Trial Outcomes & Findings for Vedolizumab IV 300 mg in the Treatment of Fistulizing Crohn's Disease (NCT NCT02630966)

NCT ID: NCT02630966

Last Updated: 2019-11-19

Results Overview

Closed fistulae are no longer draining despite gentle finger compression.

Recruitment status

COMPLETED

Study phase

PHASE4

Target enrollment

34 participants

Primary outcome timeframe

Baseline, Week 30

Results posted on

2019-11-19

Participant Flow

Participants took part in the study at 13 investigative sites in Canada, France, Italy, the Netherlands, Spain, the United Kingdom, and the United States from 10 August 2016 to 14 November 2018.

Participants with diagnosis of moderately to severely active Crohn's disease and 1 to 3 draining perianal fistula(e) of at least 2 weeks duration were randomized in 1:1 ratio to receive vedolizumab IV 300 mg dose at Weeks 0,2,6,14,22 and vedolizumab placebo-matching IV dose at Week 10 or vedolizumab IV 300 mg dose at Weeks 0,2,6,10,14,and 22.

Participant milestones

Participant milestones
Measure	Group 1: Vedolizumab IV 300 mg + Placebo Vedolizumab 300 mg, IV infusion, once, at Weeks 0, 2, 6, 14, and 22, and vedolizumab placebo-matching, IV infusion once, at Week 10 to maintain the blind.	Group 2: Vedolizumab 300 mg Vedolizumab 300 mg, IV infusion, once, at Weeks 0, 2, 6, 10, 14, and 22.
Overall Study STARTED	16	18
Overall Study COMPLETED	14	10
Overall Study NOT COMPLETED	2	8

Reasons for withdrawal

Reasons for withdrawal
Measure	Group 1: Vedolizumab IV 300 mg + Placebo Vedolizumab 300 mg, IV infusion, once, at Weeks 0, 2, 6, 14, and 22, and vedolizumab placebo-matching, IV infusion once, at Week 10 to maintain the blind.	Group 2: Vedolizumab 300 mg Vedolizumab 300 mg, IV infusion, once, at Weeks 0, 2, 6, 10, 14, and 22.
Overall Study Adverse Event	1	3
Overall Study Significant Protocol Deviation	0	2
Overall Study Voluntary Withdrawal	1	1
Overall Study Lack of Efficacy	0	2

Baseline Characteristics

Vedolizumab IV 300 mg in the Treatment of Fistulizing Crohn's Disease

Baseline characteristics by cohort

Baseline characteristics by cohort
Measure	Group 1: Vedolizumab IV 300 mg + Placebo n=16 Participants Vedolizumab 300 mg, IV infusion, once, at Weeks 0, 2, 6, 14, and 22, and vedolizumab placebo-matching, IV infusion once, at Week 10 to maintain the blind.	Group 2: Vedolizumab 300 mg n=18 Participants Vedolizumab 300 mg, IV infusion, once, at Weeks 0, 2, 6, 10, 14, and 22.	Total n=34 Participants Total of all reporting groups
Age, Continuous	35.1 years STANDARD_DEVIATION 10.35 • n=5 Participants	35.1 years STANDARD_DEVIATION 10.67 • n=7 Participants	35.1 years STANDARD_DEVIATION 10.36 • n=5 Participants
Sex: Female, Male Female	6 Participants n=5 Participants	7 Participants n=7 Participants	13 Participants n=5 Participants
Sex: Female, Male Male	10 Participants n=5 Participants	11 Participants n=7 Participants	21 Participants n=5 Participants
Ethnicity (NIH/OMB) Hispanic or Latino	0 Participants n=5 Participants	0 Participants n=7 Participants	0 Participants n=5 Participants
Ethnicity (NIH/OMB) Not Hispanic or Latino	2 Participants n=5 Participants	3 Participants n=7 Participants	5 Participants n=5 Participants
Ethnicity (NIH/OMB) Unknown or Not Reported	14 Participants n=5 Participants	15 Participants n=7 Participants	29 Participants n=5 Participants
Race (NIH/OMB) American Indian or Alaska Native	0 Participants n=5 Participants	0 Participants n=7 Participants	0 Participants n=5 Participants
Race (NIH/OMB) Asian	1 Participants n=5 Participants	0 Participants n=7 Participants	1 Participants n=5 Participants
Race (NIH/OMB) Native Hawaiian or Other Pacific Islander	0 Participants n=5 Participants	0 Participants n=7 Participants	0 Participants n=5 Participants
Race (NIH/OMB) Black or African American	1 Participants n=5 Participants	0 Participants n=7 Participants	1 Participants n=5 Participants
Race (NIH/OMB) White	12 Participants n=5 Participants	15 Participants n=7 Participants	27 Participants n=5 Participants
Race (NIH/OMB) More than one race	0 Participants n=5 Participants	0 Participants n=7 Participants	0 Participants n=5 Participants
Race (NIH/OMB) Unknown or Not Reported	2 Participants n=5 Participants	3 Participants n=7 Participants	5 Participants n=5 Participants
Region of Enrollment Canada	1 Participants n=5 Participants	0 Participants n=7 Participants	1 Participants n=5 Participants
Region of Enrollment France	2 Participants n=5 Participants	3 Participants n=7 Participants	5 Participants n=5 Participants
Region of Enrollment Italy	5 Participants n=5 Participants	6 Participants n=7 Participants	11 Participants n=5 Participants
Region of Enrollment Netherlands	2 Participants n=5 Participants	3 Participants n=7 Participants	5 Participants n=5 Participants
Region of Enrollment Spain	3 Participants n=5 Participants	2 Participants n=7 Participants	5 Participants n=5 Participants
Region of Enrollment United Kingdom	1 Participants n=5 Participants	1 Participants n=7 Participants	2 Participants n=5 Participants
Region of Enrollment United States	2 Participants n=5 Participants	3 Participants n=7 Participants	5 Participants n=5 Participants
Height	170.1 centimeter (cm) STANDARD_DEVIATION 6.35 • n=5 Participants	176.4 centimeter (cm) STANDARD_DEVIATION 10.38 • n=7 Participants	173.4 centimeter (cm) STANDARD_DEVIATION 9.17 • n=5 Participants
Weight	73.65 kilograms (kg) STANDARD_DEVIATION 15.986 • n=5 Participants	68.36 kilograms (kg) STANDARD_DEVIATION 14.661 • n=7 Participants	70.85 kilograms (kg) STANDARD_DEVIATION 15.299 • n=5 Participants
Body Mass Index (BMI)	25.40 kg per square meter (kg/m^2) STANDARD_DEVIATION 5.080 • n=5 Participants	21.84 kg per square meter (kg/m^2) STANDARD_DEVIATION 3.580 • n=7 Participants	23.52 kg per square meter (kg/m^2) STANDARD_DEVIATION 4.646 • n=5 Participants
Smoking Classification Never-smoker	7 Participants n=5 Participants	8 Participants n=7 Participants	15 Participants n=5 Participants
Smoking Classification Current smoker	7 Participants n=5 Participants	4 Participants n=7 Participants	11 Participants n=5 Participants
Smoking Classification Ex-smoker	2 Participants n=5 Participants	6 Participants n=7 Participants	8 Participants n=5 Participants

PRIMARY outcome

Timeframe: Baseline, Week 30

Population: Modified Full Analysis Set (mFAS) included all participants in FAS who had at least one draining fistula at baseline (Day 1). FAS included all randomized participants who received at least 1 dose of study medication and have a post baseline assessment of fistula healing. Data is reported for participants evaluable for this outcome measure.

Closed fistulae are no longer draining despite gentle finger compression.

Outcome measures

Outcome measures
Measure	Group 1: Vedolizumab IV 300 mg + Placebo n=12 Participants Vedolizumab 300 mg, IV infusion, once, at Weeks 0, 2, 6, 14, and 22, and vedolizumab placebo-matching, IV infusion once, at Week 10 to maintain the blind.	Group 2: Vedolizumab 300 mg n=8 Participants Vedolizumab 300 mg, IV infusion, once, at Weeks 0, 2, 6, 10, 14, and 22.
Percentage of Participants With at Least 50% Reduction From Baseline in the Number of Draining Perianal Fistulae (of Those Draining at Baseline)	75.0 percentage of participants Interval 50.5 to 99.5	75.0 percentage of participants Interval 45.0 to 100.0

SECONDARY outcome

Timeframe: Weeks 22 and 30

Population: The mFAS includes all participants in the FAS who had at least one draining fistula at baseline (Day 1). The FAS includes all randomized participants who received at least 1 dose of study medication and have a post baseline assessment of fistula healing. Data is reported for participants evaluable for this outcome measure.

Closed fistulae are no longer draining despite gentle finger compression.

Outcome measures

Outcome measures
Measure	Group 1: Vedolizumab IV 300 mg + Placebo n=11 Participants Vedolizumab 300 mg, IV infusion, once, at Weeks 0, 2, 6, 14, and 22, and vedolizumab placebo-matching, IV infusion once, at Week 10 to maintain the blind.	Group 2: Vedolizumab 300 mg n=8 Participants Vedolizumab 300 mg, IV infusion, once, at Weeks 0, 2, 6, 10, 14, and 22.
Percentage of Participants With at Least 50% Reduction of From Baseline in the Number of Draining Perianal Fistulae (of Those Draining at Baseline) at Both Weeks 22 and 30	72.7 percentage of participants Interval 46.4 to 99.0	62.5 percentage of participants Interval 24.5 to 91.5

SECONDARY outcome

Timeframe: Week 30

Population: The mFAS included all participants in the FAS who had at least one draining fistula at baseline (Day 1). The FAS included all randomized participants who received at least 1 dose of study medication and have a post baseline assessment of fistula healing. Data is reported for participants evaluable for this outcome measure.

Closed fistulae are no longer draining despite gentle finger compression.

Outcome measures

Outcome measures
Measure	Group 1: Vedolizumab IV 300 mg + Placebo n=12 Participants Vedolizumab 300 mg, IV infusion, once, at Weeks 0, 2, 6, 14, and 22, and vedolizumab placebo-matching, IV infusion once, at Week 10 to maintain the blind.	Group 2: Vedolizumab 300 mg n=8 Participants Vedolizumab 300 mg, IV infusion, once, at Weeks 0, 2, 6, 10, 14, and 22.
Percentage of Participants With 100% Perianal Fistulae Closure (of the Fistulae Draining at Baseline)	58.3 percentage of participants Interval 30.4 to 86.2	62.5 percentage of participants Interval 24.5 to 91.5

SECONDARY outcome

Timeframe: Up to Week 30

Population: mFAS included participants in FAS with \>=1 draining fistula at baseline (Day 1). FAS included all randomized participants who received \>=1 dose of study drug, have a post baseline assessment of fistula healing.

Closed fistulae are no longer draining despite gentle finger compression.The time to first fistula closure was analyzed descriptively using Kaplan-Meier product limit methods, with participants for which no fistula closure is reported being censored at the time of their last fistulae assessment or date of last record (Week 30 or early discontinuation). Estimated median time to fistula closure (and 95%CI) are reported.

Outcome measures

Outcome measures
Measure	Group 1: Vedolizumab IV 300 mg + Placebo n=14 Participants Vedolizumab 300 mg, IV infusion, once, at Weeks 0, 2, 6, 14, and 22, and vedolizumab placebo-matching, IV infusion once, at Week 10 to maintain the blind.	Group 2: Vedolizumab 300 mg n=14 Participants Vedolizumab 300 mg, IV infusion, once, at Weeks 0, 2, 6, 10, 14, and 22.
Time to First Perianal Fistulae Closure (of Those Fistulae Draining at Baseline)	30.5 days Interval 15.0 to 71.0	159.0 days Interval 16.0 to Upper limit of 95% of confidence interval (CI) was not estimable due to low number of participants with events.

SECONDARY outcome

Timeframe: Up to Week 30

Closed fistulae are no longer draining despite gentle finger compression. The time to first fistula closure was analyzed descriptively using Kaplan-Meier product limit methods, with participants for which no fistula closure is reported being censored at the time of their last fistulae assessment or date of last record (Week 30 or early discontinuation). Estimated median time to fistula closure (and 95%CI) are reported.

Outcome measures

Outcome measures
Measure	Group 1: Vedolizumab IV 300 mg + Placebo n=14 Participants Vedolizumab 300 mg, IV infusion, once, at Weeks 0, 2, 6, 14, and 22, and vedolizumab placebo-matching, IV infusion once, at Week 10 to maintain the blind.	Group 2: Vedolizumab 300 mg n=14 Participants Vedolizumab 300 mg, IV infusion, once, at Weeks 0, 2, 6, 10, 14, and 22.
Time to Last (100%) Perianal Fistulae Closure (of Those Fistulae Draining at Baseline)	45.0 days Interval 15.0 to 155.0	159.0 days Interval 16.0 to Upper limit of 95% CI was not estimable due to low number of participants with events.

SECONDARY outcome

Timeframe: Up to Week 30

Duration of fistula response was measured by number of days with/without drainage. Duration of perianal fistula response (days) was derived as the sum of days with perianal fistula response between Day 1 and the end of the study (Week 30 or early discontinuation). Perianal fistula response is defined as reduction in the number of draining perianal fistulae (of those draining at Baseline) draining of at least 50%.

Outcome measures

Outcome measures
Measure	Group 1: Vedolizumab IV 300 mg + Placebo n=14 Participants Vedolizumab 300 mg, IV infusion, once, at Weeks 0, 2, 6, 14, and 22, and vedolizumab placebo-matching, IV infusion once, at Week 10 to maintain the blind.	Group 2: Vedolizumab 300 mg n=14 Participants Vedolizumab 300 mg, IV infusion, once, at Weeks 0, 2, 6, 10, 14, and 22.
Duration of Perianal Fistulae Response (of Those Fistulae Draining at Baseline)	158.5 days Interval 0.0 to 202.0	33.5 days Interval 0.0 to 203.0

Adverse Events

Group 1: Vedolizumab IV 300 mg + Placebo

Serious events: 4 serious events

Other events: 15 other events

Deaths: 0 deaths

Group 2: Vedolizumab 300 mg

Serious events: 3 serious events

Other events: 17 other events

Deaths: 0 deaths

Serious adverse events

Serious adverse events
Measure	Group 1: Vedolizumab IV 300 mg + Placebo n=16 participants at risk Vedolizumab 300 mg, IV infusion, once, at Weeks 0, 2, 6, 14, and 22, and vedolizumab placebo-matching, IV infusion once, at Week 10 to maintain the blind.	Group 2: Vedolizumab 300 mg n=18 participants at risk Vedolizumab 300 mg, IV infusion, once, at Weeks 0, 2, 6, 10, 14, and 22.
Gastrointestinal disorders Crohn's disease	6.2% 1/16 • Up to approximately 44 weeks At each visit investigator had to document any occurrence of adverse events and abnormal laboratory findings. Any event spontaneously reported by the participant or observed by investigator was recorded, irrespective of relation to study treatment. Safety Analysis Set included all participants who received at least 1 dose of study medication.	5.6% 1/18 • Up to approximately 44 weeks At each visit investigator had to document any occurrence of adverse events and abnormal laboratory findings. Any event spontaneously reported by the participant or observed by investigator was recorded, irrespective of relation to study treatment. Safety Analysis Set included all participants who received at least 1 dose of study medication.
Gastrointestinal disorders Ileal stenosis	6.2% 1/16 • Up to approximately 44 weeks At each visit investigator had to document any occurrence of adverse events and abnormal laboratory findings. Any event spontaneously reported by the participant or observed by investigator was recorded, irrespective of relation to study treatment. Safety Analysis Set included all participants who received at least 1 dose of study medication.	0.00% 0/18 • Up to approximately 44 weeks At each visit investigator had to document any occurrence of adverse events and abnormal laboratory findings. Any event spontaneously reported by the participant or observed by investigator was recorded, irrespective of relation to study treatment. Safety Analysis Set included all participants who received at least 1 dose of study medication.
General disorders Hyperpyrexia	0.00% 0/16 • Up to approximately 44 weeks At each visit investigator had to document any occurrence of adverse events and abnormal laboratory findings. Any event spontaneously reported by the participant or observed by investigator was recorded, irrespective of relation to study treatment. Safety Analysis Set included all participants who received at least 1 dose of study medication.	5.6% 1/18 • Up to approximately 44 weeks At each visit investigator had to document any occurrence of adverse events and abnormal laboratory findings. Any event spontaneously reported by the participant or observed by investigator was recorded, irrespective of relation to study treatment. Safety Analysis Set included all participants who received at least 1 dose of study medication.
Infections and infestations Anal abscess	18.8% 3/16 • Up to approximately 44 weeks At each visit investigator had to document any occurrence of adverse events and abnormal laboratory findings. Any event spontaneously reported by the participant or observed by investigator was recorded, irrespective of relation to study treatment. Safety Analysis Set included all participants who received at least 1 dose of study medication.	0.00% 0/18 • Up to approximately 44 weeks At each visit investigator had to document any occurrence of adverse events and abnormal laboratory findings. Any event spontaneously reported by the participant or observed by investigator was recorded, irrespective of relation to study treatment. Safety Analysis Set included all participants who received at least 1 dose of study medication.
Infections and infestations Abdominal infection	6.2% 1/16 • Up to approximately 44 weeks At each visit investigator had to document any occurrence of adverse events and abnormal laboratory findings. Any event spontaneously reported by the participant or observed by investigator was recorded, irrespective of relation to study treatment. Safety Analysis Set included all participants who received at least 1 dose of study medication.	0.00% 0/18 • Up to approximately 44 weeks At each visit investigator had to document any occurrence of adverse events and abnormal laboratory findings. Any event spontaneously reported by the participant or observed by investigator was recorded, irrespective of relation to study treatment. Safety Analysis Set included all participants who received at least 1 dose of study medication.
Musculoskeletal and connective tissue disorders Arthralgia	0.00% 0/16 • Up to approximately 44 weeks At each visit investigator had to document any occurrence of adverse events and abnormal laboratory findings. Any event spontaneously reported by the participant or observed by investigator was recorded, irrespective of relation to study treatment. Safety Analysis Set included all participants who received at least 1 dose of study medication.	5.6% 1/18 • Up to approximately 44 weeks At each visit investigator had to document any occurrence of adverse events and abnormal laboratory findings. Any event spontaneously reported by the participant or observed by investigator was recorded, irrespective of relation to study treatment. Safety Analysis Set included all participants who received at least 1 dose of study medication.

Other adverse events

Additional Information

Medical Director

Takeda

Phone: 877-825-3327

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