Defining Predictors of RT Response to Vedolizumab in IBD

Study Overview
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Brief Summary
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The overall goal of the study is to develop data that can convincingly guide clinicians on the use and efficacy of vedolizumab in patients with small bowel CD. There is an unmet need to identify response to vedolizumab in small bowel CD using objective endpoints. Current data suggest that MR enterography may meet this unmet need. There is an additional unmet need to develop predictive models incorporating both clinical and baseline radiological and endoscopic variables with higher discriminatory performance in identifying longer term clinical remission with vedolizumab. Finally, this proposal is strengthened by the exploratory studies which may identify new proteomic biomarkers that correlate with longer term radiological response with vedolizumab reflecting its latency of response. If successful, these serum biomarkers may guide a personalized approach to the treatment of small bowel CD with vedolizumab, allowing early identification of PNR, monitoring disease activity and the pharmacodynamics of vedolizumab.

Official Title
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Defining Predictors of Radiological Transmural Response to Vedolizumab in Small Bowel Crohn's Disease Through Serum Proteomic Biomarkers

Conditions
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Crohn Disease of Small Intestine

Intervention / Treatment
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* Drug: Vedolizumab 300 MG Injection [Entyvio]


Participation Criteria
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Eligibility Criteria
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Inclusion Criteria: Moderate to severe disease activity small bowel CD (small bowel only or ileocecal only) visible on MRE Initiated on Vedolizumab with/without thiopurines or methotrexate ≥18 years old Exclusion Criteria: Pregnancy Age <18 Planned surgery prior to the first follow-up MRE Inability to provide informed consent. Perianal CD will be excluded since assessment requires performance of additional MRI of the pelvis. Individuals with colonic involvement other than involvement of the ascending colon and cecum. Inpatient scans will only be included if this is a MRE and adequate small bowel distension with appropriate contrast has been achieved If unable to provide informed consent Contraindications for MRE including chronic kidney disease that precludes contrast administration, implanted medical devices that are contraindicated for MRE.

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
Intervention Model: Single Group Assignment
Masking: None (Open Label)


Arms and Interventions

| Participant Group/Arm | Intervention/Treatment |
| --- | --- |
| Experimental: Vedolizumab 300 MG Injection [Entyvio]<br>Vedolizumab will be initiated at 300 mg intravenous (IV) dosing at 0, 2 and 6 weeks followed by the 1st maintenance with 300 mg IV at week 14. Patients who have not achieved clinical response at week 14 will be eligible to undergo dose escalation to 4 weekly dosing of vedolizumab depending on the judgement of the treating gastroenterologist. | Drug: Vedolizumab 300 MG Injection [Entyvio]<br>* Vedolizumab Injection<br>* Other names: Entyvio;|

What is the study measuring?
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Primary Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| Radiological response | Radiological Transmural Response will be defined per-lesion and per-patient. Per-lesion TR will be defined as a decrease in the length of inflamed small bowel lesion from baseline or improvement in any imaging findings associated with severe mural inflammation, i.e., restricted diffusion, mural thickness, intramural T2 hyperintensity, peri-enteric T2 signal, and luminal ulcerations, without development of a new penetrating or stricturing complication. Worsened lesions will be fined as those with an increased score of any imaging parameter associated with severe mural inflammation. Unchanged lesions will be defined as those with unchanged (without worsening or improving) inflammatory parameters associated with severe mural inflammation. Patients will be then classified for TR as responders if all individual lesions improved and non-responders if any of the lesions worsened, a new lesion developed at the 4 month MRE and all other scenarios not meeting definition of response. | 16±2 weeks |