Crohn's Disease
Conditions
Keywords
Drug therapy, Fistulizing Crohn´s disease, Perianal Fistula
Brief summary
The purpose of this study is to evaluate the percentage of participants with perianal fistula healing at Week 30 in 2 different dose regimens of vedolizumab intravenous (IV) 300 milligram (mg) in participants with fistulizing Crohn's disease (CD).
Detailed description
The drug being tested in this study is called vedolizumab IV. Vedolizumab IV is being tested to treat people who have fistulizing CD. This study will look at fistula healing in people who take vedolizumab IV. The study is planned to enroll approximately 100 patients. Participants will be randomly assigned (by chance, like flipping a coin) to one of the two treatment groups-which will remain undisclosed to the patient and study doctor during the study (unless there is an urgent medical need): * Group 1: Vedolizumab IV 300 mg dose at Weeks 0, 2, 6, 14 and 22, and a placebo infusion at Week 10 (dummy inactive infusion - this is a solution that looks like the study drug but has no active ingredient). * Group 2: Vedolizumab IV 300 mg dose at Weeks 0, 2, 6, 10, 14 and 22. This multi-center trial will be conducted worldwide. The overall time to participate in this study from screening to 18 weeks after the last dose is 44 weeks. Participants will make multiple visits to the clinic, and will be contacted by telephone 6 months after last dose of study drug for a follow-up assessment.
Interventions
DRUGVedolizumab
Vedolizumab 300 mg IV infusion
DRUGPlacebo
0.9% sodium chloride IV infusion
Sponsors
Takeda
Study design
Allocation
RANDOMIZED
Intervention model
PARALLEL
Primary purpose
TREATMENT
Masking
QUADRUPLE (Subject, Caregiver, Investigator, Outcomes Assessor)
Eligibility
Sex/Gender
ALL
Age
18 Years to 80 Years
Healthy volunteers
No
Inclusion criteria
1. In the opinion of the investigator, the participant is capable of understanding and complying with protocol requirements. 2. The participant or, when applicable, the participant's legally acceptable representative has signed and dated a written, informed consent form and any required privacy authorization prior to the initiation of any study procedures. 3. Has a diagnosis of CD established at least 3 months prior to randomization by clinical and endoscopic evidence and corroborated by a histopathology report. 4. Has a diagnosis of a minimum of 1 perianal draining fistula of at least 2 weeks duration as a complication of moderately to severely active CD, as identified on magnetic resonance image (MRI) at Screening. Other types of fistulae (enterocutaneous, abdominal) except rectovaginal fistulae are permitted, but the number of perianal draining fistulae is limited to 3. 5. All countries except France: The participant, historically, had an inadequate response with, lost response to, or was intolerant to either conventional therapy or a tumor necrosis factor-alpha (TNF-α) antagonist for their underlying CD (does not require treatment failure for currently active draining fistula). France only: The participant, historically, failed (ie, had an inadequate response with, lost response to, or was intolerant to) infliximab for treatment of their underlying CD or fistulizing CD. 6. If the participant had noncutting perianal seton placement as part of standard care, seton must be removed by Week 14 of the study.
Exclusion criteria
1. Has a diagnosis of ulcerative colitis or indeterminate colitis. 2. Has a perianal abscess greater than (\>) 2 centimeter (cm) or an abscess that the investigator feels requires drainage based on either clinical assessment or MRI. 3. Has a Crohn's Disease Activity Index (CDAI) score \>400. 4. Has an ileostomy, colostomy, or known fixed symptomatic stenosis of the intestine. 5. Has significant anal or rectal stenosis. 6. Has active or latent tuberculosis (TB), regardless of treatment history. 7. Has evidence of active Clostridium difficile (C. difficile) infection or is having treatment for C. difficile infection or other intestinal pathogens during Screening. 8. Has current rectovaginal fistula. 9. Currently has more than 3 draining perianal fistulae. Note: Other protocol-defined inclusion/
Design outcomes
Primary
| Measure | Time frame | Description |
|---|---|---|
| Percentage of Participants With at Least 50% Reduction From Baseline in the Number of Draining Perianal Fistulae (of Those Draining at Baseline) | Baseline, Week 30 | Closed fistulae are no longer draining despite gentle finger compression. |
Secondary
| Measure | Time frame | Description |
|---|---|---|
| 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 | Weeks 22 and 30 | Closed fistulae are no longer draining despite gentle finger compression. |
| Percentage of Participants With 100% Perianal Fistulae Closure (of the Fistulae Draining at Baseline) | Week 30 | Closed fistulae are no longer draining despite gentle finger compression. |
| Time to First Perianal Fistulae Closure (of Those Fistulae Draining at Baseline) | 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. |
| Time to Last (100%) Perianal Fistulae Closure (of Those Fistulae Draining at Baseline) | 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. |
| Duration of Perianal Fistulae Response (of Those Fistulae Draining at Baseline) | 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%. |
Countries
Canada, France, Italy, Netherlands, Spain, United Kingdom, United States
Participant flow
Recruitment details
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.
Pre-assignment details
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.
Participants by arm
| Arm | Count |
|---|---|
| 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. | 16 |
| Group 2: Vedolizumab 300 mg Vedolizumab 300 mg, IV infusion, once, at Weeks 0, 2, 6, 10, 14, and 22. | 18 |
| Total | 34 |
Withdrawals & dropouts
| Period | Reason | FG000 | FG001 |
|---|---|---|---|
| Overall Study | Adverse Event | 1 | 3 |
| Overall Study | Lack of Efficacy | 0 | 2 |
| Overall Study | Significant Protocol Deviation | 0 | 2 |
| Overall Study | Voluntary Withdrawal | 1 | 1 |
Baseline characteristics
| Characteristic | Group 2: Vedolizumab 300 mg | Group 1: Vedolizumab IV 300 mg + Placebo | Total |
|---|---|---|---|
| Age, Continuous | 35.1 years STANDARD_DEVIATION 10.67 | 35.1 years STANDARD_DEVIATION 10.35 | 35.1 years STANDARD_DEVIATION 10.36 |
| Body Mass Index (BMI) | 21.84 kg per square meter (kg/m^2) STANDARD_DEVIATION 3.58 | 25.40 kg per square meter (kg/m^2) STANDARD_DEVIATION 5.08 | 23.52 kg per square meter (kg/m^2) STANDARD_DEVIATION 4.646 |
| Ethnicity (NIH/OMB) Hispanic or Latino | 0 Participants | 0 Participants | 0 Participants |
| Ethnicity (NIH/OMB) Not Hispanic or Latino | 3 Participants | 2 Participants | 5 Participants |
| Ethnicity (NIH/OMB) Unknown or Not Reported | 15 Participants | 14 Participants | 29 Participants |
| Height | 176.4 centimeter (cm) STANDARD_DEVIATION 10.38 | 170.1 centimeter (cm) STANDARD_DEVIATION 6.35 | 173.4 centimeter (cm) STANDARD_DEVIATION 9.17 |
| Race (NIH/OMB) American Indian or Alaska Native | 0 Participants | 0 Participants | 0 Participants |
| Race (NIH/OMB) Asian | 0 Participants | 1 Participants | 1 Participants |
| Race (NIH/OMB) Black or African American | 0 Participants | 1 Participants | 1 Participants |
| Race (NIH/OMB) More than one race | 0 Participants | 0 Participants | 0 Participants |
| Race (NIH/OMB) Native Hawaiian or Other Pacific Islander | 0 Participants | 0 Participants | 0 Participants |
| Race (NIH/OMB) Unknown or Not Reported | 3 Participants | 2 Participants | 5 Participants |
| Race (NIH/OMB) White | 15 Participants | 12 Participants | 27 Participants |
| Region of Enrollment Canada | 0 Participants | 1 Participants | 1 Participants |
| Region of Enrollment France | 3 Participants | 2 Participants | 5 Participants |
| Region of Enrollment Italy | 6 Participants | 5 Participants | 11 Participants |
| Region of Enrollment Netherlands | 3 Participants | 2 Participants | 5 Participants |
| Region of Enrollment Spain | 2 Participants | 3 Participants | 5 Participants |
| Region of Enrollment United Kingdom | 1 Participants | 1 Participants | 2 Participants |
| Region of Enrollment United States | 3 Participants | 2 Participants | 5 Participants |
| Sex: Female, Male Female | 7 Participants | 6 Participants | 13 Participants |
| Sex: Female, Male Male | 11 Participants | 10 Participants | 21 Participants |
| Smoking Classification Current smoker | 4 Participants | 7 Participants | 11 Participants |
| Smoking Classification Ex-smoker | 6 Participants | 2 Participants | 8 Participants |
| Smoking Classification Never-smoker | 8 Participants | 7 Participants | 15 Participants |
| Weight | 68.36 kilograms (kg) STANDARD_DEVIATION 14.661 | 73.65 kilograms (kg) STANDARD_DEVIATION 15.986 | 70.85 kilograms (kg) STANDARD_DEVIATION 15.299 |
Adverse events
| Event type | EG000 affected / at risk | EG001 affected / at risk |
|---|---|---|
| deaths Total, all-cause mortality | 0 / 16 | 0 / 18 |
| other Total, other adverse events | 15 / 16 | 17 / 18 |
| serious Total, serious adverse events | 4 / 16 | 3 / 18 |
Outcome results
Primary
Percentage of Participants With at Least 50% Reduction From Baseline in the Number of Draining Perianal Fistulae (of Those Draining at Baseline)
Closed fistulae are no longer draining despite gentle finger compression.
Time frame: 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.
| Arm | Measure | Value (NUMBER) |
|---|---|---|
| Group 1: Vedolizumab IV 300 mg + Placebo | 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 |
| Group 2: Vedolizumab 300 mg | 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 |
Secondary
Duration of Perianal Fistulae Response (of Those Fistulae Draining at Baseline)
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%.
Time frame: Up to 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.
| Arm | Measure | Value (MEDIAN) |
|---|---|---|
| Group 1: Vedolizumab IV 300 mg + Placebo | Duration of Perianal Fistulae Response (of Those Fistulae Draining at Baseline) | 158.5 days |
| Group 2: Vedolizumab 300 mg | Duration of Perianal Fistulae Response (of Those Fistulae Draining at Baseline) | 33.5 days |
Secondary
Percentage of Participants With 100% Perianal Fistulae Closure (of the Fistulae Draining at Baseline)
Closed fistulae are no longer draining despite gentle finger compression.
Time frame: 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.
| Arm | Measure | Value (NUMBER) |
|---|---|---|
| Group 1: Vedolizumab IV 300 mg + Placebo | Percentage of Participants With 100% Perianal Fistulae Closure (of the Fistulae Draining at Baseline) | 58.3 percentage of participants |
| Group 2: Vedolizumab 300 mg | Percentage of Participants With 100% Perianal Fistulae Closure (of the Fistulae Draining at Baseline) | 62.5 percentage of participants |
Secondary
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
Closed fistulae are no longer draining despite gentle finger compression.
Time frame: 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.
| Arm | Measure | Value (NUMBER) |
|---|---|---|
| Group 1: Vedolizumab IV 300 mg + Placebo | 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 |
| Group 2: Vedolizumab 300 mg | 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 | 62.5 percentage of participants |
Secondary
Time to First Perianal Fistulae Closure (of Those Fistulae Draining at Baseline)
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.
Time frame: 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.
| Arm | Measure | Value (MEDIAN) |
|---|---|---|
| Group 1: Vedolizumab IV 300 mg + Placebo | Time to First Perianal Fistulae Closure (of Those Fistulae Draining at Baseline) | 30.5 days |
| Group 2: Vedolizumab 300 mg | Time to First Perianal Fistulae Closure (of Those Fistulae Draining at Baseline) | 159.0 days |
Secondary
Time to Last (100%) Perianal Fistulae Closure (of Those Fistulae Draining at Baseline)
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.
Time frame: 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.
| Arm | Measure | Value (MEDIAN) |
|---|---|---|
| Group 1: Vedolizumab IV 300 mg + Placebo | Time to Last (100%) Perianal Fistulae Closure (of Those Fistulae Draining at Baseline) | 45.0 days |
| Group 2: Vedolizumab 300 mg | Time to Last (100%) Perianal Fistulae Closure (of Those Fistulae Draining at Baseline) | 159.0 days |