Crohn's Disease, Ulcerative Colitis
Conditions
Brief summary
The main aim of the study is to learn if 4-weekly vedolizumab improves symptoms of Japanese participants with moderate to severe ulcerative colitis (UC) or Crohn's disease (CD). Vedolizumab is commercially available in Japan for 8-weekly treatment but not for 4-weekly treatment. The study doctors will also monitor side effects from the study treatment. This study will take place in Japan. At the first visit, the study doctor will check if each person can take part. For those who can take part, participants will receive vedolizumab intravenously once every 4 weeks. After 3 infusions of vedolizumab (which will be 12 weeks of treatment), the study doctor will assess if symptoms of the participants have improved. Participants who do not have improved symptoms after 12 weeks of treatment with vedolizumab will stop this treatment. Then, they will visit the study clinic 16 weeks after their last infusion of vedolizumab for a final check-up. Participants who have improved symptoms after 12 weeks of treatment with vedolizumab will continue to receive vedolizumab every 4 weeks. Then, after their last infusion of vedolizumab, the participants will visit the study clinic 16 weeks later for a final check-up. Finally, the study clinic will make a phone call to each participant 6 months after their last infusion to check if they have any health problems.
Interventions
DRUGVedolizumab
Vedolizumab 300 mg, IV infusion
Sponsors
Takeda
Study design
Allocation
NON_RANDOMIZED
Intervention model
PARALLEL
Primary purpose
TREATMENT
Masking
NONE
Eligibility
Sex/Gender
ALL
Age
18 Years to 80 Years
Healthy volunteers
No
Inclusion criteria
UC cohort 1. The participant has moderate to severe UC, who had previously shown clinical response in initial treatment with commercially available vedolizumab IV, then experienced secondary loss of response during maintenance therapy with commercially available vedolizumab IV Q8W. Previous "clinical response" is to be judged by the investigators referring to one of the following criteria. * Reduction of \>=2 points and \>=25% in modified Mayo score, and a decrease of \>=1 point in rectal bleeding subscore or rectal bleeding subscore of =\<1, from the start of initial treatment with commercially available vedolizumab IV. * Reduction of \>=2 points and \>=25% in partial Mayo score, and a decrease of \>=1 point in rectal bleeding subscore or rectal bleeding subscore of =\<1, from the start of initial treatment with commercially available vedolizumab IV. * Significant improvement on endoscopy (i.e., a decrease of \>=2 points in Mayo endoscopic subscore). "Secondary loss of response" is to be judged by the investigators referring to one of the following criteria. * Increase of \>=2 points in modified Mayo score, and an increase of \>=1 point in rectal bleeding subscore or rectal bleeding subscore \>=2, from the start of maintenance therapy with commercially available vedolizumab IV. * Increase of \>=2 points in partial Mayo score, and an increase of \>=1 point in rectal bleeding subscore or rectal bleeding subscore \>=2, from the start of maintenance therapy with commercially available vedolizumab IV. * Significant deterioration on endoscopy (i.e., an increase of \>=2 points in Mayo endoscopic subscore). 2. The participant has active UC as determined by a modified Mayo score of \>=5 at baseline (within 10 days prior to the start of treatment phase), with a Mayo rectal bleeding subscore of \>=1 at baseline (within 10 days prior to the start of treatment phase) and a Mayo endoscopic subscore of \>=1 as assessed by the central reader. CD cohort 1. The participant has moderate to severe CD, who had previously shown clinical response in initial treatment with commercially available vedolizumab IV, then experienced secondary loss of response during maintenance therapy with commercially available vedolizumab IV Q8W. Previous "clinical response" is to be judged by the investigators referring to one of the following criteria. * Reduction of \>=70 points in CDAI score from the start of initial treatment with commercially available vedolizumab IV. * Reduction of \>=3 points in HBI score from the start of initial treatment with commercially available vedolizumab IV. "Secondary loss of response" is to be judged by the investigators referring to one of the following criteria. * Increase of \>=70 points in CDAI score from the start of maintenance therapy with commercially available vedolizumab IV. * Increase of \>=3 points in HBI score from the start of maintenance therapy with commercially available vedolizumab IV. 2. The participant has active CD as determined by a CDAI score of \>=220 at baseline (within 10 days prior to the start of treatment phase). 3. The participant has a C-reactive protein (CRP) level \>3.0 mg/L during the screening phase.
Exclusion criteria
1. The participant has had extensive colonic resection, subtotal or total colectomy. 2. The participant has received any of the investigational or approved non-biologic therapies (e.g., cyclosporine, tacrolimus or tofacitinib, except for those specifically listed as permitted medications) for the treatment of underlying disease within 30 days or 5 half-lives of screening (whichever is longer). 3. The participant has received any investigational or approved biologic or biosimilar agent other than vedolizumab within 60 days or 5 half-lives of screening (whichever is longer). 4. The participant has a clinically significant active infection (e.g., pneumonia, pyelonephritis or coronavirus disease 2019 \[COVID-19\]) within 30 days prior to screening or during screening, or has an ongoing chronic infection. 5. The participant has known or suspected intolerance or hypersensitivity to vedolizumab or closely related compounds, or any of the vedolizumab IV excipients. 6. The participant has active cerebral/meningeal disease, or signs/symptoms of progressive multifocal leukoencephalopathy (PML) or any history of PML at screening.
Design outcomes
Primary
| Measure | Time frame | Description |
|---|---|---|
| UC Cohort: Percentage of Participants With Clinical Response at Week 12 Based on Modified Mayo Score | At Week 12 | Clinical response was defined as a reduction of greater than or equal to (\>=) 2 points and \>=25 percent (%) in modified mayo score, and a decrease of \>=1 point in rectal bleeding sub-score or rectal bleeding sub-score of less than or equal to (\<=) 1 from baseline (Week 0). Mayo score was an instrument designed to measure disease activity of UC. Modified mayo score consisted of 3 sub-scores: stool frequency, rectal bleeding, and mayo endoscopic sub-score (findings on endoscopy), each graded from 0 to 3 with higher scores indicating more severe disease. These scores were summed to give a total score range of 0 to 9. Here, a higher score indicated more severe disease. |
| CD Cohort: Percentage of Participants With Clinical Response at Week 12 | At Week 12 | Clinical response was defined as a reduction of \>=70 points in Crohn's Disease Activity Index (CDAI) score from baseline (Week 0). A CDAI was a multi-item instrument that measured severity of active Crohn's Disease monitored over 7 days included participant reported symptoms, physician-assessed signs, and laboratory markers. CDAI total score was 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 ranged approximately from 0 to 600, higher scores indicated greater disease activity. |
Secondary
| Measure | Time frame | Description |
|---|---|---|
| UC Cohort: Percentage of Participants With Clinical Remission at Week 12 Based on Modified Mayo Score | At Week 12 | Clinical remission was defined as a modified Mayo score of less than or equal to (\<=) 2, and no individual sub-score greater than (\>) 1. Mayo score was an instrument designed to measure disease activity of UC. Modified Mayo score consisted of 3 sub-scores: stool frequency, rectal bleeding, and Mayo endoscopic sub-score (findings on endoscopy), each graded from 0 to 3 with higher scores indicating more severe disease. These scores were summed to give a total score ranged of 0 to 9. Here, a higher score indicated a more severe disease. |
| UC Cohort: Percentage of Participants With Mucosal Healing at Week 12 | At Week 12 | Mucosal healing was defined as a Mayo endoscopic sub-score of \<=1, in participants with baseline Mayo endoscopic sub-score of \>=2. Mayo score consisted of 4 sub-scores: stool frequency, rectal bleeding, mayo endoscopic sub-score (findings on endoscopy) and physician's global assessment, each graded from 0 to 3 with higher scores indicating more severe disease. These scores were summed to give a total score ranged of 0 to 12. Here, a higher score indicated a more severe disease. |
| UC Cohort: Percentage of Participants With Corticosteroid-Free Remission Based on Partial Mayo Score | At Week 52 | Corticosteroid-free remission was defined as participants using oral corticosteroids at baseline (Week 0) who have discontinued oral corticosteroids and were in clinical remission based on partial Mayo score at Week 52. Clinical remission based on partial Mayo score was defined as a partial Mayo score of =\<2, and no individual sub-score \>1. Mayo score was an instrument designed to measure disease activity of UC. Partial Mayo score consists of 3 sub-scores: stool frequency, rectal bleeding, and physician's global assessment, each graded from 0 to 3 with higher scores indicated more severe disease. These scores are summed to give a total score range of 0 to 9. Here, higher scores indicated more severe disease. |
| CD Cohort: Percentage of Participants With Clinical Remission at Week 12 | At Week 12 | Clinical remission was defined as a CDAI score of \<=150. A CDAI was a multi-item instrument that measured severity of active Crohn's Disease monitored over 7 days included participant reported symptoms, physician-assessed signs, and laboratory markers. CDAI total score was 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 ranged approximately from 0 to 600, higher scores indicating greater disease activity. |
| CD Cohort: Percentage of Participants With Enhanced Clinical Response at Week 12 | At Week 12 | Enhanced clinical response was defined as a reduction of \>=100 points in CDAI score from baseline (Week 0). A CDAI was a multi-item instrument that measured severity of active Crohn's Disease monitored over 7 days included participant reported symptoms, physician-assessed signs, and laboratory markers. CDAI total score was 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 ranged approximately from 0 to 600, higher scores indicating greater disease activity. |
| CD Cohort: Percentage of Participants With Corticosteroid-Free Remission | At Week 52 | Corticosteroid-free remission was defined as participants using oral corticosteroids at baseline (Week 0) who have discontinued oral corticosteroids and are in clinical remission at Week 52. |
Countries
Japan
Contacts
STUDY_DIRECTORStudy Director
Takeda
Participant flow
Recruitment details
Participants took part in the study at 20 investigative sites in Japan from 04 June 2021.
Pre-assignment details
A total of 56 participants with ulcerative colitis (UC) or Crohn's disease (CD) were enrolled in the study. The results in this summary are based on the study's primary completion date (30 May 2025). The study is ongoing in the open-label period, and additional results will be reported upon study completion.
Baseline characteristics
| Characteristic | — |
|---|---|
| Age, Continuous | 49.5 years STANDARD_DEVIATION 16.93 |
| Ethnicity (NIH/OMB) Hispanic or Latino | 0 Participants |
| Ethnicity (NIH/OMB) Not Hispanic or Latino | 15 Participants |
| Ethnicity (NIH/OMB) Unknown or Not Reported | 0 Participants |
| Race (NIH/OMB) American Indian or Alaska Native | 0 Participants |
| Race (NIH/OMB) Asian | 56 Participants |
| Race (NIH/OMB) Black or African American | 0 Participants |
| Race (NIH/OMB) More than one race | 0 Participants |
| Race (NIH/OMB) Native Hawaiian or Other Pacific Islander | 0 Participants |
| Race (NIH/OMB) Unknown or Not Reported | 0 Participants |
| Race (NIH/OMB) White | 0 Participants |
| Sex: Female, Male Female | 22 Participants |
| Sex: Female, Male Male | 26 Participants |
Adverse events
| Event type | EG000 affected / at risk | EG001 affected / at risk |
|---|---|---|
| deaths Total, all-cause mortality | 0 / 41 | 0 / 15 |
| other Total, other adverse events | 19 / 41 | 14 / 15 |
| serious Total, serious adverse events | 3 / 41 | 6 / 15 |
Outcome results
None listed