MOdel-Informed Precision Dosing of Ustekinumab and VEdolizumab in Inflammatory Bowel Disease

Phase 4

Not yet recruiting

• Conditions: Inflammatory Bowel Diseases; Crohn Disease; Ulcerative Colitis
• Interventions: Drug: PK-model to decide when to dose Vedolizumab and Ustekinumab

• Registration Number: NCT06788340
• Lead Sponsor: Odense University Hospital

Brief Summary

The goal of this clinical trial is to investigate if dosage of Ustekinumab (UST) and Vedolizumab (VDZ) based on Model-Informed Precision Dosing (MIPD) is equally as efficient in keeping adults with Inflammatory Bowel Disease (IBD) in remission as management based on what the treating physician deems best. The main question is:

Is using pharmacokinetic-pharmacodynamic (PK-PD) models to predict the appropriate dose and dosing interval for VDZ and UST at least as effective as current practices in maintaining IBD remission.

As above mentioned the comparison-group is adults with IBD, treated with UST or VDZ, managed as the physician deems best.

Participants will:

Have blood and stool tests done, as well as answer a questionnaire 4th weekly Have their dosage frequency decided on either by the PK-model or as the physician deems best visit the clinic once every 24 weeks for checkups. Have an endoscopy done at completion of the study (if the disease is primarily located in the small intestine, MRI or capsule endoscopy will be used instead)

Detailed Description

Patients will 4th weekly have their drug-concentration in blood measured (and if low, also antidrug antibodies). Hemoglobin, Albumin, CRP and white blood cell count will also be done, as well as a stool-sample for calprotectin measurement.

For the control group however, the clinicians and patients will be blinded for the results of the blood- and stool samples, and the samples for drug concentration will not get analyzed before end of study.

4th weekly they will also answer PRO2 questionnaire, as well as the VAS-F. 8th weekly they will in addition to above mentioned also answer the EQ-5D-5L questionnaire.

At inclusion, after 24 weeks, and at 48 weeks the patients will in addition to the above mentioned also answer the short IBDQ and WPAI questionnaires, as well as be seen in the outpatient clinic to obtain HBI or SCCAI score as applicable, as well as to document any changes in concomitant medication or diseases, and to register if any serious adverse events have presented.

At completion of the trial, patients will have a endoscopy done.

In one subprotocol, the investigators will include 20 patients from Odense to have an endoscopy at both inclusion and completion. Here they will also have biopsies taken from all segments of the colon, which will be stores in a biobank for future research.

In another subprotocol 20 patients will be included to have a intestinal ultrasound done at inclusion and completion.

In a biobank for future research the investigators will also store serum-samples, buffy coat, and stool samples collected at inclusion, after 24 and 48 weeks from all included patients.

Study Timeline

• Status Verified: 2025-01
• Study First Submitted: 2025-01-07
• Study First Submitted QC: 2025-01-22
• Study First Posted: 2025-03-25
• Last Update Submitted: 2025-03-25
• Last Update Posted: 2025-03-26
• Study Start: 2025-05-01
• Primary Completion: 2027-03-01
• Study Completion: 2027-03-14

Recruitment & Eligibility

• Status: NOT_YET_RECRUITING
• Sex: All
• Target Recruitment: 166

Inclusion Criteria

• Ulcerative colitis or Crohn's disease. Diagnosed, according to universally acknowledged criteria, a minimum of 3 months prior to inclusion
• Age ≥ 18
• Stable treatment with VDZ or UST for at least 3 months prior to inclusion
• Stable disease activity, mild activity is accepted, defined by fecal calprotectin ≤ 200, and a weighted PRO2 < 14 for CD or a PRO2 ≤3 for UC
• No change in medical therapy within 3 months prior to inclusion, as concomitant therapy with other immune suppressants is allowed (Azathioprine, 6-mercaptopurine, Methotrexate, 5-aminosalicylic acid)
• The patient must be able to understand patient information material
• The patient must be able to give informed written consent

Exclusion Criteria

• Having a diagnose of indeterminate colitis
• Having a stoma or pouch
• Fistulizing disease being the primary reason for treatment with VDZ or UST
• Expected eminent change of therapy
• Expected need for surgical intervention within the coming 3 months
• Contraindication against continuing treatment with VDZ or UST, including prior acute or delayed infusion reaction to VDZ or UST
• Any active infection requiring parenteral treatment, known infection with tuberculosis, human immunodeficiency virus (HIV) or hepatitis virus.
• Any condition which the responsible physician finds incompatible with participation in the study
• Patients unable to participate in the collection of symptoms scores
• Patients who are pregnant or nursing at time of inclusion

Study & Design

• Study Type: INTERVENTIONAL
• Study Design: PARALLEL

Arm && Interventions

Group	Intervention	Description
Model-informed precision dosing of Vedolizumab/Ustekinumab	PK-model to decide when to dose Vedolizumab and Ustekinumab	Patients will have blood- and stool samples collected, as well as date and time of drug administration every 4th week. All of these informations, in addition to some informations collected at inclusion, will be used in a PK-model to prescribe when the next dosage of drug should be administered to keep the patient in the therapeutic window.

Primary Outcome Measures

Name	Time	Method
The fraction of patients in steroid-free remission	at the end of the observation period (48 weeks)	((for CD defined by PRO2 ≤ 4, for UC defined by PRO2 = 0) AND a fecal calprotectin ≤200)

Secondary Outcome Measures

Name	Time	Method
Inflammatory burden over the observational period	48 weeks	CRP, albumin, hemoglobin, leukocyte counts and fecal calprotectin. These will be collected every 4th week
The fraction of the observation period (48 weeks) where the disease is in steroid-free remission	this is registered every 4th week throughout the study duration of 48 weeks.	for CD defined by patient reported outcome 2 (PRO2) stool frequency \<= 3 and abdominal pain \< = 1, for UC defined by PRO2, number of abnormal stools for the patient, bleeding from the rectum = 0) AND a fecal calprotectin ≤ 200.
The financial costs associated with the two treatment strategies over the observation period (12 months)	through study completion, an average of 48 weeks	expenditure on medicines (both expenditure on the purchase of medicines and expenditure on the administration of medicines), expenses for doctor visits / visits to a nurse, possibly expenses for hospitalization, possibly expenses for surgery, possibly expenses for sick leave and possibly expenses for early retirement.; After end of study, the investigators will collect data on sick leave etc. from the national patient registry.
Endoscopic healing of the mucosa	at completion of study, approximately 48 weeks	for CD assessed by Simple Endoscopic Score for Crohn's Disease (SES-CD) \<3; and for UC assessed on the basis of the Ulcerative Colitis Endoscopic Index of Severity (UCEIS)≤1. If disease is primarily located in the small intestine, MRI or capsule endoscopy will be used instead, and assessed by the simplified MaRIA score \<1 or Lewis score ≤135, respectively
Changes in quality of life during the study period	48 weeks	assessed by Short Inflammatory Bowel Disease Questionnaire (SIBDQ) difference between baseline and end of study. Improvement of quality of life indicated by a positive change of the SIBDQ. SIBDQ is collected at inclusion, week 24 and week 48. A higher the score, indicates a better outcome, Maksimum score of 70 points.
Quality of life as QALYs	48 weeks	assessed by the EuroQol-5 dimensions-5 levels questionnaire (EQ-5D-5L) and converted to QALYs. The cost per QALY will also be calculated. EQ-5D-5L is collected every 8th week throughout the study. Score ranges from 5-25, a higher score indicating poorer quality of life.
Clinical Disease Activity	48 weeks	assessed by Simplified Clinical Colitis Activity Index (SCCAI) for UC and Harvey-Bradshaw Index (HBI) for CD. These are collected at inclusion and every 24th week thereafter. SCCAI score ranges from 0-19, a higher score indicating a more severe disease activity. HBI score ranges from 0-20, a higher score indicating more severe disease activity.
Expenses for analysis of drug concentration	48 weeks	patients will have drug concentrations analyzed every 4th week, the price of this will be collected
Expenses for drugs	48 weeks	patients will typically administer sc VDZ every 4th to 2nd week, iv VDZ every 12th to 4th week and UST every 12th to 4th week
Drug persistency	48 weeks	number of patients switching to another treatment during the study
Disease flares	48 weeks	assessed by consumption of glucocorticoids or IBD-related surgery
Fatigue	48 weeks.	to assess if treating according to a PK-model results in less fatigue measured by Visual Analogue Scale to Evaluate Fatigue Severity (VAS-F). Patients are asked to register how fatigued they feel every 4th week throughout the study. The VAS-F is a visual analogue scale that goes from 0-10, 10 indicating severe fatigue.
Disease impact on work productivity and performance of daily activities	48 weeks	Assessed by difference in Work Productivity and Activity Impairment questionnaire (WPAI) scores and changes in scores between patients in the intervention- and control group. WPAI is collected at inclusion and every 24th week throughout the study.; WPAI outcomes are expressed as impairment percentages, with higher numbers indicating greater impairment and less productivity.

Trial Locations

Locations (4)

Dept. of Gastrointestinal Diseases; 🇩🇰 Odense, Denmark

Dept. of Internal Medicin; 🇩🇰 Esbjerg, Denmark

Dept. of medicine; 🇩🇰 Nyborg, Denmark

Dept. of Medicine; 🇩🇰 Vejle, Denmark