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

NCT ID: NCT04982172

Last Updated: 2024-12-11

Basic Information

• Recruitment Status: COMPLETED
• Clinical Phase: PHASE4
• Total Enrollment: 80 participants
• Study Classification: INTERVENTIONAL
• Study Start Date: 2022-02-08
• Study Completion Date: 2023-02-01

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.

Conditions

Inflammatory Bowel Diseases

Study Design

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

Study Groups

Interventional arm

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).

Group Type: EXPERIMENTAL

Infliximab

Intervention Type: DRUG

Infliximab (Inflectra® \[Pfizer\]), dosage determined using model-informed precision dosing, intravenously administered

Historical control arm

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.

Group Type: ACTIVE_COMPARATOR

Infliximab

Intervention Type: DRUG

Infliximab, dosage following a dose de-escalation algorithm at the physician's discretion, intravenously administered

Interventions

Infliximab

Infliximab (Inflectra® \[Pfizer\]), dosage determined using model-informed precision dosing, intravenously administered

Intervention Type: DRUG

Infliximab

Infliximab, dosage following a dose de-escalation algorithm at the physician's discretion, intravenously administered

Intervention Type: DRUG

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.

• Minimum Eligible Age: 18 Years
• Maximum Eligible Age: 80 Years
• Eligible Sex: ALL
• Accepts Healthy Volunteers: No

Sponsors

KU Leuven

OTHER

Sponsor Role: collaborator

Universitaire Ziekenhuizen KU Leuven

OTHER

Sponsor Role: lead

Responsible Party

Responsibility Role: SPONSOR

Principal Investigators

Marc Ferrante, MD, PhD

Role: PRINCIPAL_INVESTIGATOR

UZ Leuven

Locations

UZ Leuven

Leuven, Flanders, Belgium

Countries

Belgium

References

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.

Reference Type: DERIVED

PMID: 35706358 (View on PubMed)

Other Identifiers

S64521

Identifier Type: -

Identifier Source: org_study_id