Defining Predictors of RT Response to Vedolizumab in IBD

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

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.

Study Overview

• Status: Completed
• Conditions: Crohn Disease of Small Intestine
• Intervention / Treatment: Drug: Vedolizumab 300 MG Injection [Entyvio]

• Study Type: Interventional
• Enrollment (Actual): 48
• Phase: Phase 4

Contacts and Locations

Study Locations

• United States
  • Missouri
    • St Louis, Missouri, United States, 63110
      • Washington University School of Medicine

Participation Criteria

Eligibility Criteria

• Ages Eligible for Study: 18 years and older (Adult, Older Adult)
• Accepts Healthy Volunteers: No

Description

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.

Study Plan

How is the study designed?

Design Details

• Primary Purpose: Treatment
• Allocation: N/A
• Interventional Model: Single Group Assignment
• Masking: None (Open Label)

Number of Arms

1

Arms and Interventions

Participant Group / Arm	Intervention / Treatment
Experimental: Vedolizumab 300 MG Injection [Entyvio]; 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]; Vedolizumab Injection; Other Names: Entyvio

What is the study measuring?

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.	24±2 weeks
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.	52±2 weeks

Collaborators and Investigators

• Sponsor: Washington University School of Medicine
• Investigators: Principal Investigator: Parakkal Deepak, MBBS, MS, Washington University School of Medicine

Publications and helpful links

General Publications

• Deepak P, Fletcher JG, Fidler JL, Barlow JM, Sheedy SP, Kolbe AB, Harmsen WS, Loftus EV, Hansel SL, Becker BD, Bruining DH. Radiological Response Is Associated With Better Long-Term Outcomes and Is a Potential Treatment Target in Patients With Small Bowel Crohn's Disease. Am J Gastroenterol. 2016 Jul;111(7):997-1006. doi: 10.1038/ajg.2016.177. Epub 2016 May 10.

Study record dates

Study Major Dates

• Study Start (Actual): June 8, 2018
• Primary Completion (Actual): May 22, 2024
• Study Completion (Actual): October 28, 2024

Study Registration Dates

• First Submitted: May 3, 2017
• First Submitted That Met QC Criteria: May 3, 2017
• First Posted (Actual): May 5, 2017

Study Record Updates

• Last Update Posted (Estimated): September 17, 2025
• Last Update Submitted That Met QC Criteria: September 15, 2025
• Last Verified: September 1, 2025

More Information

Terms related to this study

• Additional Relevant MeSH Terms: Intestinal Diseases; Digestive System Diseases; Gastrointestinal Diseases; Gastroenteritis; Inflammatory Bowel Diseases; Crohn Disease; Therapeutics; Drug Administration Routes; Drug Therapy; Injections; vedolizumab
• Other Study ID Numbers: 201705043 -17-001

Plan for Individual participant data (IPD)

• Plan to Share Individual Participant Data (IPD)?: UNDECIDED

Drug and device information, study documents

• Studies a U.S. FDA-regulated drug product: Yes
• Studies a U.S. FDA-regulated device product: No