Clinical trial NCT05837897: A Study of Vedolizumab in Adult Participants With Moderate to Severe Crohn's Disease
Official title: A Phase 3, Multicenter, Randomized, Parallel-Group, Double-blind, Placebo-Controlled Induction Study Followed by an Open-label Extension Period to Evaluate the Efficacy and Safety of Intravenous Vedolizumab (300 mg) Infusion Treatment in Subjects in China With Moderately to Severely Active Crohn's Disease
Study type: INTERVENTIONAL
Overall status: RECRUITING
Phase: PHASE3
Conditions: Crohn's Disease
Keywords: Drug therapy
Lead sponsor: Takeda
Sponsor class: INDUSTRY
First posted: 2023-05-01
Enrollment: 408
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: This is a study to evaluate vedolizumab for injection (300 mg) as a safe and active treatment for Crohn's Disease in adults in China. Participants will receive an injection of Vedolizumab 300 mg at scheduled weeks 0, 2, and 6, and starting at week 14, every 8 weeks over 58 weeks or starting at week 18, every 4 weeks over 54 weeks. There will be up to 20 study visits over 58 weeks to complete assessments.

Detailed description: The drug being tested in this study is called vedolizumab. Vedolizumab will be administered as an intravenous (IV) infusion in Chinese participants. This study will investigate the efficacy and safety of vedolizumab IV in participants with moderately to severely active Crohn's Disease (CD).

The study will enroll approximately 408 patients. Participants will be randomized into 2:1 in the Induction Period to receive:

* Vedolizumab IV 300 mg
* Placebo

All participants completing the Week 14 visit, irrespective of their response status, will continue in the OLE without unblinding of their baseline treatment group and will receive 300 mg vedolizumab once every 8 weeks (Q8W) starting from Week 14. Starting at Week 18 and throughout the remainder of the OLE, participants who are nonresponders or who have disease worsening based on the assessment by visit every 4 weeks, are eligible to receive 300 mg vedolizumab once every 4 weeks (Q4W).

This multi-center trial will be conducted in China. The overall time participants will be in this study is approximately 58 weeks. Participants will make a final safety follow-up visit at 18 weeks after the last dose of study drug. Participants will also be followed-up for a long-term follow-up safety survey after completion of or early termination from study via telephone, 6 months after last dose of study drug.

Eligibility criteria: Inclusion criteria:

1. The participant has a diagnosis of CD established at least 3 months before screening by clinical and endoscopic evidence corroborated by a histopathology report. Cases of CD 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. The participant has moderately to severely active CD as determined by a 2-component patient-reported outcome (PRO2) score of 14 to 34 points and a Simple Endoscopic Score for Crohn's Disease (SES-CD) score of ≥6 (or ≥4 in cases of isolated ileitis) on screening ileocolonoscopy.
3. The participant has CD involvement of the ileum and/or colon, at a minimum.
4. A participant with extensive colitis or pancolitis of \>8 years duration or limited colitis of \>12 years duration must have documented evidence that a surveillance colonoscopy was performed within 12 months before initial screening (may be performed during screening if not performed in previous 12 months).
5. A participant with a family history of colorectal cancer, personal history of increased colorectal cancer risk, age \>50 years, or other known risk factor must be up-to-date on colorectal cancer surveillance (may be performed during screening).
6. The participant has demonstrated an inadequate response to, loss of response to, or intolerance of at least 1 of the following agents as defined below:

   * Corticosteroids.
   * Immunomodulators.
   * TNF-α antagonists.

Exclusion Criteria:

I. Gastrointestinal (GI) Exclusion Criteria:

1. The participant has evidence of abdominal abscess at the initial screening visit.
2. The participant has had extensive colonic resection, subtotal or total colectomy.
3. The participant has a history of \>3 small bowel resections or diagnosis of short bowel syndrome.
4. The participant has received tube feeding, defined formula diets, or parenteral alimentation within 21 days before administration of the first dose of study drug.
5. The participant has had ileostomy, colostomy, known fixed symptomatic stenosis of the intestine, or evidence of fixed stenosis, or small bowel stenosis with prestenotic dilation.
6. Within 30 days before randomization, the participant has received any of the following for the treatment of underlying disease:

   * Nonbiologic therapies (eg, cyclosporine, thalidomide) other than those specifically listed in the Permitted Medications and Treatments section.
   * An approved or investigational nonbiologic therapy in an investigational protocol.
7. The participant has received traditional Chinese medication (TCMs) within 30 days before randomization.
8. The participant has had previous exposure to approved or investigational anti-integrins including, but not limited to natalizumab, efalizumab, etrolizumab, or abrilumab (AMG-181), or mucosal vascular addressin cell adhesion molecule 1 (MAdCAM-1) antagonists, or rituximab.
9. The participant has had previous exposure to vedolizumab.
10. The participant has used topical (rectal) treatment with 5-aminosalicylic acid (5-ASA), corticosteroid enemas/suppositories or traditional Chinese medications for CD treatment within 2 weeks of the administration of the first dose of study drug.
11. The participant requires currently or is anticipated to require surgical intervention for CD during the study.
12. The participant has a history or evidence of adenomatous colonic polyps that have not been removed.
13. The participant has a history or evidence of colonic mucosal dysplasia including low or high-grade dysplasia, as well as indeterminate for dysplasia.

    II. Infectious Disease Exclusion Criteria
14. The participant has evidence of active infection during the screening period.
15. The participant has evidence of treatment for Clostridioides difficile (C difficile) infection or other intestinal pathogen within, 28 days before first dose of study drug.
16. The participant has chronic hepatitis B virus (HBV) infection or chronic hepatitis C virus (HCV) infection.
17. The participant has active or latent tuberculosis (TB).
18. The participant has any identified congenital or acquired immunodeficiency (eg, common variable immunodeficiency, human immunodeficiency virus \[HIV\] infection, organ transplantation).
19. The participants has received any live vaccinations within 30 days before screening.
20. The participant has a clinically significant active infection (eg, pneumonia, pyelonephritis, or coronavirus disease 2019 \[COVID-19\]) within 30 days before screening or during screening, or has an ongoing chronic infection or any ongoing COVID-19-related symptom(s), if previously diagnosed as having COVID-19.

    III. General Exclusion Criteria
21. The participant has had any surgical procedure requiring general anesthesia within 30 days before enrollment or is planning to undergo major surgery during the study period.
22. The participant has any history of malignancy, except for the following: (a) adequately-treated nonmetastatic basal cell skin cancer; (b) squamous cell skin cancer that has been adequately treated and has not recurred for at least 1 year before randomization; and (c) history of cervical carcinoma in situ that has been adequately treated and has not recurred for at least 3 years before randomization. Participants with remote history of malignancy (eg, \>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 before randomization.
23. The participant has a history of any major neurological disorders, including stroke, multiple sclerosis, brain tumor, or neurodegenerative disease.

Primary outcomes:
measure: Percentage of Participants Achieving Clinical Response at Week 14
timeFrame: Up to Week 14
Secondary outcomes:
measure: Percentage of Participants Achieving Clinical Remission at Week 14
timeFrame: Up to Week 14
measure: Percentage of Participants Achieving Endoscopic Response at Week 14
timeFrame: Up to Week 14
measure: Percentage of Participants Achieving Both Clinical Response and Endoscopic Response at Week 14
timeFrame: Up to Week 14
measure: Percentage of Participants With Adverse Events (AEs), Serious Adverse Events (SAEs), Adverse Events of Special Interest (AESIs) and AEs Leading to Discontinuation
timeFrame: From first dose up to 18 weeks after the final dose of vedolizumab (Up to approximately 78 weeks)
measure: Percentage of Participants With Abnormal Change from Baseline in Vital Sign Values
timeFrame: From first dose up to 18 weeks after the final dose of vedolizumab (Up to approximately 78 weeks)
measure: Percentage of Participants With Abnormal Change from Baseline in Laboratory Values
timeFrame: From first dose up to 18 weeks after the final dose of vedolizumab (Up to approximately 78 weeks)
measure: Percentage of Participants With Abnormal Change from Baseline in Electrocardiogram (ECG) Values
timeFrame: From first dose up to 18 weeks after the final dose of vedolizumab (Up to approximately 78 weeks)
Other outcomes:
Locations:
city: Hefei
country: China
facility: The Second Hospital of Anhui Medical University
state: Anhui
city: Wuhu
country: China
facility: Yijishan Hospital of Wannan Medical College
state: Anhui
city: Beijing
country: China
facility: Peking University First Hospital
state: Beijing
city: Beijing
country: China
facility: Peking University Third Hospital
state: Beijing
city: Fuzhou
country: China
facility: The First Affiliated Hospital of Fujian Medical University
state: Fujian
city: Lanzhou
country: China
facility: Lanzhou University Second Hospital
state: Gansu
city: Foshan
country: China
facility: The First People's Hospital of Foshan
state: Guangdong
city: Guangzhou
country: China
facility: The First Affiliated Hospital, Sun Yat-sen University
state: Guangdong
city: Guangzhou
country: China
facility: Guangzhou First People's Hospital
state: Guangdong
city: Guangzhou
country: China
facility: The Second Affiliated Hospital of Guangzhou Medical University
state: Guangdong
city: Guangzhou
country: China
facility: The Third Affiliated Hospital, Sun Yat-Sen University
state: Guangdong
city: Guangzhou
country: China
facility: The Sixth Affiliated Hospital, Sun Yat-sen University
state: Guangdong
city: Huizhou
country: China
facility: Huizhou Central People's Hospital
state: Guangdong
city: Qingyuan
country: China
facility: Qingyuan Peoples Hospital
state: Guangdong
city: Shenzhen
country: China
facility: The University of Hong Kong - Shenzhen Hospital
state: Guangdong
city: Zhuhai
country: China
facility: The Fifth Affiliated Hospital Sun Yat-Sen University
state: Guangdong
city: Nanning
country: China
facility: The First Affiliated Hospital of Guangxi Medical University
state: Guangxi
city: Shijiazhuang
country: China
facility: The Second Hospital of Hebei Medical University
state: Hebei
city: Harbin
country: China
facility: The 2nd Affliated Hospital of Harbin Medical University
state: Heilongjiang
city: Nanyang
country: China
facility: Nanyang First People's Hospital
state: Henan
city: Wuhan
country: China
facility: Union Hospital Tongji Medical College Huazhong University of Science and Technology
state: Hubei
city: Wuhan
country: China
facility: Renmin Hospital of Wuhan University
state: Hubei
city: Changzhou
country: China
facility: Changzhou No.2 People's Hospital
state: Jiangsu
city: Nanjing
country: China
facility: Zhongda Hospital, Affiliated to Southeast University
state: Jiangsu
city: Suzhou
country: China
facility: Changshu No.2 People's Hospital
state: Jiangsu
city: Xuzhou
country: China
facility: Xuzhou Central Hospital
state: Jiangsu
city: Nanchang
country: China
facility: The Second Affiliated Hospital of Nanchang University
state: Jiangxi
city: Shenyang
country: China
facility: Shengjing Hospital of China Medical University
state: Liaoning
city: Yinchuan
country: China
facility: People's Hospital of Ningxia Hui Aotonomous Region
state: Ningxia
city: Yantai
country: China
facility: Yantai Yuhuangding Hospital
state: Shandong
city: Shanghai
country: China
facility: Zhongshan Hospital Fudan University
state: Shanghai
city: Shanghai
country: China
facility: Shanghai East Hospital
state: Shanghai
city: Shanghai
country: China
facility: Shanghai Changhai Hospital
state: Shanghai
city: Tianjin
country: China
facility: Tianjin Medical University General Hospital
state: Tianjin
city: Kunming
country: China
facility: The First People's Hospital of Yunnan Province
state: Yunnan
city: Hangzhou
country: China
facility: The First Affiliated Hospital, Zhejiang University School of Medicine - PPDS
state: Zhejiang
city: Ningbo
country: China
facility: The First Affiliated Hospital of Ningbo University(Ningbo First Hospital)
state: Zhejiang
city: Quzhou
country: China
facility: People's Hospital of Quzhou
state: Zhejiang
city: Taizhou
country: China
facility: Taizhou Hospital of Zhejiang Province
state: Zhejiang
city: Wenzhou
country: China
facility: The 1st Affiliated Hospital of Wenzhou Medical University
state: Zhejiang
Study officials:
affiliation: Takeda
name: Study Director
role: STUDY_DIRECTOR
References: