Predicting Response to Vedolizumab in Pediatric Inflammatory Bowel Diseases

October 24, 2022 updated by: Dr Dan Turner, Shaare Zedek Medical Center

Predicting Response to Vedolizumab in Pediatric Inflammatory Bowel Diseases (IBD) Including Drug Levels: a Multi-center Prospective Cohort Study, From the Pediatric IBD Porto Group of European Society for Paediatric Gastroenterology, Hepatology and Nutrition (ESPGHAN)

Vedolizumab (VDZ) is a humanized immunoglobulin G1 monoclonal antibody acting against α4β7 integrin which modulates lymphocyte trafficking in the gut.

Results from the adult GEMINI-1 and GEMINI-2 trials demonstrated clinical efficacy in induction and maintenance of remission in both ulcerative colitis (UC) and Crohn's disease (CD), respectively.

Recent real life cohorts in adults support the effectiveness of VDZ in inducing and maintaining remission, both in CD and UC. In pediatrics, there are very limited data on the use of VDZ besides two retrospective case series.

Data on immunogenicity and therapeutic drug monitoring (TDM) of VDZ is conflicting in adults and practically non-existent in children.

The investigators aim to prospectively explore the real life short and longer term outcomes of VDZ in pediatric IBD (including growth) and to develop a prediction model for treatment success based on VDZ trough levels and other clinical and laboratory variables.

Study Overview

Status

Completed

Conditions

Intervention / Treatment

Detailed Description

This is a multi-center prospective cohort study in which the investigators are aim to enroll 140 children under the age of 18 years, diagnosed with CD, inflammatory bowel disease unclassified (IBDU) or UC (approximately 70 in UC/IBDU and 70 in the CD group) who commenced on Vedolizumab for any reason at the discretion of the treating physician.

Patients will be followed up to 3 years at 8 different time points: week 0, week 2, week 6, week 14, week 30, week 54 (1 year), week 108 (2 years) and week 162 (3 years). Blood work will be collected at each visit during the time of venous access insertion for the drug infusion for serum and stool sample will be collected at visits 0, 14, 30, and 54. In addition, at week 0 and 14 whole blood will be collected into a PaxGene tube for gene expression analysis.

Study Type

Interventional

Enrollment (Actual)

142

Phase

  • Not Applicable

Contacts and Locations

This section provides the contact details for those conducting the study, and information on where this study is being conducted.

Study Locations

  • Denmark
      • Copenhagen, Denmark
        • Hvidovre University Hospital
  • Ireland
      • Dublin, Ireland
        • Our Lady's Children's Hospital Crumlin
  • Israel
      • Haifa, Israel
        • Rambam Medical Cener
      • Holon, Israel
        • Wolfson Medical Center
      • Jerusalem, Israel
        • Shaare Zedek Medical Center
      • Petach Tikva, Israel
        • Schneider Medical Center
      • Ramat Gan, Israel
        • Sheba Medical Center
      • Tel Aviv, Israel
        • Ichilov
      • Tzrifin, Israel
        • Assaf Harofeh
  • Slovenia
      • Ljubljana, Slovenia
        • University Children's Hospital Ljubljana
  • United Kingdom
      • Glasgow, United Kingdom
        • The Royal Hospital for Children Glasgow
  • United States
    • Connecticut
      • Hartford, Connecticut, United States, 06032
        • Connecticut Children's Medical Center
    • New Jersey
      • Morristown, New Jersey, United States
        • Atlantic Children's Health-Goryeb Children's Hospital
    • New York
      • New York, New York, United States
        • Cohen Children's Medical Center of NY, Northwell
    • Pennsylvania
      • Philadelphia, Pennsylvania, United States
        • Children's Hospital of Philadelphia

Participation Criteria

Researchers look for people who fit a certain description, called eligibility criteria. Some examples of these criteria are a person's general health condition or prior treatments.

Eligibility Criteria

Ages Eligible for Study

No older than 18 years (Child, Adult)

Accepts Healthy Volunteers

No

Genders Eligible for Study

All

Description

Inclusion Criteria:

  1. Children under the age of 18 years.
  2. IBD Diagnosis
  3. Initiating Vedolizumab therapy

Exclusion Criteria:

1. Starting Vedolizumab to prevent post operative recurrence

Study Plan

This section provides details of the study plan, including how the study is designed and what the study is measuring.

How is the study designed?

Design Details

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

Arms and Interventions

Participant Group / Arm
Intervention / Treatment
Experimental: Vedolizumab
IV Vedolizumab 177mg/m2 Body Surface Area (BSA), max. 300mg Induction regimen: 0,2,6 and then every 8 weeks
Drug: Vedolizumab
Other Names:
  • Entyvio

What is the study measuring?

Primary Outcome Measures

Outcome Measure
Measure Description
Time Frame
Complete remission at week 14
Time Frame: weeks 14

As defined by all three criteria:

i. Steroids and Exclusive enteral nutrition (EEN) (defined as >50% of daily calories with enteral nutrition)- free ii. Clinical remission (i.e. weighted Pediatric Crohn's Disease Activity Index (wPCDAI) <12.5 points in CD, and Paediatric Ulcerative Colitis Activity Index (PUCAI) <10 in UC) iii. CRP lower than 1.5 times upper normal limit (UNL) (may be substituted by Erythocytes Sedimentation Rate (ESR) if CRP missing)
weeks 14
Complete remission at week 30
Time Frame: weeks 30

As defined by all three criteria:

i. Steroids and Exclusive enteral nutrition (EEN) (defined as >50% of daily calories with enteral nutrition)- free ii. Clinical remission (i.e. weighted Pediatric Crohn's Disease Activity Index (wPCDAI) <12.5 points in CD, and Paediatric Ulcerative Colitis Activity Index (PUCAI) <10 in UC) iii. CRP lower than 1.5 times upper normal limit (UNL) (may be substituted by Erythocytes Sedimentation Rate (ESR) if CRP missing)
weeks 30
Complete remission at week 54
Time Frame: weeks 54

As defined by all three criteria:

i. Steroids and Exclusive enteral nutrition (EEN) (defined as >50% of daily calories with enteral nutrition)- free ii. Clinical remission (i.e. weighted Pediatric Crohn's Disease Activity Index (wPCDAI) <12.5 points in CD, and Paediatric Ulcerative Colitis Activity Index (PUCAI) <10 in UC) iii. CRP lower than 1.5 times upper normal limit (UNL) (may be substituted by Erythocytes Sedimentation Rate (ESR) if CRP missing)
weeks 54
Complete remission at week 108
Time Frame: weeks 108

As defined by all three criteria:

i. Steroids and Exclusive enteral nutrition (EEN) (defined as >50% of daily calories with enteral nutrition)- free ii. Clinical remission (i.e. weighted Pediatric Crohn's Disease Activity Index (wPCDAI) <12.5 points in CD, and Paediatric Ulcerative Colitis Activity Index (PUCAI) <10 in UC) iii. CRP lower than 1.5 times upper normal limit (UNL) (may be substituted by Erythocytes Sedimentation Rate (ESR) if CRP missing)
weeks 108
Complete remission at week 162
Time Frame: weeks 162

As defined by all three criteria:

i. Steroids and Exclusive enteral nutrition (EEN) (defined as >50% of daily calories with enteral nutrition)- free ii. Clinical remission (i.e. weighted Pediatric Crohn's Disease Activity Index (wPCDAI) <12.5 points in CD, and Paediatric Ulcerative Colitis Activity Index (PUCAI) <10 in UC) iii. CRP lower than 1.5 times upper normal limit (UNL) (may be substituted by Erythocytes Sedimentation Rate (ESR) if CRP missing)
weeks 162

Secondary Outcome Measures

Outcome Measure
Measure Description
Time Frame
Steroid and EEN free clinical remission (without the need for normal CRP) using PCDAI or PUCAI score and concomitant medication list.
Time Frame: week 30, week 54, week 108, week 162
week 30, week 54, week 108, week 162
Steroid and EEN free clinical response (without the need for normal CRP) using PCDAI or PUCAI score and concomitant medication list.
Time Frame: week 30, week 54, week 108, week 162
week 30, week 54, week 108, week 162
Fecal calprotectin levels
Time Frame: week 30, week 54, week 108, week 162
Levels of calprotectin will be measured in the lab using calprotectin kit.
week 30, week 54, week 108, week 162
serum CRP levels
Time Frame: week 30, week 54, week 108, week 162
CRP levels will be measured in the lab
week 30, week 54, week 108, week 162
Rate of loss of response including drug levels
Time Frame: week 30, week 54, week 108, week 162
week 30, week 54, week 108, week 162
Steroid dependency (defined as cumulative use of >4 months in a year with at least one need to increase dose while weaning)
Time Frame: week 30, week 54, week 108, week 162
week 30, week 54, week 108, week 162
Adverse events
Time Frame: week 30, week 54, week 108, week 162
week 30, week 54, week 108, week 162
Measures of mucosal inflammation as available as part of clinical care using endoscopy, imaging or capsule endoscopy.
Time Frame: week 30, week 54, week 108, week 162
week 30, week 54, week 108, week 162
Time to induction of remission
Time Frame: week 30, week 54, week 108, week 162
week 30, week 54, week 108, week 162
Longitudinal Physician Global Assessment (PGA)
Time Frame: week 30, week 54, week 108, week 162
PGA will be measured using Visual analogue scale (VAS)
week 30, week 54, week 108, week 162
Height velocity as compared with the year prior to commencing VDZ
Time Frame: week 30, week 54, week 108, week 162
week 30, week 54, week 108, week 162
Need for surgical interventions (including resections, colectomy, and dilatations)
Time Frame: week 30, week 54, week 108, week 162
week 30, week 54, week 108, week 162

Collaborators and Investigators

This is where you will find people and organizations involved with this study.

Sponsor

Shaare Zedek Medical Center

Investigators

  • Principal Investigator: Dan Turner, MD, Shaare Zedek Medical Center

Publications and helpful links

The person responsible for entering information about the study voluntarily provides these publications. These may be about anything related to the study.

General Publications

Study record dates

These dates track the progress of study record and summary results submissions to ClinicalTrials.gov. Study records and reported results are reviewed by the National Library of Medicine (NLM) to make sure they meet specific quality control standards before being posted on the public website.

Study Major Dates

Study Start (Actual)

January 1, 2017

Primary Completion (Actual)

January 1, 2022

Study Completion (Actual)

January 1, 2022

Study Registration Dates

First Submitted

July 31, 2016

First Submitted That Met QC Criteria

August 4, 2016

First Posted (Estimate)

August 10, 2016

Study Record Updates

Last Update Posted (Actual)

October 25, 2022

Last Update Submitted That Met QC Criteria

October 24, 2022

Last Verified

October 1, 2022

More Information

Terms related to this study

Keywords

Additional Relevant MeSH Terms

Other Study ID Numbers

  • VEDOKIDS

Plan for Individual participant data (IPD)

Plan to Share Individual Participant Data (IPD)?

Undecided

This information was retrieved directly from the website clinicaltrials.gov without any changes. If you have any requests to change, remove or update your study details, please contact register@clinicaltrials.gov. As soon as a change is implemented on clinicaltrials.gov, this will be updated automatically on our website as well.

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