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

NCT04982172 | Completed Phase 4

• 1 other identifier: S64521
• Study Type: interventional
• Target: 80
• Locations: 1 country
• Sites: 1

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

Outcome Measures

Primary Outcomes (1)

• Steroid-free, combined clinical and biological remission

  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.

  During one year after start of infliximab dose de-escalation

Secondary Outcomes (1)

• Steroid-free, combined clinical and biological remission

  At one year after start of infliximab dose de-escalation

Other Outcomes (7)

• Steroid-free clinical remission

  At and during one year after start of infliximab dose de-escalation

• Steroid-free biological remission

  At and during one year after start of infliximab dose de-escalation

• Infliximab trough concentration target attainment and area under the concentration-time curve

  At and during one year after start of infliximab dose de-escalation

Study Arms (2)

Interventional arm

EXPERIMENTAL

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).

Drug: Infliximab

Historical control arm

ACTIVE COMPARATOR

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.

Drug: Infliximab

Interventions

Infliximab DRUG

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

Interventional arm

Eligibility Criteria

• Age: 18 Years - 80 Years
• Sex: all
• Healthy Volunteers: No
• Age Groups: Adult (18-64), Older Adult (65+)

You may qualify if:

• 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).

You may not qualify if:

• 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.

Sponsors & Collaborators

• Universitaire Ziekenhuizen KU Leuven: lead
• KU Leuven: collaborator

Study Sites (1)

UZ Leuven

Leuven, Flanders, 3000, Belgium

Location

Related Publications (1)

• 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.

  PMID: 35706358 DERIVED

MeSH Terms

Conditions

Inflammatory Bowel Diseases

Interventions

Infliximab

Condition Hierarchy (Ancestors)

Gastroenteritis; Gastrointestinal Diseases; Digestive System Diseases; Intestinal Diseases

Intervention Hierarchy (Ancestors)

Antibodies, Monoclonal; Antibodies; Immunoglobulins; Immunoproteins; Blood Proteins; Proteins; Amino Acids, Peptides, and Proteins; Serum Globulins; Globulins

Study Officials

• Marc Ferrante, MD, PhD

  UZ Leuven

  PRINCIPAL INVESTIGATOR

Study Design

• Study Type: interventional
• Phase: phase 4
• Allocation: NON RANDOMIZED
• Masking: NONE
• Purpose: TREATMENT
• Intervention Model: PARALLEL
• Sponsor Type: OTHER
• Responsible Party: SPONSOR

Study Record Dates

• First Submitted: July 19, 2021
• First Posted: July 29, 2021
• Study Start: February 8, 2022
• Primary Completion: November 1, 2022
• Study Completion: February 1, 2023
• Last Updated: December 11, 2024

Record last verified: 2022-02

Locations

BE (1)