Intravenous vedolizumab treatment for ulcerative colitis and Crohn's disease in Japanese patients

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)

This study is testing if giving Japanese patients with moderate to severe ulcerative colitis or Crohn's disease intravenous vedolizumab every 4 weeks can help them feel better after losing their response to the treatment.

Quick facts

• Phase: Phase 3
• Study type: Interventional
• Enrollment: 158 (estimated)
• Ages: 18 Years to 80 Years
• Sex: All
• Sponsor: Takeda (Industry-sponsored)
• Drugs / interventions: vedolizumab, tofacitinib
• Locations: 20 sites (Toyota, Aichi and 19 other locations)
• Trial ID: NCT04738942 on ClinicalTrials.gov

What this trial studies

This study aims to evaluate the effectiveness of administering intravenous vedolizumab every 4 weeks to Japanese participants suffering from moderate to severe ulcerative colitis or Crohn's disease. Participants who have previously responded to vedolizumab but experienced a loss of response during maintenance therapy will receive the treatment for 12 weeks, after which their symptoms will be assessed. The study will also monitor any side effects associated with the treatment. The research is conducted across multiple locations in Japan.

Who should consider this trial

Good fit: Ideal candidates are Japanese individuals with moderate to severe ulcerative colitis or Crohn's disease who have previously responded to vedolizumab but have since lost that response.

Not a fit: Patients who have not previously shown a clinical response to vedolizumab or have mild forms of ulcerative colitis or Crohn's disease may not benefit from this study.

Why it matters

Potential benefit: If successful, this treatment could provide a more effective management option for Japanese patients with moderate to severe ulcerative colitis or Crohn's disease.

How similar studies have performed: Other studies have shown success with vedolizumab in treating ulcerative colitis and Crohn's disease, but this specific 4-week regimen is novel.

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.

Where this trial is running

Toyota, Aichi and 19 other locations

• Ieda Hospital — Toyota, Aichi, Japan (Recruiting)
• Hirosaki University Hospital — Hirosaki, Aomori, Japan (Recruiting)
• Tsujinaka Hospital — Kashiwa, Chiba, Japan (Recruiting)
• Toho University Sakura Medical Center — Sakura, Chiba, Japan (Recruiting)
• Fukuoka University Chikushi Hospital — Chikushino, Fukuoka, Japan (Recruiting)
• Sapporo Kosei General Hospital — Sapporo, Hokkaido, Japan (Not_yet_recruiting)
• Hyogo College of Medicine Hospital — Nishinomiya, Hyogo, Japan (Recruiting)
• Ofuna Chuo Hospital — Kamakura, Kanagawa, Japan (Recruiting)
• Kitasato University Hospital — Sagamihara, Kanagawa, Japan (Recruiting)
• Yokohama City University Medical Center — Yokohama, Kanagawa, Japan (Recruiting)
• Tohoku University Hospital — Sendai, Miyagi, Japan (Recruiting)
• Jichi Medical University Hospital — Shimotsuke, Tochigi, Japan (Recruiting)
• Institute of Science Tokyo Hospital — Bunkyo-ku, Tokyo, Japan (Recruiting)
• Juntendo University Hospital — Bunkyo-ku, Tokyo, Japan (Recruiting)
• Kitasato University Kitasato Institute Hospital — Minato-ku, Tokyo, Japan (Recruiting)
• Kyorin University Hospital — Mitaka, Tokyo, Japan (Recruiting)
• Keio University Hospital — Shinjuku-ku, Tokyo, Japan (Recruiting)
• Tokyo Yamate Medical Center — Shinjuku-ku, Tokyo, Japan (Recruiting)
• Infusion Clinic. — Osaka, Japan (Recruiting)
• Osaka Metropolitan University Hospital — Osaka, Japan (Recruiting)

Study contacts

• Study coordinator: Takeda Study Registration Call Center

Conditions Ulcerative Colitis; Crohn's Disease