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

What You Need to Know Before You Apply

What is the purpose of this trial?

This trial explores whether a customized dose of infliximab, a medication for Crohn's disease, can be more effective than standard dosing. The goal is to determine if a computer program that tailors the dose based on blood tests can improve treatment outcomes. Participants are divided into two groups: one receives the usual infliximab dose, while the other receives a dose adjusted by the program. Individuals diagnosed with Crohn's disease within the past three months and who have not previously used anti-TNF (tumor necrosis factor) treatments might be suitable candidates.

As a Phase 2 trial, this research measures the treatment's effectiveness in an initial, smaller group of people, offering a chance to contribute to potential advancements in Crohn's disease treatment.

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.

Is there any evidence suggesting that this trial's treatments are likely to be safe?

Research has shown that infliximab is already FDA-approved for treating Crohn's disease, indicating it has undergone testing to ensure human safety. Infliximab is generally well-tolerated, though it can cause side effects like infections and allergic reactions during or after administration. Serious side effects are rare but may include liver problems or worsening heart failure.

The precision dosing approach is new and aims to tailor the infliximab dose to each person’s needs using a computer program. This method is still under testing, so specific safety information is not yet available. However, since it involves infliximab, which is already approved, it is expected to have a similar safety profile. Participants will be closely monitored during the trial for any side effects. ^{1 2 3 4 5}

Why are researchers excited about this trial?

Researchers are excited about individualized infliximab dosing for Crohn's disease because it tailors treatment to each patient's unique needs. Unlike standard treatments, which use a one-size-fits-all dosing approach, this method uses precision dosing guided by the RoadMABTM tool to optimize drug levels and target specific markers like CRP and fecal calprotectin. This personalized approach aims to improve treatment effectiveness and reduce side effects, potentially offering a more efficient and patient-centered therapy for those with Crohn's disease.

What evidence suggests that this trial's treatments could be effective for Crohn's Disease?

This trial will compare conventional dosing with precision dosing of infliximab for treating Crohn's disease. Research has shown that precision dosing can be very effective, offering significant benefits by helping patients stay symptom-free and preventing treatment failure. One study found that a personalized approach improves the drug's effectiveness. Specifically, participants in that study who received precision dosing stayed in remission more effectively than those on standard dosing. This approach uses a computer tool to adjust doses based on individual needs, aiming for better results. ^{6 7 8 9 10}

Who Is on the Research Team?

Phillip Minar, MD,MS

Principal Investigator

Children's Hospital Medical Center, Cincinnati

Are You a Good Fit for This Trial?

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 for a Trial Participant

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

What Are the Treatments Tested in This Trial?

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.

How Is the Trial Designed?

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+

Joaquin Duato

Janssen Scientific Affairs, LLC

Chief Executive Officer since 2022

MBA from ESADE, Master of International Management from Thunderbird School of Global Management

Dr. Jijo James, MD

Janssen Scientific Affairs, LLC

Chief Medical Officer since 2014

MD from St. Johns Medical College, MPH from Columbia University

Published Research Related to This Trial

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]

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]

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]

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]

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 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 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]

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 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 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]

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 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 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]

Citations

1. pubmed.ncbi.nlm.nih.gov pubmed.ncbi.nlm.nih.gov/38576238

Simulated cost-effectiveness of a novel precision-guided ... Conclusions: PGD provides clinical and QoL benefits by maintaining remission and avoiding IFX failure; it is the most cost-effective under ...

2. clinicaltrials.gov clinicaltrials.gov/study/NCT04974099

Study Details | NCT04974099 | Personalized Infliximab ... This is a Pilot study to evaluate safety, feasibility and efficacy of utilizing pharmacokinetic modeling to provide an individualized infliximab induction ...

3. journals.lww.com journals.lww.com/ajg/fulltext/2022/10002/s824_cost_effectiveness_of_precision_guided_dosing.824.aspx

S824 Cost-Effectiveness of Precision-Guided Dosing in ... Precision-guided dosing provides substantial clinical and QoL benefits for adult CD patients by maintaining clinical remission and avoiding IFX failure.

4. accpjournals.onlinelibrary.wiley.com accpjournals.onlinelibrary.wiley.com/doi/full/10.1002/phar.2915

Simulated cost‐effectiveness of a novel precision‐guided ... Precision-guided dosing (PGD) provides a comprehensive pharmacokinetic (PK) profile that allows for biologic dosing to be personalized. We ...

5. bmjopen.bmj.com bmjopen.bmj.com/content/14/3/e077193

Precise infliximab exposure and pharmacodynamic control ... A personalised and scalable infliximab dosing intervention that starts with dose selection and continues throughout maintenance to optimise drug exposure.

6. infliximab.com infliximab.com/assets/pdfs/remicade-infliximab-dosing-and-admin-guide.pdf

Dosing and Administration Guide REMICADE® or Infliximab is administered by intravenous (IV) infusion for at least 2 hours. Infusions occur every 8 weeks after 3 induction doses. Moderately to ...

7. uhcprovider.com uhcprovider.com/content/dam/provider/docs/public/policies/comm-medical-drug/infliximab-remicade-inflectra.pdf

Infliximab (Avsola®, Inflectra®, Remicade®, & Renflexis®) o Documentation of positive clinical response to infliximab; and o Infliximab is dosed according to U.S. FDA labeled dosing for Crohn's disease; and o ...

8. zymfentra.com zymfentra.com/clinical/

ZYMFENTRA: FDA-Approved Subcutaneous Infliximab Discover ZYMFENTRA™, the subcutaneous infliximab for moderate to severe UC and CD. View administration information along with key PK, efficacy, and safety data.

9. organonpro.com organonpro.com/en-us/product/renflexis/dosing-administration/

RENFLEXIS. Same dosing as REMICADE (infliximab) RENFLEXIS 3 mg/kg given as an intravenous induction regimen at 0, 2, and 6 weeks followed by a maintenance regimen of 3 mg/kg IV every 8 weeks thereafter.

10. accessdata.fda.gov accessdata.fda.gov/drugsatfda_docs/label/2025/103772s5412lbl.pdf

REMICADE® (infliximab) for injection, for intravenous use 2 DOSAGE AND ADMINISTRATION. 2.1. Dosage in Adult Crohn's Disease. The recommended dosage of REMICADE is 5 mg/kg given as an intravenous induction regimen at 0 ...