Efficacy and Safety of Vedolizumab Combined With Upadacitinib in Patients With Ulcerative Colitis

Efficacy and Safety Analysis of Sequential Treatment of Moderate to Severe Ulcerative Colitis With Vedolizumab and Upadacitinib: A Multicenter Prospective Randomized Controlled Clinical Study

It's of great importance to effectively induce and maintain disease remission in patients with moderate to severe ulcerative colitis (UC). Vedolizumab (VDZ) is known for its high safety profile and confirmed therapeutic efficacy in UC treatment. However, according to the experience in clinical practice, the effect onset speed of vedolizumab is relatively slow. Upadacitinib (UPA), however, works quickly, which complements the defect of slow onset of VDZ induction. However, the safety of UPA used in situations such as infection and tumors is inferior to that of VDZ, and long-term use requires testing for the risk of adverse events such as deep vein thrombosis. Therefore, if the advantages of long-term maintenance therapy safety of VDZ and rapid induced remission of UPA are fully utilized, the combination of VDZ and UPA induction for 8 weeks, followed by the use of single drug VDZ in maintenance therapy, can maximize the clinical benefits of UC patients. Due to the lack of high-level clinical research data at home and abroad, we plan to conduct a multicenter prospective randomized controlled clinical study to provide the evidence-based basis for the efficacy analysis of the sequential treatment of moderate to severe UC patients with VDZ and UPA.

Study Overview

• Status: Recruiting
• Conditions: Crohn Disease
• Intervention / Treatment: Drug: Upadacitinib; Drug: Vedolizumab

• Study Type: Interventional
• Enrollment (Estimated): 334
• Phase: Not Applicable

Contacts and Locations

Study Locations

• China
  • Guangdong
    • Guangzhou, Guangdong, China, 501655
      • Recruiting
      • The Sixth Affiliated Hospital of Sun Yat-sen University
      • Contact: Jiayin Yao, Professor; Phone Number: 13826462890; Email: yjyin@mail3.sysu.edu.cn

Participation Criteria

Eligibility Criteria

• Ages Eligible for Study: Adult; Older Adult
• Accepts Healthy Volunteers: No

Description

Inclusion Criteria:

• Diagnosed UC for at least 3 months, including endoscopic evidence supporting UC and histopathological evidence supporting UC diagnosis
• Suffering from moderate to severe UC, defined as modified Mayo score ≥ 4 and endoscopic subscale (ESS) ≥ 2
• Indications for VDZ or UPA application

Exclusion Criteria:

• Patients who are unable to take oral UPA and receive regular intravenous VDZ infusion therapy
• Evidence of toxic megacolon was found during screening
• Previously underwent extensive colectomy, subtotal resection, or total colectomy, ileostomy, or colostomy due to UC
• Subjects who require surgery due to UC or plan to undergo elective surgery during the study period
• There is evidence indicating that the subjects suffer from severe, progressive, or uncontrolled kidney, liver, blood, endocrine, respiratory, mental, or neurological diseases
• Evidence of active hepatitis B or C infection during screening

Study Plan

How is the study designed?

Design Details

• Primary Purpose: Treatment
• Allocation: Randomized
• Interventional Model: Parallel Assignment
• Masking: None (Open Label)

Number of Arms

2

Arms and Interventions

Participant Group / Arm	Intervention / Treatment
Experimental: Combination treatment group; A combination treatment of vedolizumab and upadacitinib for 8 weeks in the induction therapy, then followed by a single treatment of vedolizumab in the maintenance therapy	Drug: Upadacitinib; Oral upadacitinib 45mg/d for 8 weeks in the induction therapy.; Other Names: Upadacitinib treatment; Drug: Vedolizumab; Vedolizumab 300mg intravenously on weeks 1, 2, 6, and then on every 8-week interval.; Other Names: Vedolizumab treatment
Placebo Comparator: Single treatment group; single treatment of vedolizumab both in the induction and maintenance therapy	Drug: Vedolizumab; Vedolizumab 300mg intravenously on weeks 1, 2, 6, and then on every 8-week interval.; Other Names: Vedolizumab treatment

What is the study measuring?

Primary Outcome Measures

Outcome Measure	Measure Description	Time Frame
8th-week endoscopic remission rate	endoscopic subscale (ESS) =0, which defined as endoscopic remission	8th-week
normalization rate of CRP at the 8th week	normalization rate of C reactive protein (CRP)	8th-week
Clinical remission and response rate at the 8th week	Clinical remission and response rate	8th-week
life quality score at the 8th week	Inflammatory bowel disease questionnaire (IBDQ), the total score is 32-224, with higher scores indicating better quality of life for patients.	8th-week

Secondary Outcome Measures

Outcome Measure	Measure Description	Time Frame
normalization rate of CRP at the 54th week	normalization rate of CRP	54th-week
Clinical remission and response rate at the 54th-week	Clinical remission and response rate	54th-week
life quality score at the 54th week	Inflammatory bowel disease questionnaire (IBDQ), the total score is 32-224, with higher scores indicating better quality of life for patients.	54th-week

Collaborators and Investigators

• Sponsor: Sixth Affiliated Hospital, Sun Yat-sen University

Study record dates

Study Major Dates

• Study Start (Actual): November 1, 2023
• Primary Completion (Estimated): October 31, 2025
• Study Completion (Estimated): October 31, 2026

Study Registration Dates

• First Submitted: October 11, 2023
• First Submitted That Met QC Criteria: October 18, 2023
• First Posted (Actual): October 23, 2023

Study Record Updates

• Last Update Posted (Actual): November 22, 2023
• Last Update Submitted That Met QC Criteria: November 21, 2023
• Last Verified: November 1, 2023

More Information

Terms related to this study

• Additional Relevant MeSH Terms: Digestive System Diseases; Gastrointestinal Diseases; Gastroenteritis; Colonic Diseases; Intestinal Diseases; Inflammatory Bowel Diseases; Crohn Disease; Colitis; Colitis, Ulcerative; Molecular Mechanisms of Pharmacological Action; Enzyme Inhibitors; Antirheumatic Agents; Gastrointestinal Agents; Protein Kinase Inhibitors; Janus Kinase Inhibitors; Vedolizumab; Upadacitinib
• Other Study ID Numbers: 2023ZSLYEC-469

Plan for Individual participant data (IPD)

• Plan to Share Individual Participant Data (IPD)?: NO

Drug and device information, study documents

• Studies a U.S. FDA-regulated drug product: No
• Studies a U.S. FDA-regulated device product: No
• product manufactured in and exported from the U.S.: No