Efficacy and Safety of Vedolizumab Subcutaneous (SC) as Maintenance Therapy in Crohn's Disease (CD)

• ClinicalTrials.gov Identifier: NCT02611817
• Recruitment Status: Completed
• First Posted: November 23, 2015
• Results First Posted: June 23, 2020
• Last Update Posted: May 25, 2022
• Sponsor: Takeda
• Information provided by (Responsible Party): Takeda

• Study Type: Interventional
• Study Design: Allocation: Randomized; Intervention Model: Parallel Assignment; Masking: Quadruple (Participant, Care Provider, Investigator, Outcomes Assessor); Primary Purpose: Treatment
• Condition: Crohn's Disease
• Interventions: Drug: Vedolizumab SC 108 mg; Drug: Placebo; Drug: Vedolizumab IV 300 mg
• Enrollment: 644

Participant Flow

Recruitment Details	Participants with moderate to severe Crohn's disease (CD) took part in the study at 169 investigative sites in North America, South America, Western/Northern Europe, Central Europe, Eastern Europe, East Asia, and Africa/Australia from 04 Jan 2016 to 06 Aug 2019.
Pre-assignment Details	Participants were enrolled in open-label (OL) induction phase to receive vedolizumab (VDZ) intravenous (IV). Participants with clinical response (CR) at Week 6 were randomized into double-blind maintenance phase to receive VDZ subcutaneous/placebo, and who did not achieve CR at Week 6 received 3rd infusion of OL VDZ IV and completed Week 14 visit.

Arm/Group Title	Open-label Induction Phase: Vedolizumab 300 mg IV	Maintenance Phase: Induction IV + Placebo	Maintenance Phase: Induction IV + Vedolizumab 108 mg SC
Arm/Group Description	Vedolizumab 300 milligram (mg), infusion, intravenously, once at Weeks 0, 2 in the open-label induction phase.	Vedolizumab placebo-matching injection, subcutaneously, once every 2 weeks from Week 6 up to Week 50. Participants who received vedolizumab 300 mg IV infusion in open-label induction phase and achieved clinical response at Week 6 were randomized to receive placebo in maintenance phase.	Vedolizumab 108 mg, injection, subcutaneously, once every 2 weeks from Week 6 up to Week 50. Participants who received vedolizumab 300 mg IV infusion in open-label induction phase and achieved clinical response at Week 6 were randomized to receive vedolizumab injection subcutaneously in maintenance phase.
Period Title: Open-label Induction Phase
Started	644	0	0
Completed [1]	594	0	0
Not Completed	50	0	0
Reason Not Completed
Reason not Specified	9	0	0
Lack of Efficacy	8	0	0
Pregnancy	1	0	0
Withdrawal by Subject	9	0	0
Lost to Follow-up	2	0	0
Protocol Violation	5	0	0
Adverse Event	16	0	0
[1] Completers included participants who received OL vedolizumab IV and had Week 14 visit.
Period Title: Double-blind Maintenance Phase
Started [1]	0	135	275
Completed	0	73	168
Not Completed	0	62	107
Reason Not Completed
Adverse Event	0	12	11
Randomized but not Treated	0	1	0
Reason not Specified	0	1	2
Lack of Efficacy	0	43	78
Pregnancy	0	0	1
Withdrawal by Subject	0	5	14
Lost to Follow-up	0	0	1
[1] Participants who achieved clinical response at Week 6 entered the Maintenance Phase.

Baseline Characteristics

Arm/Group Title		Induction Phase Only: Vedolizumab 300 mg IV	Maintenance Phase: Induction IV + Placebo	Maintenance Phase: Induction IV + Vedolizumab 108 mg SC	Total
Arm/Group Description		Vedolizumab 300 mg, infusion, intravenously, once at Weeks 0, 2 in the open-label induction phase Participants who did not achieve clinical response at Week 6 received third infusion of vedolizumab 300 mg IV on Week 6.	Vedolizumab placebo-matching injection, subcutaneously, once every 2 weeks from Week 6 up to Week 50. Participants who received vedolizumab 300 mg IV infusion in open-label induction phase and achieved clinical response at Week 6 were randomized to receive placebo in maintenance phase.	Vedolizumab 108 mg, injection, subcutaneously, once every 2 weeks from Week 6 up to Week 50. Participants who received vedolizumab 300 mg IV infusion in open-label induction phase and achieved clinical response at Week 6 were randomized to receive vedolizumab injection subcutaneously in maintenance phase.	Total of all reporting groups
Overall Number of Baseline Participants		235	134	275	644
Baseline Analysis Population Description		The safety analysis set-combined (SAF-C) included all participants who received at least 1 dose of study vedolizumab IV.
Age, Continuous; Mean (Standard Deviation); Unit of measure: Years
	Number Analyzed	235 participants	134 participants	275 participants	644 participants
		37.4 (12.79)	36.1 (12.93)	38.2 (13.85)	37.5 (13.29)
Sex: Female, Male; Measure Type: Count of Participants; Unit of measure: Participants
	Number Analyzed	235 participants	134 participants	275 participants	644 participants
	Female	119 50.6%	68 50.7%	118 42.9%	305 47.4%
	Male	116 49.4%	66 49.3%	157 57.1%	339 52.6%
Ethnicity (NIH/OMB); Measure Type: Count of Participants; Unit of measure: Participants
	Number Analyzed	235 participants	134 participants	275 participants	644 participants
	Hispanic or Latino	0 0.0%	1 0.7%	2 0.7%	3 0.5%
	Not Hispanic or Latino	50 21.3%	20 14.9%	60 21.8%	130 20.2%
	Unknown or Not Reported	185 78.7%	113 84.3%	213 77.5%	511 79.3%
Race (NIH/OMB); Measure Type: Count of Participants; Unit of measure: Participants
	Number Analyzed	235 participants	134 participants	275 participants	644 participants
	American Indian or Alaska Native	0 0.0%	2 1.5%	0 0.0%	2 0.3%
	Asian	23 9.8%	6 4.5%	17 6.2%	46 7.1%
	Native Hawaiian or Other Pacific Islander	2 0.9%	1 0.7%	0 0.0%	3 0.5%
	Black or African American	3 1.3%	1 0.7%	7 2.5%	11 1.7%
	White	207 88.1%	124 92.5%	250 90.9%	581 90.2%
	More than one race	0 0.0%	0 0.0%	1 0.4%	1 0.2%
	Unknown or Not Reported	0 0.0%	0 0.0%	0 0.0%	0 0.0%
Weight; Mean (Standard Deviation); Unit of measure: Kilogram (kg)
	Number Analyzed	235 participants	134 participants	275 participants	644 participants
		69.94 (18.403)	69.79 (18.103)	74.08 (18.994)	71.68 (18.684)
Body Mass Index; Mean (Standard Deviation); Unit of measure: Kilogram per square meter (kg/m^2)
	Number Analyzed	235 participants	134 participants	275 participants	644 participants
		24.20 (6.073)	23.93 (5.541)	25.06 (5.915)	24.51 (5.909)
Smoking Classification; Measure Type: Count of Participants; Unit of measure: Participants	Number Analyzed	235 participants	134 participants	275 participants	644 participants
Never smoked		140 59.6%	85 63.4%	148 53.8%	373 57.9%
Current smoker		49 20.9%	26 19.4%	54 19.6%	129 20.0%
Ex-smoker		46 19.6%	23 17.2%	73 26.5%	142 22.0%

Outcome Measures

1. Primary Outcome

Title	Percentage of Participants Achieving Clinical Remission at Week 52
Description	Clinical remission is defined as a Crohn's Disease Activity Index (CDAI) score less than or equal to (<=) 150 at Week 52. A CDAI is a multi-item instrument which measures severity of active Crohn's Disease monitored over 7 days includes participant reported symptoms, physician-assessed signs, and laboratory markers. CDAI score is equal to (=) sum of weighted scores for subjective items (number of liquid/soft stools, degree of abdominal pain, general well-being); and objective items (use of anti-diarrhoeal medication, abdominal mass, haematocrit, presence of extraintestinal manifestation, body weight). CDAI scores range approximately from 0 to 600, higher scores indicating greater disease activity.
Time Frame	Week 52

Outcome Measure Data

Analysis Population Description

The full analysis set (FAS): All randomized participants who received at least 1 dose of study SC drug (placebo or VDZ). Participants who only received induction IV therapy and were not randomized into the maintenance phase were not included in FAS. Participants in this set were analyzed according to the treatment they were randomized to receive.

Arm/Group Title	Maintenance Phase: Induction IV + Placebo	Maintenance Phase: Induction IV + Vedolizumab 108 mg SC
Arm/Group Description:	Vedolizumab placebo-matching injection, subcutaneously, once every 2 weeks from Week 6 up to Week 50. Participants who received vedolizumab 300 mg IV infusion in open-label induction phase and achieved clinical response at Week 6 were randomized to receive placebo in maintenance phase.	Vedolizumab 108 mg, injection, subcutaneously, once every 2 weeks from Week 6 up to Week 50. Participants who received vedolizumab 300 mg IV infusion in open-label induction phase and achieved clinical response at Week 6 were randomized to receive vedolizumab injection subcutaneously in maintenance phase.
Overall Number of Participants Analyzed	134	275
Measure Type: Number; Number (95% Confidence Interval); Unit of Measure: percentage of participants
	34.3; (26.3 to 43.0)	48.0; (42.0 to 54.1)

Statistical Analysis 1

Statistical Analysis Overview	Comparison Group Selection	Maintenance Phase: Induction IV + Placebo, Maintenance Phase: Induction IV + Vedolizumab 108 mg SC
	Comments	P-value was calculated by Cochran-Mantel-Haenszel (CMH) test stratified by electronic data capture (EDC) stratum according to concomitant use of corticosteroids, clinical remission status at Week 6, and previous TNF-alpha antagonist failure/exposed or concomitant immunomodulator use.
	Type of Statistical Test	Superiority
	Comments	[Not Specified]
Statistical Test of Hypothesis	P-Value	0.008
	Comments	[Not Specified]
	Method	Cochran-Mantel-Haenszel
	Comments	[Not Specified]
Method of Estimation	Estimation Parameter	Clopper-Pearson method
	Estimated Value	13.7
	Confidence Interval	(2-Sided) 95%; 3.8 to 23.7
	Estimation Comments	[Not Specified]

2. Secondary Outcome

Title	Percentage of Participants Achieving Enhanced Clinical Response at Week 52
Description	Enhanced clinical response is defined as a decrease from Baseline of greater than or equal to (>=) 100 points in the CDAI score at Week 52. A CDAI is a multi-item instrument which measures severity of active CD monitored over 7 days includes participant reported symptoms, physician-assessed signs, and laboratory markers. CDAI score = Sum of weighted scores for subjective items (number of liquid/soft stools, degree of abdominal pain, general well-being); and objective items (use of anti-diarrhoeal medication, abdominal mass, haematocrit, presence of extraintestinal manifestation, body weight). CDAI scores range approximately from 0 to 600, higher scores indicating greater disease activity.
Time Frame	Week 52

Outcome Measure Data

Analysis Population Description

The FAS included all randomized participants who received at least 1 dose of study SC drug (placebo or VDZ). Participants who only received induction IV therapy and were not randomized into the maintenance phase were not included in FAS. Participants in this set were analyzed according to the treatment they were randomized to receive.

Arm/Group Title	Maintenance Phase: Induction IV + Placebo	Maintenance Phase: Induction IV + Vedolizumab 108 mg SC
Arm/Group Description:	Vedolizumab placebo-matching injection, subcutaneously, once every 2 weeks from Week 6 up to Week 50. Participants who received vedolizumab 300 mg IV infusion in open-label induction phase and achieved clinical response at Week 6 were randomized to receive placebo in maintenance phase.	Vedolizumab 108 mg, injection, subcutaneously, once every 2 weeks from Week 6 up to Week 50. Participants who received vedolizumab 300 mg IV infusion in open-label induction phase and achieved clinical response at Week 6 were randomized to receive vedolizumab injection subcutaneously in maintenance phase.
Overall Number of Participants Analyzed	134	275
Measure Type: Number; Number (95% Confidence Interval); Unit of Measure: percentage of participants
	44.8; (36.2 to 53.6)	52.0; (45.9 to 58.0)

Statistical Analysis 1

Statistical Analysis Overview	Comparison Group Selection	Maintenance Phase: Induction IV + Placebo, Maintenance Phase: Induction IV + Vedolizumab 108 mg SC
	Comments	P-value was calculated by CMH test stratified by EDC stratum according to concomitant use of corticosteroids, clinical remission status at Week 6, and previous TNF-alpha antagonist failure/exposed or concomitant immunomodulator use.
	Type of Statistical Test	Superiority
	Comments	[Not Specified]
Statistical Test of Hypothesis	P-Value	0.167
	Comments	[Not Specified]
	Method	Cochran-Mantel-Haenszel
	Comments	[Not Specified]
Method of Estimation	Estimation Parameter	Clopper-Pearson method
	Estimated Value	7.3
	Confidence Interval	(2-Sided) 95%; -3.0 to 17.5
	Estimation Comments	[Not Specified]

3. Secondary Outcome

Title	Percentage of Participants Achieving Corticosteroid-free Remission at Week 52
Description	Corticosteroid-free remission is defined as participants using oral corticosteroids at Baseline (Week 0) who have discontinued oral corticosteroids and are in clinical remission at Week 52. Clinical remission is defined as a CDAI score <=150 at Week 52. CDAI score = Sum of weighted scores for subjective items (number of liquid/soft stools, degree of abdominal pain, general well-being); and objective items (use of anti-diarrhoeal medication, abdominal mass, haematocrit, presence of extraintestinal manifestation, body weight). CDAI scores range approximately from 0 to 600, higher scores indicating greater disease activity.
Time Frame	Week 52

Outcome Measure Data

Analysis Population Description

Participants from FAS, who used concomitant oral corticosteroid at Baseline. FAS had all participants who received at least 1 dose of SC drug. Participants who only received induction IV therapy and were not randomized into maintenance phase were not included in FAS. Participants were analyzed according to randomized treatment assignment.

Arm/Group Title	Maintenance Phase: Induction IV + Placebo	Maintenance Phase: Induction IV + Vedolizumab 108 mg SC
Arm/Group Description:	Vedolizumab placebo-matching injection, subcutaneously, once every 2 weeks from Week 6 up to Week 50. Participants who received vedolizumab 300 mg IV infusion in open-label induction phase and achieved clinical response at Week 6 were randomized to receive placebo in maintenance phase.	Vedolizumab 108 mg, injection, subcutaneously, once every 2 weeks from Week 6 up to Week 50. Participants who received vedolizumab 300 mg IV infusion in open-label induction phase and achieved clinical response at Week 6 were randomized to receive vedolizumab injection subcutaneously in maintenance phase.
Overall Number of Participants Analyzed	44	95
Measure Type: Number; Number (95% Confidence Interval); Unit of Measure: percentage of participants
	18.2; (8.2 to 32.7)	45.3; (35.0 to 55.8)

Statistical Analysis 1

Statistical Analysis Overview	Comparison Group Selection	Maintenance Phase: Induction IV + Placebo, Maintenance Phase: Induction IV + Vedolizumab 108 mg SC
	Comments	P-value was calculated by CMH test stratified by EDC stratum according to concomitant use of corticosteroids, clinical remission status at Week 6, and previous TNF-alpha antagonist failure/exposed or concomitant immunomodulator use.
	Type of Statistical Test	Superiority
	Comments	[Not Specified]
Statistical Test of Hypothesis	P-Value	0.002
	Comments	[Not Specified]
	Method	Cochran-Mantel-Haenszel
	Comments	[Not Specified]
Method of Estimation	Estimation Parameter	Clopper-Pearson method
	Estimated Value	27.1
	Confidence Interval	(2-Sided) 95%; 11.9 to 42.3
	Estimation Comments	[Not Specified]

4. Secondary Outcome

Title	Percentage of TNF-alpha Antagonist Naive Participants Achieving Clinical Remission at Week 52
Description	Clinical remission is defined as CDAI score <=150 at Week 52. CDAI score = Sum of weighted scores for subjective items (number of liquid/soft stools, degree of abdominal pain, general well-being); and objective items (use of anti-diarrhoeal medication, abdominal mass, haematocrit, presence of extraintestinal manifestation, body weight). CDAI scores range approximately from 0 to 600, higher scores indicating greater disease activity.
Time Frame	Week 52

Outcome Measure Data

Analysis Population Description

Participants from FAS, who were TNF-alpha antagonist naïve and had clinical remission. FAS had all participants who received at least 1 dose of SC drug. Participants who only received induction IV therapy and were not randomized in maintenance phase were not included in FAS. Participants were analyzed according to randomized treatment assignment.

Arm/Group Title	Maintenance Phase: Induction IV + Placebo	Maintenance Phase: Induction IV + Vedolizumab 108 mg SC
Arm/Group Description:	Vedolizumab placebo-matching injection, subcutaneously, once every 2 weeks from Week 6 up to Week 50. Participants who received vedolizumab 300 mg IV infusion in open-label induction phase and achieved clinical response at Week 6 were randomized to receive placebo in maintenance phase.	Vedolizumab 108 mg, injection, subcutaneously, once every 2 weeks from Week 6 up to Week 50. Participants who received vedolizumab 300 mg IV infusion in open-label induction phase and achieved clinical response at Week 6 were randomized to receive vedolizumab injection subcutaneously in maintenance phase.
Overall Number of Participants Analyzed	63	107
Measure Type: Number; Number (95% Confidence Interval); Unit of Measure: percentage of participants
	42.9; (30.5 to 56.0)	48.6; (38.8 to 58.5)

Statistical Analysis 1

Statistical Analysis Overview	Comparison Group Selection	Maintenance Phase: Induction IV + Placebo, Maintenance Phase: Induction IV + Vedolizumab 108 mg SC
	Comments	P-value was calculated by CMH test stratified by EDC stratum according to concomitant use of corticosteroids, clinical remission status at Week 6, and previous TNF-alpha antagonist failure/exposed or concomitant immunomodulator use.
	Type of Statistical Test	Superiority
	Comments	[Not Specified]
Statistical Test of Hypothesis	P-Value	0.591
	Comments	[Not Specified]
	Method	Cochran-Mantel-Haenszel
	Comments	[Not Specified]
Method of Estimation	Estimation Parameter	Clopper-Pearson method
	Estimated Value	4.3
	Confidence Interval	(2-Sided) 95%; -11.6 to 20.3
	Estimation Comments	[Not Specified]

Adverse Events

Time Frame	Treatment-emergent adverse events are adverse events that started after the first dose of study drug up to 18 weeks after the last dose of study drug (up to Week 68)
Adverse Event Reporting Description	At each visit investigator had to document any occurrence of adverse events and abnormal laboratory findings. Any event spontaneously reported by the participant/observed by the investigator was recorded, irrespective of the relation to study treatment. Participants were regrouped to mirror the baseline groupings for the better readability of the complex design. All participants and events (collected during the study in the induction/maintenance phase) have been accounted for the groupings.
Arm/Group Title	Induction Phase Only: Vedolizumab 300 mg IV		Maintenance Phase: Induction IV + Placebo		Maintenance Phase: Induction IV + Vedolizumab 108 mg SC
Arm/Group Description	Vedolizumab 300 mg, infusion, intravenously, once at Weeks 0, 2 in the open-label induction phase Participants who did not achieve clinical response at Week 6 received third infusion of vedolizumab 300 mg IV on Week 6.		Vedolizumab placebo-matching injection, subcutaneously, once every 2 weeks from Week 6 up to Week 50. Participants who received vedolizumab 300 mg IV infusion in open-label induction phase and achieved clinical response at Week 6 were randomized to receive placebo in maintenance phase.		Vedolizumab 108 mg, injection, subcutaneously, once every 2 weeks from Week 6 up to Week 50. Participants who received vedolizumab 300 mg IV infusion in open-label induction phase and achieved clinical response at Week 6 were randomized to receive vedolizumab injection subcutaneously in maintenance phase.
All-Cause Mortality
	Induction Phase Only: Vedolizumab 300 mg IV		Maintenance Phase: Induction IV + Placebo		Maintenance Phase: Induction IV + Vedolizumab 108 mg SC
	Affected / at Risk (%)		Affected / at Risk (%)		Affected / at Risk (%)
Total	0/235 (0.00%)		0/134 (0.00%)		0/275 (0.00%)
Serious Adverse Events
	Induction Phase Only: Vedolizumab 300 mg IV		Maintenance Phase: Induction IV + Placebo		Maintenance Phase: Induction IV + Vedolizumab 108 mg SC
	Affected / at Risk (%)	# Events	Affected / at Risk (%)	# Events	Affected / at Risk (%)	# Events
Total	39/235 (16.60%)		14/134 (10.45%)		23/275 (8.36%)
Blood and lymphatic system disorders
Anaemias † 1	1/235 (0.43%)	1	1/134 (0.75%)	1	1/275 (0.36%)	2
Leukocytosis † 1	0/235 (0.00%)	0	1/134 (0.75%)	1	0/275 (0.00%)	0
Febrile neutropenia † 1	1/235 (0.43%)	1	0/134 (0.00%)	0	0/275 (0.00%)	0
Cardiac disorders
Angina pectoris † 1	0/235 (0.00%)	0	0/134 (0.00%)	0	1/275 (0.36%)	1
Atrial fibrillation † 1	0/235 (0.00%)	0	0/134 (0.00%)	0	2/275 (0.73%)	2
Gastrointestinal disorders
Pancreatitis † 1	0/235 (0.00%)	0	1/134 (0.75%)	1	0/275 (0.00%)	0
Crohn's disease † 1	14/235 (5.96%)	14	5/134 (3.73%)	7	6/275 (2.18%)	7
Small intestinal obstruction † 1	1/235 (0.43%)	1	2/134 (1.49%)	3	1/275 (0.36%)	1
Ileal stenosis † 1	0/235 (0.00%)	0	0/134 (0.00%)	0	1/275 (0.36%)	1
Anal fistula † 1	1/235 (0.43%)	1	1/134 (0.75%)	1	1/275 (0.36%)	1
Enterovesical fistula † 1	0/235 (0.00%)	0	1/134 (0.75%)	1	0/275 (0.00%)	0
Intestinal obstruction † 1	1/235 (0.43%)	1	0/134 (0.00%)	0	2/275 (0.73%)	2
Subileus † 1	1/235 (0.43%)	1	0/134 (0.00%)	0	1/275 (0.36%)	1
Abdominal pain † 1	2/235 (0.85%)	2	0/134 (0.00%)	0	0/275 (0.00%)	0
Enterocutaneous fistula † 1	1/235 (0.43%)	2	0/134 (0.00%)	0	0/275 (0.00%)	0
Jejunal perforation † 1	1/235 (0.43%)	1	0/134 (0.00%)	0	0/275 (0.00%)	0
Large intestinal ulcer † 1	1/235 (0.43%)	1	0/134 (0.00%)	0	0/275 (0.00%)	0
Large intestine perforation † 1	1/235 (0.43%)	1	0/134 (0.00%)	0	0/275 (0.00%)	0
Nausea † 1	1/235 (0.43%)	1	0/134 (0.00%)	0	0/275 (0.00%)	0
Vomiting † 1	1/235 (0.43%)	1	0/134 (0.00%)	0	0/275 (0.00%)	0
General disorders
General physical health deterioration † 1	0/235 (0.00%)	0	0/134 (0.00%)	0	1/275 (0.36%)	1
Hepatobiliary disorders
Hepatitis cholestatic † 1	1/235 (0.43%)	1	0/134 (0.00%)	0	0/275 (0.00%)	0
Immune system disorders
Anaphylactic reaction † 1	1/235 (0.43%)	1	0/134 (0.00%)	0	0/275 (0.00%)	0
Infections and infestations
Anal abscess † 1	2/235 (0.85%)	2	1/134 (0.75%)	1	1/275 (0.36%)	1
Abdominal wall abscess † 1	1/235 (0.43%)	1	1/134 (0.75%)	2	0/275 (0.00%)	0
Abscess intestinal † 1	0/235 (0.00%)	0	0/134 (0.00%)	0	1/275 (0.36%)	1
Appendicitis † 1	0/235 (0.00%)	0	1/134 (0.75%)	1	0/275 (0.00%)	0
Gastroenteritis † 1	1/235 (0.43%)	1	1/134 (0.75%)	1	0/275 (0.00%)	0
Rectal abscess † 1	0/235 (0.00%)	0	0/134 (0.00%)	0	1/275 (0.36%)	1
Dengue fever † 1	0/235 (0.00%)	0	1/134 (0.75%)	1	0/275 (0.00%)	0
Bronchitis † 1	0/235 (0.00%)	0	1/134 (0.75%)	1	0/275 (0.00%)	0
Pneumonia † 1	1/235 (0.43%)	1	0/134 (0.00%)	0	1/275 (0.36%)	1
Abdominal abscess † 1	4/235 (1.70%)	6	0/134 (0.00%)	0	0/275 (0.00%)	0
Cellulitis † 1	1/235 (0.43%)	1	0/134 (0.00%)	0	0/275 (0.00%)	0
Colonic abscess † 1	1/235 (0.43%)	1	0/134 (0.00%)	0	0/275 (0.00%)	0
Perirectal abscess † 1	1/235 (0.43%)	1	0/134 (0.00%)	0	0/275 (0.00%)	0
Injury, poisoning and procedural complications
Gastrointestinal anastomotic complication † 1	1/235 (0.43%)	1	0/134 (0.00%)	0	1/275 (0.36%)	1
Incisional hernia † 1	0/235 (0.00%)	0	0/134 (0.00%)	0	1/275 (0.36%)	1
Gastrointestinal anastomotic stenosis † 1	0/235 (0.00%)	0	0/134 (0.00%)	0	1/275 (0.36%)	1
Infusion related reaction † 1	1/235 (0.43%)	1	0/134 (0.00%)	0	0/275 (0.00%)	0
Investigations
White blood cell count increased † 1	0/235 (0.00%)	0	0/134 (0.00%)	0	1/275 (0.36%)	1
Metabolism and nutrition disorders
Weight gain poor † 1	0/235 (0.00%)	0	1/134 (0.75%)	1	0/275 (0.00%)	0
Musculoskeletal and connective tissue disorders
Arthralgia † 1	0/235 (0.00%)	0	0/134 (0.00%)	0	1/275 (0.36%)	1
Neoplasms benign, malignant and unspecified (incl cysts and polyps)
Intraductal papilloma of breast † 1	0/235 (0.00%)	0	0/134 (0.00%)	0	1/275 (0.36%)	1
Nervous system disorders
Haemorrhagic stroke † 1	0/235 (0.00%)	0	0/134 (0.00%)	0	1/275 (0.36%)	1
Intraventricular haemorrhage † 1	0/235 (0.00%)	0	1/134 (0.75%)	1	0/275 (0.00%)	0
Hemiparesis † 1	1/235 (0.43%)	1	0/134 (0.00%)	0	0/275 (0.00%)	0
Hemiplegia † 1	1/235 (0.43%)	1	0/134 (0.00%)	0	0/275 (0.00%)	0
Psychiatric disorders
Alcoholism † 1	0/235 (0.00%)	0	0/134 (0.00%)	0	1/275 (0.36%)	1
Suicidal ideation † 1	0/235 (0.00%)	0	0/134 (0.00%)	0	1/275 (0.36%)	1
Renal and urinary disorders
Ureterolithiasis † 1	1/235 (0.43%)	1	0/134 (0.00%)	0	0/275 (0.00%)	0
1 Term from vocabulary, MedDRA (22.0); † Indicates events were collected by systematic assessment
Other (Not Including Serious) Adverse Events
Frequency Threshold for Reporting Other Adverse Events	5%
	Induction Phase Only: Vedolizumab 300 mg IV		Maintenance Phase: Induction IV + Placebo		Maintenance Phase: Induction IV + Vedolizumab 108 mg SC
	Affected / at Risk (%)	# Events	Affected / at Risk (%)	# Events	Affected / at Risk (%)	# Events
Total	40/235 (17.02%)		54/134 (40.30%)		102/275 (37.09%)
Gastrointestinal disorders
Crohn's disease † 1	7/235 (2.98%)	7	23/134 (17.16%)	25	36/275 (13.09%)	36
Abdominal pain † 1	9/235 (3.83%)	11	11/134 (8.21%)	14	21/275 (7.64%)	25
Nausea † 1	9/235 (3.83%)	10	7/134 (5.22%)	7	11/275 (4.00%)	14
Vomiting † 1	4/235 (1.70%)	5	7/134 (5.22%)	8	6/275 (2.18%)	7
Infections and infestations
Nasopharyngitis † 1	7/235 (2.98%)	8	6/134 (4.48%)	8	25/275 (9.09%)	26
Upper respiratory tract infection † 1	2/235 (0.85%)	2	5/134 (3.73%)	6	17/275 (6.18%)	23
Musculoskeletal and connective tissue disorders
Arthralgia † 1	8/235 (3.40%)	8	9/134 (6.72%)	10	17/275 (6.18%)	21
Nervous system disorders
Headache † 1	10/235 (4.26%)	10	5/134 (3.73%)	9	15/275 (5.45%)	19
1 Term from vocabulary, MedDRA (22.0); † Indicates events were collected by systematic assessment

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: Takeda
• Phone: +1-877-825-3327
• EMail: trialdisclosures@takeda.com

• Responsible Party: Takeda
• ClinicalTrials.gov Identifier: NCT02611817
• Other Study ID Numbers: MLN0002SC-3031; U1111-1168-0845 ( Registry Identifier: WHO ); 2015-000481-58 ( EudraCT Number ); NL55774.056.16 ( Registry Identifier: CCMO ); 16/LO/0090 ( Registry Identifier: NRES ); MLN0002SC-3031CTID ( Registry Identifier: Israel ); 163300410A0045 ( Registry Identifier: NREC ); 189748 ( Registry Identifier: HC-CTD ); MOH_2017-01-05_000039 ( Other Identifier: CRS ); JapicCTI-163386 ( Registry Identifier: JapicCTI )
• First Submitted: November 19, 2015
• First Posted: November 23, 2015
• Results First Submitted: May 5, 2020
• Results First Posted: June 23, 2020
• Last Update Posted: May 25, 2022