PROactive and Early Infliximab Monitoring and OPTimization in Inflammatory Bowel Disease

NCT ID: NCT06758024

Last Updated: 2025-02-28

Basic Information

• Recruitment Status: RECRUITING
• Clinical Phase: NA
• Total Enrollment: 72 participants
• Study Classification: INTERVENTIONAL
• Study Start Date: 2025-01-24
• Study Completion Date: 2027-01-31

Brief Summary

Infliximab (IFX) is a Food and Drug administration (FDA)-appoved monoclonal antibody medication targeting tumor necrosis factor (TNF) widely used in inflammatory bowel disease (IBD) to treat intestinal inflammation and improve patient's symptoms. Intravenous (iv) IFX is effective to treat hospitalized IBD patients with moderate-to-severe flares who fail iv corticosteroids (CS). However, about one-third of IBD patients do not respond to this medications and a half will loss the response after an initial response. Researchers have shown that most of these phenomena occur due to low IFX concentrations sometimes accompanied by the development of anti-drug antiboides (ADA) againts IFX.

Blood concentrations of IFX are widely variable among IBD patients despite receiving the same weight-based dose. Several patient factors including laboratory parameters and severity of intestinal inflammation influence the way an individual's body proccesses and eliminate this type of medications. Dashboard software systems can take into account patient characteristics and IFX concentrations to modelate and facilitate dosing of IFX. By using pharmacokinetics (PK) models specifically developed to facilitate IFX dosing, these softwares can provide and recommend multiple dosing regimes to help the clinicians to select the appropriate dose to achieve target and optimal IFX concentrations.

The goal of this clinical trial is to learn if early measuring of IFX blood concentrations and dashboard-guided IFX dose adjustment in Chilean IBD patients starting IFX, increases the proportion of patients with optimal IFX levels and improves patient outcomes. Researchers will measure IFX concentrations before the second (week 2) and third dose (week 6) in a prospectively collected individual patient cohort and this information along with clinical data will be analyzed with a dashboard software system and multiple dosing regime options will be provide to the attending clinicians to facilitate the selection of the next IFX weight-based dose and interval of infusions. This group will be compared with IBD patients with standard of dosing where attending clinicians make the dosing decisions based on clinical parameters. 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, develop ADA less frequently and improve clinical outcomes compared with standard dosing group.

Participants will be asked to:

• Provide clinical data about their disease and other conditions
• Provide blood samples at enrollment and before each IFX infusion (IFN) during one year
• Maintain regular clinical assessments every 3 months for one year

Detailed Description

Inflammatory bowel disease (IBD), including Crohn's disease (CD) and ulcerative colitis (UC), are chronic diseases that entail important morbidity and frequently require high-cost medications such as biologic therapies. Monoclonal antibodies against tumoral necrosis factor (anti-TNF) are effective and can modify the progressive course of IBD. In Chile, given the high cost of anti-TNF therapy, this medication is provided by a national program with universal coverage. Unfortunately, a significant proportion of IBD patients never respond (primary non-response, PNR) or experience loss of response (secondary loss of response, SLR) to anti-TNF within the first year of therapy and current evidence support that the complex pharmacokinetics of anti-TNF is involved in both scenarios. Additionally, low trough levels (TL) are associated with the development of antidrug antibodies (ADA) which reduce anti-TNF efficacy and can cause anaphylactic reactions. This is particularly relevant for intravenous infliximab (IFX) which is usually indicated in IBD patients with acute severe disease not responding to iv corticosteroids. Therefore, IFX is frequently dose escalated in patients based on clinical parameters that are thought to be related to drug clearance with conflicting evidence supporting this strategy. Several studies have demonstrated that IFX TL between 7-20 mcg/ml at week 14 of treatment is a strong and independent predictor of therapy response. Furthermore, IFX dashboard-guided dose optimization based on clinical and pharmacokinetic (PK) parameters using adaptive Bayesian modeling have demonstrated to be more precise that empirical adjustments based on the clinician intuition alone. Therefore, the goal of this study is to analyze whether early therapeutic drug monitoring (TDM) and dose adjustment based on a Bayesian model (iDOSE) in CD and UC patients initiating IFX, increases the proportion of patients with therapeutic levels (7-20 mcg/ml), reducing immunogenicity and consequently increasing the rate of disease remission. A prospective multicentric randomized clinical trial (RCT) of Chilean adult IBD inpatients starting IFX due to moderate-to-severe disease refractory to corticosteroids will be carried out. Patients will be randomized 1:1 to:

1. - Dashboard-guided dosing arm. Patients will undergo proactive TDM during induction (TL at IFN 2 and 3) with dose adjustment based on iDOSE.

2. - Standard dosing arm. Patients will receive dose adjustment based solely on clinical parameters.

Both groups will be followed-up after induction with clinical visits, TL and ADA at week 14 (INF 4), 26 and 52. Researchers expect that a higher proportion of patients in the dashboard-guided dosing arm will achieve therapeutic TL of IFX (7-20 mcg/ml) at week 14 of treatment (Primary outome). Secondary outcomes will include clinical and laboratory parameters related to therapy response at week 52 of treatment, proportion of patients experiencing PNR and SLR, patients developing ADA, as well as, adverse events, hospitalization and surgery

Conditions

Inflammatory Bowel Disease (IBD); Crohn Disease (CD); Ulcerative Colitis (UC)

Study Design

• Allocation Method: RANDOMIZED
• Intervention Model: PARALLEL
• Primary Study Purpose: TREATMENT
• Blinding Strategy: NONE

Study Groups

Dashboad-guided dosing

Eligible patients will receive IFX with proactive therapeutic drug monitoring during induction (week 2 and 6) and dashboard-guided dosing options will be suggested to their attending gastroenterologists

Group Type: OTHER

Infliximab

Intervention Type: DRUG

IFX therapeutic drug monitoring before the second and third infusion and subsequent dashboard-guided dosing regimes suggested to attending gastroenterologists based on clinical and pharmacokinetics data

Standard dosing

Eligible patients will receive IFX standard dosing during induction based solely on clinical data

Group Type: OTHER

Infliximab

Intervention Type: DRUG

No IFX therapeutic drug monitoring before the second and third infusion and subsequent dosing regimes based on clinical data

Interventions

Infliximab

IFX therapeutic drug monitoring before the second and third infusion and subsequent dashboard-guided dosing regimes suggested to attending gastroenterologists based on clinical and pharmacokinetics data

Intervention Type: DRUG

Infliximab

No IFX therapeutic drug monitoring before the second and third infusion and subsequent dosing regimes based on clinical data

Intervention Type: DRUG

Eligibility Criteria

Inclusion Criteria

• Adult inpatients with Crohn's disease, ulcerative colitis or inflammatory bowel disease-unclassified.
• Moderate-to-severe flare who fail to iv steroids and require infliximab as per standard of care by treating gastroenterologist

Exclusion Criteria

• Participant younger than 18 years
• Non-controlled infectious diseases
• Permanent ileostomy or Ileal pouch-anal anastomosis
• Pregnancy
• Patients do not consent to participate in study
• Patients unable to comply with protocol

• Minimum Eligible Age: 18 Years
• Maximum Eligible Age: 75 Years
• Eligible Sex: ALL
• Accepts Healthy Volunteers: No

Sponsors

Clínica Universidad de los Andes

OTHER

Sponsor Role: collaborator

Hospital San Juan de Dios,Chile

OTHER

Sponsor Role: collaborator

University of Chile

OTHER

Sponsor Role: collaborator

Clinica Indisa

OTHER

Sponsor Role: collaborator

Universidad de La Frontera

OTHER

Sponsor Role: collaborator

Pontificia Universidad Catolica de Chile

OTHER

Sponsor Role: lead

Responsible Party

Responsibility Role: SPONSOR

Locations

Pontificia Universidad Catolica of Chile

Santiago, , Chile

Site Status: RECRUITING

Countries

Chile

Central Contacts

Cristian Hernández-Rocha Cristian Hernández-Rocha, MD

Role: CONTACT

caherna4@uc.cl

56-22-3543838

Carolina Pavez Carolina Pavez, MD

Role: CONTACT

cdpavez@uc.cl

56-22-3543838

Facility Contacts

Maria Balcells E, MD

Role: primary

proyectos.didemuc@uc.cl

+56955048170

Other Identifiers

SA24I0002

Identifier Type: OTHER_GRANT

Identifier Source: secondary_id

240320009

Identifier Type: -

Identifier Source: org_study_id