Inflammatory Bone DiseaseNCT04921670
Infliximab Proactive Drug Monitoring in the Pediatric IBD Population
An observational study of Inflammatory Bone Disease, run by Cares, Kristen, M.D. at 1 site in United States.
Trial summary
Inflammatory bowel disease (IBD) is a chronic condition that causes inflammation of the intestinal tract. Common types of IBD include Crohn's disease, ulcerative colitis, and indeterminate colitis. Infliximab (Remicade®) is a biologic medication that is approved by the U.S. Read more about this study
- Who is it for?
- Ages 5 to 21 years
- Conditions the study is for
- Inflammatory Bone Disease
- What is being tested?
- Infliximab Assay
- Type of treatment
- Injection or infusion
- How many people
- 60 participants
- Where
- 1 siteUnited States
- Study dates
- 12 Mar 2021to 30 Aug 2025
- Phase
- Observational
- 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 5 to 21 years
- All sexes
- No healthy volunteers
- Child, Adult
Study population: Children ages 5 to 21 years of age with inflammatory bowel disease receiving infliximab therapy
Who may be able to join
- Patients 5 years to 21 years of age, inclusive, with inflammatory bowel disease receiving infliximab therapy.
- Patient or Parent/legal guardian has signed informed consent form and patient has provided written or oral assent (if applicable)
- Patients who have completed the induction course of infliximab (treated for at least 14 weeks of infliximab)
- Patients should be in stable clinical status.
- Clinical status will be assessed by the treating physician and defined as symptom free (full responder) or clear clinical improvement, but clinical symptoms still present (partial responder). Concomitant immunomodulators are allowed, which may include medications like azathioprine, methotrexate, or oral corticosteroids at a low dose(defined as 0.5 mg/kg or ≤ 20 mg if subject weights above 40 kg) if kept stable throughout the study.
Who cannot join
- Patients younger than 5 years of age or older than 21 years of age.
- Patients who are not on maintenance therapy of infliximab.
- Patients who, at screening, have infliximab antibody levels greater than 1000 ng/mL, which was previously shown to be a clinically relevant cut-off.
- Patients who fail to respond to infliximab.
- Patients who are unable to complete the entire study.
- Patients who have an antibody level > 1000 ng/mL.
- Patients who, in the opinion of the investigator, are unlikely to be able to complete the requirements of the study.
- Failure to respond to current medical management based on clinical assessment.
Trial locations and contacts
1 site in 1 country.
United States1 site
Children's Hospital of Michigan
Detroit, Michigan, 48201
About this study
Inflammatory bowel disease (IBD) is a chronic condition that causes inflammation of the intestinal tract. Common types of IBD include Crohn's disease, ulcerative colitis, and indeterminate colitis. Infliximab (Remicade®) is a biologic medication that is approved by the U.S. Food and Drug Administration (FDA) for the treatment of IBD. Previous research with infliximab has shown it to be an effective treatment for pediatric IBD, however, it can become less effective if the level of the medication in the body is not high enough or if a patient develops antibodies (proteins made by the immune system that attack foreign substances in the body) to the medication. Currently, if a patient with IBD is taking infliximab and develops either abnormal lab values or reports a worsening of symptoms the doctors will measure the level of infliximab in the blood as well as any infliximab antibodies to determine if dosing changes, to either the dose of the medication or the frequency of dosing, are needed. This process is called reactive drug monitoring. The purpose of this research study is to find out if proactive drug monitoring in patients being treated with infliximab for IBD works better for controlling IBD. Proactive drug monitoring is measuring the level of infliximab in the blood as well as infliximab antibodies on a regular basis, before symptoms worsen or lab results come back abnormal, to see if dosing changes can be made that may prevent the worsening of IBD.
Read the detailed description
Inflammatory bowel disease (IBD) is a chronic condition that leads to an inflammatory reaction in the intestinal tract.
Common subtypes of IBD include Crohn's disease, ulcerative colitis, and less often, indeterminate colitis. Symptoms of IBD vary from mild abdominal pain to profound diarrhea, weight loss, and significant anemia due to intestinal blood loss.
Infliximab is a biologic drug that is FDA approved for the treatment of Crohn's disease and ulcerative colitis in children 6 years of age or older. Infliximab is administered as an intravenous infusion with weight-based dosing (5mg/kg) and a regimen that includes an induction phase (week 0, 2, 6) followed by maintenance phase (every 8 weeks). Unfortunately, research indicates that more than half of all pediatric patients lose the initial response of biologic therapy and require either a higher dose, additional therapy with an immunomodulatory like steroids, or need to be switched to a different biologic drug. Loss of response can be due to increased clearance of drug with or without the development of antibody to the drug. Lab tests are now being used to measure the level of infliximab and the presence of anti-infliximab antibody (AIA), as it is now known that the pharmacokinetics (how a drug is processed by the body) of infliximab varies between patients. Previous research has shown a relationship between infliximab and antibody levels and clinical response. In general, low infliximab levels with or without the development of antibodies are associated with worse clinical outcomes. Currently, these lab tests are used in the clinical setting "reactively", called therapeutic drug monitoring (TDM). In other words, if a patient starts showing signs of relapse (return of abdominal pain, diarrhea, or worsening laboratory markers) while on infliximab, infliximab and antibody levels are obtained to assess for loss of response (e.g., low infliximab level or development of antibodies). If the infliximab level is low, with or without antibodies, often physicians can increase the dose of medication or frequency of the medication to treat the relapse. This has been shown to be effective and led to sustained clinical response in a number of studies. Unfortunately, if the antibody level is at an extremely high level, the window for changing the dose or frequency of dosing might be missed and the patient may need to be switched to a different biologic medication completely.
"Reactive" TDM has been recommended in clinical practice, but "proactive" TDM has yet to be implemented due to limited knowledge. In theory, by proactively obtaining infliximab and antibody levels (i.e., measuring at a pre-specified time instead of waiting until the patient develops symptoms or lab results show a loss of response), physicians may have the opportunity to prevent loss of response; thus, to make changes in the treatment regimen before a patient shows clinical signs of relapse or requires transitioning to a different biologic medication. This is especially important in the pediatric population, as IBD can be more aggressive, in addition to affecting growth, bone development, and puberty. In addition, by proactively monitoring, there is a potential safety benefit. In patients with extremely high infliximab levels, a reduction in the drug may prevent adverse events. In addition to safety, reduction in the drug dose or frequency can relieve some of the burden of cost.
Research in adult studies has reported a significant cost reduction by performing TDM with a predetermined infliximab goal level.
- Conditions
- Inflammatory Bone Disease
- Being tested
- Infliximab Assay
- Medical subject headings
- Osteitis
What participants receive
What participants receive. In a randomised study each person is assigned to one group by chance.
Infliximab AssayDiagnostic test
Participants will be assigned to standard of care or proactive drug monitoring, which is measuring infliximab levels/antibodies before every infusion
| Study group | Role | What they receive |
|---|---|---|
| Group A-Standard monitoring group (Reactive drug monitoring) | Participants assigned to this group will be managed the same as normally done per routine care, which involves adjusting their infliximab dose and/or dosing interval based on Inflammatory Bowel Disease (IBD) symptoms and routine care laboratory test results. The primary gastroenterologist will not be given the results of the infliximab and infliximab antibody level results of participants in this group unless their routine laboratory test results or IBD symptoms suggest their IBD may be worsening. | |
| • Group B- Infliximab level and infliximab antibody monitoring group (Proactive drug monitoring) | Participants assigned to the infliximab level and infliximab antibody level monitoring group will be managed based on the infliximab level and infliximab antibody level results as well as their IBD symptoms and the results of routine care laboratory tests. The goal is to keep infliximab levels in the optimal range with little to no antibodies. The primary gastroenterologist will remain blinded to the results of the infliximab level/infliximab antibody level test results and the participants' dose will be adjusted by one of the other study doctors who is not blinded to the results. Receives: Diagnostic Test: Infliximab Assay |
What is being measured
The primary outcome is the main question the study is designed to answer.
Number of relapses
The of relapses in each group (defined as need for rescue treatment, either with steroids or additional immunomodulator, or increased infliximab dose) after completing the maintenance phase of the study.
Measured: 48 weeks
Timeline
From the start of the study to its completion; the mark is today. Estimated dates are the sponsor’s plan.
- First posted10 Jun 2021
- Study start12 Mar 2021
- Primary completion30 Mar 2025 (estimated)
- Study completion30 Aug 2025 (estimated)
Resources
- Official record on ClinicalTrials.govThe registry entry this page is built from, with its full change history.
- Other trials for Inflammatory Bone DiseaseStudies 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
- Observational
- Observational model
- Cohort
- Time perspective
- Prospective
- Enrolment
- 60 participants (estimated)
Sponsor and investigators
- Lead sponsor
- Cares, Kristen, M.D.
- Sponsor type
- University, hospital or other
- Responsible party
- Sponsor
IDs, dates and publications
- ClinicalTrials.gov ID
- NCT04921670
- Sponsor's protocol ID
- INFLIXIMAB-2019
- Status last verified
- Sep 2024
- First submitted
- 20 May 2021
- Last updated
- 19 Sep 2024
- Results posted
- No
- Data monitoring committee
- No
- FDA-regulated drug
- Yes
- FDA-regulated device
- No
Study at a glance
From the registry record, last updated by the sponsor on 19 Sep 2024. Recruitment status is as the sponsor reported it: confirm with the study team.
- Official title
- Infliximab Proactive Drug Monitoring in the Pediatric IBD Population
- ClinicalTrials.gov ID
- NCT04921670
- Acronym / sponsor ID
- INFLIXIMAB-2019
- Conditions
- Inflammatory Bone Disease
- Study type
- Observational
- Recruitment status
- Unknown status
- Enrolment
- 60 participants (estimated)
- Lead sponsor
- Cares, Kristen, M.D.University, hospital or other
- Study start
- 12 Mar 2021 (actual)
- Primary completion
- 30 Mar 2025 (estimated)
- Study completion
- 30 Aug 2025 (estimated)
- First posted
- 10 Jun 2021 (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.
Inflammatory bowel disease (IBD) is a chronic condition that causes inflammation of the intestinal tract. Common types of IBD include Crohn's disease, ulcerative colitis, and indeterminate colitis. Infliximab (Remicade®) is a biologic medication that is approved by the U.S. Food and Drug Administration (FDA) for the treatment of IBD. Previous research with infliximab has shown it to be an effective treatment for pediatric IBD, however, it can become less effective if the level of the medication in the body is not high enough or if a patient develops antibodies (proteins made by the immune system that attack foreign substances in the body) to the medication. Currently, if a patient with IBD is taking infliximab and develops either abnormal lab values or reports a worsening of symptoms the doctors will measure the level of infliximab in the blood as well as any infliximab antibodies to determine if dosing changes, to either the dose of the medication or the frequency of dosing, are needed. This process is called reactive drug monitoring. The purpose of this research study is to find out if proactive drug monitoring in patients being treated with infliximab for IBD works better for controlling IBD. Proactive drug monitoring is measuring the level of infliximab in the blood as well as infliximab antibodies on a regular basis, before symptoms worsen or lab results come back abnormal, to see if dosing changes can be made that may prevent the worsening of IBD.
Detailed description
Inflammatory bowel disease (IBD) is a chronic condition that leads to an inflammatory reaction in the intestinal tract.
Common subtypes of IBD include Crohn's disease, ulcerative colitis, and less often, indeterminate colitis. Symptoms of IBD vary from mild abdominal pain to profound diarrhea, weight loss, and significant anemia due to intestinal blood loss.
Infliximab is a biologic drug that is FDA approved for the treatment of Crohn's disease and ulcerative colitis in children 6 years of age or older. Infliximab is administered as an intravenous infusion with weight-based dosing (5mg/kg) and a regimen that includes an induction phase (week 0, 2, 6) followed by maintenance phase (every 8 weeks). Unfortunately, research indicates that more than half of all pediatric patients lose the initial response of biologic therapy and require either a higher dose, additional therapy with an immunomodulatory like steroids, or need to be switched to a different biologic drug. Loss of response can be due to increased clearance of drug with or without the development of antibody to the drug. Lab tests are now being used to measure the level of infliximab and the presence of anti-infliximab antibody (AIA), as it is now known that the pharmacokinetics (how a drug is processed by the body) of infliximab varies between patients. Previous research has shown a relationship between infliximab and antibody levels and clinical response. In general, low infliximab levels with or without the development of antibodies are associated with worse clinical outcomes. Currently, these lab tests are used in the clinical setting "reactively", called therapeutic drug monitoring (TDM). In other words, if a patient starts showing signs of relapse (return of abdominal pain, diarrhea, or worsening laboratory markers) while on infliximab, infliximab and antibody levels are obtained to assess for loss of response (e.g., low infliximab level or development of antibodies). If the infliximab level is low, with or without antibodies, often physicians can increase the dose of medication or frequency of the medication to treat the relapse. This has been shown to be effective and led to sustained clinical response in a number of studies. Unfortunately, if the antibody level is at an extremely high level, the window for changing the dose or frequency of dosing might be missed and the patient may need to be switched to a different biologic medication completely.
"Reactive" TDM has been recommended in clinical practice, but "proactive" TDM has yet to be implemented due to limited knowledge. In theory, by proactively obtaining infliximab and antibody levels (i.e., measuring at a pre-specified time instead of waiting until the patient develops symptoms or lab results show a loss of response), physicians may have the opportunity to prevent loss of response; thus, to make changes in the treatment regimen before a patient shows clinical signs of relapse or requires transitioning to a different biologic medication. This is especially important in the pediatric population, as IBD can be more aggressive, in addition to affecting growth, bone development, and puberty. In addition, by proactively monitoring, there is a potential safety benefit. In patients with extremely high infliximab levels, a reduction in the drug may prevent adverse events. In addition to safety, reduction in the drug dose or frequency can relieve some of the burden of cost.
Research in adult studies has reported a significant cost reduction by performing TDM with a predetermined infliximab goal level.
Study design
- Observational model
- Cohort
- Time perspective
- Prospective
- Number of arms
- 2
| Arm | Type | Receives |
|---|---|---|
| Group A-Standard monitoring group (Reactive drug monitoring) | – | –Participants assigned to this group will be managed the same as normally done per routine care, which involves adjusting their infliximab dose and/or dosing interval based on Inflammatory Bowel Disease (IBD) symptoms and routine care laboratory test results. The primary gastroenterologist will not be given the results of the infliximab and infliximab antibody level results of participants in this group unless their routine laboratory test results or IBD symptoms suggest their IBD may be worsening. |
| • Group B- Infliximab level and infliximab antibody monitoring group (Proactive drug monitoring) | – | Diagnostic Test: Infliximab AssayParticipants assigned to the infliximab level and infliximab antibody level monitoring group will be managed based on the infliximab level and infliximab antibody level results as well as their IBD symptoms and the results of routine care laboratory tests. The goal is to keep infliximab levels in the optimal range with little to no antibodies. The primary gastroenterologist will remain blinded to the results of the infliximab level/infliximab antibody level test results and the participants' dose will be adjusted by one of the other study doctors who is not blinded to the results. |
Who may qualify
- Ages
- 5 to 21 years
- Sex
- All
- Healthy volunteers
- Not accepted
- Age groups
- Child, Adult
- Study population
- Children ages 5 to 21 years of age with inflammatory bowel disease receiving infliximab therapy
Key inclusion criteria (5 listed)
- Patients 5 years to 21 years of age, inclusive, with inflammatory bowel disease receiving infliximab therapy.
- Patient or Parent/legal guardian has signed informed consent form and patient has provided written or oral assent (if applicable)
- Patients who have completed the induction course of infliximab (treated for at least 14 weeks of infliximab)
- Patients should be in stable clinical status.
Key exclusion criteria (8 listed)
- Patients younger than 5 years of age or older than 21 years of age.
- Patients who are not on maintenance therapy of infliximab.
- Patients who, at screening, have infliximab antibody levels greater than 1000 ng/mL, which was previously shown to be a clinically relevant cut-off.
- Patients who fail to respond to infliximab.
- Patients who are unable to complete the entire study.
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 |
|---|---|---|
| Infliximab AssayParticipants will be assigned to standard of care or proactive drug monitoring, which is measuring infliximab levels/antibodies before every infusion | Diagnostic test | • Group B- Infliximab level and infliximab antibody monitoring group (Proactive drug monitoring) |
Primary outcome
Number of relapses
Time frame: 48 weeks
The of relapses in each group (defined as need for rescue treatment, either with steroids or additional immunomodulator, or increased infliximab dose) after completing the maintenance phase of the study.
Results and safety
Results are not available in the source record.
Research links
- Official record on ClinicalTrials.govLast updated by the sponsor 19 Sep 2024.
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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.
The record lists no contact. Use the official record to reach the sponsor.
1 site in 1 country: see every site and its status.
Questions about this trial
What is this clinical trial studying?
An observational study of Inflammatory Bone Disease, run by Cares, Kristen, M.D. at 1 site in United States.
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 5 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 19 Sep 2024. 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 United States. 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.
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?
The record lists no contact. The official record names the sponsor, who can be asked directly. AzTrials does not enrol participants or take referrals.
What does the primary outcome measure?
Number of relapses (time frame: 48 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 19 Sep 2024.