An Open-Label, Phase 3 Study to Evaluate the Efficacy, Safety, and Pharmacokinetics of Intravenous (IV) Vedolizumab Administered Every 4 Weeks (Q4W) in Japanese Patients with Moderate to Severe Ulcerative Colitis or Crohn's Disease who Experienced Secondary Loss of Response During Maintenance Therapy with Vedolizumab IV Administered Every 8 Weeks (Q8W)
A Study of Vedolizumab, given every 4 weeks, in Japanese Participants with Moderate to Severe Ulcerative Colitis or Crohn's Disease
Shikamura Mitsuhiro
Takeda Pharmaceutical Company Limited
1-1, Doshomachi 4-chome, Chuo-ku, Osaka
+81-662042111
smb.Japanclinicalstudydisclosure@takeda.com
Contact for Clinical Trial Information
Takeda Pharmaceutical Company Limited
1-1, Doshomachi 4-chome, Chuo-ku, Osaka
+81-662042111
smb.Japanclinicalstudydisclosure@takeda.com
Not Recruiting
June. 04, 2021
June. 04, 2021
57
Interventional
single arm study
open(masking not used)
uncontrolled control
single assignment
treatment purpose
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.
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, or has lingering COVID-19-related symptoms, if previously infected with COVID-19..
5. The subject has known or suspected intolerance or hypersensitivity to vedolizumab or closely related compounds, or any of the vedolizumab IV excipients.
6. The subject has active cerebral/meningeal disease, or signs/symptoms of progressive multifocal
leukoencephalopathy (PML) or any history of PML at screening.
18age old over
80age old under
Both
Ulcerative Colitis, Crohn's Disease
Vedolizumab 300 mg, IV infusion, for up to 12 weeks Q4W for Treatment phase, and until the date of marketing approval of vedolizumab IV Q4W or study termination for Extension phase.
1. Percentage of Participants with Clinical Response at Week 12 Based on Modified Mayo Score in UC Cohort
Timeframe; Week 12
Clinical response is defined as a 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 baseline (Week 0). Mayo score is an instrument designed to measure disease activity of UC. Modified Mayo score consists of 3 sub-scores: stool frequency, rectal bleeding, and Mayo endoscopic subscore (findings on endoscopy), each graded from 0 to 3 with higher scores indicating more severe disease. These scores are summed to give a total score range of 0 to 9. Here, higher score indicates more severe disease.
2. Percentage of Participants with Clinical Response at Week 12 in CD Cohort
Timeframe; Week 12
Clinical response is defined as a reduction of =>70 points in CDAI score from baseline (Week 0). CDAI assesses CD based on clinical signs and symptoms such as number of liquid stools, intensity of abdominal pain, general well being, presence of comorbid conditions, use of antidiarrheal, physical examination and laboratory findings. Total score ranges from 0 to 600 points. Higher score indicates more severe disease.
1. Percentage of Participants with Clinical Remission at Week 12 Based on Modified Mayo Score in UC Cohort
Timeframe; Week 12
Clinical remission is defined as a modified Mayo score of =<2, and no individual subscore >1. Mayo score is an instrument designed to measure disease activity of UC. Modified Mayo score consists of 3 sub-scores: stool frequency, rectal bleeding, and Mayo endoscopic subscore (findings on endoscopy), each graded from 0 to 3 with higher scores indicating more severe disease. These scores are summed to give a total score range of 0 to 9. Here, higher score indicates more severe disease.
2. Percentage of Participants with Mucosal Healing at Week 12 in UC Cohort
Timeframe; Week 12
Mucosal healing is defined as a Mayo endoscopic subscore of =<1, in participants with baseline Mayo endoscopic subscore of >=2. Mayo score is an instrument designed to measure disease activity of UC.
3. Percentage of Participants with Corticosteroid-Free Remission Based on Partial Mayo Score in UC Cohort
Timeframe; Week 52
Corticosteroid-free remission is defined as participants using oral corticosteroids at baseline (Week 0) who have discontinued oral corticosteroids and are in clinical remission based on partial Mayo score at Week 52. Clinical remission based on partial Mayo score is defined as a partial Mayo score of =<2, and no individual subscore >1. Mayo score is 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 indicating more severe disease. These scores are summed to give a total score range of 0 to 9. Here, higher scores indicates more severe disease.
4. Percentage of Participants with Clinical Remission at Week 12 in CD Cohort
Timeframe; Week 12
Clinical remission is defined as a CDAI score of =<150. CDAI assesses CD based on clinical signs and symptoms such as number of liquid stools, intensity of abdominal pain, general well being, presence of comorbid conditions, use of antidiarrheal, physical examination and laboratory findings. Total score ranges from 0 to 600 points. Higher score indicates more severe disease.
5. Percentage of Participants with Enhanced Clinical Response at Week 12 in CD Cohort
Timeframe; Week 12
Enhanced clinical response is defined as a reduction of >=100 points in CDAI score from baseline (Week 0). CDAI assesses CD based on clinical signs and symptoms such as number of liquid stools, intensity of abdominal pain, general well being, presence of comorbid conditions, use of antidiarrheal, physical examination and laboratory findings. Total score ranges from 0 to 600 points. Higher score indicates more severe disease.
6. Percentage of Participants with Corticosteroid-Free Remission in CD Cohort
Timeframe; Week 52
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.
Takeda Pharmaceutical Company Limited
Nakameguro Atlas Clinic IRB
Kamimeguro 1-26-1, Meguro-ku, Tokyo
+81-3-5773-5570
Approval
Feb. 03, 2020
Yes
Takeda provides access to the de-identified individual participant data (IPD) for eligible studies to aid qualified researchers in addressing legitimate scientific objectives (Takeda's data sharing commitment is available on https://clinicaltrials.takeda.com/takedas-commitment?commitment=5). These IPDs will be provided in a secure research environment following approval of a data sharing request, and under the terms of a data sharing agreement.
