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

Universitaire Ziekenhuizen KU Leuven

Status and phase: Completed; Phase 4

Conditions: Inflammatory Bowel Diseases

Treatments: Drug: Infliximab

Study type: Interventional

Funder types: Other

Identifiers

NCT04982172

S64521

Details and patient eligibility

About

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.

Enrollment: 80 patients

Sex: All

Ages: 18 to 80 years old

Volunteers: No Healthy Volunteers

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.

Trial design

Primary purpose: Treatment

Allocation: Non-Randomized

Interventional model: Parallel Assignment

Masking: None (Open label)

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80 participants in 2 patient groups

Interventional arm

Experimental group

Description:

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).

Treatment:

Drug: Infliximab

Drug: Infliximab

Historical control arm

Active Comparator group

Description:

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.

Treatment:

Drug: Infliximab

Drug: Infliximab