Model-informed Dose De-escalation of Infliximab in Patients With Inflammatory Bowel Diseases

Phase 4

Completed

• Conditions: Inflammatory Bowel Diseases
• Interventions: Drug: Infliximab

• Registration Number: NCT04982172
• Lead Sponsor: Universitaire Ziekenhuizen KU Leuven

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.

Detailed Description

Not available

Study Timeline

• Study First Submitted: 2021-07-19
• Study First Submitted QC: 2021-07-19
• Study First Posted: 2021-07-29
• Status Verified: 2022-02
• Study Start: 2022-02-08
• Primary Completion: 2022-11-01
• Study Completion: 2023-02-01
• Last Update Submitted: 2024-12-05
• Last Update Posted: 2024-12-11

Recruitment & Eligibility

• Status: COMPLETED
• Sex: All
• Target Recruitment: 80

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.

Study & Design

• Study Type: INTERVENTIONAL
• Study Design: PARALLEL

Arm && Interventions

Group	Intervention	Description
Interventional arm	Infliximab	Model-informed precision dosing of infliximab (intravenously administered) using a Bayesian forecasting software tool. Doses and dosing intervals will be derived from the software tool, aiming to maintain adequate exposure (trough concentration target 5 mg/L).
Historical control arm	Infliximab	The treating physician adjusted the intravenously administered infliximab doses and dosing intervals without being guided by a model-informed precision dosing software tool. The primary objective was to extend the dosing interval. Therefore, dose de-escalation (interval extension with/without dose adjustment) were performed following a scheme at the treating physician's discretion.

Primary Outcome Measures

Name	Time	Method
Steroid-free, combined clinical and biological remission	During one year after start of infliximab dose de-escalation	The proportion of patients maintaining steroid-free, combined clinical and biological remission during one year after infliximab dose de-escalation based on a standard dosing algorithm versus a model-informed dosing algorithm.; Combined clinical and biological remission is defined based on patient-reported outcomes (rectal bleeding score = 0 + stool frequency score ≤1 \[ulcerative colitis\], mean daily abdominal pain score ≤1 + liquid stool frequency score ≤1.5 \[Crohn's disease\]) together with normal C-reactive protein (\<5 mg/L) and faecal calprotectin (\<250 mg/kg). Steroid-free indicates the absence of any dose of any oral or rectal steroid use.

Secondary Outcome Measures

Name	Time	Method
Steroid-free, combined clinical and biological remission	At one year after start of infliximab dose de-escalation	The proportion of patients maintaining steroid-free, combined clinical and biological remission at one year after infliximab dose de-escalation based on a standard dosing algorithm versus a model-informed dosing algorithm.; Combined clinical and biological remission is defined based on patient-reported outcomes (rectal bleeding score = 0 + stool frequency score ≤1 \[ulcerative colitis\], mean daily abdominal pain score ≤1 + liquid stool frequency score ≤1.5 \[Crohn's disease\]) together with normal C-reactive protein (\<5 mg/L) and faecal calprotectin (\<250 mg/kg). Steroid-free indicates the absence of any dose of any oral or rectal steroid use.

Trial Locations

Locations (1)

UZ Leuven; 🇧🇪 Leuven, Vlaanderen, Belgium