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

Primary Purpose

Inflammatory Bowel Diseases

Status
Recruiting
Phase
Phase 4
Locations
Belgium
Study Type
Interventional
Intervention
Infliximab
Infliximab
Sponsored by
Universitaire Ziekenhuizen KU Leuven
About
Eligibility
Locations
Arms
Outcomes
Full info

About this trial

This is an interventional treatment trial for Inflammatory Bowel Diseases

Eligibility Criteria

18 Years - 80 Years (Adult, Older Adult)All SexesDoes not accept 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.

Sites / Locations

  • UZ LeuvenRecruiting

Arms of the Study

Arm 1

Arm 2

Arm Type

Experimental

Active Comparator

Arm Label

Interventional arm

Historical control arm

Arm 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).

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.

Outcomes

Primary Outcome Measures

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.

Secondary Outcome Measures

Steroid-free, combined clinical and biological remission
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.

Full Information

First Posted
July 19, 2021
Last Updated
February 11, 2022
Sponsor
Universitaire Ziekenhuizen KU Leuven
Collaborators
KU Leuven
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1. Study Identification

Unique Protocol Identification Number
NCT04982172
Brief Title
Model-informed Dose De-escalation of Infliximab in Patients With Inflammatory Bowel Diseases
Acronym
MODIFI
Official Title
Model-informed Infliximab Dose De-escalation Following Earlier Dose Escalation in Adult Patients With Inflammatory Bowel Diseases
Study Type
Interventional

2. Study Status

Record Verification Date
February 2022
Overall Recruitment Status
Recruiting
Study Start Date
February 2022 (Anticipated)
Primary Completion Date
November 2022 (Anticipated)
Study Completion Date
February 2023 (Anticipated)

3. Sponsor/Collaborators

Responsible Party, by Official Title
Sponsor
Name of the Sponsor
Universitaire Ziekenhuizen KU Leuven
Collaborators
KU Leuven

4. Oversight

Studies a U.S. FDA-regulated Drug Product
No
Studies a U.S. FDA-regulated Device Product
No
Product Manufactured in and Exported from the U.S.
No

5. Study Description

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.

6. Conditions and Keywords

Primary Disease or Condition Being Studied in the Trial, or the Focus of the Study
Inflammatory Bowel Diseases

7. Study Design

Primary Purpose
Treatment
Study Phase
Phase 4
Interventional Study Model
Parallel Assignment
Masking
None (Open Label)
Allocation
Non-Randomized
Enrollment
80 (Anticipated)

8. Arms, Groups, and Interventions

Arm Title
Interventional arm
Arm Type
Experimental
Arm 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).
Arm Title
Historical control arm
Arm Type
Active Comparator
Arm 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.
Intervention Type
Drug
Intervention Name(s)
Infliximab
Intervention Description
Infliximab (Inflectra® [Pfizer]), dosage determined using model-informed precision dosing, intravenously administered
Intervention Type
Drug
Intervention Name(s)
Infliximab
Intervention Description
Infliximab, dosage following a dose de-escalation algorithm at the physician's discretion, intravenously administered
Primary Outcome Measure Information:
Title
Steroid-free, combined clinical and biological remission
Description
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.
Time Frame
During one year after start of infliximab dose de-escalation
Secondary Outcome Measure Information:
Title
Steroid-free, combined clinical and biological remission
Description
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.
Time Frame
At one year after start of infliximab dose de-escalation
Other Pre-specified Outcome Measures:
Title
Steroid-free clinical remission
Description
The proportion of patients maintaining steroid-free clinical remission at and during one year after infliximab dose de-escalation based on a standard dosing algorithm versus a model-informed dosing algorithm. Clinical 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]). Steroid-free indicates the absence of any dose of any oral or rectal steroid use.
Time Frame
At and during one year after start of infliximab dose de-escalation
Title
Steroid-free biological remission
Description
The proportion of patients maintaining steroid-free biological remission at and during one year after infliximab dose de-escalation based on a standard dosing algorithm versus a model-informed dosing algorithm. Biological remission is defined as 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.
Time Frame
At and during one year after start of infliximab dose de-escalation
Title
Infliximab trough concentration target attainment and area under the concentration-time curve
Description
Exposure: Trough concentration (target attainment; 5 mg/L) and area under the concentration-time curve.
Time Frame
At and during one year after start of infliximab dose de-escalation
Title
Total infliximab dose and number of infusions
Description
Dosage: total infliximab dose (# mg) and number of infusions.
Time Frame
At and during one year after start of infliximab dose de-escalation
Title
Direct costs calculated based on cost of infliximab and cost related to the day hospital needed for the infusion
Description
Direct costs calculated based on cost of infliximab and cost related to the day hospital needed for the infusion (in euro).
Time Frame
At one year after start of infliximab dose de-escalation
Title
Indirect costs based on questionnaire
Description
Indirect costs based on questionnaire: iMTA Productivity Cost Questionnaire (iMTA PCQ)
Time Frame
At one year after start of infliximab dose de-escalation
Title
Health-related quality of life based on QoL questionnaire
Description
Health-related quality of life based on QoL questionnaire: Inflammatory Bowel Disease Questionnaire (IBDQ-32)
Time Frame
At one year after start of infliximab dose de-escalation

10. Eligibility

Sex
All
Minimum Age & Unit of Time
18 Years
Maximum Age & Unit of Time
80 Years
Accepts Healthy Volunteers
No
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.
Central Contact Person:
First Name & Middle Initial & Last Name or Official Title & Degree
Marc Ferrante, MD, PhD
Phone
+3216342845
Email
IBD_studies@uzleuven.be
First Name & Middle Initial & Last Name or Official Title & Degree
Erwin Dreesen, PharmD, PhD
Phone
+32 16372753
Email
erwin.dreesen@kuleuven.be
Overall Study Officials:
First Name & Middle Initial & Last Name & Degree
Marc Ferrante, MD, PhD
Organizational Affiliation
UZ Leuven
Official's Role
Principal Investigator
Facility Information:
Facility Name
UZ Leuven
City
Leuven
State/Province
Vlaanderen
ZIP/Postal Code
3000
Country
Belgium
Individual Site Status
Recruiting
Facility Contact:
First Name & Middle Initial & Last Name & Degree
Marc Ferrante, MD, PhD
Phone
+3216342845
Email
IBD_studies@uzleuven.be
First Name & Middle Initial & Last Name & Degree
Erwin Dreesen, PharmD, PhD

12. IPD Sharing Statement

Citations:
PubMed Identifier
35706358
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.
Results Reference
derived

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

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