Infliximab Optimization for Crohn's Disease

Enrolling by invitation at 25 trial locations

Overseen By Vivian Cheng

Age: Any Age

Sex: Any

Trial Phase: Phase 4

Sponsor: Beth Israel Deaconess Medical Center

Must be taking: Infliximab

Must not be taking: Adalimumab

Disqualifiers: Infections, Malignancy, Immunodeficiency, 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: Unknown

Duration: 52 weeks

What You Need to Know Before You Apply

What is the purpose of this trial?

This trial aims to determine if a new dosing method for infliximab, using a special dashboard, is more effective and safer than the usual method for improving symptoms in people with Crohn's disease. Infliximab treats intestinal inflammation in those with inflammatory bowel disease (IBD), such as Crohn's disease. The trial will compare two groups: one using standard dosing and the other using a proactive, dashboard-guided dosing approach. Suitable candidates for this trial have been diagnosed with moderately to severely active IBD, experience symptoms like chronic diarrhea or abdominal pain, and have not extensively used infliximab. As a Phase 4 trial, this research seeks to understand how the already FDA-approved and effective treatment can benefit more patients.

Do I need to stop my current medications to join the trial?

The trial protocol does not specify if you need to stop taking your current medications. However, if you are on oral corticosteroids, you may need to taper off by Week 14. It's best to discuss your specific medications with the trial team.

What is the safety track record for infliximab?

Research has shown that infliximab, the treatment being improved in this trial, is generally safe for people with Crohn's disease. The FDA has approved infliximab for this condition, indicating a good safety record. Studies on adjusting infliximab doses using a special tool to track drug levels suggest this method leads to better results than standard dosing. This approach aims to maintain the right amount of the drug in the body, even when symptoms are not present. Early data from these studies have not identified any new safety issues with this dosing strategy. As with any treatment, side effects can occur, but current evidence suggests this method is safe for patients. ^{1 2 3 4 5}

Why are researchers enthusiastic about this study treatment?

Researchers are excited about optimizing infliximab for Crohn's disease because it introduces a proactive dosing strategy using a pharmacokinetic dashboard. Unlike the standard infliximab dosing, which follows a fixed schedule, this approach tailors the dosage to the patient's unique drug levels and response. This personalized method could enhance treatment effectiveness and potentially reduce side effects, offering a more precise way to manage Crohn's disease.

What is the effectiveness track record for infliximab in treating Crohn's disease?

Studies have shown that infliximab effectively treats Crohn's disease by reducing inflammation and controlling the disease, resulting in fewer symptoms over time. In this trial, participants will join one of two treatment arms: standard infliximab dosing or proactive infliximab optimization using a pharmacokinetic dashboard. Research suggests that adjusting infliximab doses with this tool may enhance its effectiveness compared to standard dosing. Early data indicate that this method maintains better drug levels, even if a patient feels well, leading to improved outcomes. Overall, infliximab is a proven treatment, and fine-tuning its use could enhance its effectiveness. ^{1 3 6 7 8}

Are You a Good Fit for This Trial?

The OPTIMIZE Trial is for males and females aged 16-80 with moderately to severely active Crohn's Disease. Participants must have certain disease markers like elevated CRP or fecal calprotectin, and no prior significant use of Infliximab. Exclusions include those with specific CD complications, infections like tuberculosis or hepatitis B/C, recent serious infections, cancer within the last 5 years (except some skin cancers), immunodeficiency disorders, high-dose steroid use without tapering plans, pregnancy or lactation.

Inclusion Criteria

Moderately to severely active CD, defined by a total Crohn's Disease Activity Index (CDAI) score between 220 and 450 points, and at least 1 of the following: Elevated CRP > upper limit of normal, Elevated fecal calprotectin (FC) (> 250 μg/g), SES-CD > 6, or SES-CD > 3 for isolated ileal disease, Physician intends to prescribe IFX as part of the usual care of the subject, No previous use of IFX prior to enrolment in the current study, unless the participant received 1 prior dose of IFX (within 2.5 weeks of enrolment) and met all eligibility criteria at the time of starting IFX and IFX was administered according to the requirements outlined in this protocol, Able to participate fully in all aspects of this clinical trial, Written informed consent must be obtained and documented

I am a male or a non-pregnant, non-breastfeeding female aged between 16 and 80.

I have been diagnosed with Crohn's disease based on tests.

Exclusion Criteria

I do not have complications or conditions that would interfere with the study.

Timeline for a Trial Participant

Screening

Participants are screened for eligibility to participate in the trial

2-4 weeks

Treatment

Participants receive either proactive infliximab optimization using a pharmacokinetic dashboard or standard of care infliximab dosing

52 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 This trial tests if using an iDose dashboard-driven dosing method for Infliximab is more effective and safer than standard dosing in achieving and maintaining remission in Crohn's Disease patients. The study compares these two approaches to see which one better controls the symptoms of this digestive disorder.

How Is the Trial Designed?

Group I: standard of care infliximab dosing Experimental Treatment 1 Intervention

standard of care infliximab dosing

Group II: proactive infliximab optimization Experimental Treatment 1 Intervention

proactive infliximab optimization using a pharmacokinetic dashboard

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?

Beth Israel Deaconess Medical Center

Lead Sponsor

Trials

872

Recruited

12,930,000+

The Leona M. and Harry B. Helmsley Charitable Trust

Collaborator

Trials

69

Recruited

101,000+

Icahn School of Medicine at Mount Sinai

Collaborator

Trials

933

Recruited

579,000+

Published Research Related to This Trial

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]

Infliximab, an anti-TNF-alpha monoclonal antibody, was studied in 771 patients for Crohn's disease and rheumatoid arthritis, showing an acceptable safety profile with only 17% experiencing acute infusion reactions compared to 7% in the placebo group.

While infliximab was associated with a higher overall rate of infections (26% vs. 16% for placebo), there was no increased risk of serious infections or difference in mortality rates, indicating it is generally safe for use.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Long term safety of infliximab. Schaible, TF.[2019]

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]

In a study involving 6290 patients with Crohn's disease, infliximab treatment did not show a higher mortality rate compared to other therapies, indicating its long-term safety in this regard.

While there was an observed increased risk for serious infections in infliximab-treated patients, this risk was more closely linked to factors like disease severity and the use of prednisone rather than infliximab itself.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Serious infections and mortality in association with therapies for Crohn's disease: TREAT registry. Lichtenstein, GR., Feagan, BG., Cohen, RD., 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 study of 6,273 Crohn's disease patients with an average follow-up of 5.2 years, infliximab treatment did not increase mortality risk compared to other treatments, indicating its long-term safety in this regard.

However, infliximab was associated with a higher risk of serious infections, although this risk was also influenced by the severity of the disease and the use of medications like prednisone and narcotics.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Serious infection and mortality in patients with Crohn's disease: more than 5 years of follow-up in the TREAT™ registry. Lichtenstein, GR., Feagan, BG., Cohen, RD., et al.[2022]

Citations

1. pubmed.ncbi.nlm.nih.gov pubmed.ncbi.nlm.nih.gov/35365535/

Proactive infliximab optimisation using a pharmacokinetic ... The primary outcome of the study is the proportion of subjects with sustained corticosteroid-free clinical remission and no need for rescue ...

2. clinicaltrials.gov clinicaltrials.gov/study/NCT04835506

NCT04835506 | Proactive Infliximab Optimization Using a ... Preliminary data show that proactive IFX optimization to achieve a threshold drug concentration during maintenance therapy (even if the patient is asymptomatic) ...

3. bpspubs.onlinelibrary.wiley.com bpspubs.onlinelibrary.wiley.com/doi/am-pdf/10.1111/bcp.14229

A three‐year prospective study of a multidisciplinary early ... CONCLUSIONS: This study found that compared to empirical dosing, mep-. TDM is associated with improved the efficacy and safety of infliximab therapy,. This ...

4. withpower.com withpower.com/trial/infliximab-optimization-for-crohns-disease-d05fd

Infliximab Optimization for Crohn's Disease In a 52-week study involving 24 patients with Crohn's disease who previously lost response to infliximab, adalimumab demonstrated significant efficacy, with ...

5. sciencedirect.com sciencedirect.com/science/article/abs/pii/S2444382423001359

Impact of proactive of infliximab monitoring using the ... The aim of this study was to evaluate the efficacy of proactive TDM based on the Bayesian approach to optimise the IFX dose compared with the standard of care ...

6. pmc.ncbi.nlm.nih.gov pmc.ncbi.nlm.nih.gov/articles/PMC8977745/

Proactive infliximab optimisation using a pharmacokinetic ... Preliminary data indicates that proactive therapeutic drug monitoring (TDM) is associated with better outcomes compared with empiric dose ...

7. bmjopen.bmj.com bmjopen.bmj.com/content/12/4/e057656.reviewer-comments

Proactive infliximab optimisation using a pharmacokinetic ... If the OPTIMIZE trial confirms equal or better outcomes using iDose, combination therapy will likely still be used in much of the world.

8. clinicaltrials.gov clinicaltrials.gov/study/NCT06758024

NCT06758024 | PROactive and Early Infliximab Monitoring ... The main goal is to analyze if IBD patients in the dashboard-guided dosing arm achieve a higher proportion of optimal IFX concentrations at week 14 of treatment ...