Inflammatory Bowel DiseasesPhase 4EPICNCT05280405
Early Proactive Therapeutic Drug Monitoring of Infliximab in Children: EPIC Study
A Phase 4 study testing Infliximab in people with Inflammatory Bowel Diseases, run by IRCCS Burlo Garofolo at 1 site in Italy.
Trial 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. Read more about this study
- Who is it for?
- Ages 6 to 17 years
- Conditions the study is for
- Inflammatory Bowel Diseases
- What is being tested?
- Infliximab
- Type of treatment
- Injection or infusion
- Could I receive a placebo?
- No, everyone receives an active treatment
- How many people
- 86 participants
- Where
- 1 siteItaly
- Study dates
- 9 Mar 2022to 31 Jan 2025
- Phase
- Phase 4
- Are there results?
- None posted in the registry
Key requirements
Who can take part, as listed by the sponsor. Only the study team can confirm whether you are eligible, so take this list to your doctor.
- Ages 6 to 17 years
- All sexes
- No healthy volunteers
- Child
Who may be able to join
- 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
Who cannot join
- 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
Trial locations and contacts
1 site in 1 country.
Italy1 site, 1 recruiting
- Recruiting
Institute for Maternal and Child Health - IRCCS "Burlo Garofolo"
Trieste, 34137
Sara Lega, MD PhD, 0403785380, sara.lega@burlo.trieste.it
About this study
Official title: Impact of Early Proactive Therapeutic Drug Monitoring on the Durability and Efficacy of Infliximab Therapy in Pediatric Inflammatory Bowel Disease: a Multicenter Open-label Randomized-control Trial
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.
Read the detailed description
Inflammatory Bowel Disease (IBD) are relapsing disorders with progressive bowel damage leading to long-term disability.
Infliximab (IFX), is a highly effective and commonly used biologic in IBD. However, up to 40% of patients do not respond to treatment or lose response over time. Low-serum IFX concentrations and the development of antibodies to IFX (ATI) are two major factors affecting IFX efficacy, durability and safety. Standard IFX dose is administered as an IV (in the vein) infusion at 5 mg/kg in a 0, 2, and 6 weeks induction regimen followed by a maintenance regimen with infusions every 8 weeks. This standard dosing is extrapolated from adult studies. IFX has a highly variable pharmacokinetic and pharmacodynamics that is dependent on body weight, disease extent, levels of inflammation and the presence of ATI. In children and young adults with IBD all these factors often result in low-serum IFX concentrations.
Proactive therapeutic drug monitoring, consists in the measurement of drug concentrations on patient's blood, in order to adjust the following administrations (dosing or interval) and maintain a desired concentration of the medication in the body.
This study seeks to determine whether a proactive therapeutic drug monitoring strategy can improve IFX durability, efficacy and safety in children and young adults with IBD. The study will involve approximately 90 patients, aged 6 to 17 years, with IBD. All the patients enrolled in the study will receive IFX at 5mg/kg at week 0, 2 and 6. At week 6 patients will be randomly assigned to receive IFX treatment either based on IFX concentrations determined before every IFX infusion (intervention group) or at standard dosing (control group). Patients will participate in the study for 54 weeks (approximately 12 months) or until IFX discontinuation. During the study, patients will visit the study center at the time of every IFX infusion or in case of disease flares.
- Conditions
- Inflammatory Bowel Diseases
- Being tested
- Infliximab
- Keywords
- Infliximab, Proactive drug monitoring
- Medical subject headings
- Inflammatory Bowel Diseases
What participants receive
What participants receive. In a randomised study each person is assigned to one group by chance.
InfliximabDrug
Infliximab
| Study group | Role | What they receive |
|---|---|---|
| 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. Receives: 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. Receives: Drug: Infliximab |
What is being measured
The primary outcome is the main question the study is designed to answer.
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.
Measured: 54 weeks
Secondary outcomes (9)
Cumulative probability of IFX discontinuation
Time to IFX discontinuation
Measured: 54 weeks
Cumulative probability of Loss of Response
Time to Loss of Response (LOR), with LOR defined as PCDAI >= 10 or PUCAI > 10 with CRP > 0.5 mg/dl and/or FC >250 microg/g in a patient who previously responded to induction treatment.
Measured: 54 weeks
Frequency of subtherapeutic IFX concentrations
Subtherapeutic IFX concentration is defined as IFX concentration at trough < 5 microg/ml (or <10 microg/ml in perianal CD) during maintenance treatment.
Measured: 54 weeks
Frequency of Anti-Infliximab Antibodies
Evaluation of Anti-Infliximab Antibodies
Measured: 54 weeks
Frequency of infusion reactions
Infusion reactions are defined as reactions that develop during the course of the infusion or within 1-2h of its completion.
Measured: 54 weeks
Frequency of endoscopic remission
Endoscopic remission is defined in patients with Crohn's Disease as a Simple Endoscopic score for Crohn's Disease (SES-CD score) less than or equal to (<=) 2 and in patients with Ulcerative Colitis as a Mayo sub-score <= 1
Measured: 54 weeks
Frequency of patients with treatment response at the end of induction between 12 and 14 weeks
Treatment response is defined as a decrease in PCDAI by 12.5 point or in PUCAI by 10 points with decrease in CRP by 50% compared to baseline
Measured: Week 14
Frequency of patients with clinical remission at 14 weeks
Clinical remission is defined as PCDAI <10 or PUCAI <10
Measured: Week 14
Frequency of clinical and biochemical remission at week 14
Clinical and Biochemical remission is defined as PCDAI <10 or PUCAI <10 with CRP < 0.5 mg/dl and FC < 250 microg/g
Measured: Week 14
Timeline
From the start of the study to its completion; the mark is today. Estimated dates are the sponsor’s plan.
- First posted15 Mar 2022
- Study start9 Mar 2022
- Primary completion31 Jan 2024 (estimated)
- Study completion31 Jan 2025 (estimated)
Resources
- Official record on ClinicalTrials.govThe registry entry this page is built from, with its full change history.
- Other trials for Inflammatory Bowel DiseasesStudies of the same condition, open and under way.
- What the trial phases meanHow a treatment moves from first tests in people to approval.
More details
For doctors and researchers: how the study is designed, who runs it, and its registry IDs.
Study design
- Study type
- Interventional
- Phase
- Phase 4
- Primary purpose
- Treatment
- Allocation
- Randomised
- Intervention model
- Parallel groups
- Masking
- None (open label)
- Enrolment
- 86 participants (estimated)
Sponsor and investigators
- Lead sponsor
- IRCCS Burlo Garofolo
- Sponsor type
- University, hospital or other
- Responsible party
- Sponsor
IDs, dates and publications
- ClinicalTrials.gov ID
- NCT05280405
- Sponsor's protocol ID
- 2021-003220-32
- Acronym
- EPIC
- Status last verified
- Aug 2023
- First submitted
- 22 Feb 2022
- Last updated
- 18 Aug 2023
- Results posted
- No
- Data monitoring committee
- No
- FDA-regulated drug
- No
- FDA-regulated device
- No
Study at a glance
From the registry record, last updated by the sponsor on 18 Aug 2023. Recruitment status is as the sponsor reported it: confirm with the study team.
- Official title
- Impact of Early Proactive Therapeutic Drug Monitoring on the Durability and Efficacy of Infliximab Therapy in Pediatric Inflammatory Bowel Disease: a Multicenter Open-label Randomized-control Trial
- ClinicalTrials.gov ID
- NCT05280405
- Acronym / sponsor ID
- EPIC / 2021-003220-32
- Conditions
- Inflammatory Bowel Diseases
- Keywords
- Infliximab, Proactive drug monitoring
- Phase
- Phase 4
- Study type
- Interventional
- Recruitment status
- Unknown status
- Enrolment
- 86 participants (estimated)
- Lead sponsor
- IRCCS Burlo GarofoloUniversity, hospital or other
- Study start
- 9 Mar 2022 (actual)
- Primary completion
- 31 Jan 2024 (estimated)
- Study completion
- 31 Jan 2025 (estimated)
- First posted
- 15 Mar 2022 (actual)
- Results
- Not posted in the source record
Clinical summary
The research question as the sponsor registered it. This describes what the study plans to test, not what it found.
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.
Detailed description
Inflammatory Bowel Disease (IBD) are relapsing disorders with progressive bowel damage leading to long-term disability.
Infliximab (IFX), is a highly effective and commonly used biologic in IBD. However, up to 40% of patients do not respond to treatment or lose response over time. Low-serum IFX concentrations and the development of antibodies to IFX (ATI) are two major factors affecting IFX efficacy, durability and safety. Standard IFX dose is administered as an IV (in the vein) infusion at 5 mg/kg in a 0, 2, and 6 weeks induction regimen followed by a maintenance regimen with infusions every 8 weeks. This standard dosing is extrapolated from adult studies. IFX has a highly variable pharmacokinetic and pharmacodynamics that is dependent on body weight, disease extent, levels of inflammation and the presence of ATI. In children and young adults with IBD all these factors often result in low-serum IFX concentrations.
Proactive therapeutic drug monitoring, consists in the measurement of drug concentrations on patient's blood, in order to adjust the following administrations (dosing or interval) and maintain a desired concentration of the medication in the body.
This study seeks to determine whether a proactive therapeutic drug monitoring strategy can improve IFX durability, efficacy and safety in children and young adults with IBD. The study will involve approximately 90 patients, aged 6 to 17 years, with IBD. All the patients enrolled in the study will receive IFX at 5mg/kg at week 0, 2 and 6. At week 6 patients will be randomly assigned to receive IFX treatment either based on IFX concentrations determined before every IFX infusion (intervention group) or at standard dosing (control group). Patients will participate in the study for 54 weeks (approximately 12 months) or until IFX discontinuation. During the study, patients will visit the study center at the time of every IFX infusion or in case of disease flares.
Study design
- Primary purpose
- Treatment
- Allocation
- Randomised
- Intervention model
- Parallel groups
- Masking
- None (open label)
- Number of arms
- 2
| Arm | Type | Receives |
|---|---|---|
| Early-Proactive Therapeutic Drug Monitoring (E-pTDM) | Experimental | Drug: InfliximabInfliximab (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. |
| Standard dosing | Active comparator | Drug: InfliximabInfliximab (IFX) at 5mg/kg, IV at week 0, 2 and 6 followed by 5mg/kg infusions every 8 weeks. |
Who may qualify
- Ages
- 6 to 17 years
- Sex
- All
- Healthy volunteers
- Not accepted
- Age groups
- Child
Key inclusion criteria (3 listed)
- 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
Key exclusion criteria (8 listed)
- 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),
Eligibility is decided by the study team after screening; this overview does not establish that a patient qualifies. Full inclusion and exclusion criteria.
Interventions
| Intervention | Type | Arms |
|---|---|---|
| InfliximabInfliximab | Drug | Early-Proactive Therapeutic Drug Monitoring (E-pTDM), Standard dosing |
Primary outcome
Frequency of IFX discontinuation or need for treatment intensification due to non-response or LOR during the first year of treatment.
Time frame: 54 weeks
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.
9 secondary outcomes
Cumulative probability of IFX discontinuation
Time frame: 54 weeks
Cumulative probability of Loss of Response
Time frame: 54 weeks
Frequency of subtherapeutic IFX concentrations
Time frame: 54 weeks
Frequency of Anti-Infliximab Antibodies
Time frame: 54 weeks
Frequency of infusion reactions
Time frame: 54 weeks
Frequency of endoscopic remission
Time frame: 54 weeks
Frequency of patients with treatment response at the end of induction between 12 and 14 weeks
Time frame: Week 14
Frequency of patients with clinical remission at 14 weeks
Time frame: Week 14
Frequency of clinical and biochemical remission at week 14
Time frame: Week 14
Results and safety
Results are not available in the source record.
Research links
- Official record on ClinicalTrials.govLast updated by the sponsor 18 Aug 2023.
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Referral and contact
AzTrials does not enrol participants or take referrals. Contact the study team or a site listed below; they decide who can take part. This study is not recruiting at the moment.
1 site in 1 country: see every site and its status.
Questions about this trial
What is this clinical trial studying?
A Phase 4 study testing Infliximab in people with Inflammatory Bowel Diseases, run by IRCCS Burlo Garofolo at 1 site in Italy.
The full registered description is in the About this study section and the official record.
Who may be eligible to take part?
The sponsor lists 3 inclusion and 8 exclusion criteria. Eligibility is decided by the study team after screening, so read the full criteria and contact a listed site.
Is this clinical trial currently recruiting?
The record says: status not confirmed, as of the sponsor's last update on 18 Aug 2023. Status can change between updates, so confirm with the study contact before making plans.
Where is the study taking place?
The record lists 1 site in Italy. Whether a site is taking part right now should be confirmed with that site. See every site.
What are the possible benefits and risks?
They depend on the study and the treatment, and no study can promise a benefit. The study team explains the known risks during informed consent, before anyone joins; the record itself does not list them.
What does this phase mean?
Phase 4 studies take place after a treatment is approved, to learn more about its long-term benefits and risks in everyday use.
Not every study follows the same path, and some studies (observational studies, device studies) have no phase.
Are results available for this study?
Results are not available in the source record.
How can a doctor refer a patient or contact the research team?
Contact Sara Lega, MD PhD (+390403785380, sara.lega@burlo.trieste.it), or a site near the patient. AzTrials does not enrol participants or take referrals.
What does the primary outcome measure?
Frequency of IFX discontinuation or need for treatment intensification due to non-response or LOR during the first year of treatment. (time frame: 54 weeks). It is what the study was designed to measure, not a finding.
Where can I read the original study information?
Does a listing mean the treatment is approved or proven to work?
No. A listing means the study is registered. It does not show that the treatment is safe, works, or is approved by a regulator.
How often is this information updated?
AzTrials copies changed records from ClinicalTrials.gov every night and reloads the whole registry every week. The sponsor last updated this record on 18 Aug 2023.