Top-down Infliximab Study in Kids With Crohn's Disease

NCT02517684 | Completed Phase 4

• 3 other identifiers: NL52030.078.152014-005702-37MEC-2015-080
• Study Type: interventional
• Target: 100
• Locations: 3 countries
• Sites: 13

Brief Summary

The purpose of this study is to determine whether a top-down treatment approach, prescribing infliximab (IFX) and azathioprine (AZA) at diagnose, yields better outcome in comparison to the usual step-up treatment approach, starting with prednison and AZA or exclusive enteral nutrition (EEN) and AZA, in moderate-to-severe pediatric Crohn's disease (CD) patients.

Conditions

Crohn's Disease

Keywords

Crohn's disease; pediatric; infliximab; top-down; TISKids

Outcome Measures

Primary Outcomes (1)

• Clinical remission without need for additional CD related therapy or surgery

  Clinical remission is defined as a weighted Pediatric Crohn's Disease Activity Index (wPCDAI) score of less than 12.5 points

  52 weeks

Secondary Outcomes (14)

• Clinical response rates

  10 weeks

• Clinical remission rates

  10 and 52 weeks

• Mucosal healing

  10 and 52 weeks

• Change in height Z-scores

  10 and 52 weeks

• Change in BMI Z-scores

  10 and 52 weeks

Study Arms (2)

Top-down

EXPERIMENTAL

Infliximab and azathioprine; patients will receive 5 infliximab infusions of 5 mg/kg (IFX induction at week 0, 2 and 6, followed by 2 maintenance infusions every 8 weeks). IFX will be discontinued after 5 IFX infusions. Patients will also receive oral azathioprine 2-3 mg/kg, once daily as maintenance treatment.

Drug: Infliximab; Drug: Azathioprine

Step-up

ACTIVE COMPARATOR

Step-up treatment will consist of standard induction treatment by either oral prednisolone 1 mg/kg (maximum 40 mg) once daily for 4 weeks, followed by tapering in 6 weeks until stop, or EEN with polymeric feeding for 6-8 weeks after which normal foods are gradually reintroduced within 2-3 weeks. Either of these induction treatments will be combined with oral AZA 2-3 mg, once daily, as maintenance treatment.

Drug: Prednisolone; Other: Exclusive enteral nutrition; Drug: Azathioprine

Interventions

Infliximab DRUG

Also known as: Inflectra

Top-down

Prednisolone DRUG

Step-up

Exclusive enteral nutrition OTHER

Step-up

Azathioprine DRUG

Also known as: Imuran

Step-up; Top-down

Eligibility Criteria

• Age: 3 Years - 17 Years
• Sex: all
• Healthy Volunteers: No
• Age Groups: Child (0-17)

You may qualify if:

• Children (age 3-17 years, both male and female, weight \>10kg) with new-onset,

You may not qualify if:

• Patients with the following characteristics will be excluded:
• immediate need for surgery,
• symptomatic stenosis or stricture in the bowel due to scarring,
• active perianal fistulas,
• severe co-morbidity,
• severe infection such as sepsis or opportunistic infections,
• positive stool culture,
• positive Clostridium difficile assay,
• positive tuberculin test or a chest radiograph consistent with tuberculosis or malignancy,
• those already started with CD specific therapy,
• patients with a suspected or
• definitive pregnancy

Sponsors & Collaborators

• Erasmus Medical Center: lead
• ZonMw: The Netherlands Organisation for Health Research and Development: collaborator
• Hospira, now a wholly owned subsidiary of Pfizer: collaborator

Study Sites (13)

University Hospital Brussels

Brussels, Belgium

Location

University Hospitals Leuven

Leuven, Belgium

Location

Helsinki University Central Hospital

Helsinki, Finland

Location

Erasmus Medical Center

Rotterdam, South Holland, 3000 CA, Netherlands

Location

Academic Medical Center

Amsterdam, Netherlands

Location

VU University Medical Center

Amsterdam, Netherlands

Location

Amphia Hospital

Breda, Netherlands

Location

Medisch Spectrum Twente

Enschede, Netherlands

Location

Leiden University Medical Center

Leiden, Netherlands

Location

Radboud University Medical Center

Nijmegen, Netherlands

Location

Maasstad Hospital

Rotterdam, Netherlands

Location

University Medical Center Utrecht

Utrecht, Netherlands

Location

Isala hospital

Zwolle, Netherlands

Location

Related Publications (4)

• Vuijk SA, Jongsma MME, Hoeven BM, Cozijnsen MA, van Pieterson M, de Meij TGJ, Norbruis OF, Groeneweg M, Wolters VM, van Wering H, Hummel T, Stapelbroek J, van der Feen C, van Rheenen PF, van Wijk MP, Teklenburg S, Rizopoulos D, Poley MJ, Escher JC, de Ridder L. Randomised clinical trial: First-line infliximab biosimilar is cost-effective compared to conventional treatment in paediatric Crohn's disease. Aliment Pharmacol Ther. 2024 Jun;59(12):1510-1520. doi: 10.1111/apt.18000. Epub 2024 Apr 21.

  PMID: 38644588 DERIVED

• Jongsma MME, Costes LMM, Tindemans I, Cozijnsen MA, Raatgreep RHC, van Pieterson M, Li Y, Escher JC, de Ridder L, Samsom JN. Serum Immune Profiling in Paediatric Crohn's Disease Demonstrates Stronger Immune Modulation With First-Line Infliximab Than Conventional Therapy and Pre-Treatment Profiles Predict Clinical Response to Both Treatments. J Crohns Colitis. 2023 Aug 21;17(8):1262-1277. doi: 10.1093/ecco-jcc/jjad049.

  PMID: 36934327 DERIVED

• Jongsma MME, Aardoom MA, Cozijnsen MA, van Pieterson M, de Meij T, Groeneweg M, Norbruis OF, Wolters VM, van Wering HM, Hojsak I, Kolho KL, Hummel T, Stapelbroek J, van der Feen C, van Rheenen PF, van Wijk MP, Teklenburg-Roord STA, Schreurs MWJ, Rizopoulos D, Doukas M, Escher JC, Samsom JN, de Ridder L. First-line treatment with infliximab versus conventional treatment in children with newly diagnosed moderate-to-severe Crohn's disease: an open-label multicentre randomised controlled trial. Gut. 2022 Jan;71(1):34-42. doi: 10.1136/gutjnl-2020-322339. Epub 2020 Dec 31.

  PMID: 33384335 DERIVED

• Cozijnsen MA, van Pieterson M, Samsom JN, Escher JC, de Ridder L. Top-down Infliximab Study in Kids with Crohn's disease (TISKids): an international multicentre randomised controlled trial. BMJ Open Gastroenterol. 2016 Dec 22;3(1):e000123. doi: 10.1136/bmjgast-2016-000123. eCollection 2016.

  PMID: 28090335 DERIVED

MeSH Terms

Conditions

Crohn Disease

Interventions

Infliximab; Prednisolone; Azathioprine

Condition Hierarchy (Ancestors)

Inflammatory Bowel Diseases; Gastroenteritis; Gastrointestinal Diseases; Digestive System Diseases; Intestinal Diseases

Intervention Hierarchy (Ancestors)

Antibodies, Monoclonal; Antibodies; Immunoglobulins; Immunoproteins; Blood Proteins; Proteins; Amino Acids, Peptides, and Proteins; Serum Globulins; Globulins; Pregnadienetriols; Pregnadienes; Pregnanes; Steroids; Fused-Ring Compounds; Polycyclic Compounds; Thionucleosides; Sulfur Compounds; Organic Chemicals; Mercaptopurine; Purines; Heterocyclic Compounds, 2-Ring; Heterocyclic Compounds, Fused-Ring; Heterocyclic Compounds; Nucleosides; Nucleic Acids, Nucleotides, and Nucleosides

Study Officials

• Lissy de Ridder, MD PhD

  Erasmus Medical Center

  PRINCIPAL INVESTIGATOR

Study Design

• Study Type: interventional
• Phase: phase 4
• Allocation: RANDOMIZED
• Masking: NONE
• Purpose: TREATMENT
• Intervention Model: PARALLEL
• Sponsor Type: OTHER
• Responsible Party: PRINCIPAL INVESTIGATOR
• PI Title: Pediatric Gastroenterologist

Study Record Dates

• First Submitted: July 1, 2015
• First Posted: August 7, 2015
• Study Start: April 1, 2015
• Primary Completion: December 1, 2019
• Study Completion: January 1, 2024
• Last Updated: March 5, 2024

Record last verified: 2024-03

Locations

FI (1); NL (10); BE (2)