Early Proactive Therapeutic Drug Monitoring of Infliximab in Children: EPIC Study

NCT05280405 | Unknown Phase 4

• 1 other identifier: 2021-003220-32
• Study Type: interventional
• Target: 86
• Locations: 1 country
• Sites: 1

Brief Summary

The purpose of the study is to assess whether a proactive therapeutic drug monitoring strategy, introduced early during treatment, improves Infliximab (IFX) durability, efficacy and safety in children and young adults with inflammatory bowel disease. Patients with an indication to receive IFX, based on current clinical practice recommendations, will receive the drug either based on IFX concentrations determined before every IFX infusion, starting from the third infusion, or at standard dosing. Approximately 90 patients will be included in this research study. Patients enrolled will be in the study for approximately 12 months.

Conditions

Inflammatory Bowel Diseases

Keywords

Infliximab; Proactive drug monitoring

Outcome Measures

Primary Outcomes (1)

• Frequency of IFX discontinuation or need for treatment intensification due to non-response or LOR during the first year of treatment.

  Composite outcome. Treatment intensification is defined as adjunction of rescue therapies, including corticosteroids systemic or topical, azathioprine (AZA), methotrexate (MTX), 5-aminosalicylate (5-ASA) systemic or topical, or rescue IFX escalation or surgery; treatment response is defined as a decrease in Pediatric Crohn's Disease Activity Index (PCDAI) by 12.5 point or in Pediatric Ulcerative Colitis Activity Index (PUCAI) by 10 points with decrease in C reactive protein (CRP) by 50% after induction, evaluated between 12-14 weeks; loss of response (LOR) is defined as PCDAI \>= 10 or PUCAI \> 10 with CRP \> 0.5mg/dl and/or fecal calprotectin (FC) \>250 microg/g in a patient who previously responded to induction treatment.

  54 weeks

Secondary Outcomes (9)

• Cumulative probability of IFX discontinuation

  54 weeks

• Cumulative probability of Loss of Response

  54 weeks

• Frequency of subtherapeutic IFX concentrations

  54 weeks

• Frequency of Anti-Infliximab Antibodies

  54 weeks

• Frequency of infusion reactions

  54 weeks

Study Arms (2)

Early-Proactive Therapeutic Drug Monitoring (E-pTDM)

EXPERIMENTAL

Infliximab (IFX) at 5mg/kg, IV at week 0, 2 and 6. From week 6, the infusion interval will be adjusted based on pre-infusion IFX concentrations to target a trough level grater or equal to (\>=) 5 mcg/ml (\> 10 μg/ml in patients with perianal disease). For IFX concentrations below target, the infusion interval will be shortened (minimum interval 2 weeks). IFX dose increase will be performed as a second step.

Drug: Infliximab

Standard dosing

ACTIVE COMPARATOR

Infliximab (IFX) at 5mg/kg, IV at week 0, 2 and 6 followed by 5mg/kg infusions every 8 weeks.

Drug: Infliximab

Interventions

Infliximab DRUG

Infliximab

Early-Proactive Therapeutic Drug Monitoring (E-pTDM); Standard dosing

Eligibility Criteria

• Age: 6 Years - 17 Years
• Sex: all
• Healthy Volunteers: No
• Age Groups: Child (0-17)

You may qualify if:

• Anti-TNF naïve children and adolescents, 6-17 years, with a diagnosis of IBD confirmed by a prior endoscopic biopsy that is consistent with the diagnosis
• Indication to start anti-TNF therapy in accordance with current pediatric guidelines for the treatment of pediatric IBD
• Active inflammation supported by CRP \> 5mg/L and /or FC \> 150 μg/g before the 1st IFX dose

You may not qualify if:

• Consent withdrawal,
• Stenosing or penetrating disease requiring surgery, abdominal abscess, symptomatic stricture,
• Abdominal surgery within the previous 6 months,
• Acute severe ulcerative colitis attack defined by a PUCAI score Ñ 65,
• Infective contraindication to IFX treatment including positive tuberculin skin test or Quantiferon-TB test, recent opportunistic infection, infection with hepatitis B (HBV), C (HCV), human immunodeficiency virus (HIV),
• Previous exposure to anti-TNF;
• Exposure to concomitant prohibited medications including other biologics (including but not limited to ustekinumab, vedolizumab, abatacept, anakinra..), thalidomide, investigational drugs
• Pregnancy or lactation

Sponsors & Collaborators

• IRCCS Burlo Garofolo: lead

Study Sites (1)

Institute for Maternal and Child Health - IRCCS "Burlo Garofolo"

Trieste, 34137, Italy

RECRUITING

MeSH Terms

Conditions

Inflammatory Bowel Diseases

Interventions

Infliximab

Condition Hierarchy (Ancestors)

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

Central Study Contacts

Sara Lega, MD PhD

CONTACT

+390403785380; sara.lega@burlo.trieste.it

Sara Lega

CONTACT

+390403785380; sara.lega@burlo.trieste.it

Study Design

• Study Type: interventional
• Phase: phase 4
• Allocation: RANDOMIZED
• Masking: NONE
• Purpose: TREATMENT
• Intervention Model: PARALLEL
• Sponsor Type: OTHER
• Responsible Party: SPONSOR

Study Record Dates

• First Submitted: February 22, 2022
• First Posted: March 15, 2022
• Study Start: March 9, 2022
• Primary Completion: January 31, 2024
• Study Completion: January 31, 2025
• Last Updated: August 18, 2023

Record last verified: 2023-08

Locations

IT (1)