Predicting Response to Vedolizumab in Pediatric Inflammatory Bowel Diseases

Ulcerative Colitis Clinical Trial

Official title:

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)

Clinical Trial Details — Status: Completed

Administrative data

• NCT number: NCT02862132
• Other study ID #: VEDOKIDS
• Status: Completed
• Phase: N/A
• Start date: January 2017
• Est. completion date: January 2022

Study information

• Verified date: October 2022
• Source: Shaare Zedek Medical Center
• Contact: n/a
• Is FDA regulated: No
• Study type: Interventional

Clinical Trial Summary

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.

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.

Recruitment information / eligibility

• Status: Completed
• Enrollment: 142
• Est. completion date: January 2022
• Est. primary completion date: January 2022
• Accepts healthy volunteers: No
• Gender: All
• Age group: N/A to 18 Years

Eligibility

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

Related Conditions & MeSH terms

• Colitis
• Colitis, Ulcerative
• Crohn Disease
• Crohn's Disease
• Inflammatory Bowel Disease
• Inflammatory Bowel Diseases
• Intestinal Diseases
• Ulcer
• Ulcerative Colitis

Intervention

Drug:
• Vedolizumab

Locations

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

Sponsors (1)

Lead Sponsor	Collaborator
Shaare Zedek Medical Center

Countries where clinical trial is conducted

United States,  Denmark,  Ireland,  Israel,  Slovenia,  United Kingdom, 

Outcome

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