Clinical trial NCT04738942: A Study of Intravenous Vedolizumab Administered Every 4 Weeks in Japanese Participants With Moderate to Severe Ulcerative Colitis or Crohn's Disease
Official title: 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)
Study type: INTERVENTIONAL
Overall status: RECRUITING
Phase: PHASE3
Conditions: Ulcerative Colitis
Crohn's Disease
Lead sponsor: Takeda
Sponsor class: INDUSTRY
First posted: 2021-02-04
Enrollment: 158
Sex: ALL
Minimum age (years): 18
Maximum age (years): 80
Standard ages: ADULT
OLDER_ADULT
Accepts healthy volunteers: no
Allocation: NON_RANDOMIZED
Intervention model: PARALLEL
Primary purpose: TREATMENT

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.


Eligibility criteria: 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.

Primary outcomes:
measure: Percentage of Participants with Clinical Response at Week 12 Based on Modified Mayo Score in UC Cohort
timeFrame: Week 12
measure: Percentage of Participants with Clinical Response at Week 12 in CD Cohort
timeFrame: Week 12
Secondary outcomes:
measure: Percentage of Participants with Clinical Remission at Week 12 Based on Modified Mayo Score in UC Cohort
timeFrame: Week 12
measure: Percentage of Participants with Mucosal Healing at Week 12 in UC Cohort
timeFrame: Week 12
measure: Percentage of Participants with Corticosteroid-Free Remission Based on Partial Mayo Score in UC Cohort
timeFrame: Week 12
measure: Percentage of Participants with Clinical Remission at Week 12 in CD Cohort
timeFrame: Week 12
measure: Percentage of Participants with Enhanced Clinical Response at Week 12 in CD Cohort
timeFrame: Week 12
measure: Percentage of Participants with Corticosteroid-Free Remission in CD Cohort
timeFrame: Week 12
Other outcomes:
Locations:
city: Toyota
country: Japan
facility: Ieda Hospital
state: Aichi
city: Hirosaki
country: Japan
facility: Hirosaki University Hospital
state: Aomori
city: Kashiwa
country: Japan
facility: Tsujinaka Hospital
state: Chiba
city: Sakura
country: Japan
facility: Toho University Sakura Medical Center
state: Chiba
city: Chikushino
country: Japan
facility: Fukuoka University Chikushi Hospital
state: Fukuoka
city: Sapporo
country: Japan
facility: Sapporo Kosei General Hospital
state: Hokkaido
city: Nishinomiya
country: Japan
facility: Hyogo College of Medicine Hospital
state: Hyogo
city: Kamakura
country: Japan
facility: Ofuna Chuo Hospital
state: Kanagawa
city: Sagamihara
country: Japan
facility: Kitasato University Hospital
state: Kanagawa
city: Yokohama
country: Japan
facility: Yokohama City University Medical Center
state: Kanagawa
city: Sendai
country: Japan
facility: Tohoku University Hospital
state: Miyagi
city: Shimotsuke
country: Japan
facility: Jichi Medical University Hospital
state: Tochigi
city: Bunkyo-ku
country: Japan
facility: Institute of Science Tokyo Hospital
state: Tokyo
city: Bunkyo-ku
country: Japan
facility: Juntendo University Hospital
state: Tokyo
city: Minato-ku
country: Japan
facility: Kitasato University Kitasato Institute Hospital
state: Tokyo
city: Mitaka
country: Japan
facility: Kyorin University Hospital
state: Tokyo
city: Shinjuku-ku
country: Japan
facility: Keio University Hospital
state: Tokyo
city: Shinjuku-ku
country: Japan
facility: Tokyo Yamate Medical Center
state: Tokyo
city: Osaka
country: Japan
facility: Infusion Clinic.
city: Osaka
country: Japan
facility: Osaka Metropolitan University Hospital
Study officials:
affiliation: Takeda
name: Study Director
role: STUDY_DIRECTOR
References: