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

Inflammatory Bowel Diseases Clinical Trial

— MODIFI  

Official title:

Model-informed Infliximab Dose De-escalation Following Earlier Dose Escalation in Adult Patients With Inflammatory Bowel Diseases

Clinical Trial Details — Status: Recruiting

Administrative data

• NCT number: NCT04982172
• Other study ID #: S64521
• Status: Recruiting
• Phase: Phase 4
• Start date: February 2022
• Est. completion date: February 2023

Study information

• Verified date: February 2022
• Source: Universitaire Ziekenhuizen Leuven
• Contact: Marc Ferrante, MD, PhD
• Phone: +3216342845
• Email: IBD_studies[@]uzleuven.be
• Is FDA regulated: No
• Study type: Interventional

Clinical Trial 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.

Recruitment information / eligibility

• Status: Recruiting
• Enrollment: 80
• Est. completion date: February 2023
• Est. primary completion date: November 2022
• Accepts healthy volunteers: No
• Gender: All
• Age group: 18 Years to 80 Years

Eligibility

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.

Related Conditions & MeSH terms

• Inflammatory Bowel Diseases
• Intestinal Diseases

Intervention

Drug:
• Infliximab
Infliximab (Inflectra® [Pfizer]), dosage determined using model-informed precision dosing, intravenously administered
• Infliximab
Infliximab, dosage following a dose de-escalation algorithm at the physician's discretion, intravenously administered

Locations

Country	Name	City	State
Belgium	UZ Leuven	Leuven	Vlaanderen

Sponsors (2)

Lead Sponsor	Collaborator
Universitaire Ziekenhuizen Leuven	KU Leuven

Country where clinical trial is conducted

Belgium, 

Outcome

Type	Measure	Description	Time frame	Safety issue
Other	Steroid-free clinical remission	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.	At and during one year after start of infliximab dose de-escalation
Other	Steroid-free biological remission	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.	At and during one year after start of infliximab dose de-escalation
Other	Infliximab trough concentration target attainment and area under the concentration-time curve	Exposure: Trough concentration (target attainment; 5 mg/L) and area under the concentration-time curve.	At and during one year after start of infliximab dose de-escalation
Other	Total infliximab dose and number of infusions	Dosage: total infliximab dose (# mg) and number of infusions.	At and during one year after start of infliximab dose de-escalation
Other	Direct costs calculated based on cost of infliximab and cost related to the day hospital needed for the infusion	Direct costs calculated based on cost of infliximab and cost related to the day hospital needed for the infusion (in euro).	At one year after start of infliximab dose de-escalation
Other	Indirect costs based on questionnaire	Indirect costs based on questionnaire: iMTA Productivity Cost Questionnaire (iMTA PCQ)	At one year after start of infliximab dose de-escalation
Other	Health-related quality of life based on QoL questionnaire	Health-related quality of life based on QoL questionnaire: Inflammatory Bowel Disease Questionnaire (IBDQ-32)	At one year after start of infliximab dose de-escalation
Primary	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	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.	At one year after start of infliximab dose de-escalation