A Study of Intravenous Vedolizumab Administered Every 4 Weeks in Japanese Participants With Moderate to Severe Ulcerative Colitis or Crohn's Disease

Takeda

Status and phase: Active, not recruiting; Phase 3

Conditions: Ulcerative Colitis; Crohn's Disease

Treatments: Drug: Vedolizumab

Study type: Interventional

Funder types: Industry

Identifiers

NCT04738942

jRCT2031200371 (Registry Identifier)

U1111-1262-7325 (Other Identifier)

Vedolizumab-3039

Details and patient eligibility

About

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.

Enrollment: 57 patients

Sex: All

Ages: 18 to 80 years old

Volunteers: No Healthy Volunteers

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.

Trial design

Primary purpose: Treatment

Allocation: Non-Randomized

Interventional model: Parallel Assignment

Masking: None (Open label)

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57 participants in 2 patient groups

Vedolizumab 300 mg in UC cohort

Experimental group

Description:

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.

Treatment:

Drug: Vedolizumab

Vedolizumab 300 mg in CD cohort

Experimental group

Description:

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.

Treatment:

Drug: Vedolizumab