A Study to Assess Safety and Effectiveness of Adalimumab for Treating Children and Adolescents With Crohn's Disease in Real Life Conditions (LEA)

Assessing Long-term Safety and Effectiveness of Adalimumab for Treating Children and Adolescents With Crohn's Disease in Real Life Conditions-LEA

The primary objective of this study is to evaluate long-term effectiveness of adalimumab in pediatric participants starting a treatment for Crohn's disease in real life conditions, namely to describe the time to loss of clinical benefit in a time to event approach. Main secondary objectives are to describe growth and pubertal development and to describe long-term safety. The participants will be followed-up up to 10 years.

Study Overview

• Status: Terminated
• Conditions: Crohn's Disease

• Study Type: Observational
• Enrollment (Actual): 62

Contacts and Locations

Study Locations

• France
  • Angers, France, 49933
    • CHU Batiment Robert Debre /ID# 152665
  • Bordeaux, France, 33076
    • CHU Bordeaux-Hopital Pellegrin /ID# 154620
  • Bordeaux, France, 33076
    • Chu de Bordeaux Hopital /Id# 157926
  • Caen, France, 14033
    • Centre Hospitalier Universitai /ID# 155465
  • Clermont Ferrand, France, 63100
    • CHU Hopital d'Estaing /ID# 152664
  • Lille, France, 59037
    • Hopital Jeanne de Flandre /Id# 155464
  • Marseille, France, 13385
    • Hopital de la Timone /ID# 160133
  • Montivillier, France, 76290
    • Hopital Jacques Monod /ID# 152663
  • Orleans, France, 45067
    • Hopital de la Source /ID# 159947
  • Orleans, France, 45067
    • Hopital de la Source /ID# 165534
  • Paris, France, 75019
    • Robert Debre Hopital, FR /ID# 152666
  • Paris, France, 75571
    • Hopital Armand Trousseau /Id# 152669
  • Paris, France, 75571
    • Hopital Armand Trousseau /Id# 157092
  • Paris, France, 75743
    • Necker Hopital, FR /ID# 152830
  • Pierre Benite, France, 69495
    • Chu Lyon Sud /Id# 152838
  • Rennes, France, 35203
    • CHU de Rennes - Hospital Sud /ID# 152730
  • Rouen, France, 76031
    • Charles Nicolle Hosp chu rouen /ID# 152670
  • Rouen, France, 76031
    • Charles Nicolle Hosp chu rouen /ID# 158688
  • Auvergne-Rhone-Alpes
    • Pierre Benite CEDEX, Auvergne-Rhone-Alpes, France, 69495
      • Centre Hospitalier Lyon Sud /ID# 152667
    • Pierre Benite CEDEX, Auvergne-Rhone-Alpes, France, 69495
      • Centre Hospitalier Lyon Sud /ID# 152668
  • Centre-Val De Loire
    • Tours, Centre-Val De Loire, France, 37044
      • Hopital Clocheville /ID# 152831
  • Doubs
    • Besancon, Doubs, France, 25000
      • CHU de Besancon - Jean Minjoz /ID# 154197
  • Lorraine
    • Vandoeuvre les Nancy, Lorraine, France, 54500
      • Hopitaux de Brabois Adultes /ID# 152729
  • Occitanie
    • Toulouse CEDEX 3, Occitanie, France, 31025
      • CHU Toulouse /ID# 153251

Participation Criteria

Eligibility Criteria

• Ages Eligible for Study: 6 years to 17 years (Child)
• Accepts Healthy Volunteers: No
• Genders Eligible for Study: All

• Sampling Method: Non-Probability Sample

Study Population

Participants are children and adolescents with Crohn's disease

Description

Inclusion Criteria:

• With confirmed diagnosis of Crohn's disease
• Adalimumab-naïve patient (a patient having received an anti-TNF other than adalimumab may enter the study)
• Starting a treatment with adalimumab
• Guardian capable of and willing to grant authorization for use/disclosure of data collected and patient able to comply with the requirements of the study protocol.

Exclusion Criteria:

• Participants with a history of treatment with adalimumab
• Participants enrolled in a concomitant interventional clinical trial.

Study Plan

How is the study designed?

Number of groups / cohorts

1

Cohorts and Interventions

Group / Cohort
Pediatric participants receiving adalimumab; Pediatric participants receiving adalimumab for CD in real-life conditions.

What is the study measuring?

Primary Outcome Measures

Outcome Measure	Measure Description	Time Frame
Time to loss of clinical benefit	Loss of clinical benefit will be defined as one of the following: Loss of efficacy leading to adalimumab discontinuation or; Introduction / reinforcement of other immunosuppressants (ratio dose/weight) or; Introduction / reinforcement of corticosteroids (ratio dose/weight; reinforcement of corticosteroids are allowed within the 4 first months after start of adalimumab); Introduction of enteral nutrition; CD-related surgery, discontinuation of adalimumab due to adverse event, death.	Up to 12 years

Secondary Outcome Measures

Outcome Measure	Measure Description	Time Frame
Proportion of participants with dose escalation (dose and/or frequency of injections)	Dosing and/or frequency of injections is monitored to assess dose escalation.	Up to 12 years
Median percent change from baseline in C-reactive protein (CRP)	The median percent change from baseline in CRP is assessed at each time point.	From Month 0 to 12 years
Median percent change from baseline in calprotectin	The median percent change from baseline in calprotectin us assessed at each time point.	From Month 0 to 12 years
Change from baseline in weighted Pediatric Crohn's Disease Activity Index (PCDAI)	The Pediatric Activity Index (PCDAI) has become the standard outcome measure in pediatric Crohn's disease (CD) clinical research. The Weighted Pediatric Crohn's Disease Activity Index (wPCDAI) was developed to add weight to the items in the PCDAI and make it more feasible. In the wPCDAI, growth velocity, abdominal examination, and hematocrit are removed. The wPCDAI score can range from 0-125, with higher signifying severe disease activity.	From Month 0 to 12 years
Change in wPCDAI >= 37.5	A change in wPCDAI >= 37.5 indicates improvement.	From Month 0 to 12 years
Incidence rate of CD-related hospitalizations	Hospitalization will be determined from the health care utilization information.	Up to 12 years
Rate of clinical remission	Clinical remission is weighted PCDAI < 12.5 or Harvey-Bradshaw index (HBI) <5. Rate of clinical remission will be described at each time point	Up to 12 years
Proportion of participants achieving mucosal healing at each time point	Mucosal healing is assessed using SES-CD score (0 or 1).	Up to 12 years
Proportion of participants with steroid-free clinical remission at each time point	The proportion of participants with steroid-free clinical remission is assessed at each time point.	Up to 12 years
Change in weight z-score	Growth is assessed by monitoring changes in weight z-score.	From Month 0 to 12 years
Median percent change from baseline in high sensitivity C-reactive protein (hs-CRP)	The median percent change from baseline in hs-CRP is assessed at each time point.	From Month 0 to 12 years
Assessing Mucosal healing	Mucosal healing is assessed using Simple Endoscopic Score for Cronh's Disease (SES-CD) score (0 or 1).	Up to 12 years
Rate of steroid-free remission	Steroid-free remission is defined as weighted PCDAI < 12.5 or HBI <5 and no daily intake of prednisone (whatever the route). Rate of steroid-free remission will be described at each time point.	Up to 12 years
Proportion of participants with fistula remission (in participants with fistulizing CD at entry)	Fistula remission is defined as closure for at least 2 consecutive visits of all fistulae that were draining at baseline	Up to 12 years
Change in Tanner's staging	Tanner's staging is used to assess growth and pubertal development.	From Month 0 to 12 years
Proportion of participants with immunomodulator-free clinical remission at each time point	The proportion of participants with immunomodulator-free clinical remission is assessed at each time point.	Up to 12 years
Incidence rate of infectious events	The incidence rate of serious and non-serious opportunistic infections is assessed.	Up to 12 years
Incidence rate of all-cause hospitalizations	Hospitalization will be determined from the health care utilization information.	Up to 12 years
Proportion of participants with steroid tapering at each time point (steroids daily dosing lower than at baseline)	The proportion of participants with steroid tapering i.e., steroids daily dosing lower than at baseline (week 0) is assessed.	Up to 12 years
Change in height z-score	Growth is assessed by monitoring changes in height z-score	From Month 0 to 12 years
Proportion of participants with CD-related surgery	CD-related surgery includes subtotal colectomy with ileorectostomy, colectomy with ileo-anal pouch, Koch pouch, ileostomy, small bowel resection, and etc.	Up to 12 years
Incidence rate of CD- or drug-related hospitalizations	Hospitalization will be determined from the health care utilization information.	Up to 12 years

Collaborators and Investigators

• Sponsor: AbbVie

Publications and helpful links

Helpful Links

• clinical study report synopsis

Study record dates

Study Major Dates

• Study Start (Actual): September 26, 2017
• Primary Completion (Actual): October 14, 2019
• Study Completion (Actual): October 14, 2019

Study Registration Dates

• First Submitted: January 9, 2017
• First Submitted That Met QC Criteria: January 9, 2017
• First Posted (Estimate): January 11, 2017

Study Record Updates

• Last Update Posted (Actual): October 8, 2020
• Last Update Submitted That Met QC Criteria: October 6, 2020
• Last Verified: October 1, 2020

More Information

Terms related to this study

• Keywords: Crohn's Disease; Adalimumab; Humira®
• Additional Relevant MeSH Terms: Digestive System Diseases; Gastrointestinal Diseases; Gastroenteritis; Intestinal Diseases; Inflammatory Bowel Diseases; Crohn Disease
• Other Study ID Numbers: P15-759

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: No
• Studies a U.S. FDA-regulated device product: No
• product manufactured in and exported from the U.S.: No