Trial Outcomes & Findings for Study of Vedolizumab (MLN0002) in Patients With Moderate to Severe Crohn's Disease (NCT NCT00783692)

Last Updated: 2014-07-21

Results Overview

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

Recruitment status

COMPLETED

Study phase

PHASE3

Target enrollment

1116 participants

Primary outcome timeframe

Week 6

Results posted on

2014-07-21

Participant Flow

Participants took part in the study at 285 investigative sites worldwide from 23 December 2008 to 08 May 2012. 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	148	220	748	0	0	0	0
Induction Phase Treated	148	220	747	0	0	0	0
Induction Phase COMPLETED	137	199	674	0	0	0	0
Induction Phase NOT COMPLETED	11	21	74	0	0	0	0
Maintenance Phase STARTED	137	0	0	153	154	154	412
Maintenance Phase COMPLETED	42	0	0	64	73	82	163
Maintenance Phase NOT COMPLETED	95	0	0	89	81	72	249

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	7	9	24	0	0	0	0
Induction Phase Protocol Violation	0	0	1	0	0	0	0
Induction Phase Lack of Efficacy	1	3	28	0	0	0	0
Induction Phase Withdrawal by Subject	3	9	16	0	0	0	0
Induction Phase Lost to Follow-up	0	0	3	0	0	0	0
Induction Phase Other	0	0	2	0	0	0	0
Maintenance Phase Adverse Event	7	0	0	15	12	9	38
Maintenance Phase Protocol Violation	0	0	0	1	2	3	4
Maintenance Phase Lack of Efficacy	79	0	0	64	58	48	177
Maintenance Phase Withdrawal by Subject	7	0	0	7	6	9	24
Maintenance Phase Lost to Follow-up	2	0	0	1	3	2	5
Maintenance Phase Other	0	0	0	1	0	1	1

Baseline Characteristics

Study of Vedolizumab (MLN0002) in Patients With Moderate to Severe Crohn's Disease

Baseline characteristics by cohort

Baseline characteristics by cohort
Measure	Placebo n=148 Participants In the Induction Phase participants in Cohort 1 were randomized to receive double-blind placebo intravenous infusions at Week 0 and Week 2.	Induction Phase: DB Vedolizumab n=220 Participants 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 n=747 Participants 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.	Total n=1115 Participants Total of all reporting groups
Age, Continuous	38.6 years STANDARD_DEVIATION 13.16 • n=5 Participants	36.3 years STANDARD_DEVIATION 11.57 • n=7 Participants	35.6 years STANDARD_DEVIATION 12.01 • n=5 Participants	36.1 years STANDARD_DEVIATION 12.12 • n=4 Participants
Age, Customized < 35 years	67 participants n=5 Participants	111 participants n=7 Participants	404 participants n=5 Participants	582 participants n=4 Participants
Age, Customized ≥ 35 years	81 participants n=5 Participants	109 participants n=7 Participants	343 participants n=5 Participants	533 participants n=4 Participants
Age, Customized < 65 years	142 participants n=5 Participants	218 participants n=7 Participants	732 participants n=5 Participants	1092 participants n=4 Participants
Age, Customized ≥ 65 years	6 participants n=5 Participants	2 participants n=7 Participants	15 participants n=5 Participants	23 participants n=4 Participants
Sex: Female, Male Female	79 Participants n=5 Participants	115 Participants n=7 Participants	401 Participants n=5 Participants	595 Participants n=4 Participants
Sex: Female, Male Male	69 Participants n=5 Participants	105 Participants n=7 Participants	346 Participants n=5 Participants	520 Participants n=4 Participants
Ethnicity (NIH/OMB) Hispanic or Latino	5 Participants n=5 Participants	2 Participants n=7 Participants	19 Participants n=5 Participants	26 Participants n=4 Participants
Ethnicity (NIH/OMB) Not Hispanic or Latino	139 Participants n=5 Participants	214 Participants n=7 Participants	712 Participants n=5 Participants	1065 Participants n=4 Participants
Ethnicity (NIH/OMB) Unknown or Not Reported	4 Participants n=5 Participants	4 Participants n=7 Participants	16 Participants n=5 Participants	24 Participants n=4 Participants
Race/Ethnicity, Customized White	124 participants n=5 Participants	182 participants n=7 Participants	689 participants n=5 Participants	995 participants n=4 Participants
Race/Ethnicity, Customized Black	3 participants n=5 Participants	3 participants n=7 Participants	17 participants n=5 Participants	23 participants n=4 Participants
Race/Ethnicity, Customized Asian	19 participants n=5 Participants	35 participants n=7 Participants	35 participants n=5 Participants	89 participants n=4 Participants
Race/Ethnicity, Customized Other	2 participants n=5 Participants	0 participants n=7 Participants	6 participants n=5 Participants	8 participants n=4 Participants
Region of Enrollment Australia	5 participants n=5 Participants	10 participants n=7 Participants	30 participants n=5 Participants	45 participants n=4 Participants
Region of Enrollment Austria	4 participants n=5 Participants	3 participants n=7 Participants	7 participants n=5 Participants	14 participants n=4 Participants
Region of Enrollment Belgium	12 participants n=5 Participants	17 participants n=7 Participants	41 participants n=5 Participants	70 participants n=4 Participants
Region of Enrollment Bulgaria	5 participants n=5 Participants	7 participants n=7 Participants	2 participants n=5 Participants	14 participants n=4 Participants
Region of Enrollment Canada	22 participants n=5 Participants	12 participants n=7 Participants	103 participants n=5 Participants	137 participants n=4 Participants
Region of Enrollment Czech Republic	11 participants n=5 Participants	16 participants n=7 Participants	53 participants n=5 Participants	80 participants n=4 Participants
Region of Enrollment Denmark	0 participants n=5 Participants	2 participants n=7 Participants	8 participants n=5 Participants	10 participants n=4 Participants
Region of Enrollment Estonia	1 participants n=5 Participants	2 participants n=7 Participants	3 participants n=5 Participants	6 participants n=4 Participants
Region of Enrollment France	4 participants n=5 Participants	3 participants n=7 Participants	37 participants n=5 Participants	44 participants n=4 Participants
Region of Enrollment Germany	0 participants n=5 Participants	1 participants n=7 Participants	49 participants n=5 Participants	50 participants n=4 Participants
Region of Enrollment Greece	0 participants n=5 Participants	0 participants n=7 Participants	2 participants n=5 Participants	2 participants n=4 Participants
Region of Enrollment Hong Kong	2 participants n=5 Participants	0 participants n=7 Participants	0 participants n=5 Participants	2 participants n=4 Participants
Region of Enrollment Hungary	9 participants n=5 Participants	17 participants n=7 Participants	47 participants n=5 Participants	73 participants n=4 Participants
Region of Enrollment Iceland	0 participants n=5 Participants	0 participants n=7 Participants	4 participants n=5 Participants	4 participants n=4 Participants
Region of Enrollment India	10 participants n=5 Participants	19 participants n=7 Participants	5 participants n=5 Participants	34 participants n=4 Participants
Region of Enrollment Ireland	0 participants n=5 Participants	0 participants n=7 Participants	2 participants n=5 Participants	2 participants n=4 Participants
Region of Enrollment Israel	2 participants n=5 Participants	4 participants n=7 Participants	12 participants n=5 Participants	18 participants n=4 Participants
Region of Enrollment Italy	1 participants n=5 Participants	0 participants n=7 Participants	13 participants n=5 Participants	14 participants n=4 Participants
Region of Enrollment Korea, Republic of	3 participants n=5 Participants	12 participants n=7 Participants	11 participants n=5 Participants	26 participants n=4 Participants
Region of Enrollment Latvia	0 participants n=5 Participants	2 participants n=7 Participants	0 participants n=5 Participants	2 participants n=4 Participants
Region of Enrollment Malaysia	1 participants n=5 Participants	3 participants n=7 Participants	5 participants n=5 Participants	9 participants n=4 Participants
Region of Enrollment Netherlands	0 participants n=5 Participants	0 participants n=7 Participants	7 participants n=5 Participants	7 participants n=4 Participants
Region of Enrollment New Zealand	4 participants n=5 Participants	5 participants n=7 Participants	3 participants n=5 Participants	12 participants n=4 Participants
Region of Enrollment Norway	0 participants n=5 Participants	0 participants n=7 Participants	13 participants n=5 Participants	13 participants n=4 Participants
Region of Enrollment Poland	7 participants n=5 Participants	6 participants n=7 Participants	14 participants n=5 Participants	27 participants n=4 Participants
Region of Enrollment Romania	0 participants n=5 Participants	1 participants n=7 Participants	4 participants n=5 Participants	5 participants n=4 Participants
Region of Enrollment Russian Federation	4 participants n=5 Participants	9 participants n=7 Participants	15 participants n=5 Participants	28 participants n=4 Participants
Region of Enrollment Serbia	0 participants n=5 Participants	0 participants n=7 Participants	3 participants n=5 Participants	3 participants n=4 Participants
Region of Enrollment Singapore	1 participants n=5 Participants	0 participants n=7 Participants	0 participants n=5 Participants	1 participants n=4 Participants
Region of Enrollment Slovakia	3 participants n=5 Participants	5 participants n=7 Participants	10 participants n=5 Participants	18 participants n=4 Participants
Region of Enrollment South Africa	3 participants n=5 Participants	3 participants n=7 Participants	14 participants n=5 Participants	20 participants n=4 Participants
Region of Enrollment Spain	1 participants n=5 Participants	0 participants n=7 Participants	6 participants n=5 Participants	7 participants n=4 Participants
Region of Enrollment Sweden	0 participants n=5 Participants	1 participants n=7 Participants	8 participants n=5 Participants	9 participants n=4 Participants
Region of Enrollment Switzerland	0 participants n=5 Participants	1 participants n=7 Participants	9 participants n=5 Participants	10 participants n=4 Participants
Region of Enrollment Taiwan	0 participants n=5 Participants	0 participants n=7 Participants	3 participants n=5 Participants	3 participants n=4 Participants
Region of Enrollment Turkey	2 participants n=5 Participants	3 participants n=7 Participants	1 participants n=5 Participants	6 participants n=4 Participants
Region of Enrollment Ukraine	3 participants n=5 Participants	4 participants n=7 Participants	9 participants n=5 Participants	16 participants n=4 Participants
Region of Enrollment United Kingdom	0 participants n=5 Participants	0 participants n=7 Participants	6 participants n=5 Participants	6 participants n=4 Participants
Region of Enrollment United States	28 participants n=5 Participants	52 participants n=7 Participants	188 participants n=5 Participants	268 participants n=4 Participants
Body Weight	68.7 kg STANDARD_DEVIATION 18.90 • n=5 Participants	67.1 kg STANDARD_DEVIATION 19.07 • n=7 Participants	70.8 kg STANDARD_DEVIATION 19.56 • n=5 Participants	69.8 kg STANDARD_DEVIATION 19.42 • n=4 Participants
Body Mass Index (BMI)	23.7 kg/m^2 STANDARD_DEVIATION 5.77 • n=5 Participants	23.1 kg/m^2 STANDARD_DEVIATION 5.62 • n=7 Participants	24.2 kg/m^2 STANDARD_DEVIATION 6.02 • n=5 Participants	23.9 kg/m^2 STANDARD_DEVIATION 5.93 • n=4 Participants
Duration of Crohn's Disease (CD)	8.2 years STANDARD_DEVIATION 7.80 • n=5 Participants	9.2 years STANDARD_DEVIATION 8.18 • n=7 Participants	9.2 years STANDARD_DEVIATION 7.63 • n=5 Participants	9.0 years STANDARD_DEVIATION 7.77 • n=4 Participants
Duration of Crohn's Disease - Categorical < 1 year	12 participants n=5 Participants	12 participants n=7 Participants	45 participants n=5 Participants	69 participants n=4 Participants
Duration of Crohn's Disease - Categorical ≥ 1 to < 3 years	27 participants n=5 Participants	48 participants n=7 Participants	126 participants n=5 Participants	201 participants n=4 Participants
Duration of Crohn's Disease - Categorical ≥ 3 to < 7 years	45 participants n=5 Participants	49 participants n=7 Participants	191 participants n=5 Participants	285 participants n=4 Participants
Duration of Crohn's Disease - Categorical ≥ 7 years	64 participants n=5 Participants	111 participants n=7 Participants	385 participants n=5 Participants	560 participants n=4 Participants
Baseline Disease Activity - Crohn's Disease Activity Index (CDAI)	324.6 units on a scale STANDARD_DEVIATION 78.08 • n=5 Participants	327.3 units on a scale STANDARD_DEVIATION 70.67 • n=7 Participants	322.2 units on a scale STANDARD_DEVIATION 67.17 • n=5 Participants	323.6 units on a scale STANDARD_DEVIATION 69.37 • n=4 Participants
Baseline Disease Activity - Categorical CDAI ≤ 330	81 participants n=5 Participants	119 participants n=7 Participants	418 participants n=5 Participants	618 participants n=4 Participants
Baseline Disease Activity - Categorical CDAI > 330	66 participants n=5 Participants	100 participants n=7 Participants	325 participants n=5 Participants	491 participants n=4 Participants
Baseline Disease Activity - Categorical Missing	1 participants n=5 Participants	1 participants n=7 Participants	4 participants n=5 Participants	6 participants n=4 Participants
Baseline C-reactive Protein (CRP)	23.6 mg/L STANDARD_DEVIATION 27.85 • n=5 Participants	24.1 mg/L STANDARD_DEVIATION 27.23 • n=7 Participants	20.4 mg/L STANDARD_DEVIATION 27.40 • n=5 Participants	21.5 mg/L STANDARD_DEVIATION 27.45 • n=4 Participants
Baseline CRP - Categorical ≤ 2.87 mg/L	20 participants n=5 Participants	37 participants n=7 Participants	130 participants n=5 Participants	187 participants n=4 Participants
Baseline CRP - Categorical > 2.87 to ≤ 5 mg/L	14 participants n=5 Participants	25 participants n=7 Participants	75 participants n=5 Participants	114 participants n=4 Participants
Baseline CRP - Categorical > 5 to ≤ 10 mg/L	28 participants n=5 Participants	38 participants n=7 Participants	160 participants n=5 Participants	226 participants n=4 Participants
Baseline CRP - Categorical > 10 mg/L	85 participants n=5 Participants	120 participants n=7 Participants	382 participants n=5 Participants	587 participants n=4 Participants
Baseline CRP - Categorical Missing	1 participants n=5 Participants	0 participants n=7 Participants	0 participants n=5 Participants	1 participants n=4 Participants
Baseline Fecal Calprotectin	1421.2 μg/g STANDARD_DEVIATION 2076.11 • n=5 Participants	1839.9 μg/g STANDARD_DEVIATION 2624.92 • n=7 Participants	1050.1 μg/g STANDARD_DEVIATION 1558.93 • n=5 Participants	1254.2 μg/g STANDARD_DEVIATION 1908.82 • n=4 Participants
Baseline Fecal Calprotectin - Categorical ≤ 250 μg/g	34 participants n=5 Participants	51 participants n=7 Participants	201 participants n=5 Participants	286 participants n=4 Participants
Baseline Fecal Calprotectin - Categorical > 250 to ≤ 500 μg/g	27 participants n=5 Participants	25 participants n=7 Participants	112 participants n=5 Participants	164 participants n=4 Participants
Baseline Fecal Calprotectin - Categorical > 500 μg/g	81 participants n=5 Participants	134 participants n=7 Participants	406 participants n=5 Participants	621 participants n=4 Participants
Baseline Fecal Calprotectin - Categorical Missing	6 participants n=5 Participants	10 participants n=7 Participants	28 participants n=5 Participants	44 participants n=4 Participants
Disease Localization Ileum only	21 participants n=5 Participants	37 participants n=7 Participants	123 participants n=5 Participants	181 participants n=4 Participants
Disease Localization Colon only	43 participants n=5 Participants	62 participants n=7 Participants	211 participants n=5 Participants	316 participants n=4 Participants
Disease Localization Ileocolonic (both ileum and colon)	84 participants n=5 Participants	121 participants n=7 Participants	413 participants n=5 Participants	618 participants n=4 Participants
History of Prior Surgery for Crohn's Disease Yes	54 participants n=5 Participants	98 participants n=7 Participants	314 participants n=5 Participants	466 participants n=4 Participants
History of Prior Surgery for Crohn's Disease No	94 participants n=5 Participants	122 participants n=7 Participants	433 participants n=5 Participants	649 participants n=4 Participants
History of Fistulizing Disease Yes	56 participants n=5 Participants	90 participants n=7 Participants	264 participants n=5 Participants	410 participants n=4 Participants
History of Fistulizing Disease No	92 participants n=5 Participants	130 participants n=7 Participants	483 participants n=5 Participants	705 participants n=4 Participants
Draining Fistula at Baseline Yes	23 participants n=5 Participants	38 participants n=7 Participants	104 participants n=5 Participants	165 participants n=4 Participants
Draining Fistula at Baseline All Closed	2 participants n=5 Participants	1 participants n=7 Participants	8 participants n=5 Participants	11 participants n=4 Participants
Draining Fistula at Baseline No	123 participants n=5 Participants	181 participants n=7 Participants	635 participants n=5 Participants	939 participants n=4 Participants
Smoking Status Current smoker	34 participants n=5 Participants	54 participants n=7 Participants	210 participants n=5 Participants	298 participants n=4 Participants
Smoking Status Nonsmoker (never smoked)	85 participants n=5 Participants	120 participants n=7 Participants	351 participants n=5 Participants	556 participants n=4 Participants
Smoking Status Former smoker	29 participants n=5 Participants	46 participants n=7 Participants	185 participants n=5 Participants	260 participants n=4 Participants
Smoking Status Missing	0 participants n=5 Participants	0 participants n=7 Participants	1 participants n=5 Participants	1 participants n=4 Participants
Baseline Extraintestinal Manifestations Yes	107 participants n=5 Participants	133 participants n=7 Participants	456 participants n=5 Participants	696 participants n=4 Participants
Baseline Extraintestinal Manifestations No	41 participants n=5 Participants	87 participants n=7 Participants	291 participants n=5 Participants	419 participants n=4 Participants
History of Extraintestinal Manifestations Yes	123 participants n=5 Participants	177 participants n=7 Participants	619 participants n=5 Participants	919 participants n=4 Participants
History of Extraintestinal Manifestations No	25 participants n=5 Participants	43 participants n=7 Participants	128 participants n=5 Participants	196 participants n=4 Participants

PRIMARY outcome

Timeframe: Week 6

Population: Induction Study Intention 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=148 Participants Participants in Cohort 1 received double-blind placebo intravenous infusions at Week 0 and Week 2 in the Induction Phase.	DB Vedolizumab n=220 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 then 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 Achieving Clinical Remission at Week 6	6.8 percentage of participants Interval 2.7 to 10.8	14.5 percentage of participants Interval 9.9 to 19.2	—

PRIMARY outcome

Timeframe: Baseline and Week 6

Population: Induction Study ITT Population

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

Outcome measures

Outcome measures
Measure	Placebo n=148 Participants Participants in Cohort 1 received double-blind placebo intravenous infusions at Week 0 and Week 2 in the Induction Phase.	DB Vedolizumab n=220 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 then 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 Enhanced Clinical Response at Week 6	25.7 percentage of participants Interval 18.6 to 32.7	31.4 percentage of participants Interval 25.2 to 37.5	—

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 CDAI score ≤ 150. The CDAI is used to quantify the symptoms of patients with Crohn's disease and consists of eight factors, each summed after adjustment with a weighting factor. The components of the CDAI are: * Number of liquid or soft stools each day for 7 days; * Abdominal pain (graded from 0-3 on severity) each day for 7 days; * General well-being, subjectively assessed from 0 (well) to 4 (terrible) each day for 7 days; * Presence of complications; * Taking Lomotil or opiates for diarrhea; * Presence of an abdominal mass (0 as none, 2 as questionable, 5 as definite); * Hematocrit of \< 0.47 in men and \< 0.42 in women; * Percentage deviation from standard weight. The total score ranges from 0 to 600 with higher scores indicating 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=153 Participants Participants in Cohort 1 received double-blind placebo intravenous infusions at Week 0 and Week 2 in the Induction Phase.	DB Vedolizumab n=154 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=154 Participants 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: Percentage of Participants Achieving Clinical Remission at Week 52	21.6 percentage of participants Interval 15.1 to 28.1	39.0 percentage of participants Interval 31.3 to 46.7	36.4 percentage of participants Interval 28.8 to 44.0

SECONDARY outcome

Timeframe: Baseline and Week 6

Population: Induction Study ITT Population; last observation carried forward (LOCF) imputation was used. Baseline CRP was missing for one participant in the placebo group.

C-reactive protein (CRP) is a protein found in the blood, the levels of which rise in response to inflammation. Normal concentration in healthy human serum is usually lower than 10 mg/L, slightly increasing with age. Higher levels indicate mild inflammation (10-40 mg/L) and active inflammation (40-200 mg/L).

Outcome measures

Outcome measures
Measure	Placebo n=147 Participants Participants in Cohort 1 received double-blind placebo intravenous infusions at Week 0 and Week 2 in the Induction Phase.	DB Vedolizumab n=220 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 then randomized to receive double-blind treatment with vedolizumab 300 mg every 4 weeks (Q4W) from Week 6 to Week 50.
Induction Phase: Change From Baseline in C-Reactive Protein (CRP) Levels at Week 6	-0.5 mg/L Interval -27.6 to 12.1	-0.9 mg/L Interval -20.6 to 10.3	—

SECONDARY outcome

Timeframe: Baseline and Week 52

Population: Maintenance Study ITT Population

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

Outcome measures

Outcome measures
Measure	Placebo n=153 Participants Participants in Cohort 1 received double-blind placebo intravenous infusions at Week 0 and Week 2 in the Induction Phase.	DB Vedolizumab n=154 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=154 Participants 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: Percentage of Participants With Enhanced Clinical Response at Week 52	30.1 percentage of participants Interval 22.8 to 37.3	43.5 percentage of participants Interval 35.7 to 51.3	45.5 percentage of participants Interval 37.6 to 53.3

SECONDARY outcome

Timeframe: Week 52

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

Participants using oral corticosteroids at Baseline, who discontinued corticosteroids and were in clinical remission (CDAI score ≤ 150) at Week 52 achieved corticosteroid-free clinical remission. The CDAI quantifies the symptoms of patients with Crohn's disease and consists of eight factors, summed after adjustment with a weighting factor. The total score ranges from 0 to 600 with higher scores indicating greater disease activity. All participants who prematurely discontinued for any reason were considered as not achieving corticosteroid-free clinical remission.

Outcome measures

Outcome measures
Measure	Placebo n=82 Participants Participants in Cohort 1 received double-blind placebo intravenous infusions at Week 0 and Week 2 in the Induction Phase.	DB Vedolizumab n=82 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=80 Participants 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: Percentage of Participants in Corticosteroid-free Clinical Remission at Week 52	15.9 percentage of participants Interval 7.9 to 23.8	31.7 percentage of participants Interval 21.6 to 41.8	28.8 percentage of participants Interval 18.8 to 38.7

SECONDARY outcome

Timeframe: Assessed every 4 weeks from Week 6 to Week 50, and at Week 52

Population: Maintenance Study ITT Population

Durable clinical remission is defined as CDAI score ≤ 150 points at 80% or more of study visits during the Maintenance Phase, including the Week 52 visit (11 of 13 study visits). The CDAI quantifies the symptoms of patients with Crohn's disease and consists of eight factors, summed after adjustment with a weighting factor. The total score ranges from 0 to 600 with higher scores indicating 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=153 Participants Participants in Cohort 1 received double-blind placebo intravenous infusions at Week 0 and Week 2 in the Induction Phase.	DB Vedolizumab n=154 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=154 Participants 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: Percentage of Participants With Durable Clinical Remission	14.4 percentage of participants Interval 8.8 to 19.9	21.4 percentage of participants Interval 14.9 to 27.9	16.2 percentage of participants Interval 10.4 to 22.1

Adverse Events

Placebo

Serious events: 23 serious events

Other events: 96 other events

Deaths: 0 deaths

VDZ/PBO

Serious events: 23 serious events

Other events: 96 other events

Deaths: 0 deaths

VDZ/VDZ

Serious events: 199 serious events

Other events: 476 other events

Deaths: 0 deaths

Serious adverse events

Other adverse events

Other adverse events
Measure	Placebo n=148 participants at risk Participants who received double-blind placebo intravenous infusions in the Induction Phase and continued to receive placebo during the Maintenance Phase.	VDZ/PBO n=153 participants at risk Participants who received vedolizumab during the Induction Phase and were then randomized to receive placebo during the Maintenance Phase.	VDZ/VDZ n=814 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.
Musculoskeletal and connective tissue disorders Arthritis	6.1% 9/148 • 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).	1.3% 2/153 • 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).	2.8% 23/814 • 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	12.8% 19/148 • 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).	18.3% 28/153 • 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% 97/814 • 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	6.1% 9/148 • 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).	3.3% 5/153 • 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).	3.8% 31/814 • 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	8.1% 12/148 • 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).	11.8% 18/153 • 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).	10.8% 88/814 • 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 Crohn's disease	18.9% 28/148 • 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).	15.0% 23/153 • 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% 84/814 • 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	14.2% 21/148 • 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).	11.8% 18/153 • 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).	9.7% 79/814 • 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 Vomiting	6.8% 10/148 • 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).	8.5% 13/153 • 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).	5.9% 48/814 • 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 Diarrhoea	3.4% 5/148 • 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).	7.8% 12/153 • 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).	3.8% 31/814 • 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 upper	2.7% 4/148 • 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% 8/153 • 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).	2.5% 20/814 • 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 Nasopharyngitis	6.8% 10/148 • 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% 14/153 • 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).	12.3% 100/814 • 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	7.4% 11/148 • 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).	3.3% 5/153 • 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).	6.6% 54/814 • 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 Pyrexia	11.5% 17/148 • 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).	14.4% 22/153 • 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).	12.5% 102/814 • 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% 5/148 • 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).	5.9% 9/153 • 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).	6.5% 53/814 • 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	12.8% 19/148 • 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).	13.7% 21/153 • 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).	13.5% 110/814 • 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