Clinical trial NCT03221036: Efficacy and Safety of Vedolizumab IV in Chinese Participants With Ulcerative Colitis
Official title: A Phase 3, Multicenter, Randomized, Double-Blind, Placebo-Controlled, Parallel-Group Study to Examine the Efficacy and Safety of Intravenous Vedolizumab (300 mg) Infusion Treatment in Chinese Subjects With Moderately to Severely Active Ulcerative Colitis
Study type: INTERVENTIONAL
Overall status: RECRUITING
Phase: PHASE3
Conditions: Moderately to Severely Active Ulcerative Colitis
Keywords: Drug therapy
Lead sponsor: Takeda
Sponsor class: INDUSTRY
First posted: 2017-07-18
Enrollment: 402
Sex: ALL
Minimum age (years): 18
Maximum age (years): 80
Standard ages: ADULT
OLDER_ADULT
Accepts healthy volunteers: no
Allocation: RANDOMIZED
Intervention model: PARALLEL
Primary purpose: TREATMENT

Brief summary: The purpose of this study is to assess the effect of vedolizumab intravenous IV as induction and maintenance treatment in Chinese participants with moderately to severely active ulcerative colitis (UC).

Detailed description: The drug being tested in this study is called Vedolizumab. Vedolizumab will be administered as an intravenous (IV) infusion. This study will investigate the efficacy and safety of vedolizumab IV as induction and maintenance therapy in participants with moderately to severely active ulcerative colitis (UC).

The study will enroll approximately 302 moderately to severely active patients with ulcerative colitis.

The Induction Phase contained 2 cohorts of participants: Cohort 1 participants will be randomized 1:2 in a double-blinded manner to receive:

* Vedolizumab IV 300 mg
* Placebo IV

Cohort 2 participants will be treated with open-label vedolizumab. The second cohort was enrolled to ensure that the sample size of Induction Phase responders randomized into the Maintenance Study provided sufficient power for the Maintenance Study primary efficacy analysis.

Participants will receive induction therapy of Vedolizumab 300 mg or matching placebo, intravenous (IV) infusion at Weeks 0, 2, and 6. At Week 10, participants will be assessed for clinical response based on complete clinic Mayo score. Results of Week 10 clinical response will determine the treatment pathway in maintenance phase.

In the Maintenance Phase, participants who received vedolizumab in the induction phase and achieved clinical response at Week 10 will be randomized 1:1 in a double-blinded manner to receive vedolizumab IV 300 mg or placebo starting from Week 14 (i.e., Weeks 14, 22, 30, 38, 46, and 54).

This multi-center trial will be conducted in China. The overall time to participate in this study is 60 weeks. Participants will make multiple visits to the clinic, and will be contacted by telephone, 6 months after last dose of investigational product (IP) for a long term follow-up safety survey.

Eligibility criteria: Inclusion Criteria:

1. Has a diagnosis of ulcerative colitis (UC) established at least 3 months prior to Screening by clinical and endoscopic evidence corroborated by a histopathology report. Cases of UC established at least 6 months before randomization for which a histopathology report is not available will be considered based on the weight of evidence supporting the diagnosis and excluding other potential diagnoses and must be discussed with the sponsor on a case-by case basis before randomization.
2. Has moderately to severely active UC as determined by a complete Mayo score of 6-12 with an endoscopic subscore ≥2 within 10 days prior to the first dose of IP. The endoscopy can be performed during the Screening Phase (Day -10 to Day -5 to allow for central reading prior to first dose at Week 0).
3. Has evidence of UC extending proximal to the rectum (≥15 cm of involved colon).
4. Participants with extensive colitis or pancolitis of \>8 years duration or left-sided colitis \>12 years duration must have documented evidence that a surveillance colonoscopy was performed within 12 months of the initial Screening Visit (may be performed during screening).
5. Participants with a family history of colorectal cancer, personal history of increased colorectal cancer risk, age \>50 years, or other known risk factors must be up-to-date on colorectal cancer surveillance (may be performed during screening).
6. Has demonstrated an inadequate response to, loss of response to, or intolerance of at least 1 of the following agents: corticosteroids, immunomodulators, or tumor necrosis factor alpha (TNF-α) antagonists.

Exclusion Criteria:

1. Has evidence of abdominal abscess or toxic megacolon at the initial Screening Visit.
2. Has had extensive colonic resection, subtotal or total colectomy.
3. Has an existing ileostomy, colostomy, or known fixed symptomatic stenosis of the intestine. A history of ileostomy or colostomy that has been reversed may be acceptable.
4. Has had any previous exposure to approved or investigational anti-integrins (for example, natalizumab, efalizumab, etrolizumab, or AMG-181) or mucosal address in cell adhesion molecule-1 (MAdCAM-1) antagonist, or rituximab.
5. Has used a topical (rectal) treatment with 5-acetyl salicylic acid (5-ASA) or corticosteroid enemas/suppositories or traditional Chinese medications for treatment of UC within 2 weeks of the administration of the first dose of IP.
6. Currently requires or is anticipated to require surgical intervention for UC during the study.
7. Has a history or evidence of adenomatous colonic polyps that have not been removed or has a history or evidence of colonic mucosal dysplasia including low or high-grade dysplasia, as well as indeterminate for dysplasia.
8. Has a suspected or confirmed diagnosis of Crohn's enterocolitis, indeterminate colitis, ischemic colitis, radiation colitis, diverticular disease associated with colitis, or microscopic colitis.
9. Has evidence of or has had treatment for C. difficile infection or other intestinal pathogen within 28 days prior to randomization.
10. Has chronic hepatitis B virus (HBV) infection or chronic hepatitis C virus (HCV) infection.
11. Has active or latent TB.
12. Has any identified congenital or acquired immunodeficiency (for example, common variable immunodeficiency, human immunodeficiency virus \[HIV\] infection, organ transplantation).
13. Has any history of malignancy, except for the following: (a) adequately treated non-metastatic basal cell skin cancer; (b) squamous cell skin cancer that has been adequately treated and that has not recurred for at least 1 year prior to randomization; and (c) history of cervical carcinoma in situ that has been adequately treated and that has not recurred for at least 3 years prior to randomization. Subjects with remote history of malignancy (for example, \>10 years since completion of curative therapy without recurrence) will be considered based on the nature of the malignancy and the therapy received and must be discussed with the sponsor on a case-by-case basis prior to randomization.
14. Has a history of any major neurological disorders, including stroke, multiple sclerosis, brain tumor, or neurodegenerative disease.
15. Has a positive progressive multifocal leukoencephalopathy (PML) subjective symptom checklist at Screening or prior to the administration of the first dose of IP at Week 0.

Primary outcomes:
measure: Induction Phase: Percentage of Participants with Clinical Response at Week 10
timeFrame: Week 10
measure: Maintenance Phase: Percentage of Participants with Clinical Remission at Week 60
timeFrame: Week 60
Secondary outcomes:
measure: Induction Phase: Percentage of Participants with Clinical Remission at Week 10
timeFrame: Week 10
measure: Induction and Maintenance Phase: Percentage of Participants with Mucosal Healing at Weeks 10 and 60
timeFrame: Weeks 10 and 60
measure: Maintenance Phase: Percentage of Participants with Durable Clinical Response at Weeks 10 and 60
timeFrame: Weeks 10 and 60
measure: Maintenance Phase: Percentage of Participants with Durable Clinical Remission at Weeks 10 and 60
timeFrame: Weeks 10 and 60
measure: Maintenance Phase: Percentage of Participants Using Oral Corticosteroids at Baseline who have Discontinued Corticosteroids and are in Clinical Remission at Week 60
timeFrame: Week 60
Other outcomes:
Locations:
city: Hefei
country: China
facility: Gastroenterology
state: Anhui
city: Beijing
country: China
facility: Gastroenterology
state: Beijing
city: Beijing
country: China
facility: Gastroenterology
state: Beijing
city: Chongqing
country: China
facility: Gastroenterology
state: Chongqing Sichuan
city: Chongqing
country: China
facility: Gastroenterology
state: Chongqing
city: Fuzhou
country: China
facility: Gastroenterology
state: Fujian
city: Xiamen
country: China
facility: Gastroenterology
state: Fujian
city: Zhangzhou
country: China
facility: Gastroenterology
state: Fujian
city: Guangzhou
country: China
facility: Gastroenterology
state: Guangdong
city: Guangzhou
country: China
facility: Gastroenterology
state: Guangdong
city: Guangzhou
country: China
facility: Gastroenterology
state: Guangdong
city: Guangzhou
country: China
facility: Gastroenterology
state: Guangdong
city: Meizhou
country: China
facility: Gastroenterology
state: Guangdong
city: Shantou
country: China
facility: Gastroenterology
state: Guangdong
city: Shijiazhuang
country: China
facility: Gastroenterology
state: Hebei
city: Zhengzhou
country: China
facility: Gastroenterology
state: Henan
city: Wuhan
country: China
facility: Gastroenterology
state: Hubei
city: Wuhan
country: China
facility: Gastroenterology
state: Hubei
city: Wuhan
country: China
facility: Gastroenterology
state: Hubei
city: Changsha
country: China
facility: Gastroenterology
state: Hunan
city: Changsha
country: China
facility: Gastroenterology
state: Hunan
city: Changsha
country: China
facility: Gastroenterology
state: Hunan
city: Nanjing
country: China
facility: Gastroenterology
state: Jiangsu
city: Nanjing
country: China
facility: Gastroenterology
state: Jiangsu
city: Wuxi
country: China
facility: Gastroenterology
state: Jiangsu
city: Nanchang
country: China
facility: Gastroenterology
state: Jiangxi
city: Changchun
country: China
facility: Gastroenterology
state: Jilin
city: Shenyang
country: China
facility: Gastroenterology
state: Liaoning
city: Yinchuan
country: China
facility: Gastroenterology
state: Ningxia
city: Shanghai
country: China
facility: Gastroenterology
state: Shanghai
city: Shanghai
country: China
facility: Gastroenterology
state: Shanghai
city: Shanghai
country: China
facility: Gastroenterology
state: Shanghai
city: Shanghai
country: China
facility: Gastroenterology
state: Shanghai
city: Taiyuan
country: China
facility: Gastroenterology
state: Shanxi
city: Xi'an
country: China
facility: Gastroenterology
state: Shanxi
city: Chengdu
country: China
facility: Gastroenterology
state: Sichuan
city: Kunming
country: China
facility: Gastroenterology
state: Yunnan
city: Hangzhou
country: China
facility: Gastroenterology
state: Zhejiang
city: Hangzhou
country: China
facility: Gastroenterology
state: Zhejiang
Study officials:
affiliation: Takeda
name: Medical Director Clinical Science
role: STUDY_DIRECTOR
References: