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

Study Overview
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Brief Summary
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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.

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

Conditions
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Crohn Disease

Intervention / Treatment
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* Drug: Upadacitinib
* Drug: Vedolizumab


Participation Criteria
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Eligibility Criteria
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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

Ages Eligible for Study
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Minimum Age: 18 Years

Sexes Eligible for Study
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All

Accepts Healthy Volunteers
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No

Study Plan
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How is the study designed?
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Design Details

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


Arms and Interventions

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

What is the study measuring?
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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 |