Clinical trial NCT02862132: Predicting Response to Vedolizumab in Pediatric Inflammatory Bowel Diseases
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)
Study type: INTERVENTIONAL
Overall status: COMPLETED
Phase: NA
Conditions: Crohn's Disease
Ulcerative Colitis
Inflammatory Bowel Disease
Keywords: VDZ: Vedolizumab
UC: Ulcerative colitis
CD: Crohn's disease
TDM: Therapeutic drug monitoring
Lead sponsor: Shaare Zedek Medical Center
Sponsor class: OTHER
First posted: 2016-08-10
Enrollment: 142
Sex: ALL
Maximum age (years): 18
Standard ages: CHILD
ADULT
Accepts healthy volunteers: no
Allocation: NA
Intervention model: SINGLE_GROUP
Primary purpose: TREATMENT

Brief 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.

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.

Eligibility criteria: 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

Primary outcomes:
measure: Complete remission at week 14
timeFrame: weeks 14
measure: Complete remission at week 30
timeFrame: weeks 30
measure: Complete remission at week 54
timeFrame: weeks 54
measure: Complete remission at week 108
timeFrame: weeks 108
measure: Complete remission at week 162
timeFrame: weeks 162
Secondary outcomes:
measure: Steroid and EEN free clinical remission (without the need for normal CRP) using PCDAI or PUCAI score and concomitant medication list.
timeFrame: week 30, week 54, week 108, week 162
measure: Steroid and EEN free clinical response (without the need for normal CRP) using PCDAI or PUCAI score and concomitant medication list.
timeFrame: week 30, week 54, week 108, week 162
measure: Fecal calprotectin levels
timeFrame: week 30, week 54, week 108, week 162
measure: serum CRP levels
timeFrame: week 30, week 54, week 108, week 162
measure: Rate of loss of response including drug levels
timeFrame: week 30, week 54, week 108, week 162
measure: Steroid dependency (defined as cumulative use of >4 months in a year with at least one need to increase dose while weaning)
timeFrame: week 30, week 54, week 108, week 162
measure: Adverse events
timeFrame: week 30, week 54, week 108, week 162
measure: Measures of mucosal inflammation as available as part of clinical care using endoscopy, imaging or capsule endoscopy.
timeFrame: week 30, week 54, week 108, week 162
measure: Time to induction of remission
timeFrame: week 30, week 54, week 108, week 162
measure: Longitudinal Physician Global Assessment (PGA)
timeFrame: week 30, week 54, week 108, week 162
measure: Height velocity as compared with the year prior to commencing VDZ
timeFrame: week 30, week 54, week 108, week 162
measure: Need for surgical interventions (including resections, colectomy, and dilatations)
timeFrame: week 30, week 54, week 108, week 162
Other outcomes:
Locations:
city: Hartford
country: United States
facility: Connecticut Children's Medical Center
state: Connecticut
city: Morristown
country: United States
facility: Atlantic Children's Health-Goryeb Children's Hospital
state: New Jersey
city: New York
country: United States
facility: Cohen Children's Medical Center of NY, Northwell
state: New York
city: Philadelphia
country: United States
facility: Children's Hospital of Philadelphia
state: Pennsylvania
city: Copenhagen
country: Denmark
facility: Hvidovre University Hospital
city: Dublin
country: Ireland
facility: Our Lady's Children's Hospital Crumlin
city: Haifa
country: Israel
facility: Rambam Medical Cener
city: Holon
country: Israel
facility: Wolfson Medical Center
city: Jerusalem
country: Israel
facility: Shaare Zedek Medical Center
city: Petach Tikva
country: Israel
facility: Schneider Medical Center
city: Ramat Gan
country: Israel
facility: Sheba Medical Center
city: Tel Aviv
country: Israel
facility: Ichilov
city: Tzrifin
country: Israel
facility: Assaf Harofeh
city: Ljubljana
country: Slovenia
facility: University Children's Hospital Ljubljana
city: Glasgow
country: United Kingdom
facility: The Royal Hospital for Children Glasgow
Study officials:
affiliation: Shaare Zedek Medical Center
name: Dan Turner, MD
role: PRINCIPAL_INVESTIGATOR
References:
citation: Atia O, Shavit-Brunschwig Z, Mould DR, Stein R, Matar M, Aloi M, Ledder O, Focht G, Urlep D, Hyams J, Broide E, Weiss B, Levine J, Russell RK, Turner D. Outcomes, dosing, and predictors of vedolizumab treatment in children with inflammatory bowel disease (VEDOKIDS): a prospective, multicentre cohort study. Lancet Gastroenterol Hepatol. 2023 Jan;8(1):31-42. doi: 10.1016/S2468-1253(22)00307-7. Epub 2022 Oct 26.