4 Participants
Race/Ethnicity, Customized Asian	32 participants n=5 Participants	36 participants n=7 Participants	67 participants n=5 Participants	135 participants n=4 Participants
Race/Ethnicity, Customized Other	0 participants n=5 Participants	1 participants n=7 Participants	13 participants n=5 Participants	14 participants n=4 Participants
Race/Ethnicity, Customized Hispanic or Latino	5 participants n=5 Participants	10 participants n=7 Participants	31 participants n=5 Participants	46 participants n=4 Participants
Race/Ethnicity, Customized Not Hispanic or Latino	140 participants n=5 Participants	211 participants n=7 Participants	481 participants n=5 Participants	832 participants n=4 Participants
Race/Ethnicity, Customized Not reported	4 participants n=5 Participants	4 participants n=7 Participants	9 participants n=5 Participants	17 participants n=4 Participants
Region of Enrollment Australia	7 participants n=5 Participants	17 participants n=7 Participants	29 participants n=5 Participants	53 participants n=4 Participants
Region of Enrollment Austria	4 participants n=5 Participants	3 participants n=7 Participants	12 participants n=5 Participants	19 participants n=4 Participants
Region of Enrollment Belgium	7 participants n=5 Participants	14 participants n=7 Participants	35 participants n=5 Participants	56 participants n=4 Participants
Region of Enrollment Bulgaria	2 participants n=5 Participants	1 participants n=7 Participants	3 participants n=5 Participants	6 participants n=4 Participants
Region of Enrollment Canada	16 participants n=5 Participants	14 participants n=7 Participants	62 participants n=5 Participants	92 participants n=4 Participants
Region of Enrollment Czech Republic	7 participants n=5 Participants	12 participants n=7 Participants	19 participants n=5 Participants	38 participants n=4 Participants
Region of Enrollment Denmark	2 participants n=5 Participants	7 participants n=7 Participants	5 participants n=5 Participants	14 participants n=4 Participants
Region of Enrollment Estonia	1 participants n=5 Participants	4 participants n=7 Participants	5 participants n=5 Participants	10 participants n=4 Participants
Region of Enrollment France	1 participants n=5 Participants	3 participants n=7 Participants	13 participants n=5 Participants	17 participants n=4 Participants
Region of Enrollment Germany	0 participants n=5 Participants	1 participants n=7 Participants	16 participants n=5 Participants	17 participants n=4 Participants
Region of Enrollment Greece	0 participants n=5 Participants	1 participants n=7 Participants	4 participants n=5 Participants	5 participants n=4 Participants
Region of Enrollment Hong Kong	0 participants n=5 Participants	0 participants n=7 Participants	1 participants n=5 Participants	1 participants n=4 Participants
Region of Enrollment Hungary	2 participants n=5 Participants	6 participants n=7 Participants	8 participants n=5 Participants	16 participants n=4 Participants
Region of Enrollment Iceland	0 participants n=5 Participants	1 participants n=7 Participants	2 participants n=5 Participants	3 participants n=4 Participants
Region of Enrollment India	18 participants n=5 Participants	16 participants n=7 Participants	24 participants n=5 Participants	58 participants n=4 Participants
Region of Enrollment Ireland	0 participants n=5 Participants	0 participants n=7 Participants	1 participants n=5 Participants	1 participants n=4 Participants
Region of Enrollment Israel	0 participants n=5 Participants	1 participants n=7 Participants	1 participants n=5 Participants	2 participants n=4 Participants
Region of Enrollment Italy	1 participants n=5 Participants	9 participants n=7 Participants	11 participants n=5 Participants	21 participants n=4 Participants
Region of Enrollment Korea, Republic of	5 participants n=5 Participants	10 participants n=7 Participants	26 participants n=5 Participants	41 participants n=4 Participants
Region of Enrollment Latvia	1 participants n=5 Participants	2 participants n=7 Participants	0 participants n=5 Participants	3 participants n=4 Participants
Region of Enrollment Malaysia	5 participants n=5 Participants	2 participants n=7 Participants	2 participants n=5 Participants	9 participants n=4 Participants
Region of Enrollment Netherlands	1 participants n=5 Participants	0 participants n=7 Participants	2 participants n=5 Participants	3 participants n=4 Participants
Region of Enrollment New Zealand	0 participants n=5 Participants	5 participants n=7 Participants	6 participants n=5 Participants	11 participants n=4 Participants
Region of Enrollment Norway	2 participants n=5 Participants	1 participants n=7 Participants	6 participants n=5 Participants	9 participants n=4 Participants
Region of Enrollment Poland	2 participants n=5 Participants	6 participants n=7 Participants	52 participants n=5 Participants	60 participants n=4 Participants
Region of Enrollment Russian Federation	9 participants n=5 Participants	15 participants n=7 Participants	25 participants n=5 Participants	49 participants n=4 Participants
Region of Enrollment Singapore	0 participants n=5 Participants	0 participants n=7 Participants	1 participants n=5 Participants	1 participants n=4 Participants
Region of Enrollment South Africa	4 participants n=5 Participants	5 participants n=7 Participants	10 participants n=5 Participants	19 participants n=4 Participants
Region of Enrollment Spain	0 participants n=5 Participants	0 participants n=7 Participants	2 participants n=5 Participants	2 participants n=4 Participants
Region of Enrollment Switzerland	2 participants n=5 Participants	1 participants n=7 Participants	3 participants n=5 Participants	6 participants n=4 Participants
Region of Enrollment Turkey	0 participants n=5 Participants	3 participants n=7 Participants	3 participants n=5 Participants	6 participants n=4 Participants
Region of Enrollment United Kingdom	2 participants n=5 Participants	0 participants n=7 Participants	4 participants n=5 Participants	6 participants n=4 Participants
Region of Enrollment United States	47 participants n=5 Participants	64 participants n=7 Participants	127 participants n=5 Participants	238 participants n=4 Participants
Body Weight	72.4 kg STANDARD_DEVIATION 17.65 • n=5 Participants	72.4 kg STANDARD_DEVIATION 17.11 • n=7 Participants	74.2 kg STANDARD_DEVIATION 19.32 • n=5 Participants	73.4 kg STANDARD_DEVIATION 18.51 • n=4 Participants
Body Mass Index (BMI)	24.6 kg/m^2 STANDARD_DEVIATION 5.11 • n=5 Participants	24.9 kg/m^2 STANDARD_DEVIATION 4.85 • n=7 Participants	25.3 kg/m^2 STANDARD_DEVIATION 6.05 • n=5 Participants	25.1 kg/m^2 STANDARD_DEVIATION 5.62 • n=4 Participants
Duration of Ulcerative Colitis	7.1 years STANDARD_DEVIATION 7.25 • n=5 Participants	6.1 years STANDARD_DEVIATION 5.08 • n=7 Participants	7.2 years STANDARD_DEVIATION 6.61 • n=5 Participants	6.9 years STANDARD_DEVIATION 6.39 • n=4 Participants
Categorical Duration of Ulcerative Colitis < 1 year	13 participants n=5 Participants	13 participants n=7 Participants	38 participants n=5 Participants	64 participants n=4 Participants
Categorical Duration of Ulcerative Colitis ≥1 - < 3 years	44 participants n=5 Participants	63 participants n=7 Participants	121 participants n=5 Participants	228 participants n=4 Participants
Categorical Duration of Ulcerative Colitis ≥ 3 - < 7 years	39 participants n=5 Participants	77 participants n=7 Participants	163 participants n=5 Participants	279 participants n=4 Participants
Categorical Duration of Ulcerative Colitis ≥ 7 years	53 participants n=5 Participants	72 participants n=7 Participants	197 participants n=5 Participants	322 participants n=4 Participants
Categorical Duration of Ulcerative Colitis Missing	0 participants n=5 Participants	0 participants n=7 Participants	2 participants n=5 Participants	2 participants n=4 Participants
Baseline Mayo Score	8.6 units on a scale STANDARD_DEVIATION 1.68 • n=5 Participants	8.5 units on a scale STANDARD_DEVIATION 1.78 • n=7 Participants	8.6 units on a scale STANDARD_DEVIATION 1.76 • n=5 Participants	8.6 units on a scale STANDARD_DEVIATION 1.75 • n=4 Participants
Baseline Disease Activity Complete Mayo score < 6	5 participants n=5 Participants	6 participants n=7 Participants	14 participants n=5 Participants	25 participants n=4 Participants
Baseline Disease Activity Complete Mayo score of 6 to 8 (inclusive)	70 participants n=5 Participants	105 participants n=7 Participants	249 participants n=5 Participants	424 participants n=4 Participants
Baseline Disease Activity Complete Mayo score of 9 to 12 (inclusive)	74 participants n=5 Participants	114 participants n=7 Participants	258 participants n=5 Participants	446 participants n=4 Participants
Baseline Fecal Calprotectin	2369.9 μg/g STANDARD_DEVIATION 3258.82 • n=5 Participants	2552.2 μg/g STANDARD_DEVIATION 3800.36 • n=7 Participants	1442.7 μg/g STANDARD_DEVIATION 1855.61 • n=5 Participants	1868.8 μg/g STANDARD_DEVIATION 2753.28 • n=4 Participants
Categorical Baseline Fecal Calprotectin ≤ 250 μg/g	27 participants n=5 Participants	37 participants n=7 Participants	94 participants n=5 Participants	158 participants n=4 Participants
Categorical Baseline Fecal Calprotectin > 250 to ≤ 500 μg/g	20 participants n=5 Participants	20 participants n=7 Participants	82 participants n=5 Participants	122 participants n=4 Participants
Categorical Baseline Fecal Calprotectin > 500 μg/g	92 participants n=5 Participants	156 participants n=7 Participants	329 participants n=5 Participants	577 participants n=4 Participants
Categorical Baseline Fecal Calprotectin Missing	10 participants n=5 Participants	12 participants n=7 Participants	16 participants n=5 Participants	38 participants n=4 Participants
Disease Localization Proctosigmoiditis	22 participants n=5 Participants	25 participants n=7 Participants	69 participants n=5 Participants	116 participants n=4 Participants
Disease Localization Left-sided colitis	59 participants n=5 Participants	92 participants n=7 Participants	188 participants n=5 Participants	339 participants n=4 Participants
Disease Localization Extensive colitis	18 participants n=5 Participants	25 participants n=7 Participants	66 participants n=5 Participants	109 participants n=4 Participants
Disease Localization Pancolitis	50 participants n=5 Participants	83 participants n=7 Participants	198 participants n=5 Participants	331 participants n=4 Participants
Smoking Status Current smoker	11 participants n=5 Participants	12 participants n=7 Participants	32 participants n=5 Participants	55 participants n=4 Participants
Smoking Status Nonsmoker	88 participants n=5 Participants	145 participants n=7 Participants	322 participants n=5 Participants	555 participants n=4 Participants
Smoking Status Former smoker	50 participants n=5 Participants	68 participants n=7 Participants	167 participants n=5 Participants	285 participants n=4 Participants
History of Extraintestinal Manifestations Yes	44 participants n=5 Participants	74 participants n=7 Participants	180 participants n=5 Participants	298 participants n=4 Participants
History of Extraintestinal Manifestations No	105 participants n=5 Participants	151 participants n=7 Participants	341 participants n=5 Participants	597 participants n=4 Participants

PRIMARY outcome

Timeframe: Baseline and Week 6

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

Outcome measures

Outcome measures
Measure	Placebo n=149 Participants Participants in Cohort 1 received double-blind placebo intravenous infusions at Week 0 and Week 2 in the Induction Phase.	DB Vedolizumab n=225 Participants Participants in Cohort 1 received double-blind vedolizumab 300 mg, administered by intravenous infusion at Week 0 and Week 2 in the Induction Phase.	Vedolizumab Q4W 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.
Induction Phase: Percentage of Participants With a Clinical Response at Week 6	25.5 percentage of participants Interval 18.5 to 32.5	47.1 percentage of participants Interval 40.6 to 53.6	—

PRIMARY outcome

Timeframe: Week 52

Population: 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.

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.

Outcome measures

Outcome measures
Measure	Placebo n=126 Participants Participants in Cohort 1 received double-blind placebo intravenous infusions at Week 0 and Week 2 in the Induction Phase.	DB Vedolizumab n=122 Participants Participants in Cohort 1 received double-blind vedolizumab 300 mg, administered by intravenous infusion at Week 0 and Week 2 in the Induction Phase.	Vedolizumab Q4W n=125 Participants 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.
Maintenance Phase: Percentage of Participants in Clinical Remission at Week 52	15.9 percentage of participants Interval 9.5 to 22.3	41.8 percentage of participants Interval 33.1 to 50.6	44.8 percentage of participants Interval 36.1 to 53.5

SECONDARY outcome

Timeframe: Week 6

Population: Induction Study ITT Population

Outcome measures

Outcome measures
Measure	Placebo n=149 Participants Participants in Cohort 1 received double-blind placebo intravenous infusions at Week 0 and Week 2 in the Induction Phase.	DB Vedolizumab n=225 Participants Participants in Cohort 1 received double-blind vedolizumab 300 mg, administered by intravenous infusion at Week 0 and Week 2 in the Induction Phase.	Vedolizumab Q4W 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.
Induction Phase: Percentage of Participants in Clinical Remission at Week 6	5.4 percentage of participants Interval 1.7 to 9.0	16.9 percentage of participants Interval 12.0 to 21.8	—

SECONDARY outcome

Timeframe: Week 6

Population: Induction Study ITT Population

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.

Outcome measures

Outcome measures
Measure	Placebo n=149 Participants Participants in Cohort 1 received double-blind placebo intravenous infusions at Week 0 and Week 2 in the Induction Phase.	DB Vedolizumab n=225 Participants Participants in Cohort 1 received double-blind vedolizumab 300 mg, administered by intravenous infusion at Week 0 and Week 2 in the Induction Phase.	Vedolizumab Q4W 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.
Induction Phase: Percentage of Participants With Mucosal Healing at Week 6	24.8 percentage of participants Interval 17.9 to 31.8	40.9 percentage of participants Interval 34.5 to 47.3	—

SECONDARY outcome

Timeframe: Baseline, Week 6 and Week 52

Population: Maintenance Study ITT Population

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.

Outcome measures

Outcome measures
Measure	Placebo n=126 Participants Participants in Cohort 1 received double-blind placebo intravenous infusions at Week 0 and Week 2 in the Induction Phase.	DB Vedolizumab n=122 Participants Participants in Cohort 1 received double-blind vedolizumab 300 mg, administered by intravenous infusion at Week 0 and Week 2 in the Induction Phase.	Vedolizumab Q4W n=125 Participants 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.
Maintenance Phase: Percentage of Participants With Durable Clinical Response	23.8 percentage of participants Interval 16.4 to 31.2	56.6 percentage of participants Interval 47.8 to 65.4	52.0 percentage of participants Interval 43.2 to 60.8

SECONDARY outcome

Timeframe: Week 52

Population: Maintenance Study ITT Population

Outcome measures

Outcome measures
Measure	Placebo n=126 Participants Participants in Cohort 1 received double-blind placebo intravenous infusions at Week 0 and Week 2 in the Induction Phase.	DB Vedolizumab n=122 Participants Participants in Cohort 1 received double-blind vedolizumab 300 mg, administered by intravenous infusion at Week 0 and Week 2 in the Induction Phase.	Vedolizumab Q4W n=125 Participants 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.
Maintenance Phase: Percentage of Participants With Mucosal Healing at Week 52	19.8 percentage of participants Interval 12.9 to 26.8	51.6 percentage of participants Interval 42.8 to 60.5	56.0 percentage of participants Interval 47.3 to 64.7

SECONDARY outcome

Timeframe: Week 6 and Week 52

Population: Maintenance Study ITT Population

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.

Outcome measures

Outcome measures
Measure	Placebo n=126 Participants Participants in Cohort 1 received double-blind placebo intravenous infusions at Week 0 and Week 2 in the Induction Phase.	DB Vedolizumab n=122 Participants Participants in Cohort 1 received double-blind vedolizumab 300 mg, administered by intravenous infusion at Week 0 and Week 2 in the Induction Phase.	Vedolizumab Q4W n=125 Participants 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.
Maintenance Phase: Percentage of Participants With Durable Clinical Remission	8.7 percentage of participants Interval 3.8 to 13.7	20.5 percentage of participants Interval 13.3 to 27.7	24.0 percentage of participants Interval 16.5 to 31.5

SECONDARY outcome

Timeframe: Week 52

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

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.

Outcome measures

Outcome measures
Measure	Placebo n=72 Participants Participants in Cohort 1 received double-blind placebo intravenous infusions at Week 0 and Week 2 in the Induction Phase.	DB Vedolizumab n=70 Participants Participants in Cohort 1 received double-blind vedolizumab 300 mg, administered by intravenous infusion at Week 0 and Week 2 in the Induction Phase.	Vedolizumab Q4W n=73 Participants 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.
Maintenance Phase: Percentage of Participants With Corticosteroid-free Remission at Week 52	13.9 percentage of participants Interval 5.9 to 21.9	31.4 percentage of participants Interval 20.6 to 42.3	45.2 percentage of participants Interval 33.8 to 56.6

Adverse Events

Placebo

Serious events: 17 serious events

Other events: 67 other events

Deaths: 0 deaths

Vedolizumab Then Placebo

Serious events: 20 serious events

Other events: 69 other events

Deaths: 0 deaths

Vedolizumab

Serious events: 77 serious events

Other events: 321 other events

Deaths: 0 deaths

Serious adverse events

Other adverse events

Other adverse events
Measure	Placebo n=149 participants at risk Participants who received double-blind placebo intravenous infusions in the Induction Phase and continued to receive placebo during the Maintenance Phase.	Vedolizumab Then Placebo n=126 participants at risk Participants who received vedolizumab during the Induction Phase and were then randomized to receive placebo during the Maintenance Phase.	Vedolizumab n=620 participants at risk 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.
Infections and infestations Nasopharyngitis	7.4% 11/149 • 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).	11.9% 15/126 • 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).	12.9% 80/620 • 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).
Infections and infestations Upper respiratory tract infection	5.4% 8/149 • 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).	10.3% 13/126 • 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).	8.4% 52/620 • 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).
Infections and infestations Bronchitis	3.4% 5/149 • 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).	5.6% 7/126 • 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).	3.7% 23/620 • 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).
Gastrointestinal disorders Colitis ulcerative	13.4% 20/149 • 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).	17.5% 22/126 • 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).	9.2% 57/620 • 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).
Gastrointestinal disorders Nausea	7.4% 11/149 • 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).	6.3% 8/126 • 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).	6.1% 38/620 • 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).
Gastrointestinal disorders Abdominal pain	4.7% 7/149 • 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).	1.6% 2/126 • 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).	5.5% 34/620 • 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).
Nervous system disorders Headache	8.7% 13/149 • 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).	11.9% 15/126 • 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).	12.9% 80/620 • 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).
Musculoskeletal and connective tissue disorders Arthralgia	6.7% 10/149 • 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).	11.9% 15/126 • 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).	9.0% 56/620 • 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).
Respiratory, thoracic and mediastinal disorders Cough	4.7% 7/149 • 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).	4.8% 6/126 • 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).	5.8% 36/620 • 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).
Blood and lymphatic system disorders Anaemia	6.7% 10/149 • 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).	3.2% 4/126 • 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).	5.6% 35/620 • 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).
General disorders Fatigue	3.4% 5/149 • 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).	4.0% 5/126 • 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).	5.2% 32/620 • 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).

Additional Information

Medical Director

Millennium Pharmaceuticals Inc

Phone: 800-778-2860

Email: [email protected]

Results disclosure agreements

Principal investigator is a sponsor employee 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.
Publication restrictions are in place

Restriction type: OTHER