Clinical trial NCT04982172: Model-informed Dose De-escalation of Infliximab in Patients With Inflammatory Bowel Diseases
Official title: Model-informed Infliximab Dose De-escalation Following Earlier Dose Escalation in Adult Patients With Inflammatory Bowel Diseases
Study type: INTERVENTIONAL
Overall status: COMPLETED
Phase: PHASE4
Conditions: Inflammatory Bowel Diseases
Lead sponsor: Universitaire Ziekenhuizen KU Leuven
Sponsor class: OTHER
Collaborators: name: KU Leuven
First posted: 2021-07-29
Enrollment: 80
Sex: ALL
Minimum age (years): 18
Maximum age (years): 80
Standard ages: ADULT
OLDER_ADULT
Accepts healthy volunteers: no
Allocation: NON_RANDOMIZED
Intervention model: PARALLEL
Primary purpose: TREATMENT

Brief summary: This is a monocentric, two-arm, non-randomised, non-blinded, historically controlled, interventional trial. The purpose of this trial is to investigate the effect of model-informed infliximab dose de-escalation on the infliximab exposure and therapeutic outcome as compared to standard dose de-escalation in patients with inflammatory bowel diseases.


Eligibility criteria: Inclusion Criteria:

* The subject or, when applicable, the subject's legally acceptable representative signs and dates a written informed consent form and any required privacy authorisation prior to the initiation of any study procedures.
* The subject is aged 18 to 80 years inclusive.
* The subject has a good understanding of the Dutch language.
* The subject is diagnosed with moderately to severely active ulcerative colitis or Crohn's disease, confirmed by clinical, endoscopic, histological, and/or imaging criteria.
* The subject was in maintenance therapy, later lost their response to treatment and subsequently gained steroid-free, clinical and biological remission following infliximab dose escalation (i.e., by increasing the dose and/or shortening the dosing interval) and had an infliximab trough concentration ≥5 mg/L.
* Adequate contraception in female subjects of reproductive age (oral contraception, intra-uterine device, sterilisation or barrier method).

Exclusion Criteria:

* The subject is aged \<18 years or \>80 years.
* The subject receives infliximab prophylactically (e.g. in the immediate postoperative setting).
* The subject has an ostomy or an ileal anal pouch anastomosis.
* If female subjects, when pregnant (based on a positive serum sample) or lactating or intending to become pregnant or nurse before, during or within 15 weeks after the last dose of study drug; or intending to donate ova during such time period.
* The subject is participating in another interventional clinical trial.

Primary outcomes:
measure: Steroid-free, combined clinical and biological remission
timeFrame: During one year after start of infliximab dose de-escalation
Secondary outcomes:
measure: Steroid-free, combined clinical and biological remission
timeFrame: At one year after start of infliximab dose de-escalation
Other outcomes:
measure: Steroid-free clinical remission
timeFrame: At and during one year after start of infliximab dose de-escalation
measure: Steroid-free biological remission
timeFrame: At and during one year after start of infliximab dose de-escalation
measure: Infliximab trough concentration target attainment and area under the concentration-time curve
timeFrame: At and during one year after start of infliximab dose de-escalation
measure: Total infliximab dose and number of infusions
timeFrame: At and during one year after start of infliximab dose de-escalation
measure: Direct costs calculated based on cost of infliximab and cost related to the day hospital needed for the infusion
timeFrame: At one year after start of infliximab dose de-escalation
measure: Indirect costs based on questionnaire
timeFrame: At one year after start of infliximab dose de-escalation
measure: Health-related quality of life based on QoL questionnaire
timeFrame: At one year after start of infliximab dose de-escalation
Locations:
city: Leuven
country: Belgium
facility: UZ Leuven
state: Vlaanderen
Study officials:
affiliation: UZ Leuven
name: Marc Ferrante, MD, PhD
role: PRINCIPAL_INVESTIGATOR
References:
citation: Kantasiripitak W, Outtier A, Wicha SG, Kensert A, Wang Z, Sabino J, Vermeire S, Thomas D, Ferrante M, Dreesen E. Multi-model averaging improves the performance of model-guided infliximab dosing in patients with inflammatory bowel diseases. CPT Pharmacometrics Syst Pharmacol. 2022 Aug;11(8):1045-1059. doi: 10.1002/psp4.12813. Epub 2022 Jun 15.