What side effects are associated with this type of intervention?

Common treatments for Crohn's Disease include infliximab, azathioprine, and glucocorticoids. Infliximab can cause side effects such as infections, infusion reactions, and the development of anti-drug antibodies. Azathioprine may lead to gastrointestinal complaints (nausea, vomiting, diarrhea), rash, fever, malaise, hematologic side effects (depression of all cell lines), and increased liver function tests. Glucocorticoids are associated with significant side effects, including adrenal suppression, increased risk of infections, and other systemic effects such as weight gain, hypertension, and osteoporosis.

What prior FDA approvals exist?

The FDA has approved several biologic agents and immunomodulators for the treatment of Crohn's Disease. Notable biologics include infliximab (Remicade), an anti-TNF agent, and ustekinumab (Stelara), which targets interleukin-12 and interleukin-23. Vedolizumab (Entyvio), another biologic, works by inhibiting the migration of T-lymphocytes into the gut. Immunomodulators such as azathioprine and 6-mercaptopurine are also commonly used. These treatments are often part of combination therapy to induce and maintain remission in patients with moderate to severe Crohn's Disease. Personalized dosing based on blood test results aims to optimize the efficacy and safety of these treatments.

What other types of research exist?

Promising novel alternatives for personalized dosing in Crohn's Disease patients include: 1) Mechanism-based mathematical models that identify alternative treatment regimens for better tumor control, 2) Predictive algorithms for immunotherapy response, such as those used for pembrolizumab in metastatic melanoma, and 3) Bayesian forecasting programs like OPT for predicting dose requirements in neutropenic patients. These approaches leverage clinical data and advanced modeling to optimize treatment regimens.

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Anti-TNF-alpha Monoclonal Antibody

Personalized Infliximab Dosing for Crohn's Disease (REMODEL Trial)

Phase 2 & 3

Recruiting

Led By Phillip Minar, MD, MS

Research Sponsored by Children's Hospital Medical Center, Cincinnati

Eligibility Criteria Checklist

Specific guidelines that determine who can or cannot participate in a clinical trial

Must have

Fecal calprotectin >250 µg/g or fecal lactoferrin >10 µg/g (up to 6 weeks prior to starting infliximab) or endoscopic evidence of active Crohn's disease (up to 90 days prior to starting infliximab)

Starting infliximab (or biosimilar)

Must not have

Prior treatment with infliximab, adalimumab, certolizab or golimumab (or anti-TNF biosimilar)

Planned continuation of methotrexate during study

Timeline

Screening 3 weeks

Treatment Varies

Follow Up 2 years

Awards & highlights

No Placebo-Only Group

Summary

This trial is testing a computer program that helps doctors decide the best dose of infliximab for children and young adults with moderate to severe Crohn's disease. The program uses blood test results to figure out how quickly the medicine leaves the body and suggests the right amount to give. The goal is to see if this method is safer, more effective, and more cost-effective than current methods. Infliximab has been widely studied and used for treating Crohn's disease, showing beneficial effects in both adults and children.

Who is the study for?

This trial is for children and young adults aged 6 to 22 with Crohn's Disease who haven't used anti-TNF drugs like infliximab. They must have active disease signs, no recent infections or surgeries affecting the gut, not be pregnant, and agree to specific testing. Those with other autoimmune diseases or using certain medications can't join.

What is being tested?

The study tests a personalized dosing strategy using RoadMAB and a computer program that decides on drug doses based on blood test results. It aims to see if this method reaches optimal drug levels better than standard dosing in treating Crohn's Disease.

What are the potential side effects?

While the trial doesn't specify side effects of RoadMAB, similar treatments may cause immune system changes, risk of infection, allergic reactions during infusion, headaches, stomach issues and potential impact on liver function.

Eligibility Criteria

Inclusion Criteria

You may be eligible if you check “Yes” for the criteria below

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I have recent tests showing active Crohn's disease.

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I am starting treatment with infliximab or a similar medication.

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I have never been treated with anti-TNF drugs.

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I have been diagnosed with Crohn's Disease.

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I am between 6 and 22 years old.

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I am not pregnant.

Exclusion Criteria

You may be eligible for the trial if you check “No” for criteria below:

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I have been treated with medications like infliximab or adalimumab before.

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I will continue taking methotrexate during the study.

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I will continue taking 6-mercaptopurine or azathioprine during the study.

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I have not had IV corticosteroids in the last two weeks.

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I am unable to understand or agree to the study's procedures and risks.

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I have a history of an autoimmune disease.

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I have had an internal fistula in the last year.

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I have a stoma or have had major bowel surgery causing short bowel syndrome.

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I have been diagnosed with ulcerative colitis or an unspecified inflammatory bowel disease.

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I do not have a severe intestinal blockage or abscess in my abdomen or near my anus.

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I haven't had a Clostridium difficile infection or stomach flu in the last two weeks.

Timeline

Screening ~ 3 weeks3 visits

Treatment ~ Varies

Follow Up ~ 2 years

Screening ~ 3 weeks

Treatment ~ Varies

Follow Up ~2 years

This trial's timeline: 3 weeks for screening, Varies for treatment, and 2 years for reporting.

Treatment Details

Study Objectives

Study objectives can provide a clearer picture of what you can expect from a treatment.

Primary study objectives

Completion feasibility

Enrollment feasibility

Obtain safety data for optimal dosing strategy and sample size estimation

+3 more

Secondary study objectives

Evaluate accuracy of infliximab concentration targets

Evaluate accuracy of infliximab concentration targets - Incidence

Evaluate accuracy of infliximab concentration targets - Maintenance

+10 more

Awards & Highlights

No Placebo-Only Group

All patients enrolled in this study will receive some form of active treatment.

Trial Design

1Treatment groups

Experimental Treatment

Group I: RoadMAB dashboard systemExperimental Treatment2 Interventions

The intervention includes utilizing Clinical and Patient Decision Support Software (RoadMABTM) that will guide the selection of the first infliximab dose followed by subsequent infliximab dose and dosing interval during the maintenance phase. During induction, three infusions will occur at 0, 2 and 6 weeks, respectively. The RoadMABTM dashboard will utilize PK modeling software to provide an infliximab starting dose recommendation (range of 5-12 mg/kg) based on the patients biochemical profile. As noted, dosing frequency (weeks) during induction will not be altered during this study. Following the first three doses, the clinician will be informed of their patients PK profile within the RoadMABTM program and with a shared document (paper). RoadMABTM will provide additional dosing recommendations after each infusion (based on the latest drug concentration measures and blood biomarkers) with the final dose and interval selected by the treating physician.

0 / 17Eligibility criteria met

Research Highlights

Information in this section is not a recommendation. We encourage patients to speak with their healthcare team when evaluating any treatment decision.

Mechanism Of Action

Side Effect Profile

Prior Approvals

Other Research

Common treatments for Crohn's Disease include biologics, thiopurines, and glucocorticoids. Biologics like infliximab work by targeting and neutralizing tumor necrosis factor-alpha (TNF-alpha), a key inflammatory mediator, thereby reducing inflammation and immune response. Thiopurines, such as azathioprine and 6-mercaptopurine, act as immunosuppressants by interfering with DNA synthesis in immune cells, leading to decreased immune activity. Glucocorticoids, like prednisone, reduce inflammation by inhibiting multiple inflammatory pathways. Personalized dosing based on blood test results, as studied in the trial, is crucial because it helps achieve optimal drug levels, minimizing side effects and maximizing therapeutic efficacy, which is particularly important for managing the variable and chronic nature of Crohn's Disease.

A high-fiber diet may improve bowel function and health-related quality of life in patients with Crohn disease.