Individualized Infliximab Dosing for Crohn's Disease

(REMODEL-CD Trial)

Recruiting at 10 trial locations

Overseen By Phillip Minar, MD, MS

Age: < 65

Sex: Any

Trial Phase: Phase 2 & 3

Sponsor: Children's Hospital Medical Center, Cincinnati

Must be taking: Infliximab

Must not be taking: Methotrexate, Azathioprine

Disqualifiers: Ulcerative colitis, Anti-TNF use, others

No Placebo Group All trial participants will receive the active study treatment (no placebo)

Prior Safety Data This treatment has passed at least one previous human trial

Approved in 4 Jurisdictions This treatment is already approved in other countries

Compensation: Varies

Number of Visits: 3

180 Participants Needed

Trial Summary

What is the purpose of this trial?

Approximately 3 million people in the United States are living with inflammatory bowel disease, which includes Crohn's Disease (CD). There are limited treatment options approved for use in children and adults with Crohn's disease. Physicians need better ways to inform decisions on treatment. The main reason for this research study is to determine if a computer program that calculates an individualized dose based on a patient's blood testing results (precision dosing) can better achieve the best possible response to infliximab compared to standard dosing (conventional dosing).

Do I have to stop taking my current medications for the trial?

The trial does not specify if you need to stop taking your current medications, but you cannot use methotrexate or 6-mercaptopurine during the first three doses of infliximab. It's best to discuss your current medications with the trial team.

What data supports the effectiveness of the drug Infliximab for Crohn's disease?

Research shows that Infliximab, an anti-TNF-alpha antibody, is effective in treating active Crohn's disease, maintaining remission, and managing fistulas (abnormal connections between organs). It is particularly useful when standard treatments have not been successful. ^{1 2 3 4 5}

What is the safety profile of Infliximab for Crohn's Disease?

Infliximab is generally considered safe for treating Crohn's Disease, but it can cause some side effects. These include infusion reactions (like allergic reactions during the treatment), infections, and a potential risk of cancer. It's important for patients to be monitored during and after infusions to catch any serious side effects early. ^{4 6 7 8 9}

How is the drug Infliximab unique for treating Crohn's disease?

Infliximab is unique for treating Crohn's disease because it allows for individualized dosing based on patient-specific factors like weight and treatment response, which can improve outcomes and reduce nonresponse compared to standard dosing methods. ^{3 10 11 12 13}

Research Team

Phillip Minar, MD,MS

Principal Investigator

Children's Hospital Medical Center, Cincinnati

Eligibility Criteria

This trial is for children and adults aged 6 to 22 with Crohn's Disease who are new to anti-TNF therapy and about to start infliximab. They must have active disease, confirmed diagnosis within the last 90 days, no recent severe infections or surgeries planned, not be hospitalized for severe CD complications, and not pregnant. Consent is required.

Inclusion Criteria

I was diagnosed with Crohn's disease in the last 3 months.

I am between 6 and 22 years old and have never taken anti-TNF drugs but am starting infliximab.

I have given my written agreement to participate.

Exclusion Criteria

I have or will have surgery related to my digestive system soon.

I have had an internal fistula in the last 6 months.

I have previously used anti-TNF medications.

Timeline

Screening

Participants are screened for eligibility to participate in the trial

2-4 weeks

Induction Treatment

Participants receive infliximab dosing at 0, 2, and 6 weeks to achieve targeted drug concentrations

6 weeks

3 visits (in-person)

Maintenance Treatment

Participants continue with infliximab dosing every 4-8 weeks based on drug concentration monitoring

46 weeks

Follow-up

Participants are monitored for safety and effectiveness after treatment

4 weeks

Treatment Details

Interventions

• Infliximab

Trial Overview The study tests if precision dosing of Infliximab using a computer program based on blood tests can lead to better treatment outcomes compared to standard dosing in patients with Crohn's Disease. The goal is personalized medication management.

Participant Groups

Group I: Precision dosing Experimental Treatment 2 Interventions

Induction: 5-12.5 mg/kg at 0, 2, and 6 weeks to target a week6 concentration of 18-24 μg/mL with dosing support provided by the RoadMABTM clinical decision support tool. Maintenance: 5-15 mg/kg every 4-8 weeks to achieve apriori pharmacokinetic and pharmacodynamic targets (CRP, disease activity scores and fecal calprotectin) with dosing support provided by the RoadMABTM clinical decision support tool.

Group II: Conventional dosing Active Control 1 Intervention

Induction Phase: 5-7.5 mg/kg at 0, 2, and 6 weeks. Maintenance Phase : 5-10 mg/kg at every 4-8 weeks based on results of drug concentration monitoring for a flat target of 5-10 μg/mL.

Infliximab is already approved in European Union, United States, Canada, Japan for the following indications:

Approved in European Union as Remicade for:

• Ankylosing Spondylitis
• Crohn's Disease
• Ulcerative Colitis
• Psoriatic Arthritis
• Rheumatoid Arthritis
• Plaque Psoriasis

Approved in United States as Remicade for:

• Ankylosing Spondylitis
• Crohn's Disease
• Ulcerative Colitis
• Psoriatic Arthritis
• Rheumatoid Arthritis
• Plaque Psoriasis

Approved in Canada as Remicade for:

• Ankylosing Spondylitis
• Crohn's Disease
• Ulcerative Colitis
• Psoriatic Arthritis
• Rheumatoid Arthritis
• Plaque Psoriasis

Approved in Japan as Remicade for:

• Ankylosing Spondylitis
• Crohn's Disease
• Ulcerative Colitis
• Psoriatic Arthritis
• Rheumatoid Arthritis
• Plaque Psoriasis

Who Is Running the Clinical Trial?

Children's Hospital Medical Center, Cincinnati

Lead Sponsor

Trials

844

Recruited

6,566,000+

National Institute of Diabetes and Digestive and Kidney Diseases (NIDDK)

Collaborator

Trials

2,513

Recruited

4,366,000+

Janssen Scientific Affairs, LLC

Industry Sponsor

Trials

165

Recruited

579,000+

Ricardo Attar

Janssen Scientific Affairs, LLC

Chief Executive Officer since 2008

PhD in Molecular Biology, University of Buenos Aires

Dr. Anastasia G. Daifotis

Janssen Scientific Affairs, LLC

Chief Medical Officer since 2023

MD

Findings from Research

In a study of 97 patients (59 with Crohn's disease and 38 with ulcerative colitis), the need for infliximab dose intensification was significantly higher in ulcerative colitis patients at a rate of 3.9% per patient-month compared to 1.4% for Crohn's disease patients.

Patients with ulcerative colitis also experienced a shorter median time to dose intensification (6.6 months) compared to those with Crohn's disease (10.7 months), and the overall administration costs of infliximab were higher for ulcerative colitis patients, indicating a greater financial burden.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Need for infliximab dose intensification in Crohn's disease and ulcerative colitis. Taxonera, C., Olivares, D., Mendoza, JL., et al.[2021]

Infliximab therapy was effective in treating severe and refractory Crohn's disease, with 79% of patients showing an objective response and 72% achieving remission during an average follow-up of 8 months.

The treatment also had a steroid-sparing effect in 73% of patients, and those on immunosuppressive therapy experienced a significantly lower relapse rate (18% vs. 56%), indicating that combining therapies may enhance treatment outcomes.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

[Treatment of Crohn's disease with anti-TNF alpha antibodies (infliximab): results of a multicentric and retrospective study]. Doubremelle, M., Bourreille, A., Zerbib, F., et al.[2015]

In a 1-year study involving 263 adults with Crohn's disease and ulcerative colitis, targeting infliximab trough concentrations (TC) of 3-7 μg/mL led to a significant increase in remission rates for Crohn's disease patients, improving from 65% to 88% after dose optimization.

While continued concentration-based dosing did not show a superior remission rate compared to clinically based dosing (66% vs 69%), it was associated with fewer disease relapses (7% vs 17%), suggesting it may provide better long-term stability for patients.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Trough concentrations of infliximab guide dosing for patients with inflammatory bowel disease. Vande Casteele, N., Ferrante, M., Van Assche, G., et al.[2022]

Remicade (Infliximab) has been shown to be effective in treating active Crohn's disease, maintaining remission, and managing fistulae, but it is not recommended as a first-line treatment.

Due to potential risks, including unknown malignancy rates, Remicade should be administered in a controlled setting with monitoring for adverse reactions, and further studies are needed to gather more data on its efficacy and side effects.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Anti-TNF antibody in Crohn's disease--status of information, comments and recommendations of an international working group. Lochs, H., Adler, G., Beglinger, C., et al.[2015]

In a 52-week study involving 24 patients with Crohn's disease who previously lost response to infliximab, adalimumab demonstrated significant efficacy, with clinical remission rates increasing from 35% at baseline to 58% at week 52.

Adalimumab was well tolerated, with no patients experiencing intolerance and no serious toxicities reported, indicating it is a safe option for maintaining remission in these patients.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Adalimumab maintenance therapy for Crohn's disease with intolerance or lost response to infliximab: an open-label study. Peyrin-Biroulet, L., Laclotte, C., Bigard, MA.[2015]

A survey of 96 gastroenterologists revealed that while 86% frequently use infliximab, only 48% prescribe immunomodulators beforehand, indicating a potential gap in optimal treatment practices.

Many gastroenterologists underestimated the risks of serious adverse effects associated with infliximab, such as serious infections and malignancies, highlighting the need for improved education on treatment protocols and side effects.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Prescribing patterns and awareness of adverse effects of infliximab: a health survey of gastroenterologists. Donovan, M., Lunney, K., Carter-Pokras, O., et al.[2018]

Infliximab is an important treatment option for Crohn's disease, showing a relatively low rate of adverse events in premarketing trials, but recent studies in larger patient groups have highlighted the need for careful safety considerations before treatment.

The review emphasizes the importance of understanding immunological factors related to infliximab therapy and offers practical guidelines for healthcare providers to improve patient management during infliximab infusions.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Infliximab therapy in Crohn's disease: safety issues. Hommes, DW., van Deventer, SJ.[2015]

In a 1-year study of 73 Crohn's disease patients treated with infliximab, the treatment showed a high clinical response rate of 81% for active luminal disease and 87% for fistulous disease, indicating its effectiveness.

Infliximab treatment was found to be safe, with only 17% of patients experiencing adverse events, and it allowed for steroid tapering in 73% of responding patients with luminal disease and 100% with fistulous disease, highlighting its steroid-sparing potential.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Infliximab treatment for Crohn's disease: one-year experience in a Dutch academic hospital. Hommes, DW., van de Heisteeg, BH., van der Spek, M., et al.[2019]

Anti-TNF therapy, specifically infliximab, is effective in treating active Crohn's disease, as confirmed by controlled trials.

However, the use of infliximab is associated with serious safety concerns, including increased risks of infections, autoimmune disorders, and potential links to cancer and lymphoma.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

[Anti-TNF (infliximab) treatment in Crohn disease: safety profile]. Carroccio, A., Di Prima, L., Pirrone, G., et al.[2019]

A retrospective review of 268 patients with inflammatory bowel disease (IBD) showed that over 90% started infliximab treatment at a dose of 5 mg/kg, with 79% of Crohn's disease patients and 61% of ulcerative colitis patients maintaining this dose consistently during the first year.

The study suggests that weight-based dosing of infliximab, along with patient response, allows for effective maintenance therapy in IBD, indicating a predictable treatment pattern that may help in managing costs.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Stability of infliximab dosing in inflammatory bowel disease: results from a multicenter US chart review. Waters, H., Vanderpoel, J., McKenzie, S., et al.[2015]

A population pharmacokinetic model for infliximab (IFX) in children with Crohn disease showed high predictive accuracy, with 88% of predicted concentrations within ±1.0 μg/mL of actual measurements from a cohort of 34 children.

Individualized dosing strategies are essential, as standard dosing of 5 mg/kg every 8 weeks only achieves optimal drug levels (>3 μg/mL) in 32% of patients, indicating that more frequent dosing may be necessary for many children.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Application of Population Pharmacokinetic Modeling for Individualized Infliximab Dosing Strategies in Crohn Disease. Frymoyer, A., Hoekman, DR., Piester, TL., et al.[2019]

Infliximab is effective for treating moderate to severe Crohn's disease, helping induce and maintain remission, and is particularly beneficial for patients with fistulizing Crohn's disease by reducing the number of draining fistulas.

The recommended initial dose is 5 mg/kg, with a preferred induction regimen of three doses at 0, 2, and 6 weeks, and it is advised to use concomitant immunosuppressive therapy to improve treatment outcomes and reduce the risk of adverse reactions.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Infliximab in the treatment of Crohn's disease: a user's guide for clinicians. Sandborn, WJ., Hanauer, SB.[2015]

In a study of 174 patients with inflammatory bowel disease (IBD), over half of the infliximab doses given were found to be subtherapeutic, indicating that many patients were not receiving adequate medication to achieve effective drug levels.

Using precision dosing models like iDOSE can improve treatment outcomes, but it may also lead to significantly higher drug costs, with increases of 102% and 29% for different target trough concentration ranges.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Application of a Precision-Dosing Model to a Real-World Cohort of Patients on Infliximab Maintenance Therapy: Drug Usage and Cost Analysis. Nguyen, AL., Gibson, PR., Upton, RN., et al.[2023]

References

1. United States pubmed.ncbi.nlm.nih.gov

Need for infliximab dose intensification in Crohn's disease and ulcerative colitis. [2021]

2. France pubmed.ncbi.nlm.nih.gov

[Treatment of Crohn's disease with anti-TNF alpha antibodies (infliximab): results of a multicentric and retrospective study]. [2015]

3. United States pubmed.ncbi.nlm.nih.gov

Trough concentrations of infliximab guide dosing for patients with inflammatory bowel disease. [2022]

4. Germany pubmed.ncbi.nlm.nih.gov

Anti-TNF antibody in Crohn's disease--status of information, comments and recommendations of an international working group. [2015]

5. England pubmed.ncbi.nlm.nih.gov

Adalimumab maintenance therapy for Crohn's disease with intolerance or lost response to infliximab: an open-label study. [2015]

6. United States pubmed.ncbi.nlm.nih.gov

Prescribing patterns and awareness of adverse effects of infliximab: a health survey of gastroenterologists. [2018]

7. Netherlands pubmed.ncbi.nlm.nih.gov

Infliximab therapy in Crohn's disease: safety issues. [2015]

8. England pubmed.ncbi.nlm.nih.gov

Infliximab treatment for Crohn's disease: one-year experience in a Dutch academic hospital. [2019]

9. Italy pubmed.ncbi.nlm.nih.gov

[Anti-TNF (infliximab) treatment in Crohn disease: safety profile]. [2019]

10. England pubmed.ncbi.nlm.nih.gov

Stability of infliximab dosing in inflammatory bowel disease: results from a multicenter US chart review. [2015]

11. United States pubmed.ncbi.nlm.nih.gov

Application of Population Pharmacokinetic Modeling for Individualized Infliximab Dosing Strategies in Crohn Disease. [2019]

12. United States pubmed.ncbi.nlm.nih.gov

Infliximab in the treatment of Crohn's disease: a user's guide for clinicians. [2015]

13. England pubmed.ncbi.nlm.nih.gov

Application of a Precision-Dosing Model to a Real-World Cohort of Patients on Infliximab Maintenance Therapy: Drug Usage and Cost Analysis. [2023]