Individualized Infliximab Dosing for Crohn's Disease
(REMODEL-CD Trial)
Recruiting in Palo Alto (17 mi)
+10 other locations
Overseen byPhillip Minar, MD,MS
Age: < 65
Sex: Any
Travel: May Be Covered
Time Reimbursement: Varies
Trial Phase: Phase 2 & 3
Recruiting
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
Prior Safety Data
Approved in 4 Jurisdictions
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.
12345What 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.
46789How 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.
310111213Eligibility 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
Clinical activity and luminal inflammation, defined by PCDAI≥10 (<18 years old) or CDAI ≥150 (≥18 years old) in last 60 days before the decision to start infliximab, SES-CD>6, or SES-CD>3 for isolated ileal disease within the last 60 days or a fecal calprotectin >250 μg/g within last 75 days prior to screening, C-reactive protein >1.0 mg/dL in last 30 days and/or fecal calprotectin >250 μg/g within last 75 days prior to screening, Negative TB (tuberculosis) interferon-gamma release test and a negative urine pregnancy test for female patients (if menstruation has started)
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.
+2 more
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.
+15 more
Trial 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
Participant Groups
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.
2Treatment groups
Experimental Treatment
Active Control
Group I: Precision dosingExperimental Treatment2 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 dosingActive Control1 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
Find a Clinic Near You
Research Locations NearbySelect from list below to view details:
Nationwide Children's HospitalColumbus, OH
Nemours Children's Health System-WilmingtonWilmington, DE
Medical College of Wisconsin, Children's of WisconsinMilwaukee, WI
Cleveland Clinic Children's HospitalCleveland, OH
More Trial Locations
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Who Is Running the Clinical Trial?
Children's Hospital Medical Center, CincinnatiLead Sponsor
National Institute of Diabetes and Digestive and Kidney Diseases (NIDDK)Collaborator
Janssen Scientific Affairs, LLCIndustry Sponsor
References
Need for infliximab dose intensification in Crohn's disease and ulcerative colitis. [2021]To compare the need for infliximab dose intensification in two cohorts of patients with Crohn's disease (CD) or ulcerative colitis (UC).
[Treatment of Crohn's disease with anti-TNF alpha antibodies (infliximab): results of a multicentric and retrospective study]. [2015]To evaluate the results of infliximab therapy, an anti-TNF-alpha antibody, in patients with severe and refractory Crohn's disease or with fistulas, treated outside the setting of a therapeutic trial.
Trough concentrations of infliximab guide dosing for patients with inflammatory bowel disease. [2022]Infliximab, a tumor necrosis factor antagonist, is effective for treating patients with Crohn's disease (CD) and ulcerative colitis (UC). We aimed to determine whether dosing based on therapeutic drug monitoring increases rate of remission and whether continued concentration-based dosing is superior to clinically based dosing of infliximab for maintaining remission in patients with CD and UC.
Anti-TNF antibody in Crohn's disease--status of information, comments and recommendations of an international working group. [2015]The chimeric anti-TNF antibody Remicade (Infliximab) has recently been approved for human use by the FDA and is now available on the market. Since there is considerable interest in this kind of treatment among patients with Crohn's disease, an international working group has summarized the presently available information about efficacy, side effects and possible problems of this treatment. Studies show that Remicade is effective in the treatment of active Crohn's disease, maintaining remission and fistulae. The working group does not see Infliximab as a first-line treatment for Crohn's disease. It may be used in active phase recurrent disease, chronic active disease and fistulae if standard treatment was not successful. For the surveillance special attention has to be given to the unknown malignancy rate of Infliximab. Infusion should be performed in an institution, routinely performing intravenous infusions and a two-hour surveillance of the patients should be guaranteed to recognize anaphylactic reactions or acute side effects. There is presently no information indication that the combination with immunosuppressants might increase risks or side effects of this treatment. Due to the limited information available the working group would prefer to use Remicade in studies only and recommends central collection and documentation of all data on efficacy and side effects for the next year.
Adalimumab maintenance therapy for Crohn's disease with intolerance or lost response to infliximab: an open-label study. [2015]Adalimumab is effective in inducing remission in patients with active Crohn's disease who had secondary failure to infliximab therapy.
Prescribing patterns and awareness of adverse effects of infliximab: a health survey of gastroenterologists. [2018]We sought to determine prescribing patterns and awareness of adverse drug reactions to infliximab among gastroenterologists. A questionnaire was developed and mailed to all gastroenterologists in Maryland and Washington, D.C. Ninety-six of 336 (28.6%) gastroenterologists responded; 86% of respondents use infliximab often or sometimes and 48% infuse infliximab on-site. Only 48% of respondents use immunomodulators prior to infusing infliximab. Thirty-three percent of respondents do not prescribe maintenance infliximab. Respondents reported that infusion reactions occur in 12.9% of infliximab infusions. Most respondents order a purified protein derivative prior to starting infliximab. Respondents underestimated the risk of serious infection, death, demyelinating diseases, and malignancy and overestimated the risk of congestive heart failure. We conclude that a substantial number of gastroenterologists underutilize immunomodulators and fail to prescribe maintenance infliximab. Further, respondents were unaware of the frequency of major adverse events associated with infliximab. Education regarding treatment algorithms in CD and infliximab-related side effects is needed.
Infliximab therapy in Crohn's disease: safety issues. [2015]Infliximab has become a valuable addition to the therapeutic arsenal for Crohn's disease. Although the rate of adverse events was relatively low in the premarketing trials, several investigators have recently reported experience in large groups of patients. This has shed more light on safety aspects of infliximab therapy, which should change the approach towards patients prior to infliximab infusion. This review discusses some immunological aspects that are relevant for infliximab therapy and provides guidelines for daily practice.
Infliximab treatment for Crohn's disease: one-year experience in a Dutch academic hospital. [2019]The aim of this study was to report the 1-year clinical experience with infliximab treatment for Crohn's disease (CD) in the Netherlands. All 73 CD patients receiving infliximab infusions were prospectively followed during 1 year after the drugs' registration in the Netherlands. Clinical response and adverse events were assessed for both active luminal disease as well as fistulous disease. A total of 212 infusions were administered to 57 patients with active luminal CD and 16 patients with fistulous CD. The mean duration between infusions was 60 days. In 17% of patients, adverse events were recorded, of which one was serious. The response rate was 81% in active luminal CD and 87% in fistulous disease. Response rates were highest in patients receiving concomitant methotrexate as maintenance therapy. Steroids could successfully be tapered off in 73% of responding luminal CD patients and 100% of responding CD patients with fistulae. Eleven patients showed a loss of response to continuous infliximab readministration. Our clinical experience with infliximab for active luminal and fistulous CD showed that the administration is safe, effective, and has high steroid-sparing efficacy. Higher response rates were seen with methotrexate as concomitant medication.
[Anti-TNF (infliximab) treatment in Crohn disease: safety profile]. [2019]Anti-tumor necrosis factor (anti-TNF) therapy is an important therapeutic addition in the treatment of active Crohn's disease. Although controlled trials have confirmed the efficacy of anti-TNF (infliximab) treatment, serious toxicities related to the therapies have emerged. The purpose of this article was to review the safety profile of infliximab, and in particular analyse the infectious complications, the autoimmune disorders and the theoretical risk of cancer and lymphoma.
Stability of infliximab dosing in inflammatory bowel disease: results from a multicenter US chart review. [2015]Infliximab dosing for inflammatory bowel disease (IBD) is based on patient weight and treatment response. Understanding dosing patterns may provide insight into treatment response and predictability of treatment cost. The purpose of this medical record review was to assess dose and dose frequency of infliximab maintenance treatment in patients with IBD using patient chart data.
Application of Population Pharmacokinetic Modeling for Individualized Infliximab Dosing Strategies in Crohn Disease. [2019]The pharmacokinetics of infliximab (IFX) is highly variable in children with Crohn disease (CD), and a one-size-fits-all approach to dosing is inadequate. Model-based drug dosing can help individualize dosing strategies. We evaluated the predictive performance and clinical utility of a published population pharmacokinetic model of IFX in children with CD.
Infliximab in the treatment of Crohn's disease: a user's guide for clinicians. [2015]Induction therapy with infliximab is indicated for treatment of signs and symptoms, and induction and maintenance of remission in patients with moderate to severely active inflammatory Crohn's disease with an inadequate response to conventional therapy, and for reduction in the number of draining fistulas in patients with fistulizing Crohn's disease. Emerging indications for infliximab therapy in patients with Crohn's disease include maintenance of fistula improvement (reduction in the number of draining perianal or enterocutaneous fistulas) and complete fistula response (no draining fistulas) in patients with fistulizing Crohn's disease, steroid sparing in steroid-treated patients, early use in hospitalized patients who have not failed conventional medical therapy where there is either a severe clinical presentation or a rapid onset of action is desired, and in a variety of unusual and extra-intestinal manifestations of Crohn's disease. An infliximab dose of 5 mg/kg is recommended initally, but some patients who require maintenance dosing may benefit from increasing the infliximab dose over a range of 5-10 mg/kg. An induction regimen of 3 doses at 0, 2, and 6 weeks is the preferred dosing strategy for inducing remission. The optimal dosing interval for patients who require retreatment appears to be every 8 weeks for most patients. Concomitant immunosuppressive therapy with azathioprine, 6-mercaptopurine, or methotrexate may result in improved outcomes due to a reduction in the frequency of human anti-chimeric antibody formation, acute infusion reactions, and a reduced risk of delayed hypersensitivity-like reactions and formation of antinuclear antibodies. Pretreatment with diphenhydramine (and in selected cases of acetaminophen and, rarely, corticosteroids) is recommended in patients with a history of infusion reactions and patients at risk for delayed hypersensitivity-like reactions. Patients with evidence of active infection should not receive infliximab until the infection is adequately treated, and all patients should be screened for tuberculosis prior to initiating infliximab therapy.
Application of a Precision-Dosing Model to a Real-World Cohort of Patients on Infliximab Maintenance Therapy: Drug Usage and Cost Analysis. [2023]Precision-dosing models forecast infliximab doses to achieve targeted trough concentrations in patients with inflammatory bowel disease (IBD). These models have shown to reduce nonresponse and improve patient outcomes. We compared infliximab doses determined by iDOSE precision dosing with standard dosing, and the associated drug costs, in patients with IBD. In this retrospective study, patients with IBD treated with infliximab every 8 weeks at 5 mg/kg were included. An infliximab dose was named dose X if 3 previous infliximab doses, laboratory values including trough infliximab concentrations, and the patient's weight were recorded. The actual dose X was compared to an iDOSE-predicted dose X. Net drug use and costs were evaluated. A total of 174 patients-56% men; median age, 36 (interquartile range, 29-47) years; 135 with Crohn disease; and 31 with ulcerative colitis-were included, with 417 dose X recordings. Median prior infliximab therapy was 2 (0-4) years. Comparing actual dose X with predicted dose X, 52% and 32% of doses were subtherapeutic when aiming for trough concentrations of 5-10 and 3-7 μg/mL, respectively. Treatment costs increased by 102% and 29% for the 2 trough ranges, respectively. On multivariate regression analysis, subtherapeutic infliximab concentrations were associated with ulcerative colitis compared with Crohn disease (odds ratio, 9.81; 95% confidence interval, 1.28-75.40; P = .028) and predose X infliximab trough concentration [odds ratio, 0.07; 95% confidence interval, 0.03-0.15; P